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.

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.

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.

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.

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.

Ozonated sunflower oil (OSO) is an established therapeutic agent and nutraceutical harboring various therapeutic values, including antiallergic, derma-protective, and broad-spectrum antimicrobial activity. Conversely, the medicinal aspects of OSO for wound healing, tissue regeneration, and treatment of inflammation in dyslipidemia have yet to be fully elucidated. Herein, a comparative effect of OSO and sunflower oil (SO) was investigated to heal cutaneous wound and tissue regeneration of zebrafish impediment by carboxymethyllysine (CML) toxicity, following impact on hepatic inflammation and blood lipid profile. After OSO (final 2%, 1 μL) and SO's (final 2%, 1 μL) treatment, substantial healing was elicited by OSO in the cutaneous wound of zebrafish impaired by CML (final 25 mg). As an important event of wound healing, OSO scavenges the reactive oxygen species (ROS), rescues the wound from oxidative injury, and triggers the essential molecular events for the wound closer. Furthermore, the intraperitoneal injection of OSO was noted to counter the CML-induced adversity and prompt tissue regeneration in the amputated tail fin of zebrafish. Additionally, OSO counters the CML-induced neurotoxicity and rescues the zebrafish from acute mortality and paralysis, along with meticulous recovery of hepatic inflammation, fatty liver changes, and diminished ROS and proinflammatory interleukin (IL)-6 production. Besides, OSO efficiently ameliorated CML-induced dyslipidemia by alleviating the total blood cholesterol (TC), triglyceride (TG) and increasing high-density lipoproteins cholesterol (HDL-C). The outcome of multivariate assessment employing principal component analysis and hierarchical cluster analysis supports a superior therapeutic potential of OSO over SO against the clinical manifestation of CML. Conclusively, OSO owing to its antioxidant and anti-inflammatory potential, counters CML-induced toxicity and promotes wound healing, tissue regeneration, hepatoprotection, improved blood lipid profile, and survivability of zebrafish.

The potential of sericin, a protein derived from silkworms, is explored in bone graft applications. Sericin's biocompatibility, hydrophilic nature, and cost-effectiveness make it a promising candidate for enhancing traditional graft materials. Its antioxidant, anti-inflammatory, and UV-resistant properties contribute to a healthier bone-healing environment, and its incorporation into 3D-printed grafts could lead to personalized medical solutions. However, despite these promising attributes, there are still gaps in our understanding. The precise mechanism through which sericin influences bone cell growth and healing is not fully understood, and more comprehensive clinical trials are needed to confirm its long-term biocompatibility in humans. Furthermore, the best methods for incorporating sericin into existing graft materials are still under investigation, and potential allergic reactions or immune responses to sericin need further study.

In this study, we designed a functional neuro-cardiac model to help us examine the role of neuronal regulation and confirm the importance of neural innervation techniques for cardiac tissue regeneration. A three-dimensional (3D) bioprinted neuro-cardiac scaffold composed of a mixture of gelatin-alginate and alginate-genipin-fibrin hydrogels was developed with a 2:1 ratio of AC16 cardiomyocytes (CMs) and retinoic acid differentiated SH-SY5Y neuronal cells (NCs) respectively. A unique semi-3D bioprinting approach was adopted where the CMs were mixed in the cardiac bioink and printed using an anisotropic accordion design to mimic the physiological tissue architecture in vivo. The voids in this 3D structure were methodically filled in using a NCs-gel mixture and cross-linked. Confocal fluorescent imaging using Microtubule-associated protein 2 (MAP-2) antibodies for labeling NCs, and the MyoD1 antibody for CMs revealed functional coupling between the two cell types in the final cross-linked structure. This data confirmed the development of a physiologically functional neuro-cardiac model that can be used to study neuro-cardiac modulation under physiological and pathological conditions.

Angiogenesis is new blood vessel formation from existing vessels and is a critical first step in tissue repair following chronic disturbances in healing and degenerative tissues. Chronic pathoanatomic tissues are characterized by a high number of inflammatory cells, overexpression of inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), the presence of mast cells, T cells, reactive oxygen species, and matrix metalloproteinases, and a decreased angiogenic capacity. Multiple studies have demonstrated that autologous orthobiological cellular preparations (e.g., platelet-rich plasma [PRP]) im-prove tissue repair and regenerate tissues. There are many PRP devices on the market. Unfortunately, they differ greatly in platelet numbers, cellular composition, and bioformulation. PRP is a platelet concentrate consisting of a high concentration of platelets with or without certain leukocytes, platelet-derived growth factors (PGFs), cytokines, molecules, and signaling cells. Several PRP products have immunomodulatory capacities that can influence resident cells in a diseased microenvironment, inducing tissue repair or re-generation. Generally, PRP is a blood-derived product, regardless of its platelet number and bioformulation, and the literature indicates both positive and negative patient treatment outcomes. Strangely, the literature does not designate specific PRP preparation qualifications that can potentially contribute to tissue re-pair. Moreover, the literature scarcely addresses the impact of platelets and leukocytes in PRP on (neo)angiogenesis other than a general one-size-fits-all statement that “PRP has angiogenic capabilities.” Here, we review the cellular composition of all PRP constituents, including leukocytes, and describe the importance of platelet dosing and bioformulation strategies in orthobiological applications to initiate angiogenic pathways that re-establish microvasculature networks, facilitating the supply of oxygen and nutrients to impaired tissues.

The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT), obtained by mechanical fragmentation, on radiographic bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration while the NT group underwent TPLO alone. The adipose tissue was collected from the thigh region and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray exam preoperatively, immediately postoperatively (T0) and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12= complete remodelling) was used at T0, T1 and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76%–100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complications.

Thermoplastic molded regenerated silk was proposed as structural material in tissue engineering applications, mainly for application in bone. The protocol allows to obtain a compact non-porous material with a compression modulus in the order of a Giga Pascal starting from silk fibroin by compressing a silk fibroin lyophilized sponge of powder in mold at temperature higher than the glass transition temperature (Tg). The main purpose of the produced resin was the osteofixation and other structural applications in which the lack of porosity was not an issue. In this work, we introduced the use of citric acid in the thermoplastic molding protocol of SF to obtain a porosity inside the structural material. In addition to the previously developed protocols the addition of citric acid allowed us to obtain a structural material. The CA powder during the compression acted as a template for the pore formation. In addition, the CA was able to effectively crosslink the SF chain improving the mechanical strength. This effect was proved both evaluating the compression modulus and by studying the spectra obtained by Fourier infrared spectroscopy (FTIR). This protocol may be applied in the near future to the production of a structural bone scaffold.

G protein-coupled receptors (GPCRs) are expressed essentially on all cells, facilitating cellular responses to external stimuli, and are involved in nearly every biological process. Several members of this family play significant roles in the regulation of adipogenesis and adipose me-tabolism. However, the expression and functional significance of a vast number of GPCRs in adipose tissue are unknown. We used a high-throughput RT-PCR panel to determine the expres-sion of the entire repertoire of non-sensory GPCRs in mouse white, and brown adipose tissue and assess changes in their expression during adipogenic differentiation of murine adipocyte cell line, 3T3-L1. In addition, the expression of GPCRs in subcutaneous adipose tissues from lean, obese, and diabetic human subjects was evaluated by re-analyzing RNA-sequencing data. We detected a total of 292 and 271 GPCRs in mouse white and brown adipose tissue, respectively. There is a significant overlap in the expression of GPCRs between the two adipose tissue depots but several GPCRs are specifically expressed in one of the two tissue types. Adipogenic differ-entiation of 3T3-L1 cells had a profound impact on the expression of several GPCRs. RNA se-quencing of subcutaneous adipose from healthy human subjects detected 255 GPCRs and obesity significantly changed the expression of several GPCRs in adipose tissue. Finally, we report sev-eral highly expressed GPCRs with no known role in adipose biology whose expression was sig-nificantly altered during adipogenic differentiation and/or in the diseased human subjects. These GPCRs could play an important role in adipose metabolism and serve as a valuable translational resource for obesity and metabolic research.

