Adipose stem cells (ASCs) have multilineage differentiation capacity and hold great potential for regenerative medicine. Compared to bone-marrow-derived mesenchymal stem cells (bmMSCs), ASCs are easier to isolate from abundant sources with significantly higher yields. It is generally accepted that bmMSCs show age-related changes in their proliferation and differentiation potentials, whereas this aspect is still controversial in the case of ASCs. In this review, we evaluated the existing data on the effect of donor age on the osteogenic potential of human ASCs. Overall, a poor agreement has been achieved because of inconsistent findings in the previous studies. Finally, we attempted to delineate the possible reasons behind the lack of agreements reported in the literature. ASCs represent a heterogeneous cell population and the osteogenic potential of ASCs can be influenced by donor-related factors such as age, but also gender, lifestyle, and the underlying health and metabolic state of donors. Furthermore, future studies should consider experimental factors in in-vitro conditions, including passaging, cryopreservation, culture conditions, variations in differentiation protocols, and readout methods.

This study aims at the sustainable valorization of eggshells (ES) from different countries of origin in cement concrete as a cement replacement for Hong Kong. For this purpose, sixteen different eggs from different regions across the world were selected from the local market. Firstly, the extent of uniformity in the weight and mineral content of sampled eggshells were assessed by a specific gravity test and thermogravimetric analysis (TGA), respectively. It was found that specific gravity varies between 2.02 and 2.39, with an average value of 2.20 ± 0.01, whereas CaCO₃ varies between 94.65% and 97.23%, with an average value of 96.33%. These values were a bit lower than those of extra-pure limestone (LS) because of the organic part and the porous structure of eggshells. Secondly, three different eggshells were selected for cement replacement in cement concrete, both in the uncalcined and calcined states, based on having the highest, medium, and lowest CaCO₃ content, respectively. To get the calcined eggshells, the eggshells were calcined at 800^oC for three hours. It was found that the strength of eggshells varies with CaCO₃, but the variation was acceptable. The calcined eggshells showed comparatively more compressive strength and were close to the LS because of the free CaO and the absence of an organic part. In general, the variation in the basic properties of eggshells from different regions across the world is negligible and suitable to use as a cement replacement with acceptable variation in strength in Hong Kong.

Vulnerable carotid plaques are responsible for 20% of the ischemic strokes. The identification of those asymptomatic carotid plaques that will become symptomatic is essential but remains unclear. Our main goal was to investigate whether the amount of the peri-carotid adipose tissue, estimated by the extra-media thickness (EMT) is associated with the atherosclerotic characteristics at the carotid bifurcation in patients with PAD. An observational, prospective, single-center, longitudinal study was conducted. 177 patients performed carotid Doppler-ultrasound. The following data was collected: EMT, intima-media thickness (IMT), presence of carotid plaques, area of the highest plaque, and grade of internal carotid stenosis. From each carotid bifurcation a right and left EMT was determined. We analyzed both the mean EMT (calculated as the mean between the right and the left EMT) and the EMT ipsilateral to the carotid bifurcation. The presence of carotid plaques was associated with a higher mean EMT, [Median=1.14; IQR=0.66 versus Median=0.97; IQR=0.40; p=.001]. A positive correlation was found between mean EMT and IMT (right: ρ=.20; p=.010; left: ρ=.21; p=.007) and between mean EMT and area of the largest carotid plaque (right: ρ=.17; p=.036; left: ρ=.22; p=.004). Left carotid stenosis ≥ 70% was associated with higher mean EMT. [Median=1.55; IQR=0.68 versus Median=1.00; IQR=0.46; p=.019]. Patients with “acute culprit” carotid stenosis had a higher ipsilateral EMT [Left ipsilateral EMT: Median=1.46; IQR=0.63; “non-acute”: Median=0.94; IQR=0.43; p=.009; Right ipsilateral EMT: Median=2.25; IQR=0.62; “non-acute”: Median=1.00; IQR=0.51; p=.015]. This difference was not found in the contra-lateral EMT. Six months after the neurologic event, EMT ipsilateral to an “acute culprit” carotid stenosis decreased (p=.036). The amount of peri-carotid adipose tissue, estimated with EMT was associated with atherosclerosis at the carotid arteries. In particularly EMT could be a non-invasive marker of “acute culprit” carotid stenosis, easily determined in clinical practice. These findings may have implications in personalized medicine, for the determination of the best treatment approach.

The assessment of Health-Related Quality of Life (HRQoL) in Thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of Transfusion-Dependent Thalassemia (TDT) patients in Greece. This was a multicentre, cross-sectional study conducted in 2017, involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower, compared to the general population in Greece. The mean summary score of TranQol was relatively high (71±14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment in a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

The relationship between epicardial adipose tissue (EAT) and atrial fibrillation (AF) has gained interest in recent years. Previous literature on the topic presents great heterogeneity, focusing especially on computed tomog-raphy imaging. Aim of the present study is to determine whether an increased volume of left atrial (LA) EAT evaluated at routine pre-procedural cardiac magnetic resonance imaging (MRI) relates to AF recurrences after catheter ablation. 50 patients undergoing AF cryoballoon ablation and pre-procedural cardiac MRI allowing quantification of LA EAT were enrolled. In one patient segmentation of LA EAT could not be achieved. After a median follow-up of 16.0 months, AF recurrences occurred in 17 patients (34%). Absolute volume of EAT was not different in patients with and without AF recurrences (10.35 ml vs. 10.29 ml; p-value=0.963), whereas volume of EAT indexed on the LA (EATi) was lower, albeit non statistically significant, in patients free from arrhythmias (12.77% vs. 14.06%; p-value=0.467). Receiver operating characteristic curve testing the ability of EATi to predict AF recurrence after catheter ablation showed sub-optimal performance (AUC: 0.588). The finest identified cut-off of EATi was 10.65%, achieving a sensitivity of 0.5, a specificity of 0.82, a positive predictive value of 0.59 and a negative predictive value of 0.76. Patients with values of EATi lower than 10.65% showed greater survival free from arrhythmias than patients with values above this cut-off (84% vs. 48%; p-value=0.04). In conclusion, indexed LA EAT volume evaluated at cardiac MRI independently relates to arrhythmia recurrence after AF cryoballoon ablation.

Epilepsy is a chronic neurological disorder characterized by recurring seizures resulting from abnormal neuronal hyperexcitability. In the case of pharmacoresistant epilepsy requiring resection surgery, identifying the epileptogenic zone (EZ) is crucial. Fast ripples (FRs; 200-600 Hz) are one of the promising biomarkers that can aid in EZ delineation. However, recording FRs requires small surface electrodes. These microelectrodes suffer from high impedance, which significantly impacts FR observability and detection. In this study, we explored the potential of a conductive polymer coating to enhance FR observability. We employed biophysical modeling to compare two types of microelectrodes: Gold (Au) and Au coated with the conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (Au/PEDOT:PSS). These electrodes were then implanted in the CA1 hippocampal neural network of epileptic mice to record FRs during epileptogenesis. Results showed that polymer-coated electrodes demonstrate two-order lower impedance and a higher transfer function amplitude and cut-off frequency. Consequently, FRs recorded with the PEDOT:PSS coated microelectrode yielded significantly higher signal energy compared to the uncoated one. The coating with PEDOT:PSS improved the observability of recorded FRs and therefore their detection. This work paves the way for the development of signal-specific microelectrodes design allowing better targeting of pathological biomarkers.

In a 24-week-long experiment, 31 rats were assigned to one of 3 groups: a Control group receiving standard chow and water, a Fructose group receiving standard chow and a 20% fructose solution, or an STZ+lipids group that received a fat-enriched diet following a single 25 mg/kg streptozotocin injection at the onset of the diet. Both groups experienced significantly increased caloric intake but did not gain weight above the Control group level. Adipocytes in subcutaneous and visceral adipose depots of both groups had smaller size compared to control and higher density in tissue. Respirometric analyses unveiled a substantial increase in mitochondrial respiration across all adipose tissue types in both dietary intervention groups, with greater changes observed in the Fructose group. Correlation analyses demonstrated that in both experimental groups high tissue respiration is associated with better biochemical profile and closer to control adipose tissue morphology. Increased tissue respiration in adipose depots could be an important mechanism of resilience to excessive caloric intake.

A rather large portion of the population is sleep restricted in modern society, either by necessity or by choice. Epidemiological studies have observed that lack of sleep and poor sleep quality are associated with several pathological states, ranging from neuropsychiatric to metabolic diseases. To date, only a few studies have investigated the molecular consequences of sleep loss at the level of peripheral organs involved in maintaining metabolic homeostasis such as the white adipose tissue (WAT). From a molecular point of view, two key transcriptional regulators of WAT function are sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptors gamma (PPARγ). Both genes interact with specific targets involved in multiple metabolic processes, including adipocyte differentiation, browning and lipid metabolism. In this study, we assessed the effects of chronic sleep restriction (CSR) on the interplay between SIRT1 and PPARγ in mediating WAT metabolism in young adult mice. We found that CSR up-regulated expression of SIRT1 and some of its transcriptional targets involved in lipid metabolism and mitochondrial functions of adipocytes. Results suggest that CSR induces SIRT1-mediated metabolic remodeling of WAT to support an increased energy demand due to sleep loss.

Aggressive angiomyxoma (AAM) is a rare and benign mesenchymal tumor, localized predominantly in the female pelvis. Its invasive growth and local recurrence are challenging for professionals. Histologically, AAM is a tumor with a myxoid, highly vascularized stroma. The diagnosis is made relatively late due to nonspecific symptoms. Treatment of AAM is extensive local surgical excision. Gonadotropin-releasing hormone agonists are added postoperatively. The prognosis is good and metastasis is rare. We present a case of an AAM located in the left greater labial area in a 50-year-old woman initially diagnosed as left inguinal hernia. The tumor was extirpated under epidural anaesthesia on the date of the patient's informed consent. The patient was prescribed postoperative therapy with Zoladex 3,6 mg according to the schedule. The patient was subjected to monthly gynecological check-ups for one year after the surgical intervention. To date, no recurrence of the underlying disease has been detected. Long-term results show a good trend. In conclusion, we can say that the optimal treatment of AAM is wide local excision. Рadicality is not recommended because of the risk of postoperative complications. Postoperative administration of GnRH-a is advisable to avoid recurrences. All patients undergo regular follow-up examinations for long-term.

The high prevalence of childhood obesity is known to increase the risk of non-communicable diseases typically found in adults, such as cardiovascular disease and type 2 diabetes mellitus. However, worldwide childhood obesity cases continue to rise, thus comprehending its multiple causes to build healthier approaches and revert this scenario is urgent. Obesity development is now strongly associated with high fructose intakes, so mitigating the idea that fructose is a ‘natural nutrient’ and therefore beneficial to health, may be required, since. Excessive consumption of this highly lipogenic sugar leads to white fat accumulation, stimulates adipogenesis and causes white adipose tissue (WAT) inflammation, oxidative stress and dysregulated adipokine release. Unfortunately, dietary consumption of fructose is not always evident to consumers, as it is commonly added as a sweetener in food and sugar-sweetened beverages (SSB). Global consumption of fructose has increased dramatically in recent years. Therefore, it is important that the population has access to reliable information about food ingredients, via food labels. Consumers also need scientific education to understand potential health risks to themselves and their children. Here we discuss the impact of excessive fructose intake on adipose tissue biology, its contribution to childhood obesity and make suggestions for reversing this trend.

Vascular endothelial growth factors (VEGFs) are regarded as the key vasculogenic mediators in the human body, of which VEGF-A is considered as one of the important types. It is the major growth factor possessing increasing vascular permeability as well as angiogenesis properties. This article provides intuition into the different effects of VEGF-A on vessels in ovarian hyper stimulation syndrome (OHSS) which is defined as a complication of in-vitro fertilization for infertility treatment, and obesity, a universally health problem. These are two dissimilar pathways outcomes for VEGF-A effects, thereby This article reviews updated information about the mentioned disorders and reveals that how this kind of growth factor yields different results on vasculature by activating distinct intracellular signaling in endothelial cells.

Abstract Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently been emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes of gene expression patterns and functional pathways in BLCA patients with different expression of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays and in vivo nude mice xenograft models, respectively. Finally, chromatin isolation by RNA purification (ChIRP) experiment were further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase, and promoted the apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate transcription program and then affect BLCA progression. Conclusion: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.

This study focuses on the modification of ion-exchange membranes by incorporating phosphorylated dendrimer into sulfonated polytetrafluoroethylene membranes to enhance specific selectivity between mono-/divalent ions, using the Ca2+/Na+ pair as an example. The research employs mechanical, physico-chemical, and electrochemical analyses to explore the effects of P-H20 incorporation on membrane properties. Bulk modification significantly increases membrane selectivity towards calcium ions (specific permselectivity coefficient rises from 1.5 to 7.2), while maintaining the same level of the limiting current density. Other findings indicate that bulk modification significantly changes the transport-channel structure of the membrane and alters the mechanism of over-limiting mass transfer. The over-limiting current for the pristine membrane is mainly due to non-equilibrium electroconvection, while modified membranes actively participate in the water-splitting reaction, leading to the suppression of the electroconvection. Despite this drawback, the decrease of the over-limiting potential drop results in a decrease in specific energy consumption from 0.11 to 0.07 kWh/mol. In the under-limiting current mode, the specific energy consumption for all studied membranes remains within the same limits of 0.02-0.03 kWh/mol.

The loss or dysfunction of skeletal tissue often necessitates surgical intervention, particularly in cases involving trauma, tumors, or abnormal development leading to critical-sized defects. Despite autografts being considered the gold standard for bone grafts, their limitations and complications prompt the exploration of alternative approaches for bone repair and regeneration. Current advancements in bone tissue engineering have led to innovative strategies aiming to regenerate injured bone structures, providing viable alternatives to traditional autografts or allografts. Among these strategies, Hydrogel Microparticles (HMPs) have emerged as promising scaffolds due to their notable characteristics, including high porosity and mechanical tunability. HMPs play an important role in facilitating vasculature formation, mineral deposition, and overall bone tissue regeneration. HMPs, fabricated through various techniques, exhibit versatility in functions such as drug and cell delivery, structural scaffolding, and bioinks for 3D printing. In addition, these microgels can be injected for minimally invasive delivery and can display modular properties with different designs and configurations. This review exclusively focuses on the advancements in HMPs for bone regeneration, delving into synthesis and functionalization techniques while highlighting their diverse applications documented in the literature. Our aim is to shed light on the unique benefits and potential of HMPs in the intricate field of engineering bone tissue.

This paper constitutes an original and new methodology for the determination of the surface properties of carbon fibers in the two oxidized and untreated forms by inverse gas chromatography technique at infinite dilution based on the effect of the temperature on the surface area of the various organic molecules adsorbed on the carbon fibers. The studied thermal effect proved a large deviation of the classical methods or models relative to the new determination of the surface properties of carbon fibers, such as the dispersive component of their surface energy, the free surface energy, the free specific energy, the enthalpy and entropy of adsorption of molecules on the carbon fibers. The obtained specific enthalpy and entropy of adsorption for the polar solvents led to the determination of the Lewis’s acid-base constants of carbon fibers. Different molecular models and chromatographic methods were used to quantify the surface thermodynamic properties of carbon fibers and compared to the thermal model. The obtained results proved that the oxidized carbon fibers gave more specific interaction energy and greater acid-base constants than that of the untreated carbon fibers and thus highlighting the important role of the oxidization on the acid-base of fibers. The determination of the specific acid-base surface energy of the two carbon fibers showed greater values of the oxidized carbon fibers relative to the untreated carbon fibers. An important basic character was highlighted for the two studied carbon fibers, larger than the acidic character. It was observed that the Lewis’s acid-base constants of the oxidized carbon fibers are larger than that of the untreated fibers with more accentuated basic charterer. This result was confirmed by all molecular models and chromatographic methods.

3D Printing (3DP) technology has revolutionized the field of the use of bioceramics for maxillofacial and periodontal applications, offering unprecedented control over the shape, size, and structure of bioceramic implants. In addition, bioceramics have become attractive materials for these applications due to their biocompatibility, biostability, and favorable mechanical properties. However, despite their advantages, bioceramic implants are still associated with inferior biological performance issues after implantation, such as slow osseointegration, inadequate tissue response, and increased risk of implant failure. To address these challenges, researchers have been developing strategies to improve the biological performance of 3D printed bioceramic implants. The purpose of this review is to provide an overview of 3DP techniques and strategies for bioceramic materials designed for bone regeneration. The review also addresses the use and incorporation of active biomolecules in 3D printed bioceramic constructs to stimulate bone regeneration. By controlling the surface roughness, and chemical composition of the implant, the construct can be tailored to promote osseointegration and reduce the risk of adverse tissue reactions. Additionally, growth factors, such as bone morphogenic proteins (rhBMP-2) and pharmacologic agent (dipyridamole), can be incorporated to promote the growth of new bone tissue. Incorporating porosity into bioceramic constructs can improve bone tissue formation and the overall biological response of the implant. As such, by employing surface modification, combining with other materials, and incorporation of 3DP workflow can lead to better patient healing outcomes.

The Sarcoma Assessment Measure (SAM) was developed as a sarcoma-specific patient-reported outcome measure to be used in clinical practice. We have reported in detail how SAM has been developed in collaboration with patients and healthcare professionals. The aim of this paper is to report the preliminary validation of SAM. The 22-item SAM was administered alongside a validated quality of life questionnaire and measure of activities of daily living. Linear modelling was used to build a measure, which had predictive validity in comparison to more established outcome measures. Of the 762 patients who participated in the study, 44.1% identified as male, and participant age ranged from 13-82 years. Clinically, participants presented with a range of soft tissue (82.2%) and bone (21.8%) sarcomas. Our preliminary analysis indicates that SAM accounts for 35% of the Global quality of life scale and 18% of the TESS so psychometrically it overlaps with quality of life and activities of daily living, but also measures distinct concerns. This demonstrates that this measure picks up issues that are important to patients with sarcoma that are not reflected in other measures. We have established the preliminary validity of SAM and believe it has utility as a patient-reported outcome measure both as a research tool and for assessing the impact of symptoms and dysfunction related to sarcoma as part of clinical care. Further validation using a larger and more clinically diverse sample is now needed.

Scaffolds for tissue engineering are expected to respond to a challenging combination of physical and mechanical requirements, guiding the research towards the development of novel hybrid materials. This study introduces innovative three-dimensional bioresorbable scaffolds, in which a stiff poly(lactic acid) lattice structure is meant to ensure temporary mechanical support, while a bioactive gelatin-chitosan hydrogel is incorporated to provide a better environment for cell adhesion and proliferation. The scaffolds present a core-shell structure, in which the lattice core is realized by additive manufacturing, while the shell is nested throughout the core by grafting and crosslinking a hydrogel forming solution. After subsequent freeze-drying, the hydrogel network forms a highly interconnected porous structure that completely envelops the poly(lactic acid) core. Thanks to this strategy, it is easy to tailor the scaffold properties for a specific target application, by properly designing the lattice geometry and the core/shell ratio, which are found to significantly affect the scaffold mechanical performance and its bioresorption. Compression stiffness and strength provided by poly(lactic acid) lattices are overall within the range of values displayed by human bone tissue and remain stable after prolonged immersion in water at body temperature for several weeks. On the other hand, the hydrogel undergoes gradual and homogeneous degradation over time, but the core-shell integrity and structural stability are nevertheless maintained during at least 7-week hydrolytic degradation tests. In vitro experiments with human mesenchymal stromal cells reveal that the core-shell scaffolds are biocompatible and their physical-mechanical properties and architecture are suitable to support cell growth and osteogenic differentiation, as demonstrated by hydroxyapatite formation. These results suggest that the bioresorbable core-shell scaffolds can be considered, and further studied, in view of clinically relevant endpoints in bone regenerative medicine.

In livestock, brucellosis is mainly an asymptomatic disease except for abortion, therefore two serological tests are used for diagnosis as no single test is suitable. Abattoir samples enable a combination of culture, molecular and serological tests to detect brucellosis. This study assessed Brucella specific PCR (ITS-PCR) to detect brucellosis and to conduct molecular characterization of Brucella spp. isolated from PCR-positive livestock (n=565) slaughtered at abattoirs and the appropriate sample tissue(s). ITS-PCR detected Brucella DNA in 33.6% cattle, 14.5% sheep and 4.7% pig tissues. Impure Brucella cultures from PCR-positive tissues were 43.6% (44/94) cattle, 51.7% (15/29) sheep, and 50% (2/4) pigs with predominantly B. abortus identification with AMOS-PCR and low isolation of mixed B. abortus and B. melitensis in all species. In cattle 33% of isolates were from lymph nodes while in sheep 38.0% were from liver and kidney and only from tonsils in pigs (2/4). Brucella infections identified with AMOS-PCR were present in seropositive and mainly seronegative (75.6-100%) livestock with the potential to cause brucellosis during pregnancy or breeding. This study demonstrated the value of the polyphasic approach, especially with chronic infections and the potential risk of these asymptomatic animals.

African Swine Fever (ASF) poses a significant threat to domestic pig populations worldwide. This study investigates the histopathological alterations in confirmed ASF-positive domestic pigs, focusing on over 100 cases from 2018 to 2021. Biological material from 118 pigs, confirmed ASF-positive via PCR examination, was histopathologically examined. Tissue samples from various organs were processed, embedded, and analyzed using hematoxylin and eosin staining. Immunohistochemistry (IHC) was employed to detect the major capsid protein (p72) of the ASF virus.Histological examination revealed characteristic ASF lesions, including severe hemorrhages, lymphoid depletion, and inflammatory infiltrates. Vascular anomalies leading to hemorrhagic events were widespread. Microthromboses were prevalent in lymph nodes and kidneys. IHC detected p72 in various organs, with tonsils consistently showing the highest viral presence.This comprehensive study underscores the pivotal role of lymph nodes, spleen, and kidneys in ASF pathogenesis, highlighting prominent vascular involvement and hemorrhagic manifestations. The study establishes the efficacy of IHC in detecting ASF virus, even in autolyzed tissue samples. Tonsils emerge as a consistent epicenter of viral presence, shedding light on the intricate pathogenesis of ASFV.

Obesity affects nearly 660 million adults worldwide and is known for its many comorbidities. Although the phenomenon of obesity is not fully understood, science regularly reveals new determinants of this pathology. Among them, the persistent organic pollutants (POPs) have been recently highlighted. Mainly lipophilic, POPs are normally stored in adipose tissue and can lead to adverse metabolic effects when released into the bloodstream. The main objective of this narrative review is to discuss the different pathways by which physical activity may counteract POPs adverse effects. The research that we carried out seems to indicate that physical activity could positively influence several pathways negatively influenced by POPs, such as insulin resistance, inflammation, lipid accumulation, adipogenesis and gut microbiota dysbiosis that are associated with the development of obesity. This review also indicates how, through the controlled mobilization of POPs, physical activity could be a valuable approach to reduce the concentration of POPs in the bloodstream. These findings suggest that physical activity should be used to counteract the adverse effects of POPs. However, future studies should accurately assess its impact in specific situations such as bariatric surgery where weight loss promotes POPs blood release.

Study design: Creating and psychometric testing of a new QoL Questionnaire about Physiotherapeutic Specific Exercises of Scoliosis (Questionnaire of Physiotherapeutic Specific Exercises of Scoliosis -QPSSE). Purpose: The purpose of this study is to create a reliable and valid questionnaire for patients suffering mild and moderate adolescent idiopathic scoliosis (AIS) who have been treated with Physiotherapeutic Specific Exercises of Scoliosis (PSSE) in order to evaluate their quality of life. Materials and Methods: The developed questionnaire was based on a thorough literature review as well as on authors experience. It consists of 53 questions, of which 37 have a positive meaning, 15 have a negative meaning, and one is multiple choice question, additionally there are six “open” questions. Except for the multiple choice question, all other questions are answered on a Likert scale ranging from 1 to 5 scores. 5 represents a positive meaning or very much, whereas 1 stands for a negative meaning or not at all. Questions were developed by the authors who subsequently categorized the 53 questions into the following 8 domains: physical functioning, self-image, Physiotherapeutic Scoliosis-Specific Exercises (PSSEs), psychosocial functioning, cognitive functioning, compliance, motivation and pain. A pilot study was conducted so that we could calculate Cronbach’s Alpha based on the outcome. Due to the COVID-19 pandemic, the authors worked through the Zoom online platform to structure the questionnaire. Results: Pearson's correlation coefficient was used for all correlations evaluated. P values of less than 0.05 were considered to be significant. Internal consistency was evaluated with Cronbach's alpha. Although there were very few missing values, accounting for 0.78% of the total values of the questionnaire, expectation maximization likelihood algorithm was used to impute data. IBM® SPSS® Statistics Software v.25 was used for the analysis. Cronbach's alpha coefficients for the overall score was 0.84. Conclusion: This original QPSSE was found to be a reliable and valid tool for AIS treated conservatively with PSSE and for their clinicians.

Cathinone is a natural stimulant found in Catha edulis and commonly used in new psychoactive substances. The objective of this study was to examine the disposition kinetics and metabolic profile of cathinone and its metabolite cathine through a single oral dose of cathinone administration in rats. Cathine and cathinone concentrations were identified and quantified using ion trap liquid chromatography (LC-IT/MS), while the metabolic profile was determined using the quadrupole time of flight UPLC-QTOF/MS method in the serum, brain, lung, liver, kidney, and heart over a period of 0, 0.5, 2.5, 6, 12, 24, 48, and 72 hours. The findings revealed a dynamic interplay between the pharmacokinetics of cathinone and its impact on organ-specific biomarkers. The distribution of cathinone and cathine was determined in serum, brain, heart, lung, kidney, and liver. The highest concentration of cathinone was found in the kidney at 1438.6 ug/L. It gradually decreased to 1.97 within 48 hours and disappeared after 72 hours. Within half an hour, cathinone levels in the lungs, liver, and heart were found to be 859, 798.9, and 385.8 ug/L, respectively. However, within 2.5 hours, these levels decreased to 608.1, 429.3, and 309.1 ug/L and kept decreasing until they became undetectable after 24 hours. The concentration of cathinone in the rat brain reduces quickly, dropping to undetectable levels within six hours, with levels decreasing from 712.7 ug/L after just 30 minutes. In the brain and serum, cathine reached its highest levels at 2.5 hours, while in other organs, it peaked at 0.5 hours. This indicates that the conversion of cathinone to cathine is slower in the brain and serum. The study found that cathinone's pharmacokinetics have a significant impact on organ-specific biomarkers. After administering the cathinone, there was a sharp change in biomarker levels, particularly in the liver and brain, during the initial hours. It is essential to investigate the correlation between the changes in biomarkers found in the brain and the levels of cathinone and cathine. The results have significant implications for drug development, pharmacovigilance, and clinical practices involving cathinone. In conclusion, this comprehensive analysis of cathinone's impact on organ-specific biomarkers provides a basis for informed decision-making in medical practices and further research into the cathinone's pharmacological properties.

Abstract: Extensive research shows nurses’ work environment to be particularly stressful. This study develops, explores, and psychometrically tests a new profession specific ques-tionnaire identifying generalized and specific resistance resources, that make it possible to measure resources to manage work-related stress. An exploratory study design was em-ployed. The questionnaire was developed inspired by the MEASURE approach and the salutogenic theory of health. Building on the results from a literature review of nursing re-search and salutogenesis, supplemented by twelve interviews with hospital nurses, an item pool was generated. A first version was pilot tested in a group of nurses who were studying to become specialist nurses. A second version of the questionnaire was psycho-metrically tested on nurses in close patient care (n = 475), analysed using Principal Com-ponent Analysis as the extracting technique to identify the underlying structure of the questionnaire. The Principal Component Analysis revealed a four-component model of 19 items. “Manageability as a resource for handling the workload” was the strongest compo-nent, accounting for 21 % of the explained variance. “Contacts with patients as resources for nurses’ job satisfaction” (17.8 %). “Professional attitudes are labelled as resources to nursing” (15 %). “Colleagues are important resources for remaining in the nursing profes-sion” (11 %). The structure of the questionnaire indicates its usefulness in clinical practice for measuring resistance resources.

Bacteriotherapy is emerging as a strategic and effective approach to treat infections by providing putatively harmless bacteria (i.e., probiotics) as antagonists to pathogens. A proper delivery of probiotics or their metabolites (i.e., post-biotics) can avail itself of biomaterial encapsulation by innovative manufacturing technologies. This review paper aims at providing the most recent biomaterial-assisted strategies proposed to treat infections or disbiosis using bacteriotherapy. We revised the encapsulation processes across multiscale biomaterial approaches, which could be ideal to target different tissues and suit diverse therapeutic opportunities. Hydrogels, and in particular polysaccharides, are the focus of this review, as they have been reported to better sustain vitality of the live cells incorporated. Specifically, the approaches for fabricating hydrogel-based devices with increasing dimensionality (D), namely, 0D (i.e., particles), 1D (i.e., fibers), 2D (i.e., fiber meshes), and 3D (i.e., scaffolds) endowed with probiotics, were detailed by describing their advantages and challenges, along with a future overlook in the field. Electrospinning, electrospray and 3D bioprinting were investigated as new biofabrication methods for probiotic encapsulation within multidimensional matrices. Finally, examples of biomaterial-based systems for cell and post-biotic release were reported.