The gastrointestinal and genitourinary tracts share several similarities. Primarily, these tissues are composed of hollow structures lined by an epithelium through which materials need to flow with the help of peristalsis brought by muscle contraction. In the case of the gastrointestinal tract, solid or liquid food must circulate to be digested and absorbed and the waste products eliminated. In the case of the urinary tract, the urine produced by the kidneys must flow to the bladder, where it is stored until its elimination from the body. Finally, in the case of the vagina, it must allow the evacuation of blood during menstruation, accommodate the male sexual organ during coitus, and is the natural way to birth a child. The present review describes the anatomy, pathologies and treatments of such organs, emphasizing tissue engineering strategies.

Background: Instrument-assisted soft tissue mobilization (IASTM) is thought to alter fluid dynamics in human soft tissue. The aim of this study was to investigate the influence of IASTM on the thoracolumbar fascia (TLF) on the water content of the lumbar myofascial tissue. Methods: 21 healthy volunteers were treated with IASTM. Before and after the procedure and 5 and 10 minutes later, lumbar bioimpedance was measured by bioimpedance analysis (BIA) and TLF stiffness by indentometry. Tissue temperature was recorded at the measurement time points using an infrared thermometer. Results: Bioimpedance increased significantly from 58.3 to 60.4 Ω (p < 0.001) at 10-minute follow-up after the treatment. Temperature increased significantly from 36.3 to 36.6° Celsius from 5 to 10 minutes after treatment (p = 0.029), while lumbar myofascial stiffness did not change significantly (p = 0.84). Conclusions: After the IASTM intervention, there was a significant increase in bioimpedance, likely due to a decrease in water content in myofascial lumbar tissue. Further studies in a randomized control trial design are needed to extrapolate the results in healthy subjects to a symptomatic population as well and to confirm the reliability of BIA in myofascial tissue.

Novel advanced biomaterials have recently gained great attention, especially in surgical minimally invasive techniques. Applying sophisticated design and engineering methods, various elastomer-hydrogel systems (EHS) with outstanding performance have been developed in last decades. Those systems composed of elastomers and hydrogels are very attractive due to their high biocompatibility, injectability, controlled porosity and often antimicrobial properties. Moreover, elastomeric properties and bioadhesiveness are making them suitable for soft tissue engineering. Herein, we present the advances in current state-of-the-art design principles and strategies for strong interface formation inspired by nature (bio-inspiration), diverse properties and applications of elastomer-hydrogel systems in different medical fields, in particular, in tissue engineering. Functionalities of those systems, including adhesive properties, injectability, antimicrobial properties and degradability applicable to tissue engineering will be discussed in a context of future efforts towards development of advanced biomaterials.

Porous tantalum (Ta) is a promising biomaterial and has been applied in orthopedics and dentistry for nearly two decades. The high porosity and interconnected pore structure of porous Ta promise fine bone ingrowth and new bone formation within the inner space, which further guarantee rapid osteointegration and bone-implant stability in long term. Porous Ta has high wettability and surface energy that can facilitate adherence, proliferation and mineralization of osteoblasts. Meanwhile, low elastic modulus and high friction coefficient of porous Ta can effectively avoid stress shield effect, minimize marginal bone loss and ensure primary stability. Accordingly, the satisfactory clinical application of porous Ta based implants or prostheses are mainly derived from its excellent biological and mechanical properties. With the advent of additive manufacturing, personalized porous Ta based implants or prostheses have shown their clinical value in the treatment of individual patient who need specially designed implant or prosthesis. In addition, many modification methods have been introduced to enhance the bioactivity and antibacterial property of porous Ta with promising in vitro and in vivo research results. In any case, choosing suitable patients is of great importance to guarantee surgical success after porous Ta insertion.

The three-dimensional printing of scaffolds is an interesting alternative to the traditional techniques of periodontal regeneration. This technique uses computer assisted design and manufacturing after CT scan. After 3D modelling, individualized scaffolds are printed by extrusion, selective laser sintering, stereolithography, or powder bed inkjet printing. These scaffolds can be made of one or several materials such as natural polymers, synthetic polymers, or bioceramics. They can be monophasic or multiphasic and tend to recreate the architectural structure of the periodontal tissue. In order to enhance the bioactivity and have a higher regeneration, the scaffolds can be embedded with stem cells and/or growth factors. This new technique could enhance a complete periodontal regeneration. This review summarizes the application of 3D printed scaffolds in periodontal regeneration. The process, the materials and designs, the key advantages and prospects of 3D bioprinting are highlighted, providing new ideas for tissue regeneration.

Inflammation plays a key role in the development and progression of type-2 diabetes (T2D), a disease characterised by peripheral insulin resistance and systemic glucolipotoxicity. Visceral adipose tissue (AT) is the main source of inflammation early in disease course. Macrophages are innate immune cells that populate all peripheral tissues, including AT. Dysregulated AT macrophage (ATM) responses to microenvironmental changes are at the root of aberrant inflammation and development of insulin resistance, locally and systemically. The inflammatory activation of macrophages is regulated at multiple levels: cell surface receptor stimulation, intracellular signalling, transcriptionally and metabolically. This review will cover the main mechanisms involved in AT inflammation and insulin resistance in T2D. First, we will describe the physiological and pathological changes in AT that lead to inflammation and insu- lin resistance. We will next focus on the transcriptional and metabolic mechanisms described that lead to the activation of ATMs. We will discuss more novel metabolic mechanisms that influence macrophage polarisation in other disease or tissues contexts that may be relevant to future work in insulin resistance and T2D.

Purpose: to assess any differences on marginal bone loss between bone-level or tissue-level dental implants through a review of literature until September 2019. Materials and methods: MEDLINE, Embase and other database were searched by two independent authors. The search was limited to articles in English. Results: The search provided 1028 records and, after removing the duplicates through titles and abstracts screening, 45 full-text articles were assessed for eligibility. For qualitative analysis 20 articles were included, 17 articles of them for quantitative analysis. A total of 1161 patients (mean age 54,4 years) and 2933 implants were observed, 1427 (Tissue-level) and 1506 (Bone-level). The survival rate and the success rate were more than 90%, except for 2 studies with a success rate of 88% and 86.2%. No studies reported any differences between groups in term of success and survival rates. Three studies showed that BL-implants had statistically less marginal bone loss (P< 0.05). Only one study reported statistically less marginal bone loss in TL-implants (P< 0.05). In the most part of the studies, differences between implant types in marginal bone loss were not statistically significant. Conclusion: Despite to the peri-implant tissue around transmucosal implants has been reported to be inflammation-free because of the absence of bacterial infiltration in the micro-gap between the fixture and abutment, no clinical and radiological differences were highlighted between groups from the included studies after a variable period of follow-up ranged between 1 to 5 years.

Background. Specific clinical risk factors that may be associated with ambulatory outcome following thrombolysis therapy in ischemic stroke patients with pre-stroke depression is not fully understood. This was investigated. Methods. Multivariate analyses were performed to identify predictors of functional ambulatory outcomes. Patient demographics and clinical risk factors served as predictive variables, while improvement or no improvement in ambulatory outcome was considered as the primary outcome. Results. A total of 595 of these patients received rtPA of which 310 patients presented with pre-stroke depression, 217 had no improvement in functional outcome, while 93 patients presented with an improvement in functional outcome. Carotid artery stenosis (OR= 11.577, 95% CI, 1.281 – 104.636, P=0.029) and peripheral vascular disease (OR= 18.040, 95% CI, 2.956-110.086, P=0.002) were more likely to be associated with an improvement in ambulation. Antihypertensive medications (OR= 7.810, 95% CI, 1.401 –43.529, P=0.019),previous TIA (OR= 0.444, 95% CI, 0.517 –0.971, P=0.012), and congestive heart failure (OR= 0.217, 95% CI, 0.318 –0.402, P=0.030) were associated with a no improvement in ambulation. Conclusion. After adjustment for covariates, more clinical risk factors were associated with no improvement when compared with improvement in functional outcome following thrombolysis therapy in an acute ischemic stroke population with pre-stroke depression.

Abstract: The broad clinical use of synthetic vascular grafts for vascular diseases is limited by their thrombogenicity and low patency rate, especially for vessels with a diameter inferior to 6 mm. Alternatives such as tissue-engineered blood grafts (TEBGs) have gained increasing interest. Among the different manufacturing approaches, 3D bioprinting presents numerous advantages and enables the fabrication of multi-scale, multi-material, and multicellular tissues with heterogeneous and functional intrinsic structures. Extrusion-, inkjet- and light-based 3D printing techniques have been used for the fabrication of TEBG out of hydrogels, cells, and/or solid polymers. This review discusses the state-of-the-art research on the use of 3D printing for TEBG with a focus on the biomaterials and deposition methods.

High porosity and mass transport properties of microfiltration polymeric membranes benefits nutrients supply to cells when used as scaffolds in interstitial perfusion bioreactors for tissue engineering. High nutrients transport is assumed when pore size and porosity of the membrane are in the micrometric range. The present work demonstrates that the study of membrane fouling by proteins present in the culture medium, though not done usually, should be included in the routine testing of new polymer membranes for this intended application. Two poly(ε-caprolactone) microfiltration membranes presenting similar average pore size (~0.7µm) and porosity (>80%) but different external surface porosity and pore size have been selected as case study. The present work demonstrates that a membrane with lower surface pore abundance and smaller external pore size (~0.67 µm), combined with adequate hydrodynamics and tangential flow filtration mode is usually more convenient to guarantee high flux of nutrients. On the contrary, having large external pore size (~1.70µm) and surface porosity would incur in important internal protein fouling that could not been prevented with the operation mode and hydrodynamics of the perfusion system. Additionally, the use of glycerol in the drying protocols of the membranes might cause plasticization and a consequent reduction of mass transport properties due to membrane compaction by the pressure exerted to force perfusion. Therefore, preferentially, drying protocols that omit the use of plasticizing agents are recommended.

The treatment of large-area bone defects remains a challenge; however, various strategies have been developed to improve the performances of scaffolds in bone tissue engineering. In this study, poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) scaffold was coated with Asp-Gly-Glu-Ala (DGEA)-incorporated collagen for the repair of rat skull defect. Our results indicated that the mechanical strength and hydrophilicity of PLGA/HA scaffold were clearly improved and conducive to cell adhesion and proliferation. The collagen-coated scaffold with DGEA significantly promoted the repair of skull defect. These findings indicated that a combination of collagen coating and DGEA improved scaffold properties for bone regeneration, thereby providing a new potential strategy for scaffold design.

Gastroparesis (GP) is associated with depletion of interstitial cells of Cajal (ICC) and enteric neurons, which leads to pyloric dysfunction followed by severe nausea, vomiting and delayed gastric-emptying. Regenerating these fundamental structures with stem cell therapy, would be helpful to restore gastric function in GP. Mesenchymal stem cells (MSC) have been successfully used in animal models of other gastrointestinal (GI) diseases including colitis. However, no study has been performed with these cells on GP animals. In this study, we explored if mouse MSC can be delivered from a hydrogel-scaffold to the luminal surfaces of GP mice stomach. Mouse MSC was seeded atop alginate-gelatin, coated with poly-L-lysine. These cell-gel constructs were placed atop stomach explants facing the luminal side. MSC grew uniformly all across the gel surface within 48 hr. When placed atop the lumen of the stomach, MSC migrated from the gels to the tissues as confirmed by positive staining with Vimentin and N-cadherin. The feasibility of transplanting a cell-gel construct to deliver stem cells in the stomach wall was successfully shown in a mice GP model, thereby making a significant advance towards envisioning the transplantation of an entire tissue-engineered ‘gastric patch’ or ‘microgels’ with stem cells, and growth factors.

The objective of this case report is to introduce a customized CAD/CAM freeze-dried bone allograft (FDBA) block for its use in Guided Bone Regeneration (GBR) procedures for severely deficient maxillary bones. Additionally, a special newly developed remote incision technique is presented to avoid wound dehiscence. The results show an optimal integration behaviour of the FDBA block after six months and the formation of new vital bone. Thus, the results of the present case report confirm the use of the customized CAD/CAM bone block for augmentation of complex defects in the maxillary aesthetic zone as a successful treatment concept.

The rapid development of electric vehicles, unmanned aerial vehicles, and wearable electronic devices has led to a high interest in research related to the synthesis of graphene with a high specific surface area for energy applications. However, the problem of graphene synthesis scalability, as well as the lengthy duration and high energy intensity of the activation processes of carbon materials, are significant disadvantages. In this study, a reactor was developed for the green, simple, and scalable electrochemical synthesis of graphene oxide with a low oxygen content of 14.1 %. The resulting material was activated using a fast joule heating method. The processing of mildly oxidized graphene with a high–energy short electrical pulse (32 ms) made it possible to obtain a graphene–based porous carbon material with a specific surface area of up to 1984.5 m2/g. The low energy intensity, simplicity, and use of environmentally friendly chemicals render the proposed method scalable.

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.

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.

Initially introduced almost thirty years ago for the express purpose of providing electronic warfare systems the capabilities to detect, characterize, and identify radar emitters, Specific Emitter Identification (SEI) has recently received a lot of attention within the research community as a physical layer technique for securing Internet of Things (IoT) deployments. This attention is due in large part to SEI’s demonstrated success in passively and uniquely identifying wireless emitters using traditional machine learning and the success of Deep Learning (DL) within the natural language processing and computer vision areas. SEI exploits distinct and unintentional features present within an emitter’s transmitted signals. The existence of these distinctive and unintentional features is attributed to slight manufacturing and assembly variations that exist within and between the components, sub-systems, and systems that comprise an emitter’s Radio Frequency (RF) front end. Although sufficient to facilitate SEI, these features do not hinder normal operations such as detection, channel estimation, timing, and demodulation. However, despite the plethora of SEI publications, it has remained largely a focus of academic endeavors that primarily focus on proof-of-concept demonstration and little to no use in operational networks for various reasons. The focus of this survey is a review of SEI publications from the perspective of its use as a practical, effective, and usable IoT security mechanism, thus we use IoT requirements and constraints (e.g., wireless standard, nature of their deployment) as a lens through which each reviewed paper is analyzed. Previous surveys have not taken such an approach and have only used IoT as motivation, a setting, or a context. In this survey, we consider operating conditions, SEI threats, SEI at scale, publicly available data sets, and SEI considerations that are dictated by the fact that it is to be employed by IoT devices or IoT infrastructure.