Intermittent cold exposure has garnered increased attention in popular culture, largely for its proposed effects on mood and immune function, but there are also suggestions that the energy wasting mechanisms associated with thermogenesis may decrease body weight and fat mass. Considering the continued and worsening prevalence of obesity and type II diabetes, any protocol that can reduce body weight and/or improve metabolic health would be a substantial boon. Here, we present a narrative review exploring the research related to ICE and adipose tissue. Any publicly available original research examining the effects of repeated bouts of ICE with adipose related outcomes was included. While ICE does not consistently lower bodyweight or fat mass, there does seem to be evidence for ICE as a positive modulator of the metabolic consequences of obesity, such as glucose tolerance and insulin signaling. Further, ICE consistently increases the activity of brown adipose tissue (BAT) and transitions white adipose tissue to a phenotype more in line with BAT. Lastly, the combined effects of ICE and exercise do not seem to provide any additional benefit, at least when exercise is done during ICE bouts. The majority of the current literature on ICE is based in rodent models where animals are housed in cold rooms, which does not reflect protocols likely to be implemented in humans such as cold-water immersion. Future research could specifically characterize ICE via cold water immersion in combination with controlled calorie intake to clearly determine the effects of ICE as it would be implemented in humans looking to lower bodyweight via reductions in fat mass.

Insulin icodec of Novo Nordisk is a novel long-acting insulin analogue that exhibits an extended duration of action, providing a promising treatment option for individuals with diabetes. It has been reported that the incorporation of fatty acid moieties into insulin icodec plays a crucial role in its prolonged action, as these fatty acid chains facilitate the formation of stable hexameric structures, thereby delaying insulin absorption and promoting sustained release. Yet, the underlying biophysics still is elusive of the roles of the three site-specific mutations (Y14A\_E, Y37B\_H, F46B\_H) of insulin icodec in its prolonged activity. Thus, through a comprehensive structural and biophysical analysis of the insulin (both native and icodec) structures bound to its receptor, this article delves deep into the biophysics underlying the molecular design of insulin icodec, and identified a delicate biophysical mechanism through which two missense mutations of insulin icodec (Y37B\_H and F46B\_H) contribute to its prolonged duration of action. Overall, this structural and biophysical investigation provides valuable insights into the mechanisms underlying the relationship between three site-specific mutations and prolonged duration of action of insulin icodec, while understanding these modifications at a structural and biophysical level can aid in the rational design of future long-acting insulin analogues, offering further enhanced therapeutic options for diabetic patients.

Critical sized bone defects and articular cartilage injuries resulting from trauma, osteonecrosis or age-related degeneration are often nonhealing by the physiological repairing mechanisms, thus representing a clinic issue due to the relevant epidemiological incidence. Current treatment approaches consist of autologous or allogenic grafting, which are associated with painfulness, morbidity, risk of infections and rejection. Novel tissue-engineering approaches, aiming at the reconstruction of damaged tissues, have been proposed as alternative solutions to these conven-tional methods. These approaches are based on the combination of three fundamental compo-nents: autologous or allogenic cells, a scaffold and growth-stimulating signals, which are gener-ally referred to as the tissue engineering triad. Three-dimensional polymer networks are fre-quently used as scaffolds to allow cell proliferation and tissue regeneration. In this scenario, cryogels are giving promising results as cell scaffolds over other polymer networks, thanks to their peculiar properties. In particular, cryogels possess an interconnected porous structure and a typical sponge-like behaviour, which facilitate the cellular infiltration and ingrowth. Their properties can be appropriately adjusted to match the requirements of the specific tissue or or-gan that it is intended to regenerate. In this review it is reported the state of the art on the fabri-cation and employment of cryogels in supporting osteo or chondro-genic differentiation for the re-building of more organized tissues. Moreover, it will highlight current progress and future perspectives in the implementation of this technology in the clinical practice.

In this study, an optimized multi-material system was designed and developed to print samples in various applications, including biomedical fields (e.g., mandibular bone loss). To improve the mechanical and biological properties of scaffolds utilized for dental bone loss applications, a multi-material setup was devised, which employs digital light processing technology. This setup consists of a linear system comprising two resin vats and one ultrasonic cleaning tank, enabling the integration of diverse materials and structures to optimize the composition of the scaffold. This approach was used to print multi-material PLLA scaffolds containing 20 wt.%. HA on the interior side, and PLLA containing 1 wt.% GO on the exterior surface of the scaffold, which were evaluated mechanically and biologically after printing. The scaffold was designed using a triply periodic minimal surface (TPMS) lattice structure, which is known to possess favorable mechanical and biological properties. Various multi-material samples were successfully printed and evaluated to illustrate the multiple-material setup's potential for ensuring proper function, cleaning, and adequate interface bonding. By numerically evaluating several TMPS structures, a novel Gyroid TPMS scaffold with a nominal porosity of 50% was developed and validated experimentally. The biological properties of the scaffolds were also evaluated, including surface morphology, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay, and cell adhesion. Based on the results, multi-material components with the least contaminations with suitable mechanical and biological properties were successfully printed. By combining PLLA-HA and PLLA-GO, this innovative technique holds tremendous potential for enhancing the effectiveness of regenerative procedures in the field of dentistry.

Background: We aimed to evaluate the impact of two different phytotherapeutic agents on the decision making regarding prostate biopsy in patients with higher-than-normal prostate-specific antigen (PSA) levels. Methods: From June 2022 to May 2023, all patients attending two urological institutions due to higher-than-normal PSA levels were randomized to receive either oral capsules of Curcuma Longa, Boswellia, Pinus pinaster and Urtica dioica (Group A) or Serenoa Repens 320 mg (Group B), for 3 months. At the follow-up visit after 3 months all patients underwent PSA test and multiparametric magnetic resonance imaging (mpMRI). Results: In the per-protocol analysis, data from 66 patients in Group A and 76 in Group B were analyzed. Fifty patients in Group A (75.7%) showed a significant reduction of total PSA compared to 49 in Group B (64.4%) (p<0.001). Twenty-eight patients had PI-RADS III or higher at mpMRI: 12 in Group A and 14 in Group B. Twenty-three patients (34.8%) in Group A underwent prostate biopsy based on mpMRI findings and PSA values and 59 (77.6%) in Group B (p<0.001). Three patients in Group A showed a significant reduction of total PSA value while having positive findings at mpMRI (6%) compared with 9 in Group B (19.5%) (p<0.001). On the contrary, 7 patients in Group A did not show a significant reduction of total PSA value and had negative findings at mpMRI (43%) compared to 22 in Group B (81.4%) (p&lt;0.001). Conclusions: In conclusion, a three-month course of a combination of Curcuma Longa, Boswellia, Pinus pinaster, and Urtica dioica seems an interesting tool to avoid unnecessary prostate biopsies in men with higher-than-normal PSA levels.

Tendon injuries, while prevalent, present a significant challenge in fully restoring their structural and functional integrity. Utilizing alpha-smooth muscle actin (α-SMA)-Ai9-scleraxis (Scx)-green fluorescent protein (GFP) transgenic mice, which exhibit both Scx (a tendon cell marker) and α-SMA (a myofibroblast marker), we explored Met's effects on tendon healing and repair and its mechanisms of action. Our findings revealed that intraperitoneal (IP) injections of Met -administered before or after injury, as well as both - effectively prevent the release of HMGB1 into the tendon matrix and reduce circulating levels of HMGB1. Additionally, Met treatment increased and activated AMPK and suppressed TGF-β1 levels within the healing tendon. These interventions also improved tendon healing by blocking the migration of α-SMA+ myofibroblasts, reducing the prevalence of disorganized collagen fibers and collagen type III, and enhancing the presence of collagen type I. These outcomes highlight Met's anti-fibrotic properties on acutely injured tendons and suggest its potential for repurposing as a therapeutic agent to minimize scar tissue formation in tendon injuries, which could have profound implications in clinical practice.

The research presents a novel synthetic photosensitizer for photodynamic therapy (PDT) of malignant tumors - meso-tetra(3-pyridyl) bacteriochlorin, which absorbs at 747 nm (in the long-wavelength region of the spectrum) and is stable when stored in the dark. H2Py4BC demonstrates pronounced photoinduced activity in vitro against tumor cells of various genesis (IC50 varies from 21 to 68 nM for НЕр2, EJ, S37, CТ26, and LLC cultured cells) and provides in vivo pronounced antitumor efficacy in the treatment of mice bearing small or large S37, Colo26, and LLC metastatic tumors, as well as in the treatment of rats bearing RS-1 liver cholangioma. As a result, total regress of primary tumor nodules and cure of 40 to 100% of the animals were proved by the experiment criteria, MRI, and histological analysis. Meso-tetra(3-pyridyl) bacteriochlorin quickly penetrates and accumulates in the tumor tissue and internal organs of mice, and after 24 hours 80% of the dye is excreted from skin as well as 87% - 92% from liver, kidneys, and spleen.

Defects in low-density lipoprotein receptor (LDLR) are associated with familial hypercholesterolemia (FH), manifested by atherosclerosis and cardiovascular disease. Defective LDLR in hepatocytes leads to increased blood cholesterol level that damage vascular cells, especially endothelial cells, through oxidative stress and inflammation. However, the distinctions between endothelial cells from individuals with normal and defective LDLR are not yet fully comprehended. In this study, we obtained and examined endothelial derivatives of induced pluripotent stem cells (iPSC) generated previously from conditionally healthy donors and compound heterozygous FH patients carrying pathogenic LDLR alleles. In normal iPSC-derived endothelial cells (iPSC-EC), we detected the LDLR protein predominantly in its mature form, while iPSC-EC from patients with FH display reduced level of mature LDLR and show abolished low-density lipoprotein uptake. RNA-seq of iPSC-EC with mutant LDLR revealed a unique transcriptome profile comprising downregulated genes related to monocarboxylic acid transport, exocytosis and cell adhesion, as well as upregulated signaling pathways of cell secretion and leukocyte activation. Overall, these findings suggest that LDLR defects increases susceptibility of endothelial cells to inflammation and oxidative stress. This, combined with elevated extrinsic cholesterol levels, may result in accelerated endothelial dysfunction, contributing to early progression of atherosclerosis and other cardiovascular pathologies related to FH.

Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using the fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33–60 years in the first study) were scanned twice, 7 years apart. An age-related decrease in MPF was found in global WM, GM, and mixed WM-GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2-5%), genu of the corpus callosum (CC) (4.0%) and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM-GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics.

Intrauterine adhesions (IUA) has become one of the main causes of female infertility, how to effectively prevent postoperative re-adhesion has been a clinical challenge. In this study, a mussel-inspired dual-network hydrogel was proposed for postoperative anti-adhesion of IUA. First, calcium alginate/polyacrylamide (CA-PAM) hydrogel was prepared by covalent and Ca2+ cross-linking. Benefiting from abundant phenolic hydroxyl groups, polydopamine (PDA) was introduced to further enhance the adhesion ability and biocompatibility. This CA-PAM hydrogel immersed in 10 mg/mL dopamine solution possessed remarkable mechanical strength (elastic modulus > 5 kPa) and super stretchability (with a breaking elongation of 720%). At the same time, it shown excellent adhesion more than 6 kPa. Surprisingly, the coagulation index of the hydrogel was 27.27 ± 4.91, demonstrating attractive coagulation performance in vitro and the potential for rapid hemostasis after surgery.

Regenerative Medicine and Tissue Engineering are interdisciplinary fields that combine cell biology, material science, and bioengineering to develop therapies for tissue repair and regeneration. This field has made significant advances in recent years, particularly in the use of stem cells and biomaterials. Advancements in cell-based therapies have involved the use of cells to repair or replace damaged tissues and organs. Tissue engineering involves using scaffolds and growth factors to promote tissue regeneration. However, a major challenge in this field is the formation of adhesions, which can cause complications, such as intestinal obstruction and chronic pain. Adhesion barriers are used to prevent adhesion of tissues and organs during recovery, thereby reducing the risk of complications. Anti-adhesion materials, such as polysaccharides, proteins, and synthetic polymers, are used to create a physical barrier between tissues and prevent adhesion. These materials can be used alone or in combination, but their effectiveness varies.

Nanotechnology has become an increasingly promising medical field, particularly scar removal. Scar removal is a complex process involving regenerating damaged skin tissue, and nanotechnology presents unique solutions to this issue. One potential application of nanotechnology is using nanofibers as scaffolds to support the growth of new skin tissue. These fibres can also be loaded with drugs or growth factors to promote tissue regeneration and reduce scarring. Another potential application is nanocarriers for drug delivery to specific body areas, which can promote tissue regeneration and reduce scarring.Additionally, nanotechnology has been utilized to create new materials for skin regeneration, such as "nano skin" that mimics the structure of natural skin. Nanoprobes have also been developed for the detection of scar tissue and the monitoring of its progression. These potential nanotechnology applications offer exciting possibilities for the future of scar removal and skin repair. With further research and development, nanotechnology has the potential to revolutionize scar removal and provide more effective solutions for tissue regeneration.

The research methods were used to investigate the following questions: Does a mobility training intervention change tissue stiffness, joint range of motion, and compensate for possible imbalances? Do the interventions influence the pressure pain threshold and the overall well-being?

For Lentinula edodes, its characteristic flavor is the key determinant for consumer pref-erences. However, the tissue-specific volatile flavor variations of the fruiting body have been overlooked. Here, we comprehensively investigated volatile flavor profiles of different tissues including the pileus skin, context, gill and stipe of the fruiting body of two widely cultivated L. edodes strains (T2 and 0912). We show that the eight-carbon and sulfur com-pounds, which represented 43.2-78.0% and 1.4-42.9% to the total volatile emissions for strain 0912 and T2, dominated their volatiles profiles. The sulfur compounds could rep-resent 32.2% and 42.9% to the total volatile emissions for the context of the strain 0912 and T2, respectively, whereas only represented 1.4% for the stipes of the strain 0912 and 9.0% for the skin of strain T2. Proportions of the predominant C8 compounds (1-Octen-3-one, 1-Octen-3-ol and 3-Octanone) and sulfur compounds (Lenthionine, 1,2,4-Trithiolane, Di-methyl disulfide and Dimethyl trisurfide) changed depending on tissues and strains. We further reveal that the overall volatile flavor profiles varied greatly in different tissues and strains. With machine learning algorithm, we show that volatile profiles could 100% pre-dict strains 0912 and T2. The prediction accuracy for different tissues could also reach 100%. Our results highlight the tissue-specific volatile flavor variations of the L. edodes fruiting body.