For Convolutional Neural Network (CNN), Depthwise Separable CNN (DSCNN) is a preferred architecture for Application Specific Integrated Circuit (ASIC) implementation on edge devices. It can benefit from a multi-mode approximate multiplier proposed in this work. The proposed approximate multiplier uses two 4-bit multiplication operations to implement a 12-bit multiplication operation by reusing the same multiplier array. With this approximate multiplier, sequential multiplication operations are pipelined in a modified DSCNN to fully utilize the PE array in the convolutional layer. This Approximate (A-DSCNN) was implemented on TSMC 40-nm CMOS process with a supply voltage of 0.9 V. At the clock frequency of 200 MHz, the design achieves 4.78 GOPs/mW while occupying 1.24 mm x 1.24 mm silicon area. Compared to conventional DSCNN implemented in a similar process node, the chip area and power consumption were reduced by 53% and 25%, while the throughput was improved by 17%.

Autistic spectrum disease (ASD) is an increasingly common diagnosis nowadays with a prevalence of 1-2% in most countries. Its complex causality – a combination of genetic, immune, metabolic and environmental factors - is translated into pleiomorphic developmental disorders of various severity, which have in common two main aspects: repetitive, restrictive behaviors, and difficulties in social interaction varying from awkward habits and verbalization to complete lack of interest from the ASD child for the outside world. The wide variety of ASD causes also makes it very difficult to find a common denominator – a disease biomarker and medication – and currently there is no commonly used diagnostic and therapeutic strategy besides clinical evaluation and psychotherapy.It is known that inflammation is present in a majority of ASD children, and blood inflammatory markers, together with metabolic, electrophysiological markers and imagistics are useful for ASD diagnostic validation and treatment; however, they tend to leave out a sizeable proportion of ASD kids who do not have such modifications. Genetic testing – whole exome sequencing or targeted profiling on about 500 ASD-linked genes- may also provide good insight into pathophysiology, however many times its results are more restrictive rather than offering additional therapeutic options.Here we describe a new biomarker for ASD - the neuron-specific enolase (NSE) - which was elevated above the normal clinical range (less than 16.3 ng/mL) in the vast majority of ASD kids tested in our study (40 of 41, or 97.5%). This finding opens up a new direction for diagnostic confirmation, dynamic evaluation and therapeutic intervention for ASD kids.

Cross-species investigations on cancer invasiveness are a new approach that identified new biomarkers potentially useful for improving tumor diagnosis and prognosis in clinical medicine and veterinary science. In this study, we combined proteomic analysis of four experimental rat malignant mesothelioma (MM) tumors with analysis of ten patient-derived cell lines to identify common features associated to mitochondrial proteome rewiring. The comparison of significant abundance changes between invasive and non-invasive rat tumors rat tumors gave a list of 433 proteins, including twenty-six proteins reported to be exclusively located in mitochondria. Next, we analyzed the differential expression of genes encoding the mitochondrial proteins of interest in five primary epithelioid and five primary sarcomatoid human MM cell lines, and the most impressive increase was observed in the expression of the long-chain acyl coenzyme A dehydrogenase (ACADL). To evaluate the role of this enzyme in the migration/invasiveness, two epithelioid and two sarcomatoid human MM cell lines derived from patients with the highest and lowest overall survival were studied. Interestingly, sarcomatoid vs epithelioid cell lines were characterized by higher migration and fatty oxidation rates, in agreement with ACADL findings. These results suggest that evaluating mitochondrial proteins in MM specimens might identify tumors with higher invasiveness.

In this study, a numerical simulation of fluid flow through railway ballast in the time domain is presented, providing a model for unsteady-state flow. It is demonstrated that the position of the free surface with respect to time can also be used to solve the steady flow case. The effect of ballast fouling is included in the model to capture the realistic behavior of railway ballast, which is critical to understanding the impact of flooding. A thorough comparison with a range of previous studies, including theoretical and experimental approaches, is made and very close agreement is obtained. The significant impact of ballast fouling on fluid flow and its potential consequences for railway infrastructure are highlighted by the simulation. Valuable insights into the behavior of water flow through porous media and its relevance to railway ballast management are offered by this study.

Most existing cancer therapies negatively affect normal tissue as well as cancerous tissue. A potentially effective strategy for treating cancer that precludes off-target damage and could be an option for most patients would involve targeting one or more mutations that are ubiquitous in the given patient’s tumor(s). To effect this strategy, one would employ multi-region sequencing of a patient’s primary tumor and metastases to seek out mutations that are shared between all or at least most regions. Once the target or targets are known, one would ideally rapidly generate a molecular switch for at least one of said ubiquitous mutations that can distinguish the mutated DNA, RNA, or protein from the wild-type version and subsequently trigger a therapeutic response. I propose that the therapeutic response involve the replication of an oncolytic virus or intracellular bacterium, as any mutation can theoretically be detected by a vector that enters the cell - and automatic propagation could be very helpful. Moreover, the mutation “signal” can be easily enhanced through transcriptional and translational (if the target is an intracellular protein) enhancement. Importantly, RNA may make the best target for the molecular switches in terms of amplification of the signal and ease of targeting.

Recent advance in electric propulsion systems have demonstrated that these engines can be used for for long-duration interplanetary voyages. Constant specific impulse engine described as a thrust-limited engine is an example of this type of engine, processing the ability to operate at a constant level of impulse. The determination of minimum-fuel, planar heliocentric Earth-to-Mars low-thrust trajectories of spacecraft using a constant specific impulse is discussed considering the first-order necessary conditions derived from Lawden’s primer vector theory. The minimum-fuel low-thrust Earth-to-Mars optimization problem is then solved in two-dimensional, heliocentric frame using both indirect and direct methods. In the indirect method, two-point-boundary-value problems are derived to solve boundary value problems for ordinary differential equations. In the direct method, a general-purpose optimal control software called GPOPS-II is adopted to solve these optimal control problems. Numerical examples using two different optimization methods are presented to demonstrate the characteristics of minimum-fuel planar low-thrust trajectories with on-off-on thrust sequences at three chosen flight times and available maximum powers. The results are useful for broad trajectory search in the preliminary phase of mission designs.

The development of electric aircrafts is becoming an important technology for achieving the goals set by the European Commission for the reduction of gases emissions by 2050 in the aeronautical transportation system. However, there is a gap between the values of specific power in commercial electric machines and the ones required for aeronautical applications. Therefore, the search for alternative materials and non-conventional designs is mandatory. One emergent solution is using superconducting machines and systems to overcome the current limits of conventional electrical machines. This work reviews the new hybrid and all-electric aircraft tendencies, complementing it with recent research on the design and development of high specific power superconducting machines. This includes the main topologies for hybrid and all-electric aircraft, with an overview of the ongoing worldwide projects of these types of aircrafts, systematizing the main characteristics of their propulsion systems. It also includes the research on superconducting machines for the purpose of high specific power, considering the impact on the redesign of aircraft systems in the electrical, cooling, and fuel source sense.

In plant cells the conventional route to the vacuole involves the endoplasmic reticulum, the Golgi and the prevacuolar compartment. However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage. Given the high sequence similarity between the PSIs domains, we sought to depict the differences in terms of post-translational modifications. In fact, one feature that draws our attention is that one is N-glycosylated and the other one is not. Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole. This is also true when the PSI domain is analyzed in the context of the full-length cardosin. Regardless of opening exciting research gaps, the results obtained so far need a more comprehensive study of the mechanisms behind this unconventional direct sorting to the vacuole.