This study focused on the precise detection and concordant analysis of circulating tumor cells (CTCs) to verify the usefulness of CTCs as promising clinical markers. CTCs are traditionally achieved using immune-fluorescence and morphological techniques. By combining two prostate cancer-specific genes (PSA and PSMA) and two epithelial-specific genes (EpCAM and KRT19), the CTC detection efficiency can be enhanced. The detection rates of localized prostate cancer (LPC), locally advanced prostate cancer (LAPC), metastatic hormone-sensitive prostate cancer (mHSPC), and metastatic castration-resistive prostate cancer (mCRPC) were 63.04 % (29/46), 70.59% (34/51), 94.34% (50/53), and 90% (126/140), respectively. Subsequent correlation analysis between the four genes, baseline PSA, and CTC count revealed that only the CTC count correlated with baseline PSA in the localized stages of prostate cancer, whereas all four genes were correlated with baseline PSA and CTC count in the metastatic stages of prostate cancer. The precise detection of CTCs using both numerical and transcriptomic analyses can improve the accuracy of biomarker investigations. This study provides valuable insights into the limitations of serum PSA testing and offers a promising alternative to diagnose and manage prostate cancer via the CTC number and specific genes for prostate cancer.

Biological function depends on the composition as well as structure of the organism, that is the organization of interactions between its parts. In multicellular organisms, the complex communication between cells is crucial for the coordination of cellular functions (growth, differentiation, apoptosis), compartmentalization of cellular processes within the organism, and the integration of cells into functioning higher levels of structural organization. Here we focus on the interaction among cells, as the basic level of biological organization, capable of a remarkable degree of autonomy and self-maintenance. While a wealth of data on putative cell interactions has recently become available, its biological interpretation depends on expectations we have for the structure of these interaction networks. This contribution is an attempt at formulating basic questions we may ask about cell interaction data. We build on the understanding that cells fulfill two general functions: the integrity-maintaining and the organismal service function. We derive the expected patterns of cell interactions considering two intertwined aspects: the immediate functional and the evolutionary. Based on these, we propose several guidelines for analysis and interpretation of transcriptional cell-interactome data.

In this paper we report on the use of an in-house developed solid-state hybrid microwave and radiofrequency generator operating at frequencies of 2.45 GHz and/or 480 kHz for cancer ablation in various tissues. The generator has demonstrated increased accuracy due to its custom-designed hardware, which incorporates the latest technologies and algorithms to control the emitted power versus temperature profile of the treated sample. In particular, the hybrid generator incorporates control systems based on impedance or reflected power measurements that allow controlled ablation without causing unwanted carbonisation and without including areas where tissue damage is not desired. Tests performed ex-vivo on chicken breast and bovine liver show that radiofrequency ablation (RFA) is very effective for performing controlled ablations with minimally invasive probes, such as cardiac pathologies, small lesions, tissues with particular composition, while microwave ablation (MWA) is optimal for performing large ablations in highly vascularised tissues, such as liver cancer, where it is necessary to achieve higher temperatures.

In Geo Polymer bricks (GPB), fly ash content which is a waste from power plants is converted into bricks by chemical treatment. GPB can be dried by using appropriate curing methods. Conven-tionally electric oven curing is one of the prominent methods. Using solar dryer instead of elec-trical oven gives added advantage of saving high grade electrical energy. So in this work solar dryer with PCM (Phase Change materials) Paraffin Wax and without PCM is used for curing ap-plication. GPB are gaining added advantage when compared to conventional bricks like cement and sand bricks in terms of strength. GPB has been taken as specimen for comparing the com-pressive, tensile split strength and flexural strength by electrical energy based curing and solar energy based curing. It is experimentally observed that solar energy based curing with PCM and without PCM exhibits higher compressive strength, higher tensile split strength and flexural strength when compared to electrical energy based curing. Solar curing with PCM shows higher compressive strength, higher tensile split strength and flexural strength when compared to Solar curing without PCM. Open solar curing is a traditional technique but nowadays aggressive cli-matic conditions can lead to severe damage of Geo polymers. The novelty of this work is to suggest to study the effect of PCM like paraffin wax in solar drying on curing time, mechanical properties of GPB.

Due to its distinctive chemical and biological properties, pectin has recently drawn much attention in biomedical and tissue engineering applications. Polymers like pectin with cell-instructive properties are attractive natural biomaterials for tissue repair and regeneration. Besides, bioactive pectin and pectin-based composites exhibit improved characteristics to deliver active molecules. Pectin and pectin-based composites serve as interactive matrices or scaffolds by stimulating cell adhesion and cell proliferation and enhancing tissue remodeling by forming an extracellular matrix in vivo. Several bioactive properties, such as immunoregulatory, antibacterial, anti-inflammatory, anti-tumor, and antioxidant activities, contribute to the pectin's and pectin-based composite's enhanced applications in tissue engineering and drug delivery systems.This paper reviews the promising characteristics of pectin or pectic polysaccharides and highlights its potential applications in drug delivery and tissue engineering. Tissue engineering scaffolds containing pectin and pectin-based conjugates or composites demonstrate essential features such as non-toxicity, tunable mechanical properties, biodegradability, and suitable surface properties. The design and fabrication of pectic composites are versatile for tissue engineering and drug delivery applications.

This study is based on the fatty acid and amino acid profile of 7 edible insect species: Acheta domesticus, Alphitobius diaperinus, Blaptica dubia, Galleria mellonella, Locusta migratoria, Tenebrio molitor and Zophobas morio. The fatty acid distribution within lipid classes (neutral lipids, glycolipids and phospholipids) was studied, while the amino acid profile was used to calculate the species-specific nitrogen-protein conversion factor (Kp). The profiles were used to evaluate the nutritional quality of the lipids and proteins. Oleic acid was the predominant fatty acid in all insects except for A. domesticus, in which a larger percentage of linoleic acid was found. The majority of the lipids were neutral lipids. L. migratoria showed a remarkably high content of α-linolenic acid in its phospholipid fraction, while T. molitor phospholipids were the only fraction in which a measurable amount of docosahexaenoic acid was found. Overall, in most insects, the phospholipid fraction had the highest polyunsaturated fatty acid content compared to the other classes, which may be protective in terms of autoxidative stability. Kp values in the range of 4.17 to 6.43 were obtained. Within the nutritional quality indices, all insects showed healthy fatty acid and high quality amino acid profiles.

Extensive damage to peripheral nerves is a health problem with few therapeutic alternatives. In this context, the development of tissue engineering seeks to obtain materials that can help recreate environments conducive to cellular development and functional repair of peripheral nerves. Different hydrogels have been studied and presented as alternatives for future treatments to emulate the morphological characteristics of nerves. Along with this, other research proposes the need to incorporate electrical stimuli into treatments as agents that promote cell growth and differentiation; however, no precedent correlates the simultaneous effects of the types of hydrogel and electrical stimuli. In this research, the neural differentiation of PC12 cells we are evaluated, relating the effect of collagen, alginate, GelMA, and PEGDA hydrogels with electrical stimulation modulated in four different ways. Our results show significant correlations for different culture conditions, allowing us to develop new experimental schemes for new materials in peripheral nerve engineering.

Gold nanoparticles (AuNPs) have been used in a broad range of applications conferring to bio-molecules diverse proprieties such as deliver, stabilization and reduction of adverse effects of drugs or plant ex-tracts. Polyphenolic compounds from Bacopa procumbens (BP) are able to modulate proliferation, adhesion, migration and cell differentiation, reducing artificial scratch area in fibroblast cultures and promoting wound healing in in vivo model. Here, chemically synthetized AuNPs conjugated with BP (AuNP-BP) were characterized by Uv-Vis, ATR-FTIR, DLS and zeta-potential. Results showed over-lapping FTIR spectra of polyphenolic compounds from B. procumbens capping the AuNPs, stable size by the DLS and zeta potential, AuNP-BP was 44.58 nm, the zeta-potential of AuNPs was -36.3±12.3 mV after conjugation with the BP; - (AuNP-BP), the zeta-potential was reduced to -18-2±7.02 mV. Enhancement of wound healing effect were evaluated by morphometric, histochemical and FTIR changes in rat wound excision model. Results showed that the nanoconjugation process reduced 100 folds BP concentrations to have the same wound healing effect of BP alone. Besides histological and FTIR spec-troscopy analyses, demonstrated that AuNP-BP treatment displayed better macroscopical performance; the reduction on inflammatory cells, and the increased synthesis and better organization of collagen fibers.

Podocalyxin (PODXL) overexpression is associated with poor clinical outcomes in various tumors. PODXL is involved in tumor malignant progression through the promotion of invasiveness and metastasis. Therefore, PODXL has been considered as a promising target of monoclonal antibody (mAb)-based therapy. However, PODXL also plays an essential role in normal cells such as vascular and lymphatic endothelial cells.Therefore, cancer-specificity or selectivity is required for the reduction of adverse effects on normal cells. Here, we developed an anti-PODXL cancer-specific mAb (CasMab), PcMab-6 (IgG₁, kappa), by immunizing mice with soluble PODXL ectodomain derived from a glioblastoma LN229 cell.PcMab-6 reacted with the PODXL-positive LN229 cells, but not with PODXL-knockout LN229 cells in flow cytometry. Importantly, PcMab-6 recognized pancreatic ductal adenocarcinoma (PDAC) cell lines (MIA PaCa-2, Capan-2, and PK-45H), but did not react with normal lymphatic endothelial cells (LECs). In contrast, one of the non-CasMabs, PcMab-47 showed high reactivity to both the PDAC cell lines and LECs. Next, we engineered PcMab-6 into a mouse IgG_2a type (PcMab-6-mG_2a) and a humanized IgG₁-type (humPcMab-6) mAbs, and further produced the core fucose-deficient types (PcMab-6-mG_2a-f and humPcMab-6-f, respectively) to potentiate the antibody-dependent cellular cytotoxicity (ADCC). Both PcMab-6-mG_2a-f and humPcMab-6-f exerted ADCC and complement-dependent cellular cytotoxicity in the presence of effector cells and complements, respectively. In the PDAC xenograft model, both PcMab-6-mG_2a-f and humPcMab-6-f exhibited potent antitumor effects. These results indicated that humPcMab-6-f could apply to antibody-based therapy against PODXL-expressing pancreatic cancers.

In the last two decades, gelatin-based hydrogels have been widely used as tissue engineering scaffolds due to their excellent biocompatibility, biodegradability, easy processability, transparency, non-toxicity, and reasonable structural similarity to the natural extracellular matrix (ECM). However, intrinsic low mechanical properties of gelatin are not structurally and mechanically suitable to support cell growth and proliferation. That’s why various crosslinking strategies including physical, chemical, enzymatic and combination of them as well as networking patterns including double network, interpenetrating network and nano reinforcing mechanism have been utilized to enhance the structural stability and mechanical integrity of gelatin. In this review, the advances in modulating the mechanical properties of gelatin-based hydrogels for the design and development of structurally stable scaffolds for tissue engineering are discussed. The optimized crosslinking parameters with the adequate mechanical properties of gelatin-based hydrogels are reviewed. Gelatin-based scaffolds for a wide range of tissue engineering applications, such as bone, cartilage, cardiac, skin, and nerve tissue engineering are also outlined. Lastly, current challenges and future perspectives in this research field are presented.

The Suter curves for Wh and Wm characteristics of collected and the first time presented Four-quadrant (4Q) diagrams of 11 radial pump-turbine models with different specific speeds (nq=24.34, nq=24.8, nq=27, nq=28.6, nq=38, nq=41.6, nq=41.9, nq=43.83, nq=50, nq=56, and nq=64.04) are given in the paper, as well as the Suter curves for 2 pump models (nq=25, and nq=41.8) which were already published in the literature. These 11+2 curves were analyzed to establish a certain universal law of behavior in dependence on the specific speed. For the determination of existing laws in behavior, the fitting procedure using the Regression and Spline methods was used. The paper presents a research plan and structures that include: data collection of four-quadrant diagrams for models of pump-turbines and pumps with different specific speeds (nq), the procedure of recalculation of Four-quadrant diagrams of the models into Suter curves for Wh and Wm characteristics, the definition of the optimal point for the pump and turbine operating mode in pump-turbine models for different specific speeds, and developing numerical models in the MATLAB program to obtain the Universal Equation for the Wh and Wm characteristics. The scientific contribution of this paper is the firstly published original mathematical curve named Universal Equation for the Wh and Wm characteristics for radial pumps and pump-turbines. Application of the equation has been demonstrated at the pumping station where two radial pumps are installed. The calculation of transient processes was performed using the numerical model developed by the authors in the mathematical program MATLAB. Comparison of the transition process results has been made for the two cases - when input data in the numerical model have been firstly used with the values of Suter curves for Wh and Wm characteristics obtained by recalculation from the Four-quadrant operating characteristics (Q11, n11, M11) of model’s specific speed, and then secondly with the values of the Suter curves for Wh and Wm characteristics obtained from the Universal Equation.

In recent decades, porous scaffolds for bone tissue engineering (BTE) have gained significant attention. Considerable research efforts have been dedicated to investigating the impact of scaffold pore size on a diverse array of biological processes, including cell-scaffold interactions, substance transportation, and vascularization. However, the multi-scale hierarchical porosity, a key structural characteristic of natural bone, has rarely been replicated in BTE scaffolds due to the challenges of controlling the scaffold structure across multiple length scales. With the advancement of manufacturing technology, there has been increasing research on biomimetic multi-scale hierarchical materials, which are also gaining favor in the field of BTE. Therefore, there is an urgent need to review multi-scale hierarchical porous BTE scaffolds. This paper aims to review the role and fabrication methods of multi-scale porous BTE scaffolds at different length scales, the design and manufacturing of new BTE scaffolds for bone regeneration.