The Sentinel Application Platform (SNAP) architecture facilitates Earth Observation data processing (http://step.esa.int/main/toolboxes/snap/). In this work we present results from a new Snow Processor for SNAP. We also describe physical principles behind the developed snow property retrieval technique based on the analysis of Ocean and Land Colour Instrument (OLCI) onboard Sentinel-3A/B measurements over clean and polluted snow fields. Using OLCI spectral reflectance measurements in the range 400-1020nm, we derive important snow properties such as spectral and broadband albedo, snow specific surface area, snow extent and grain size on the spatial grid of 300m. The algorithm also incorporates cloud screening and atmospheric correction procedures over snow surfaces. We present validation results using ground measurements from Antarctica, the Greenland ice sheet and the French Alps. We find the spectral albedo retrieved with accuracy of better than 3% on average, making our retrievals sufficient for a variety of applications. Broadband albedo is retrieved with the average accuracy of about 5% over snow. Therefore, the uncertainties of satellite retrievals are close to experimental errors of ground measurements. The retrieved surface grain size shows good agreement with ground observations. Snow specific surface area observations are also consistent with our OLCI retrievals. We present snow albedo and grain size mapping over the inland ice sheet of Greenland for areas including dry snow, melted/melting snow and impurity rich bare ice. The algorithm can be applied to OLCI Sentinel-3 measurements providing an opportunity for creation of long – term snow property records essential for climate monitoring and data assimilation studies - especially in the Arctic region, where we face rapid environmental changes including reduction of snow/ice extent and, therefore, planetary albedo.

In Europe we can see a change in the social structure in the last period. Average life expectancy has increased dramatically over the last 50 years. Because of the improved life situation and advanced level of health care, older people are slower. With advancing age, the likelihood of experiencing a variety of constraints such as visual impairment, reduced hearing or physical ability increases. In such a life stage tenants are often forced to leave their long-term living space because these homes can not serve "new" individual needs and the resulting personal protection goal. This transition from the privacy of their home to the new environment often appears to be a painful change. They will take their familiar and well-known surroundings, because their homes can not be adapted to serve new needs. It must be the policy’s role to create a new inclusive social space and the requirement for architects and designers to create new goals for the design of an adaptable environment. This is a comprehensive approach to the design of the outer and inner space that could serve people even if there is an unexpected situation and changes in movement and physiological limitations of older people. The contribution shows the results of the survey conducted in Germany and Slovakia. In the survey respondents expressed their opinion on what they considered important in creating an adaptive environment. Results are processed graphically with explanation. The results were mainly for designers and developers of the indoor environment. Based on the results of the questionnaire survey, studies of possible modifications in the interior of the flats were then prepared. The contribution yielded these results in three age groups of respondents; i. people aged 35, 50 and over 50.

Oral cancer represents a significant global public health challenge, contributing substantially to cancer incidence and mortality. Despite established risk factors such as tobacco use and alcohol consumption, early detection remains crucial for effective treatment. This study introduces a novel approach using a transistor-based biosensor system for detecting the P90 (CIP2A) protein. We have tested the presence of CIP2A in human leukoplakia samples that can rise into oral squamous cell carcinoma. The method employs commercially available glucose test strips functionalized with P90 antibodies, providing high sensitivity and a low limit of detection, which is five orders lower than commercial ELISA kits. A specially designed printed circuit board (PCB) facilitates accurate measurements, and the device's performance is optimized through characteristic tests. Human sample testing validates the biosensor's effectiveness in distinguishing samples after cell lysis. This study contributes to advancing accurate and cost-effective diagnostic approaches for oral pre-cancer and cancer tissues.

To establish simulated micro-gravity conditions, biological organisms are placed on a simulated microgravity system, which primarily rotate in two or three dimensions and rely on slow sedimentation with latency to detect gravity. Fluid dynamics arise as a consequence of rotation of the chambers with in which the cells are filled. To minimize the effects of centrifugal forces, it is necessary to position the samples as close to the center of rotation as possible. Strong shear forces and velocities within the vessel can have an adverse impact on cells, making this a critical topic in cell biology. During experimental investigation, this specific phenomenon is not apparent, but numerical modelling readily illustrates and is not widely analyzed in literature's. Furthermore, bulk flask are frequently employed on random positioning machines (RPM), not merely because they demand a substantial quantity of reagents. The flask presented in the study can be easily developed and fitted in conventional cell culture plates containing medium and reagents similar to those used in ground experiments, thus allowing it to remain close to the center of rotation. In the present study, a series of fluid dynamics simulations are performed to examine the impact of shear forces within the microvessel presented under varying conditions using a foreign medium condition, and these results are compared with existing vessels by observing the effects of shear forces and maximum velocity zones.

Objective: Aims to investigate the effects of empagliflozin (EMPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, on renal fibrosis in male diabetic Sprague-Dawley (SD) rat model. Methods: Streptozotocin(STZ) were injected to establish diabetes model, EMPA (10 mg/kg·d) or normal saline (NS) were administered for four weeks. The changes in renal fibrosis-related biomarkers, include vimentin (VIM), collagen types I(Col-I), collagen types III(Col-III), fibroblast-specific protein 1(FSP-1), connective tissue growth factor (CTGF), fibronectin (FN) were evaluated. Renal pathology, serum glucose levels and urinary protein excretion were also assessed. Results: Biomarkers of renal fibrosis were significantly reduced in the EMPA group compared to those in the NS group after 4-week treatment, including VIM (519.84±83.37 vs. 663.27±91.84 ng/ml, P<0.05), Col-I (21.27±1.46 vs. 25.71±2.82 ng/ml , P<0.05) and Col-III (7.06±1.12 vs. 9.43±1.36 ng/ml, P<0.05), FSP-1 (4.38±0.81 vs. 5.70±0.78 ng/ml, P<0.05), and CTGF (1147±217 vs. 1556±235 pg/ml, P<0.05),respectively. Nevertheless, compared to normal control (NC) group, the levels of renal fibrosis-related biomarkers in the EMPA group showed no significant differences except for VIM, which was VIM (336.66±28.87 vs. 519.84±83.37 ng/mL, P<0.001). NS group rats showed notable renal tubular dilation and casts, EMPA group exhibited only mild tubular dilation. Conclusion: These findings suggest that empagliflozin reverse renal fibrosis potentially through inhibiting CTGF-mediated epithelial-mesenchymal transition.

In dermatological practice, disturbances of the skin microbiome are found in various infectious and inflammatory dermatoses featuring one or more skin lesions with loss of tissue, directly exposing skin layers to microbial invasions. Literature data on the incidence of cutaneous-onset sepsis are, however, scarce. This retrospective observational study assessed hospital admissions for primary skin lesions with vs. without bacterial infections and sepsis during 2020-2022 in the largest emergency hospital in NE Romania. Of 509 patients 441 had infected lesions, 78 had sepsis caused by venous ulcers microbial eczema cellulitis, superinfected bullous dermatoses, erysipelas, erythroderma. Cultured samples revealed S. aureus, P. aeruginosa, E. coli, with K. pneumoniae, S. β-hemolytic associated with sepsis even if rarer. Clinical manifestations included ulcerations, erosions, fissures, excoriations, bullae, vesicles, pruritus, tumefaction, edema, fever, chills, pain, adenopathy, mildly altered mental status. Underlying chronic heart failure, atrial fibrillation, anemia, type-1 diabetes mellitus were comorbidities associated with infection and sepsis. Significant associations and risk factors, including their combined effects, are discussed to draw attention to the need for further research and adequate management to prevent sepsis in adult patients of any age presenting with infected skin lesions (especially cellulitis) and comorbidities (especially type 1 diabetes mellitus and anemia).

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.

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.

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.

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.