Introduction Despite efforts to use scaffolds to treat meniscus tears, minimal progress has been made in facilitating meniscus regeneration and return of function. Our research objective was to develop a meniscus repair and regeneration implant by applying a resorbable scaffold in combination with cells and growth factors. We report here the results of using platelet-rich plasma (PRP) as a source of growth factors to induce fibrochondrogenic differentiation of human adipose-derived mesenchymal stem cells (hADSC) in a three-dimensional (3D) Type I collagen-based scaffold in vitro. Methods Scaffold Preparation. Type I collagen scaffolds were prepared following a protocol previously published. Two different densities of scaffolds, high density (HD) and low density (LD), were produced for in vitro study. hADSC and PRP Preparation. hADSCs were cultured to the fifth passage to reach the desired number for experimentation. PRP was collected from human blood and activated. Cell Culture Procedure. Effects of PRP on hADSC proliferation and differentiation into fibrochondrogenic cells were examined in four scaffold groups: LD, HD, LD+PRP and HD+PRP. hADSCs were seeded onto scaffolds (n=5) at a concentration of 2 × 106 cells/scaffold. 1% of PRP was added to the experimental media. Cellular proliferation was assessed at 1, 7, 14, and 21 days. Differentiation was measured using qRT-PCR on Days 14 and 21. qRT-PCR analysis of gene expression was completed with primers for COLLAGEN 1 and AGGRECAN. Data Analysis. ANOVAs were conducted (two-tailed tests) at the .05 significance level. Results Cellular proliferation of hADSCs seeded on each scaffold increased over time. Similar trend was observed for cells seeded on HD scaffolds with and without PRP. hADSC showed significant increase in cellular proliferation on the LD scaffolds at Days 1 and 7. At Day 21, PRP treatment and LD scaffold had a synergistic positive effect on Type I collagen gene expression. PRP did not elevate type I collagen gene in the HD group, the HD scaffold alone had the same level of type I collagen gene expression as LD+PRP. Aggrecan expression was elevated in the presence of PRP in both the HD and LD scaffold groups, indicating enhanced fibrochondrogenic differentiation of hADSCs. Effective cell infiltration was observed across both HD and LD scaffolds with and without PRP treatment. HD scaffolds displayed larger cell clusters and more extensive cell migration over time compared to LD scaffolds. However, LD scaffolds resulted a more uniform cellular distribution than HD scaffolds. Conclusion Our study demonstrates that PRP can play an important role in directing hADSCs towards fibrochondrogenic differentiation in Type I collagen-based scaffolds in vitro. Additionally, our study shows that collagen scaffold density can influence the spatial distribution and cellular behavior of infiltrated cells.

Severe COVID-19 is frequently associated with thromboembolic complications. Increased platelet activation and platelet-leukocyte aggregate formation can amplify thrombotic responses by inducing tissue factor (TF) expression on leukocytes. Here, we characterized TF-positive extracellular vesicles (EVs) and their cellular origin in 12 patients suffering from severe COVID-19 (time course, 134 samples overall) and 25 healthy controls. EVs exposing phosphatidylserine (PS) were characterized by flow cytometry. Their cellular origin was determined by staining with anti-CD41, anti-CD45, anti-CD235a, and anti-CD105 as platelet, leukocyte, red blood cell, and endothelial markers. We further investigated the association of EVs with TF, platelet factor 4 (PF4), C-reactive protein (CRP) and high mobility group box-1 protein (HMGB-1). COVID-19 patients showed higher levels of PS-exposing EVs compared to controls. The majority of these EVs originated from platelets. A higher amount of EVs in patient samples were associated with CRP, HMGB-1, PF4, and TF, as compared to EVs from healthy donors. In COVID-19 samples, 16.5% of all CD41+ EVs displayed the leukocyte marker CD45, and 55.5% of all EV aggregates (CD41+CD45+) co-expressed TF, which reflects the interaction of platelets and leukocytes in COVID-19 on an EV level.

Background. This study aimed to establish a prognostic nomogram for predicting overall survival (OS) and cancer-specific survival (CSS) of patients with early-onset endometrial cancer (EOEC). Methods. Patients diagnosed with EOEC during 2004-2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were performed to ascertain the independent factors impacting the prognosis of EOEC patients, while a prognostic nomogram was established. Its performance was verified by the receiver operating characteristic (ROC) curves, and calibration plots. The prediction accuracy and clinical net benefit between the model, TNM stage and SEER stage were further compared by the concordance index (C-index) and decision curve analysis (DCA). Results. A total of 4415 eligible patients with EOEC were identified and enrolled in this study. Independent prognostic factors for OS and CSS were confirmed by multivariate Cox regression, which were further incorporated to constructed a nomogram. ROC curves and calibration curves indicated an optimal accuracy of the nomogram. Meanwhile, the C-index and DCA showed the predictive capability and the clinical applicability of the nomogram was superior over the TNM stage and SEER stage. Conclusions. Nomogram based on risk factors was developed as an individualized tool to predict OS and CSS for EOEC patients. The novel tool will assist in patient counseling and selection of appropriate therapeutic regimens.

Key thermophysical properties necessary for the successful design and use of CoCrFeNi alloy in thermophysical applications have been measured experimentally, and the results have been compared with literature values and results previously obtained for commercial Ni-Cr alloys and equiatomic CoCrFeNi alloy. In particular, the thermal diffusivity, coefficient of thermal expansion (CTE), and specific heat capacity were measured for the as-cast and homogenized equiatomic CoCrFeNi alloy over a temperature range allowing the thermal conductivity to be calculated up to 1173 K. The thermal conductivity and thermal diffusivity of the equiatomic CoCrFeNi alloy were found to deviate from monotonic behavior in the temperature range from 773 to 1100 K. Such a deviation was previously observed in the behavior of the temperature dependence of CTE and specific heat capacity of the equiatomic CoCrFeNi alloy. The non-linear behavior is primarily the result of order/disorder phenomena for the as-cast and homogenized sample, as well as additionally for the as-cast sample, non-equilibrium solidification under arc melting conditions. The measured data of thermophysical properties are provided for thermally differently treated samples, and it is shown that there is a difference in the behavior of the temperature dependences of CTE, thermal diffusivity, and heat capacity.

Basketball playing entails the repetitive performance of short intense actions using lower limb explosive power. As such, it is important to measure this capability in basketball players, especially among young players, and to optimize training programs and game plans. After presenting an in-depth understanding of the specific physiological requirements when playing basketball, as well as the type of movements required, The aim of this review is to better understand the importance of the physiological energy systems in basketball, to examine the contribution of each energy system and, accordingly, to heighten awareness of the importance and dominance of the alactic anaerobic physiological system in basketball, for actions requiring high level explosive power. This review of the literature depicts the horizontal and vertical physical movements and physiological requirements entailed in playing basketball, and presents eight standardized anaerobic alactic measurement tools relevant to the game. As some of these tests suit a number of ball games, the findings of this review article are important for making order of the elements unique to basketball as well as additional parameters to consider when testing basketball players. By reliably and validly testing the anaerobic alactic capabilities of basketball players, test results can be used for training purposes and for improving game outcomes. Despite the fact that much of the information in this review is familiar to coaches, highlighting the specific needs of basketball may help them to choose the most suitable tools, and may also shed light on new directions for developing basketball-specific assessment tests.

Background and objectives: Unrestricted kinematic alignment total knee arthroplasty (KA-TKA) with a soft tissue respecting technique (STRT) is a soft tissue-dependent tibial resection entailing restoration of the original soft tissue tension using ligamentotaxis after resurfacing the femur, based on the concept of restoring the native or pre-osteoarthritis alignment in each patient. However, there is no consensus on the indications of unrestricted KA-TKA with STRT. We modified the STRT, followed by investigation of the effects of surgery on the postoperative hip-knee-ankle angle (HKAA). Materials and Methods: We retrospectively analyzed the clinical background data, including the preoperative and postoperative HKAA, of 87 patients who underwent unrestricted KA-TKA with the modified STRT. Univariate and multivariate analyses were performed to determine the factors affecting the postoperative HKAA. A receiver operating characteristic (ROC) curve was plot-ted to investigate the change in the cut-off values of preoperative HKAA with respect to the safe zone of the postoperative HKAA. We generated two regression models, the linear regression model and generalized additive model (GAM) using machine learning, to predict the postopera-tive HKAA. Results: Univariate and multivariate analyses revealed the preoperative HKAA as the factor most relevant to the postoperative HKAA. ROC analysis revealed that the preoperative HKAA exhibited high predictive utility, with a cut-off value of -10°, when the safe range of postoperative HKAA was set at ± 5°. The GAM was the superior machine learning model, indicating a non-linear association between the preoperative and postoperative HKAA. Patients with preoperative HKAAs ranging from -18° to 4° were more likely to fall within the ± 5° safe range of the postoperative HKAA. Conclusions: The preoperative HKAA influences the postoperative HKAA in unrestricted KA-TKA with the modified STRT. Machine learning using the GAM may contribute to the selection of patients eligible for the surgical approach.

Demethyleneberberine is an active component extracted from the Chinese herbal drug Cortex Phellodendri. It is also a metabolite of the berberine in animals and humans. However, the pharmacokinetics, tissue distribution and excretion of demethyleneberberine have not been reported. The present study aimed to investigate the pharmacokinetic parameters of demethyleneberberine by developing a method of high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The detection was performed by using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 324.4→308.3 for demethyleneberberine and 465.5→350.3 for IS. After oral administration of demethyleneberberine in rats and mice, the pharmacokinetics, tissue distribution, and excretion of desmethylberberine in rats and mice were comparatively studied for the first time. The plasma concentration of desmethylberberine reached its peak within 5 min after oral administration in both rats and mice. The bioavailability of rats and mice was comparable, ranging from 4.47% to 5.94%, higher than that of berberine. The total excretion of desmethylberberine in urine, feces and bile is 7.28~9.77%. These findings provide valuable insights into the pharmacological and clinical research on desmethylberberine.

Atrial fibrillation (AF) is a common cardiac arrhythmia associated with significant morbidity and mortality. The role of epicardial adipose tissue (EAT), particularly in the left atrium, has garnered attention in the pathophysiology of AF. This review aims to provide an overview of the association between the thickness of left atrial epicardial adipose tissue (LA-EAT) and the incidence of AF, while exploring the arrhythmogenic effects of LA-EAT and the impact of epicardial fat tissue changes with age and in pathological conditions. A comprehensive search of PubMed was conducted, and relevant studies were selected based on their inclusion criteria. The findings suggest that increased LA-EAT thickness is associated with an elevated risk of AF, potentially mediated through inflammatory and proarrhythmic effects. Age-related changes in epicardial fat tissue and alterations in pathological conditions, such as obesity, metabolic syndrome, and cardiovascular diseases, further contribute to the development and progression of AF. Further research is needed to deepen our understanding of these mechanisms and their clinical implications.

Cell sheet (CS) engineering using human MSC is of significant interest for regenerative medicine and this rapidly growing field translates to clinical use in a number of indications. Nevertheless, little is known of factors that define the timing of CS assembly from primary cultures which is important for planning treatments in both – autologous and allogeneic modes of use. We used a comparative in vitro approach with primary donors’ (n=14) adipose-derived MSC and evaluated the impact of healthy subject’s characteristics (age and sex), MSC culture features (population doubling time and lag-phase) and extracellular matrix (ECM) composition along with factors related to connective tissue formations (-SMA and FAP-) on CS assembly duration.

De novo regeneration of Cannabis sativa L. (cannabis) using tissue culture techniques remains unreliable and infrequent. Conventional methods for the regeneration and transformation of cannabis have not achieved the reliability and replicability needed to be integrated into research and breeding programs. Protoplast systems are effective for gene expression studies, transformation and genome editing technologies, and opens the possibility of somatic hybridization to create interspecific hybrids. To date, leaf-derived protoplast have been isolated for transient gene expression studies, but attempts at protoplast-to-plant regeneration have not been reported. The present study aims to test the efficacy of using a callus culture system, as an abundant source for protoplast isolation and lays the groundwork for a protoplast-to-plant regeneration system. Using hypocotyl-derived callus cultures, which are known to have relatively greater regenerative potential, the efficacy of protoplast isolation and initial cell division were assessed. In this study, the effect of 2-aminoindane-2-phosphonic acid (AIP) in callus culture media and the effect of subculture frequency on protoplast yield were assessed. This study found that inclusion of AIP at 1 mM resulted in a 334% increase in protoplast yield compared with AIP-free medium, representing the first known use of AIP in cannabis tissue culture. Inclusion of AIP led to a 28% decrease in total soluble phenolics and 52% decrease in tissue browning compared to the control medium. Lastly, a two-phase culture system for protoplast regeneration was tested. At a concentration of 2.0×10^5 protoplasts per mL, division was observed, providing the first know report of cell division from cannabis protoplasts and setting the stage for future development of a protoplast-to-plant regeneration system.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

In the present study, the efficiency of a biomimetic approach by coating demineralized bone matrix (DBM) amorphous calcium phosphate (DBM+CaP), including its combination with serum albumin (DBM+CaP+BSA), was investigated. The intact structure of DBM promotes the transformation of amorphous calcium phosphate (CaP) into DPCD with a characteristic plate shape and particle size of 5–35 µm. The inclusion of BSA in the coating resulted in a better and more uniform distribution of CaP on the surface of DBM trabeculae. MG63 cells showed that both the obtained forms of CaP and its complex with BSA did not exhibit cytotoxicity up to a concentration of 10 mg/ml in vitro. Ectopic (subcutaneous) implantation in rats revealed pronounced biocompatibility, as well as strong osteoconductive, osteoinductive, and osteogenic effects for both DBM+CaP and DBM+CaP+BSA, but more pronounced effects for DBM+CaP+BSA. In addition, for the DBM+CaP+BSA samples, a pronounced full physiological intrafibrillar biomineralization and proangiogenic effect with the formation of bone-morrow-like niches, accompanied by pronounced processes of intramedullary hematopoiesis, indicating a powerful osteogenic effect of this composite have been achieved.

Recently, “mature” silkworms (MS) of Bombix mori have been considered as a potential nutraceutical, with a number of health benefits reported for steamed and lyophilized MS powder (SMSP). However, no obesity-related effects have been reported for SMSP. In the present study, anti-obesity effects of SMSP were investigated in adult mice in vivo, aged 12 weeks at the onset of drug administration, fed normal diet (ND) and high-fat diet (HFD), respectively, for 12 weeks. SMSP significantly suppressed body weight gain, intra-abdominal adipose tissue, and food efficiency in both ND-fed and HFD-fed adult mice. In addition, SMSP significantly decreased food intake and liver weight in HFD-fed mice, indicating that SMSP suppressed appetite and simultaneously reduced the conversion of feed into body weight in HFD-fed mice. SMSP also significantly lowered serum levels of glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, asparagine transaminase, alanine transaminase, and alkaline phosphatase. However, SMSP had no significant effect on the weights of kidney, spleen, and thymus and serum levels of blood urea nitrogen and creatinine. Taken together, the above results suggest that SMSP has potent anti-obesity effects and is safe for long-term use as a potential therapeutic and/or nutraceutical in both obese patients and non-obese individuals.

Background: The high prevalence of learning disabilities among children confirm that learning disabilities are surprisingly common. In absence of routine screening, many children still go undetected with a huge individual and family burden, while at the same time existing interventions are conflicting. The purpose of the study is to report on the design, implementation and evaluation of an innovative pilot intervention aiming to improve the quality of life of the family of students with specific learning disabilities. Method: For the purposes of this study, we used an experimental research design, using two groups (intervention and control). The intervention included four meetings with parents of children from the intervention group. To assess the quality of life of the students' family and the parenting style, the following measuring tools were used. They conducted at times and locations convenient to each participant. The instruments used to measure outcomes were two standard weighted questionnaires, the parenting style questionnaire and the family quality of life questionnaire. Findings: The results showed that the intervention program had significantly positive effects on both parenting style and children’s quality of life. Specifically, a decrease in parental authoritarianism and an increase in parental support were observed. Also, an increase in child-parent interaction, emotional and general well-being was found. Conclusion: The intervention program did improve the quality of life of the children by increasing all the variables related to the measurement of their quality of life.

The Korean water deer (WD), the dominant wildlife species in South Korea, is classified as vul-nerable on the IUCN Red List. Beside their several unique characteristics, they have a lower in-cidence of tick bites compared to other Cervidae species, particularly roe deer (RD). In natural environments, ticks exhibit questing behavior by waiting on grasses to climb onto host's hair coat. They use sensory organs to detect signals such as body temperature and chemicals from the host's skin, then move to preferred feeding location. Therefore, we conducted a comparative analysis of the skin tissue and hair features of both species to compare the factors leading to lower incidence of tick bites in WD. Notably, WD had significantly larger blood vessels, sebaceous glands, and sweat glands which maintain the barrier functions of the skin (p≤0.004), irregular scale surfaces in hair cuticles, and stiff and 2.83-times thicker primary hair diameter (p<0.001). Each parameters made the ticks difficult to move onto the epidermis of WD. To our knowledge, this is the first report which is focused on the comparative analysis for skin and hair feature in WD and RD. We suggest that these differences may attribute to evade tick bites in WD.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterized by marked clinical and genetic heterogeneity. Ethnic groups underrepresented in studies may have distinctive characteristics. We sought to evaluate the clinical and genetic landscape of Russian HCM patients. A total of 193 patients (52% male; 95% Eastern Slavic origin; median age 56 years) were clinically evaluated, including genetic testing, and prospectively followed to document outcomes. As a result, 48% had obstructive HCM, 25% had HCM in family, 21% were asymptomatic, and 68% had comorbidities. During 2.8 years of follow-up, the all-cause mortality rate was 2.86%/year. A total of 5.7% received an implantable cardioverter-defibrillator (ICD), 21% septal reduction therapy. Sequencing analysis of 176 probands identified 64 causative variants in 66 patients (38%); recurrent variants were MYBPC3 p.Q1233* (8), MYBPC3 p.R346H (2), MYH7 p.A729P (2), TPM1 p.Q210R (3) and FLNC p.H1834Y (2); 10 were multiple variant carriers (5.7%); 5 had non-sarcomeric HCM, ALPK3, TRIM63 and FLNC; thin filament variant carriers had a worse prognosis for heart failure (HR = 7.9, p=0.007). In conclusion, in the Russian HCM population, the low use of ICD and relatively high mortality should be noted by clinicians; some distinct recurrent variants are suspected to have a founder effect; family studies on some rare variants enriched the worldwide knowledge in HCM.

This study presents the encapsulation of two amino acid-based ionic liquids (AAILs), 1-Ethyl-3-methylimidazolium glycine [Emim][Gly] and 1-Ethyl-3-methylimidazolium alanine [Emim][Ala], in a highly porous metal organic framework (MOF-177), to generate state-of-the-art composites for post-combustion CO2 capture. The thermogravimetric analysis (TGA) demonstrated a successful encapsulation of the AAILs, consequently dramatically reducing the composites' surface area and pore volume. Both [Emim] [Gly]@MOF-177 and [Emim][Ala]@MOF-177 had close to 3 times the CO2 uptake of MOF-177 at 20 wt.% loading, 0.2 bar, and 303 K. Additionally, 20-[Emim][Gly]@MOF-177 and 20-[Emim] [Ala]@MOF-177 enhanced their CO2/N2 selectivity from 5 (pristine MOF-177) to 13 and 11, respectively.

Tomato (Solanum lycopersicum L.) is a high value horticultural crop in Kenya. Nutritionally, the crop is rich in niacin, carotene, thiamine, and vitamin C. Mwea in Kirinyaga County is one of the major tomato growing areas in Kenya. Tomato production in Kenya is hindered by losses due to diseases caused by pathogens that include plant parasitic nematodes (PPN). Among the plant parasitic nematodes, the root-knot nematode (RKN) is the most predominant in Mwea. This study investigated the soil parameters that influence the distribution of the RKN for the purpose of mapping their distribution. This is important since it ensures that nematicide application is only to specific sites where these nematodes are found thereby saving on input costs as well as protecting the environment. The study consisted of surveys conducted in geo-referenced tomato production fields in seven (7) tomato production sites in Tebere and Mwea. Sampling was done in a stratified random manner in both rainfed and irrigated tomato production fields in both dry and rainy seasons for determination of the spatial and temporal distribution of nematodes, respectively. Nematode extraction was done using the centrifugal floatation technique and identification done to genera level using morphological features. Soil characteristics determining PPN distribution patterns in tomato production fields of Mwea were measured using standard methods. Soil parameters measured included soil pH, electrical conductivity, elevation and soil texture. The PPN incidence and diversity was determined using the Shannon-Weiner species diversity index. Detrended canonical correspondence analysis (DCCA) was performed to interpret and summarize major patterns of variation within the soil variable data and to estimate the ability of each soil variable to reflect variance in the entire PPN data set. Fourteen (14) genera of nematodes were identified with the diversity between 0.6 and 1.2. RKN distribution differed significantly (p<0.05) among the sites. Among the soil samples analyzed, 81% were positive for RKN infestation. There was an insignificant difference (p>0.05) between nematode densities in the dry and rainy seasons. Rainfed fields exhibited a significantly higher (p<0.05) RKN population densities compared to irrigated fields. The study established a great variability in the soil parameters in the area. The RKN distribution pattern, density and abundance were inversely correlated (p<0.05) with the soil pH and positively correlated (p<0.05) with soil EC. Based on the inverse relationship between soil pH and RKN distribution in the Mwea ecosystem, maps of nematode distribution and soil pH were developed. This enables the possibility of a site specific system for management of RKN

The clinical requirement for a good esthetic result for immediate implant placement is the absence of dehiscence in the anterior facial alveolar bone. In the presence of a dehiscence, it is recommend-ed to use a connective tissue graft in addition to immediate implant placement or to change to ear-ly implant placement. However, the literature focusing on dehiscence is scarce, and the influence of different placement times and combined use of connective tissue graft on postoperative esthetics in cases with dehiscence is unclear. Therefore, we quantitatively evaluated the pre-extraction de-hiscence morphology and postoperative changes in the facial tissue of implants in three groups: immediate implant placement (Group I), immediate implant placement with connective tissue graft (Group IC), and early implant placement (Group E). Fifty-two implants were obtained (20 in Group I, 16 in Group IC, and 16 in Group E). A wider dehiscence increases the risk of soft tissue regression, which was one reason for choosing early implant placement. A combination of imme-diate implant placement and connective tissue graft, or early implant placement, tended to result in less soft tissue regression due to the thicker postoperative facial soft tissue volume.

Background: This study aimed to investigate the effect of fascial manipulation (FM) of the deep cervical fascia (DCF) and sequential yoga poses (SYP) on pain and function in individuals with mechanical neck pain (MNP). Method: Following the predefined criteria, ninety-nine individuals with MNP were recruited, randomised and assigned to either the intervention group (IG) (n=51) or the control group (CG) (n=48). Individuals in the IG received FM (4 sessions in 4 weeks) along with the home-based SYP (4 weeks). The CG participants received the usual care (cervical mobilization and thoracic manipulation (4 sessions in 4 weeks) along with unsupervised therapeutic exercises (4 weeks). The participants underwent baseline and weekly follow-up measurements of pain using a numerical pain rating scale (NPRS) and elbow extension range of motion (EEROM) during upper limb neurodynamic test 1 (ULNT1). The baseline and the 4th session follow-up measurements of the Patient-specific Functional Scale (PSFS) and Fear-avoidance Behavior Questionnaire (FABQ) were also taken. Results: A repeated-measures ANOVA was performed. The mean differences between the IG and CG on NPRS 3rd and 4th sessions are -1.009 (p&lt; 0.05) and -1.701 (p&lt; 0.001), respectively; on EEROM in the 4th session is 20.120 (p&lt; 0.001); on FABQ during the follow-up is -5.036 (p&lt;0.001), showing a statistically significant difference, whereas on PSFS during follow-up is 0.263 (p=0.566), suggesting no significant differences in PSFS. Conclusion: FM and SYP can aid in reducing pain and fear avoidance behavior as well as improving the function and extensibility of the upper quarter region.

Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, where it not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying the specific bone involvement, focusing on the complex interactions that occur between bone tissue's own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined osteoimmunology. Specifically, we have comprehensively elaborated on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis lead to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility.

Hydrogels prepared from natural polymer have attracted extensive attentions in biomedical fields such as drug delivery, wound healing, and regenerative medicine due to their good biocompatibility, degradability and flexibility. This review outlines the commonly used natural polymer in hydrogel preparation, including cellulose, chitosan, collagen/gelatin, alginate, hyaluronic acid and starch. The polymeric structure and process/synthesis of natural polymers are illustrated, and natural polymer-based hydrogels including the hydrogel formation and properties are elaborated. Subsequently, the biomedical application of hydrogels based on natural polymer in drug delivery, tissue regeneration, wound healing and other biomedical field is summarized. Finally, the future perspectives of natural polymers and hydrogels based on them are discussed. For natural polymer, novel technologies such as enzymatic and biological methods are developed to improve the structural properties and the development of new natural based polymers or natural polymer derivatives with high performance is still very important and challenging. For natural polymer-based hydrogels, novel hydrogel materials, like double-network hydrogel, multifunctional composite hydrogels and hydrogel microrobots are designed to meet the advanced requirements in biomedical application, and new strategies such as dual-crosslinking, microfluidic chip, micropatterning and 3D/4D bioprinting, have been explored to fabricate advanced hydrogel materials with designed properties for biomedical application. Overall, natural polymeric hydrogels have attracted increasing interests in biomedical application, and the development of novel natural polymer-based materials and new strategies/methods for hydrogel fabrication is badly desirable and still challenging.

Non-alcoholic steatohepatitis (NASH) is a complex disease resulting from chronic liver injury associated with obesity, type 2 diabetes, and inflammation. Recently, multi-target drugs have been proposed to treat complex diseases including NASH; however, their manufacturing pro-cesses remain time- and cost-intensive and inefficient. Therefore, to overcome these limitations, we developed UniStac, a novel enzyme-mediated conjugation platform for multi-specific drug development. UniStac demonstrated high conjugation yields, optimal thermal stabilities, and robust biological activities. Through such platform, we designed a tetra-specific compound, C-192, targeting Glucagon-like peptide 1 (GLP-1), Glucagon (GCG), Fibroblast growth factor 21 (FGF21), and Interleukin-1 receptor antagonist (IL-1RA) simultaneously for the treatment of NASH. The biological activity and treatment efficacy of C-192 were confirmed both in vitro and in vivo using a methionine–choline-deficient (MCD) diet-induced mouse model. C-192 exhibited profound therapeutic efficacies compared to conventional drugs, including liraglutide and dulaglutide. C-192 significantly improved alanine transaminase levels, triglyceride accumula-tion, and the non-alcoholic fatty liver disease activity score. Our results collectively provide clin-ical feasibility of UniStac for developing multi-specific drugs, and C-192 as an innovative thera-peutic opportunity for severe NASH, as it exerts synergistic effects across multiple targets.

Adult human thymus degenerates into adipose tissue (TAT). In contrast to subcutaneous adipose tissue (SAT), TAT has been reported to exhibit enhanced angiogenic properties in elderly people. We have previously shown that vascular endothelial growth factor A (VEGFA) is the most abundant angiogenic growth factor in TAT of patients with ischemic cardiomyopathy (IC), and that VEGFA levels are increased in elderly (&gt;70 years) compared with middle-aged patients. This makes TAT a promising candidate for angiogenic therapies and the regeneration of ischemic tissues following coronary surgery. MicroRNAs (miRNAs) have emerged as attractive therapeutic targets, especially those that regulate angiogenic processes. The study's purpose is to determine the miRNA network associated with both VEGFA pathway regulation and enrichment of age-linked angiogenesis in the TAT.

Exosomes are membrane-bound, biologically active nanovesicles of size 30-200 nm produced by many cell types, such as both mammalian and plant cells. They are wrapped in a phospholipid bilayer and play a significant role in intercellular communications. The ease in their isolation and the ability of plant-derived exosome-like nanovesicles (PDEVs) to efficiently deliver bioactive constituents into mammalian cells have made them popular in contemporary research. PDEVs share many characteristics with mammalian EVs (MEVs), including shape, size, surface charge, and consist of bioactive molecules like lipids, proteins, nucleic acids, and tiny metabolites. However, the chemical composition profile of PDEVs and their biogenesis mechanism differ significantly from those of MEVs. They have been widely explored as potential therapeutic agents and are considered as good alternatives to act as a carrier for drug delivery. The present work elucidates the isolation of exosome-like-nanovesicles (henceforth exosomes) from the culture supernatants of an in vitro cultured callus tissue derived from a bone healing plant known for its osteogenic activity, i.e., Cissus quadrangularis. The physical and biological properties of exosomes were successfully studied using different characterization techniques. To assess their therapeutic potential, we studied the internalisation of calcein-AM labeled exosomes by human derived mesenchymal stromal cells (hMSCs). Additionally, we evaluated the potential of exosomes in the migration of cells in a cell scratch assay with hMSCs and their effect on amelioration of oxidative stress was investigated on preosteoblast MC3T3-E1 cells that were pre-treated with these exosomes. Furthermore, we investigated their proliferation and differentiation to osteoblasts like cells with the help of resazurin assay and alkaline phosphatase assay (ALP). The obtained results provide a primary justification for the use of Cissus quadrangularis-derived exosomes as a nanocarrier for drug molecules for various therapeutic bone applications.

Domain-specific systems-on-chip (DSSoCs) aim to narrow the gap between general-purpose processors and application-specific designs. CPU clusters enable programmability, while hardware accelerators tailored to the target domain minimize task execution times and power consumption. Traditional operating system (OS) schedulers can diminish the potential of DSSoCs as their execution times can be orders of magnitude larger than the task execution time. To address this problem, we propose a dynamic adaptive scheduling (DAS) framework that combines the advantages of a fast, low-overhead scheduler and a sophisticated, high-performance scheduler with a larger overhead. We present a novel runtime classifier that chooses the better scheduler type as a function of the system workload, leading to improved system performance and energy-delay product (EDP). Experiments with five real-world streaming applications indicate that DAS consistently outperforms fast, low-overhead, and slow, sophisticated schedulers. DAS achieves a 1.29x speedup and 45% lower EDP than the sophisticated scheduler under low data rates and a 1.28x speedup and 37% lower EDP than the fast scheduler when the workload complexity increases. Furthermore, we demonstrate that the superior performance of the DAS framework also applies to hardware platforms, with up to a 48% and 52% reduction in execution time and EDP, respectively.