The digestive organs are highly sensitive to the influence of orbital flight factors and can limit the professional activities of crew members aboard the International Space Station. Connective tissue as a system-forming matrix of the integrative-buffer metabolic environment is of particular relevance in space biomedicine, ensuring the functioning of internal organs under an altered gravitational stimulus. However, the adaptive mechanisms of the fibrous extracellular matrix of the gastric and intestinal connective tissue have not been fully investigated under prolonged microgravity weightlessness. Using histochemical techniques, the authors experimentally studied the state of collagen fibers in the specific tissue microenvironment of the gastric and intestinal membranes in C57BL/6N mice after a 30-day space flight, subsequent 7-day ground readaptation, and in animals of the relevant control groups. The 30-day stay of laboratory animals aboard the Bion-M 1 biosatellite resulted in a reduction in the fibrous extracellular matrix of connective tissue in the studied digestive organs, excepting the gastric lamina propria. An increased fibrillogenesis was revealed in the gastrointestinal mucous membranes of animals in 7 days after the biosatellite landing, if compared with the parameters of animals of the space flight group. During the experiment with ground simulated orbital flight conditions, changes in collagen fibers were not significant compared to the vivarium control group. Thus, the results obtained evidence gravisensitivity of the fibrous extracellular matrix of the intraorgan connective tissue. This fact also highlights the necessity to further improve gastrointestinal tract-related preventive measures for astronauts during orbital flight.

Prostate cancer is the most occurred malignant disease in the male population in over one-half of the countries and still constitutes the fifth leading cause of death in 2020, worldwide. Metastatic prostate cancer is a lethal malignancy that mostly is terminated within several years through the patient's death. Researchers should focus on the phenomenon which is rigorously appertaining to metastatic cascade and operating as an initiator of metastases to provide the knowledge needed to solve the problem of diagnostics and treatment of advanced prostate cancer patients. The epithelial-mesenchymal transition is one such phenomenon. The current review is based mainly on three papers published in 2021, which describe the most important tissue-specific factors managing epithelial-mesenchymal transition and are discussed with scientific papers published in acknowledged journals. The effect of the current review is the specification of profiles of precise tissue factors predicting the progression of the prostate neoplasm to its metastatic stage in a new edition.

Nanocomposite hydrogels offer remarkable potential for applications in bone tissue engineering. They are synthesized through the chemical or physical crosslinking of polymers and nanomaterials, allowing for the enhancement of their behaviour by modifying the properties and compositions of the nanomaterials involved. However, their mechanical properties require further enhancement to meet the demands of bone tissue engineering. Here, we present an approach to improve the mechanical properties of nanocomposite hydrogels by incorporating polymer grafted silica nanoparticles into a double network inspired hydrogel (gSNP Gels). The gSNP Gels were synthesised via a graft polymerization process using a redox initiator. gSNP Gels were formed by grafting 2-acrylamido-2-methylpropanesulfonic acid (AMPS) as the first network gel followed by a sequential second network acrylamide (AAm) onto amine functionalized silica nanoparticles (ASNPs). We utilized glucose oxidase (GOx), to create an oxygen-free atmosphere during polymerization resulting in higher polymer conversion compared to argon degassing. The gSNP Gels showed excellent compressive strengths of 13.9 ± 5.5 MPa, a strain of 69.6 ± 6.4%, and a water content of 63.4% ± 1.8. The synthesis technique demonstrates a promising approach to enhance the mechanical properties of hydrogels, which can have significant implications for bone tissue engineering and other soft tissue applications.

Adipose tissue is a crucial organ in energy metabolism and thermoregulation. Adipose tissue phenotype is controlled by various signaling mechanisms under pathophysiological conditions. Type II transmembrane serine proteases (TTSPs) are a group of trypsin-like enzymes anchoring on the cell surface. These proteases act in diverse tissues to regulate physiological processes, such as food digestion, salt-water balance, iron metabolism, epithelial integrity, and auditory nerve development. More recently, several members of the TTSP family, namely, hepsin, matriptase-2, and corin, have been shown to play a role in regulating lipid metabolism, adipose tissue phenotype, and thermogenesis, via direct growth factor activation or indirect hormonal mechanisms. In mice, hepsin deficiency increases adipose browning and protects from high-fat diet-induced hyperglycemia, hyperlipidemia, and obesity. Similarly, matriptase-2 deficiency increases fat lipolysis and reduces obesity and hepatic steatosis in high-fat diet-fed mice. In contrast, corin deficiency increases white adipose weights and cell sizes, suppresses adipocyte browning and thermogenic responses, and causes cold intolerance in mice. These findings highlight an important role of TTSPs in modifying cellular phenotype and function in adipose tissue. In this review, we provide a brief description about TTSPs and discuss recent findings regarding the role of hepsin, matriptase-2, and corin in regulating adipose tissue phenotype, energy metabolism, and thermogenic responses.

Necrotizing fasciitis is a life-threatening soft-tissue infection affecting the deep fascia and subcutaneous tissue. It is characterized by a fulminant course and high mortality rates. NF of the head and neck is very rare, most cases being odontogenic in origin. Streptococcus spp. and Staphylococcus spp. are the most common isolated organisms. If the infection progresses to descending mediastinitis the prognosis becomes very poor. Since the initial clinical features can be similar to those of a non-necrotizing deep cervical infection, a high degree of suspicion is critical for an early diagnosis. Computed tomography scan can be useful in the diagnosis and to define the extent of the infection. Early and aggressive surgical debridement of all compromised tissue and antibiotic therapy and fluid resuscitation are essential and should not wait for bacterial culture results. Despite prompt and adequate treatment, mortality of CNF can be as high as 35%.

Traumatic brain injury (TBI) affects millions of people annually, however, our knowledge of the diffuse pathologies associated with TBI is limited. As diffuse pathologies, including axonal injury and neuroinflammatory changes, are difficult to visualize in the clinical population, animal models are used. In the current study we used the central fluid percussion injury (CFPI) model in a micro pig to study the potential scalability of these diffuse pathologies in a gyrencephalic brain of a species with inflammatory systems very similar to humans. We found that both axonal injury and microglia activation within the thalamus and corpus callosum are positively correlated to the weight-normalized pressure pulse, while subtle changes in blood gas and mean arterial blood pressure are not. We also found that the majority of tissue generated up to 10 years previously is viable for immunofluorescent labeling after long-term refrigeration storage. This study indicates that a micro pig CFPI model could allow for specific investigations of various degree of diffuse pathological burdens following TBI.

This review article deals with the design of bioactive calcium phosphate coatings deposited on metallic substrates to produce bone implants. The bioceramic coating properties are used to create a strong bonding between the bone implants and the surrounding bone tissue. They provide a fast response after implantation and increase the lifespan of the implant in the body environment. The first part of the article describes the different compounds belonging to the calcium phosphate family and their main properties for applications in biomaterials science. The calcium to phosphorus atomic ratio (Ca/P)at. and the solubility (Ks) of these compounds define their behavior in a physiological environment. Hydroxyapatite is the gold standard among calcium phosphate materials, but other chemical compositions/stoichiometries have also been studied for their interesting properties. The second part reviews the most usual deposition processes to produce bioactive calcium phosphate coatings for bone implant applications. Plasma spraying is the main industrial process, but magnetron sputtering, pulsed laser deposition, electrospray deposition, electrophoretic deposition, and electrodeposition are also widely studied in academic and industrial research. The last part describes the main physicochemical properties of calcium phosphate coatings and their impact on the bioactivity of bone implants in a physiological environment.

Background and Aims: Liver cirrhosis leads to clinically significant portal hypertension. Transjugular intrahepatic portosystemic shunt (TIPS) has been shown to effectively reduce the degree of portal hypertension and treat its complications. However, poor nutritional status has been shown to be associated with hepatic encephalopathy, acute on chronic liver failure, and mortality following TIPS placement. The purpose of this systematic review is to create another perspective and evaluate the effect of TIPS placement on the nutritional status of patients with liver cirrhosis. Methods: A comprehensive search of four major electronic databases was conducted to identify studies that assessed the nutritional status of cirrhotic patients before and after TIPS placement. The risk of bias was evaluated using ROBINS-I guidelines. Results: Fifteen studies were analyzed in this review. The results indicate that among the 11 studies that evaluated changes in ascites-free weight and body mass index or body cell mass, 10 reported an improvement in one or more measures. Furthermore, all 7 studies that evaluated changes in muscle mass demonstrated an increase in muscle mass. Among the 4 studies that evaluated subcutaneous fat tissue, 3 showed a significant expansion, while 2 out of 3 studies evaluating visceral fat tissue reported a significant reduction. Conclusion: The results of this systematic review suggest that TIPS placement is associated with improvement in the nutritional status of cirrhotic patients, indicated by an increase in ascites-free weight, body mass index, and muscle mass. Additionally, TIPS placement leads to a shift in the distribution of fat mass, with a preference for subcutaneous over visceral adipose tissue. Notably, sarcopenic patients seem to benefit the most from TIPS placement in terms of the nutritional status.

In humans and animal models, intermittent fasting (IF) interventions promote body weight loss, improve metabolic health, and are thought to lower cardiovascular disease risk. However, there is a paucity of reports on the relevancy of such nutritional interventions in the context of dyslipidemia and atherosclerotic cardiovascular diseases. The present study assessed the metabolic and atheroprotective effects of intermittent fasting intervention (IF) in atherosclerosis-prone apolipoprotein E-deficient (Apoe-/-) mice. Groups of male and female Apoe-/- mice were fed a regular (chow) or atherogenic (high-fat, high-cholesterol, HFCD) diet for 4 months, either ad libitum or in an alternate-day fasting manner. The results show that IF intervention improved glucose and lipid metabolism independently of sex. However, IF only decreased body weight gain in males fed chow diet and differentially modulated adipose tissue parameters and liver steatosis in a diet composition-dependent manner. Finally, IF prevented spontaneous aortic atherosclerotic lesions formation in mice fed chow diet, irrespective of sex but failed to reduce HFCD-diet-induced atherosclerosis. Overall, the current work indicates that IF interventions can efficiently improve glucose homeostasis and treat atherogenic dyslipidemia, but a degree of caution is warranted with regard to the individual sex and the composition of the dietary regimen.

Diffuse optical tomography (DOT) is an optical medical imaging method that can assess the structural properties of tissues and their functional characteristics, such as hemoglobin concentration, water content, as well as lipid concentration, via three-dimensional image reconstruction. This paper presents the theoretical basis and working principle of diffuse optical tomography. The paper explains how the optical properties of tissue can be imaged by photon migration techniques based on diffusion theory. The author presents the reasoning for near-infrared (NIR) imaging as the most effective technique in terms of quantitative recovery of spectroscopic optical parameters. This work also listed various advantages, applications, and challenges of DOT. The paper also briefly discusses current progress in near-infrared medical imaging and its future direction.

Obesity is characterized by chronic low-grade inflammation. Caveolin-1 (CAV1), a structural and functional protein found in adipose tissues (AT), is augmented in obese individuals. We aimed to define the inflammatory mediators that influence CAV1 gene regulation and associated mechanism in obesity. Using subcutaneous AT from 27 (7 lean/20 obese) normoglycemic individuals, in vitro human adipocyte models, and in vivo mice models, we found elevated CAV1 expression in obese AT and a positive correlation between the gene expression of CAV1, tumor necrosis factor alpha (TNF-α), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). CAV1 gene expression was associated with that of proinflammatory cytokines/chemokines, and their cognate receptor (r ≥ 0.447, p ≤ 0.030) but not with anti-inflammatory markers. CAV1 expression was correlated with CD163, indicating a prospective role for CAV1 in adipose inflammatory microenvironment. Unlike wild-type animals, mice lacking TNF-α exhibited reduced levels of CAV1 mRNA/proteins, which were elevated by administering exogenous TNF-α. Mechanistically, TNF-α induces CAV1 gene transcription by mediating NF-kB binding to its two regulatory elements located in the CAV1 proximal regulatory region. The interplay between CAV1 and TNF-α signaling pathway is interesting and has potential as a target for therapeutic interventions in obesity and metabolic syndromes.

Mesenchymal stem cells (MSCs) are involved in the process of extracellular matrix (ECM) remodeling where collagens play a pivotal role. We recently demonstrated that the remodeling of adsorbed collagen type I might be disordered upon oxidation following its fate in the presence of human adipose-derived MSC (ADMSCs). With the present study, we intended to learn more about the effect of polyphenolic antioxidant Epigallocatechin gallate (EGCG) attempting to mimic the conditions of oxidative stress in vivo and its putative prevention by antioxidants. Collagen Type I was isolated from mouse tail tendon (MTC) and labeled with FITC before oxidizing according to Fe2+/H2O2 protocol. FITC-collagen remodeling by ADMSC was assessed morphologically before and after EGCG pretreatment and confirmed via detailed morphometry analysis measuring the anisotropy index (AI) and fluorescence intensity (FI) in selected regions of interest (ROI), namely: outside the cells; over the cells and central (nuclear perinuclear) region, whereas the pericellular proteolytic activity was measured by de-quenching of fluorescent collagen probes (FRET effect). Here we provide morphological evidence that MTC undergoes significant reorganization by the adhering ADMSC along with the substantial activation of pericellular proteolysis, and further confirm that both processes are suppressed upon collagen oxidation. An important observation was that this abrogated remodeling cannot be prevented by the EGCG pretreatment. Conversely, the detailed morphometry analysis showed that oxidized FITC-collagen rather tends to accumulate beneath the cells and around the cell’s nuclei suggesting the activation of alternative routes for its removal, such as internalization and/or transcytosis. Morphometry analysis also revealed that both processes are supported by EGCG pretreatment.

Phospholipid metabolism, including phosphatidylcholine (PC) biosynthesis, is crucial for various biological functions and is associated to longevity. Phosphatidylethanolamine N-methyltransferase (PEMT) is a protein that catalyzes the biosynthesis of PC, the levels of which change in various organs such as brain and kidney during aging. However, the role of PEMT for systemic PC supply is not fully understood. To address how PEMT affects aging-associated energy metabolism in tissues responsible for nutrient absorption, lipid storage and energy consumption, we employed NMR-based metabolomics to study liver, plasma, intestine (duodenum, jejunum, ileum), brown/white adipose tissues (BAT, WAT), and skeletal muscle of young (9–10 weeks) and old (96–104 weeks) wild-type (WT) and PEMT knockout (KO) mice. We found that the effect of PEMT-knockout was tissue-specific and age-dependent. Deficiency of PEMT affected the metabolome of all tissues examined, among which the metabolome of BAT from both young and aged KO mice was dramatically changed in comparison to WT mice, whereas the metabolome of jejunum was only slightly affected. As for aging, the absence of PEMT increased the divergence of metabolome during aging of liver, WAT, duodenum and ileum and decreased the impact on skeletal muscle. Overall, our results suggest that PEMT plays a previously unexplored critical role in both aging and energy metabolism.

Fatty acids (FFAs) are important biological molecules that serve as a major energy source and are key components of biological membranes. Besides, FFAs play important roles in metabolic regulation and contribute to the development and progression of metabolic disorders like diabetes. Recent studies have shown that FFAs can act as important ligands of G-protein coupled receptors (GPCRs) on the surface of cells and impact key physiological processes. Free fatty acid activated receptors include FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41) and FFAR4 (GPR120). FFAR2 and FFAR3are activated by short chain fatty acids like acetate, propionate and butyrate whereas FFAR1 and FFAR4 are activated by medium and long chain fatty acids like palmitate, oleate, linoleate and others. FFARs have generated considerable attention over the last few years and have become attractive pharmacological targets in the treatment of type 2 diabetes and metabolic syndrome. Several lines of evidence point to their importance in the regulation of whole-body metabolic homeostasis including adipose metabolism. Here we summarize our current understanding of the physiological functions of FFAR isoforms in adipose biology and explore the prospect of FFAR based therapies to treat patients with obesity and Type 2 Diabetes.