A comparative study of the physicochemical properties of natural bentonite clays of Pogodayevо (Republic of Kazakhstan, mod.1) and Dash-Salakhli (Republic of Azerbaijan, mod.2) deposits and modification of the bentonite clay with polyhydroxocations of iron (III) and aluminium (III). It-wasestablished that the modification of natural bentonitesusing polyhydroxocations of iron (III) and aluminium(III) by the method of "co-precipitation" leads to a change in their chemical composition, structural and sorption properties. The results showed that hydroxy-aluminum cations ([Al3O4(OH)24(H2O)12]7+) and poly-hydroxyl-Fe or polyoxo-Fe were intercalated into clay layers, which led to an increase in the values of d001 and specific surface areas compared to those of the original bentonite, from 37 to 120 for the Pogodaevo bentonite and from 51 to 172 respectively for bentonite from the Dash-Salakhli deposit. It is shown that modified sorbents based on natural bentonite are finely porous objects with a predominance of pores of 1.5−6.0 nm in size. As a result, there is a significant increase in the specific surface area of sorbents. Modification of bentonite with polyhydroxocations of iron (III) and aluminium (III) by the "co-precipitation" method also leads to an increase in the sorption capacity of the sorbents obtained with respect to nickel (II) cations. Modified bentonites were used for the adsorption of Ni (II) ions from the model solution. Ni (II) was absorbed in a neutral pH solution. The study of equilibrium adsorption showed that the data are in good agreement with the Langmuir isotherm model. The maximum adsorption capacity of the Ni (II) monolayer obtained from the Langmuir equation was 25.0 mg/g (mod. 1_Al_5-c), 18.2 mg/g (mod. 2_Al_5-c) for Al-bentonite and 16.7 mg/g (mod. 1_Fe_5-c), 10.1 (mod. 2_Fe_5-c) for Fe-bentonite. The kinetics of adsorption is considered. The high content of Al-OH anion exchange centresin them determines the higher sorption activity of Al-modified bentonites.

Silk fibroin (SF) extracted from Bombyx mori cocoons is a biocompatible and biodegradable polymer shows potential as matrices for tissue engineering and regenerative medicine, or con-trolled drug delivery systems. Regenerated fibroin, obtained by removing sericin from natural silk, is water-soluble. Its aqueous solutions can be processed into a variety of materials, for example, fibrous matrices, using the electrospinning method. In this article, the concentration dependences of the properties of aqueous solutions of regener-ated fibroin, that determine the possibility of obtaining electrospun mats for tissue-engineering applications, are studied. A slowdown in the growth of viscosity after a concentration of fibroin of 30% and a decrease in the transparency of the solution were found; this may be due to the on-set of conformational rearrangements: the transition of fibroin from the random coils, charac-teristic for dilute solutions, to the anisotropic conformation of the helix and the appearance of β-pleated sheets. Fibrous mats from regenerated fibroin were obtained from solutions with a concentration of 10 and 20%. Two methods were used to prevent solubility of fibroin-based matrices: conversion of fibroin to the β-conformation by treatment with an ethanol solution and chemical cross-linking with gen-ipin (Gp). The structures of the fibrous samples were studied by AFM and confocal laser scan-ning microscopy. The composition of the moulding solution for the electrospinning of regener-ated fibroin fibrous matrices and the conditions for their modification have been optimised. It has been shown that the composition of fibroin with chitosan contributes to a decrease in the solubility of electrospun fibrous matrices by increasing the number of amino groups available for modification by Gp, and also leads to a decrease in the diameter of the fibers. Electrospun fiber matrices based on regenerated SF, modified by cross-linking with Gp in water-alcohol solutions, promote cell growth and proliferation and may be promising for tissue engineering.

Sacroiliac (SI) joint dysfunction can lead to debilitating pain but can be treated with minimally invasive sacroiliac joint fusion (SIJF). This treatment is commonly performed using 2D fluoroscopic guidance. This makes placing the implants without damaging surrounding neural structures challenging. Virtual surgical planning (VSP) using simulated fluoroscopic images may improve perioperative guidance. This article describes a workflow with VSP in SIJF using simulated fluoroscopic images and evaluates achieved implant placement accuracy. Routinely collected survey data on the added value of VSP were also evaluated. Ten interventions were performed on 10 patients by the same surgeon, comprising 30 implants; the median age was 39 years, and all patients were female. The overall mean implant placement accuracy was 4.9 ± 1.26 mm and 4.0 ± 1.44°. There were no malpositioning complications. The VSP helped the surgeon understand the anatomy and determine the optimal position and length of the implants. The average Likert scale score of the survey was 4.7, suggesting a positive role of VSP for SIJF. Planned positions of the implants could be reproduced in surgery with clinically acceptable accuracy and VSP was a valuable asset for the surgeon.

Vascular inflammation is recognized as the primary trigger of acute coronary syndrome (ACS). However, current noninvasive methods are not capable of accurately detecting coronary inflammation. Epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT), in addition to their role as an energy reserve system, have been found to contribute to the development and progression of coronary artery calcifica-tion, inflammation, and plaque vulnerability. They also participate in the vascular re-sponse during ischemia, sympathetic stimuli, and arrhythmia. As a result, the evalua-tion of EAT and PCAT using imaging techniques such as computed tomography (CT), cardiac magnetic resonance (CMR), and nuclear imaging has gained significant atten-tion. PCAT-CT attenuation, which measures the average CT attenuation in Hounsfield units (HU) of the adipose tissue, reflects adipocyte differentiation/size and leukocyte infiltration. It is emerging as a marker of tissue inflammation and has shown prognos-tic value in coronary artery disease (CAD), being associated with plaque development, vulnerability, and rupture. In patients with acute myocardial infarction (AMI), an in-flammatory pericoronary microenvironment promoted by dysfunctional EAT/PCAT has been demonstrated, and more recently, it has been associated with plaque rupture in non-ST-segment elevation myocardial infarction (NSTEMI). Endothelial dysfunc-tion, known for its detrimental effects on coronary vessels and its association with plaque progression, is bidirectionally linked to PCAT. PCAT modulates the secretory profile of endothelial cells in response to inflammation and also plays a crucial role in regulating vascular tone in the coronary district. Consequently, dysregulated PCAT has been hypothesized to contribute to type 2 myocardial infarction with non-obstructive coronary arteries (MINOCA) and coronary vasculitis. Recently, quan-titative measures of EAT derived from coronary CT angiography (CCTA) have been included in artificial intelligence (AI) models for cardiovascular risk stratification. These models have shown incremental utility in predicting major adverse cardiovas-cular events (MACE) compared to plaque characteristics alone. Therefore, the analysis of PCAT and EAT, particularly through PCAT-CT attenuation, appears to be a safe, valuable, and sufficiently specific noninvasive method for accurately identifying cor-onary inflammation and subsequent high-risk plaque. These findings have been sup-ported by biopsy and in vivo evidence. Although speculative, these pieces of evidence open the door to a fascinating new strategy in cardiovascular risk stratification. The incorporation of PCAT and EAT analysis, mainly through PCAT-CT attenuation, could potentially lead to improved risk stratification and guide early targeted primary pre-vention and intensive secondary prevention in patients at higher risk of cardiac events.

Alveolar bone atrophy after tooth extraction presents significant difficulties when planning delayed-immediate implant treatment to replace a lost tooth. Socket augmentation is an effective therapy that limits the post extraction volumetric changes and facilitates implant placement whilst reducing the need for staged grafting. However, socket augmentation and osteoconductive graft conversion is a slow process that could take 4-6 months. PRF and its variants have significant bio-enhancement effect on wound healing and regeneration through release of platelet drived growth factors, bioactive substances, cytokines. Leukocytes in PRF also play a significant role in enhancing tissue regeneration as part of osteo-immune response. Use of PRF during socket augmentation is highly effective in enhancing extraction site healing and graft integration by angiogenesis, cell proliferation, recruitment, and differentiation through release of growth factors and bioactive substances mediated by platelets and leukocytes. PRF with SA is recommended as an adjunct to SA as a sole biomaterial or in combination with xenograft or allograft bone substitutes to enhance tissue regeneration and to reduce risk of infection, osteitis and postoperative pain in extraction sockets

Background: Glycogen storage diseases (GSDs), known as glycogenoses, belong to inborn metabolic defects in the glycogen metabolism pathway. Several types of GSDs are distinguished, including Ia, Ib, III, VI, and IX. GSDs manifest as excessive glycogen deposition in the liver and muscles, resulting in the dysfunction of these organs. Therefore, the treatment of choice is multitherapy that, due to dietary restrictions, may lead to nutritional deficiencies and organ complications. This study aims to assess anthropometric, body composition, skeletal status, results of selected laboratory tests, dietary, lifestyle and physical capacity analyses in patients with glycogenoses and compare the results between GSD I and GSD III-VI-IX groups. Results: The results indicate that GSD patients were overweight or obese (44% of patients had BMI +1SD or +2SD) with high percentage of fat tissue (50% of patients had above 30% of body fat) and inadequate bone mineralisation (total body less head: median z-score -0.9, L2-L4 segment: median z-score -1.65). GSD I patients had the highest risk of developing obesity (67% of them had above 30% of body fat) and osteoporosis (total body less head: median z-score -1.0, L2-L4 segment: median -1.7). Conclusions: Special attention should be paid to appropriate diet and supplementation in patients with glycogenoses.

Cytokines are mediators of inflammation that could lead to fibrosis. The aim was to monitor cytokine levels in saliva and serum after locally fractionated radiotherapy of the head and neck in mice and investigate associations with salivary gland fibrosis and hyposalivation. C57BL/6 mice were randomized to sham or X-ray irradiation of 66 Gy in 10 fractions over 5 days. Blood and saliva were collected on day -7, 5, 35, 80 and 105 with following cytokine analysis. The harvested submandibular salivary gland was assessed for presence of fibrosis. Decision tree regression analysis was used to investigate whether cytokine levels could predict late endpoints in terms of hyposalivation or fibrosis. Significant formation of fibrosis in gland tissue and reduced saliva production was found after irradiation. The pro-inflammatory cytokines IL-1α, TNF, TIMP1, G-CSF, KC and MIP-1α showed increased levels in saliva in irradiated mice and strong correlation with late endpoints. The decision tree analysis largely separated controls from irradiated animals with IL-1α being the strongest predictor. Pro-inflammatory cytokines in saliva, but not in serum, were associated with late endpoints. This indicates that cytokine expression in saliva is a good biomarker for local salivary gland damage with IL-1α as the strongest single predictor.

Tissue bioengineering has been assuming a pivotal role in implementing alternatives to conven-tional ossicular middle ear replacement prostheses to overcome extrusion while preserving acoustic properties. This in vitro study aims to explore for the first time in current literature the feasibility of a biohybrid middle ear prosthesis composed of titanium surrounded by bone ex-tracellular matrix as bio-coating. We have hereby studied the adhesion and proliferation of human adipose-derived mesenchymal stem cells (hASC) on titanium scaffolds in vitro. Moreover, we identified the osteogenic differentiation of hASC using immunofluorescence assay to analyze osteoblasts gene expression profile (Alp, Runx2, Col1a1, Osx, and Bglap) and we accounted the presence of collagen as a marker of hASC ability to secrete extracellular matrix. We utilized scanning electron microscopy to evaluate the presence of extracellular matrix on the scaffolds. Our preliminary data demonstrated the titanium ability to support human adipose-derived mesenchymal stem cell colonization, proliferation, and osteoblastic differentiation, to obtain a biohybrid device. Our experience seems encouraging, we advocate further in vivo research to corroborate our results towards bone transplantation.

Psychological readiness following Anterior Cruciate ligament Reconstruction (ACLR) correlates with different return to sport outcomes. However, the relationship between strength and power and psychological readiness remains unexplored. The aim of this study was to investigate the relationship between the Anterior Cruciate Ligament Return to Sport After Injury (ACL-RSI) scores and various hamstrings and quadriceps strength and power variables. Twelve participants (20.7±2.5 years old; 174.2±7.5 cm; 70.2±8.5 kg; 18.2±8.3% of body fat) who had an ACLR nine months or more before the study completed the ACL-RSI questionnaire and isokinetic strength testing of the hamstrings and quadriceps (60°.s-1 and 180°.s-1). Based on ACL-RSI scores, they were divided into “cases” and “controls”, deemed not psychologically ready and psychologically ready to return to previous sport performance (PILOS), respectively. The main findings are that quadriceps’ and hamstrings’ rate of torque development (RTD) and time since surgery were determinants of psychological readiness following ACLR. Furthermore, compared to controls cases showed significantly lower angle-specific quadriceps and hamstrings torque close to extension and lower RTD, but no difference in peak torque. These results suggest that physiotherapists should facilitate athletes’ RTS by focusing on the restoration of RTD and strength at angles close to full knee extension.

Bone growth plate abnormalities and skull shape defects are seen in hypophosphatasia, a heritable disorder in humans that occurs due to deficiency of Tissue Nonspecific Alkaline Phosphatase (TNAP, Alpl) enzyme activity. Abnormal development of the cranial base growth plates (synchondroses) and abnormal skull shapes have also been demonstrated in global TNAP-/- mice. To distinguish local vs. systemic effects of TNAP on skull development, we utilized P0-Cre to knockout TNAP only in cranial neural crest derived tissues using TNAP flox mice. Here we show that TNAP deficiency in cranial neural crest leads to leads to skull shape defects and deficient growth of the intersphenoid synchondrosis (ISS). ISS chondrocyte abnormalities included increased proliferation in resting and proliferative zones with decreased apoptosis in hypertrophic zones. ColX expression is increased, indicative of premature differentiation in the absence of TNAP. Sox9 expression is increased in both resting and prehypertrophic zones of mutant mice. Expression of PTHrP and IHH were also increased. Finally, cranial base organ culture revealed that inorganic phosphate (Pi) and pyrophosphate (PPi) have specific effects on cell signaling and phenotype changes in the ISS. Together, these results demonstrate that TNAP expression in growth plate chondrocytes is essential for normal development, and that the mechanism likely involves Sox9, PTHrP, IHH and PPi.

This study aimed to evaluate the proliferation and migration of fibroblast cells derived from chronic wounds and investigate the impact of low-level laser therapy (LLLT) on their growth and migration. A total of 60 dermal samples were obtained from three sites of chronic pressure ulcers and diabetic ulcers in 20 patients. Following collection in the operating room, the dermal samples were isolated using the procedure described by Freshney RI. Fibroblasts from the wound base (Site 1) exhibited a slow proliferation rate and a decrease in proliferative capacity. Fibroblasts from wound margins (Site 2) and adjacent healing skin (Site 3) could be successfully isolated and maintained for multiple generations without any morphological changes. Fibroblasts from chronic wounds at Sites 2 and 3 showed slower proliferation rates and reduced migration capabilities compared to normal dermal fibroblasts (control samples). The fibroblast cells were exposed to LLLT at different energy levels (2.5, 3, and 3.5 J/cm2). The laser-treated groups demonstrated a significantly higher increase in cell count compared to the control sample, with the highest increase observed at an energy level of 3 J/cm2. These findings suggest that LLLT at an energy level of 3 J/cm2 could effectively enhance fibroblast migration, indicating its potential as a therapeutic intervention for chronic wounds.

Regenerative endodontic procedures (REPs) aim at recreating dental pulp tissue using biomaterials such as hydrogels. Their bioactivity is mostly linked to the nature of biomolecules or chemical compounds that will compose the endodontic hydrogel. However, many other parameters, such as hydrogel concentration, type, bioactive molecules solubility, of apex size were reported to influence the hydrogel behavior, leading to the inability to predict the clinical outcome. This lack of knowledge and the various parameters that should be considered, suggest that biological activity of endodontic hydrogel is impossible to anticipate and could hinder the bench to bedside transition. We formulated in this article our opinion that most of these parameters could be identified, described, and studied. A second part of the document lists some challenges and perspectives, including development of future mathematical models able to explain and predict the bioactivity of these endodontic hydrogel in clinic.

Genetic engineering technology offers opportunities to improve many important agronomic traits in crops, including insect-resistance. However, genetically modified (GM) exogenous proteins in edible tissues of transgenic crops has become an issue of intense public concern. To advance the application of GM techniques in maize, a Cre/loxP-based strategy was developed for manipulating the transgenes in green tissues while locking it in non-green tissues. In the strategy, the site-specific excision can be used to switch on or off the expression of transgenes at specific tissues. In this work, two basic transgenic maize named KEY carrying the Cre gene and LOCK containing the Vip3A gene with a blocked element, were obtained based on their separate fusion gene cassettes. The expression level and concentration of Vip3A were observed with high specific accumulation in green tissues (leaf and stem), and only a small amount in root and kernel tissues in the KEY × LOCK hybrids. The insect-resistance of transgenic maize against two common lepidopteran pests, Ostrinia furnacalis and Spodoptera frugiperda, was assessed in the laboratory and field. The results indicated that the hybrids possessed high resistance levels against the two pests, with mortality rates above 73.6% and damage scales below 2.4 compared with the control group. Our results suggested that the Cre/loxP-mediated genetic engineering approach has a competitive advantage in GM maize. Overall, findings from this study are significant for providing a feasible strategy for transgenes avoiding expression in edible parts and exploring novel techniques toward the biosafety of GM plants.

FLASH-RT represents a novel therapeutic radiation modality that holds remarkable potential for mitigating radiation therapy’s adverse side effects. This cutting-edge technology allows for the sparing of healthy tissue while precisely targeting cancerous cells by administering an ultra-high dose-rates of typically between 10 and 30 Gy in less than a few hundred milliseconds. FLASH-RT has demonstrated impressive results in small-animal models, prompting scientists to adapt and advance existing technologies to make it a viable treatment option for humans. However, producing the ultra-high-dose-rate radiation required for the therapy remains a significant challenge. Several radiation sources, such as very high energy electrons (VHEEs), low energy electrons, x-rays, and protons, have been studied for their ability to deliver the necessary dose. Among them, FLASH-x-ray has gained the most attention owing to its capacity to penetrate deeply seated tumours. Despite the complexity of the process, the potential advantages of FLASH-RT make it an exciting area of research. To achieve the FLASH effect, high-frequency, pulsed irradiated accelerator technology can be employed. Sparing healthy tissue, it may allow for more aggressive and effective cancer treatments, leading to a better quality of life for patients. Ongoing research and development will be necessary to refine and optimize this approach to radiation therapy.

Obtaining a proper position for THA’s components is a crucial aspect for the implant perfor-mance and consequently patient outcomes. Patient specific kinematic seems to be a key factor to reach the optimal implant positioning. The aim of this study was to assess the accuracy and safety of a computed dynamic analysis system which through patient specific guides tries to improve implant positioning and functional orientation according to patient’s spinopelvic mobility and anatomy.A total of 100 consecutive patients were prospectively enrolled. All patients received an OPS dynamic hip preoperative planning. A TC scan protocol follow up analysis has done at 6 month after surgery.The mean deviation from the planned acetabular inclination and anteversion was 4.3° e 3.8° respectively. The 98% of cases was within +/- 10° of Lewinnek safe zone both for inclination and anterversion. The height of osteotomy deviated on the average of 1.6mm. The 100% cases were included within 4mm of osteotomy. Patient specific and laser guided instru-mentation is safe and accurately reproduce the dynamic planning in terms of components orien-tation, osteotomy level, leg length and offset.

Modeling and assessing the sustainability of machining systems has been considered to be a crucial approach to improving the environmental performance of the machining processes. As the most common machining system, the computer numerical control (CNC) milling system is a typical man-machine cooperative system where the activities of the machine tool and operator generate material and energy consumption. However, the energy consumption of the operator in the CNC milling system has often been ignored in most existing research. Therefore, existing methods fail to provide a comprehensive understanding of the sustainability of the CNC milling system. To fill this gap, an exergy loss assessment method is proposed to investigate the sustainability of the CNC milling system, where the energy consumption of the operator, the energy consumption of the machine tool, and material consumption are taken into consideration. The key performance indexes of the energy consumption of the operator, the energy consumption of the machine tool, the exergy loss, and the specific exergy loss (SEL) are analyzed and modeled. To demonstrate the feasibility of the proposed method, a case study was carried out on a three-axis machining center (XH714D), in which SEL was found to be 88.04J/mm3. The proposed method is effective to assess the sustainability of the CNC milling system, and the established exergy loss models build a good basis for exergy efficiency optimization.

Conductive nanocomposites play a significant role in tissue engineering by providing a platform to support cell growth, tissue regeneration, and electrical stimulation. In this present study, a set of electroconductive nanocomposite hydrogels based on gelatin (G), chitosan (CH) and conductive carbon black (CB) was synthesized with the aim to develop novel biomaterials for tissue regeneration application. Incorporation of conductive carbon black (10, 15 and 20 wt %) significantly improved electrical conductivity and enhanced mechanical properties with the increased CB content. We employed an oversimplified unidirectional freezing technique to impart anisotropic morphology with interconnected porous architecture. An investigation into whether any anisotropic morphology affects the mechanical properties of hydrogel was conducted by performing compression and cyclic compression tests in each direction parallel and perpendicular to macroporous channels. Interestingly, nanocomposite with 10 % CB produced both anisotropic morphology and mechanical property, whereas anisotropic pore morphology diminished at higher CB concentration (15 and 20 %) imparting denser texture. Collectively, the nanocomposite hydrogels showed great structural stability as well as good mechanical stability and reversibility. Under repeated compressive cyclic at 50 % deformation, the nanocomposite hydrogels showed preconditioning, characteristic hysteresis, nonlinear elasticity, and toughness. Overall, the collective mechanical behavior resembled the mechanics of soft tissues. Electrical impedance associated to the hydrogels was studied in terms of modulus and phase in dry and wet condition. The electrical properties conducted in wet conditions, which is more physiologically relevant, showed low impedance at high frequencies due to capacitive currents. Overall, impedance of the nanocomposite hydrogels decreased with increased CB concentrations. These gelatin-chitosan–carbon black nanocomposite hydrogels show great promise for use as conducting substrates for the growth of electro-responsive cells in tissue engineering.

The genetic diversity of coronavirus (CoV) is high, and its infection in animals has not yet been fully revealed. By RT-PCR detection of partial RNA dependent RNA polymerase (RdRp) gene of CoV, we screened a total of 502 small mammals belonging to 18 species in 12 genera and 4 orders collected in Dali and Nujiang Prefecture of Western Yunnan Province, China. The prevalence of β-CoV in Chevrieri's field mouse (Apodemus chevrieri) and Lancangjiang field mouse (A. ilex) were 3.54% (4/113) and 6.67% (6/90), respectively; the prevalence of α-CoV in White-footed Indochinese rat (Rattus nitidus) and long-tailed red-toothed shrew (Episoriculus leucops) was 75% (3/4) and 5.88% (1/17), respectively. The co-infection rates of β-CoV and α-CoV in Kachin red-backed vole (Eothenomys cachinus), Norway rat (R. norvegicus) were 2.22% (2/90), 3.85% (1/26) respectively. The identity of the partial RdRp genes obtained of 13 strains of β-CoV was 83.42%-99.23% at nucleotide level, and it is worth noting that the two strains from Kachin red-backed vole showed highly homology to BOV-36/IND/2015 from Indian bovine and DcCoV-HKU23 from one-humped camel (Camelus dromedarius) in Morocco, the nucleotide similarity between 97.86%-98.33%. Similarly, the identity of the 7 strains of α-CoV among the partial RdRp sequences was 94.00%-99.18% at nucleotide levels. The viral load in different tissues was measured by quantitative RT-PCR (qRT-PCR). The average CoV viral load in small mammalian intestinal tissue was 1.25×106copies/g, differently, the mean CoV viral load in liver, heart, lung, spleen and kidney tissue was from 1.29×103 to 4.02×103copies/g, which revealed that CoV has extensive tropism of intestinal tissue in small mammals (P &lt; 0.0001). This result revealed the genetic diversity, epidemiology, and infective tropism of α-CoV and β-CoV in small mammals from Dali and Nujiang, which deepens the comprehending of the retention and infection of coronavirus in natural hosts.

Introduction: This study aimed to evaluate whether radiomic features extracted solely from the edema of soft tissue sarcomas (STS) could predict the occurrence of lung metastasis in comparison with features extracted solely from the tumoral mass. Materials and Methods: We retrospectively analyzed magnetic resonance imaging (MRI) scans of 32 STSs including 14 with lung metastasis and 18 without. Segmentation of the tumor mass and edema was performed for each MRI examination. A total of 107 radiomic features were extracted for each mass segmentation and 107 radiomic features for each edema segmentation. A two-step feature selection process was applied. Two predictive features for the development of lung metastasis were selected from the mass-related features, as well as two predictive features from the edema-related features. Two random forest models were created based on these selected features; 100 random subsampling runs were performed. Key performance metrics including accuracy and area under the ROC curve (AUC) were calculated, and the resulting accuracies were compared. Results: The model based on mass-related features achieved a median accuracy of 0.83 and a median AUC of 0.88, while the model based on edema-related features achieved a median accuracy of 0.75 and a median AUC of 0.79. Statistical analysis comparing the accuracies of the two models revealed no significant difference. Conclusion: Both models showed promise in predicting the occurrence of lung metastasis in soft tissue sarcomas. These findings suggest that radiomic analysis of edema features can provide valuable insights into the prediction of lung metastasis in soft tissue sarcomas.

Pulmonary hypertension (PH) is a severe vascular complication of connective tissue diseases (CTD). Patients with CTD may develop PH belonging to different groups: 1) pulmonary arterial hypertension (PAH), 2) PH secondary to lung disease and/or hypoxia, 3) PH due to left heart disease, and 4) chronic thromboembolic pulmonary hypertension (CTEPH). PAH most often develops in systemic scleroderma (SSc), mostly in its limited variant. PAH-CTD is a progressive disease characterized by poor prognosis, therefore the early diagnosis should be established A specific treatment for PAH-CTD is currently available and recommended: prostacyclin derivative (treprostinil, epoprostenol, iloprost, selexipag), nitric oxide and natriuretic pathway: stimulators of soluble guanylate cyclase (sGC: riociguat) and phosphodiesterase 5 inhibitors (PDE5i: sildenafil, tadalafil), endothelin receptor antagonists (ERA: bosentan, macitentan, ambrisentan). Moreover, novel drugs e.g. sotatercept are intensively investigated in the clinical trials. The aim of this paper is to review the literature on the recent advances in treatment strategy and prognosis of patients with PAH-CTD.

Ubiquitin-Specific-peptidase 22 (Usp22) cleaves ubiquitin moieties from numerous proteins, in particular transcription factors. Recently, it was reported that Usp22 acts as negative regulator of interferon-dependent responses. In the current study, we investigated the role of Usp22 deficiency upon acute viral infection with lymphocytic choriomeningitis (LCMV) virus. We found that lack of Usp22 on bone marrow derived cells (Usp22 fl/fl Vav1-Cre mice) reduced induction of type I and II interferons. Limited type I interferon response did not influence virus replication. However, restricted expression of PD-L1 led to increased frequencies of functional virus-specific CD8+ T cells and rapid death of Usp22 deficient mice. CD8+ T cell depletion experiments revealed that accelerated CD8+ T cells were responsible for enhanced lethality in Usp22 deficient mice. In conclusion, we found that the lack of Usp22 generated a pathological CD8+ T cell response, which gave rise to severe disease in mice.

Adipose tissue has acquired considerable importance due to its role in maintaining body homeostasis. Beyond storing energy, adipose tissue is essential in numerous processes of energy metabolism, food intake, endocrine and immunological functions as well as neromodulatory functions by secreting hormones that participate in the regulation of homeostasis and being responsive to soluble proteins secreted by other tissues. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favouring the secretion of deleterious adipocytokines that benefit a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases. Obesity is a disease that has increased rapidly in recent decades and is caused by environmental, hormonal, and genetic factors, which probably work in combination. Environmental factors that contribute to the increase in obesity include decreased physical activity, associated with increased screen time, increased accessibility and consumption of foods rich in fats and sugars. Weight loss should be recommended for all obese patients and overweight patients with comorbidities. For many patients who need to lose weight for medical reasons, the initial goal is to lose 5-10% of their body weight in the first 6 months. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity and in Chile, the Chilean Society of Metabolic and Bariatric Surgery led the process of adopting the adult obesity clinical practice guideline, which establishes changes in the approach to managing obesity as a chronic disease, with an emphasis on multifactorial lifestyle interventions that include dietary changes, increased physical activity, and behavioural modifications. Pharmacotherapy, medical devices, and bariatric surgery are other options for patients who need additional interventions, so the objective of this review is to know the pathophysiological mechanisms of obesity from its origin to the current treatments available for treatment.

Hydrogels (gels) are attractive tools for tissue engineering and regenerative medicine due to their potential for drug delivery and ECM-like composition. In this study, we use rheology to characterize GelMA/alginate gels loaded with human platelet lysate (PL). We then characterize these gels from a physicochemical perspective and evaluate their ability to transport PL proteins, their pore size, and their rate of degradation. Finally, their biocompatibility is evaluated. We describe how alginate changes the mechanical behavior of the gels from elastic to viscoelastic after ionic (calcium-mediated) crosslinking. In addition, we positively report the release of PL proteins and relate it to the degradation profile of the gels and the biocompatibility of the gels. Thus, the developed gels represent attractive substrates for both cell studies and bioactive materials.