Several types of soft tissue sarcomas have peripheral infiltrative growth characteristics called tail-like lesions. The efficacy of neoadjuvant therapy for tumors with tail-like lesions has not been elucidated. From 2012 to 2019, we analyzed 36 patients with soft tissue sarcoma with tail-like lesions treated with neoadjuvant therapy, including chemotherapy, radiotherapy, or both. The ef-fect of neoadjuvant therapy on the tail sign was investigated by analyzing the change in tail-like lesions during neoadjuvant therapy and histological responses. The median length of the tail-like lesion reduced from 29.5 mm at initiation to 19.5 mm after neoadjuvant therapy. The extent of shrinkage in tail-like lesion was related to the histopathological responses in the main part. Com-plete disappearance of the tail-like lesion was observed in 12 patients; however, it was not related to achieving a microscopically negative margin. The oncologic outcomes did not significantly differ between cases with complete disappearance of tail-like lesions or not. This study indicated the shrinkage of tail-like lesions did not have significant effect on complete resection or improve-ment of clinical outcomes. A more comprehensive evaluation is needed to elaborate on the surgi-cal strategy.

Oxidative phosphorylation (OxPhos) is the basic function of mitochondria although the land-scape of mitochondrial functions is continuously growing to include more aspects of cellular homeostasis. Thanks to the application of -omics technologies to the study of the OxPhos system, novel features emerge from the cataloging of novel proteins as mitochondrial thus adding de-tails to the mitochondrial proteome and defining novel metabolic cellular interrelations, espe-cially in the human brain. We focussed on the diversity of bioenergetics demand and different aspects of mitochondrial structure, functions, and dysfunction in the brain. Definition as ‘mitoexome’, ‘mitoproteome’ and ‘mitointeractome’ have entered the field of ‘mitochondrial medicine’. In this context, we reviewed several genetic defects that hamper the last step of aerobic metabolism mostly involving the nervous tissue as one of the most prominent energy-dependent tissues and, as consequence, as a primary target of mitochondrial dysfunction. The dual genetic determination of the OxPhos complexes is one of the reasons for the complexity of the geno-type-phenotype correlation when facing human diseases associated with mitochondria defects; clinically, are characterized by extremely heterogeneous symptoms, ranging from organ-specific to multisystemic dysfunction with different clinical courses. Finally, we briefly discuss the fu-ture directions of the multi-omics study of human brain disorders.

Sugar-sweetened beverages are associated with metabolic dysfunction, particularly in those with increased risk factors. Artificial sweeteners (AS) are often promoted as a healthier alternative, yet findings remain conflicting as to their effects on metabolic function. Further, there is a lack of data exploring the interaction between AS and high-fat diets (HFD). We therefore examined the effects of HFD and the AS Acesulfame-potassium (Ace-K) on glucose intolerance and adipose tissue physiology in male and female C57BL/6 mice. 40 mice were randomised to receive either a) a control diet (CDCon; standard control diet/water), b) control diet and Ace-k (CDAS; CD/7.5mM AS in drinking water), c) HFD (HFCon; HFD (45%kcal from fat)/water), or d) HF and AS (HFAS; HFD/7.5mM AS in drinking water) for 6 weeks. A HFD increased body weight in male and female mice independently of AS supplementation. AS induced sex-specific effects protecting against HFD-induced hyperglycaemia and adipocyte hypertrophy in male mice and reducing inflammatory gene expression in the adipose tissue. Conversely in females, AS induced hyperinsulinemia in HFD mice and increased expression of immune-related genes. These findings suggest that supplementation of HFD with AS exacerbates metabolic dysfunction in female mice. This work supports the importance of studying sexually dimorphic responses to an altered nutritional environment and highlights the need for further investigation into the intake of AS, particularly in those already at risk of metabolic disease such as the obese or overweight.

Beta cells couple stimulation by glucose with insulin secretion and impairments in this coupling play a central role in diabetes mellitus. To clarify the effect of cAMP and the role of Epac2A in intracellular calcium signals and intercellular coupling, we performed functional multicellular calcium imaging in beta cells in mouse pancreas tissue slices after stimulation with glucose and forskolin in wild-type and Epac2A knock-out mice. Increased cAMP evoked calcium signals in otherwise sub-stimulatory glucose and beta cells from Epac2A knock-out mice displayed a faster activation. During the plateau phase, beta cells from Epac2A knock-out mice displayed a slightly higher active time in response to glucose compared with wild-type littermates, and increased cAMP increased the active time via a large increase in oscillation frequency and small decrease in oscillation duration in both Epac2A knock-out and wild-type mice. Functional network properties during stimulation with glucose did not differ in Epac2A knock-out mice, but the presence of Epac2A was crucial for the protective effect of increased cAMP in preventing a decline in beta cell functional connectivity with time. Finally, increased cAMP prolonged beta cell activity during deactivation in an Epac2A-independent manner.

Self-assembled structures mostly arises through enzyme-regulated phenomena in nature under persistent conditions. Enzymatic reactions are one of main biological processes in fabrication and construction of supramolecular hydrogel networks required for biomedical applications. The enzymatic processes provide a unique opportunity to integrate hydrogel formation. In most of cases, structure and substrates of hydrogels are adjusted by enzyme catalysis due to the chemo-, regio- and stereo-selectivity of enzymes. Hydrogels processed by using various enzyme schemes showed remarkable characteristics as dynamic frames for cells, bioactive molecules and drugs in biomedical applications. A novel class of enzyme-mediated crosslinking hydrogels mimics the extracellular matrices by displaying unique physicochemical properties and functionalities like water-retention capacity, drug loading ability, biodegradability, biocompatibility, biostability, bioactivity, optoelectronic properties, self-healing ability, shape memory ability. In recent years, many enzymatic systems investigated hydrogel cross-linking. Results of biocompatible hydrogel products show that these mechanisms of crosslinking can fulfill requirements for variety of biomedical applications including tissue engineering, wound healing and drug delivery.

Mesenchymal stem cells (MSCs) showed in vitro mesoderm-lineage differentiation and self-renew capacity. However, no comparative study was reported on the biological characteristics of stem cells derived from skeletal muscle (SM-MSCs), dermal skin (DS-MSCs), and adipose tissues (A-MSCs) from a single donor in camels. The present study aimed to evaluate the influence of MSCs source on stem cell characteristics. We evaluated proliferation capacity and mesoderm-lineage differentiation potential from SM-MSCs, DS-MSCs, and A-MSCs. They showed spindle-like morphology after homogenization. The proliferation ability was no significant difference in all groups. Furthermore, the portion of the cell cycle and expression of pluripotent markers (Oct4, Sox2, and Nanog) were similar in all cell lines at passage 3. The differentiation capacity of A-MSCs into adipocytes was significantly higher than that of SM-MSCs and DS-MSCs. However, the osteoblast differentiation capacity of A-MSCs was significantly lower than that of SM-MSCs and DS-MSCs. Additionally, after osteoblast differentiation, the ALP activity and calcium content was significantly decreased in A-MSCs as compared to SM-MSCs and DS-MSCs. To the best of our knowledge, we primally established MSCs from the single camel and demonstrated their comparative characteristics including expression of pluripotent factors and proliferation, and in vitro differentiation capacity into adipocytes and osteoblasts.

Hydrogels are used for various biomedical applications due to their biocompatibility, capacity to mimic the extracellular matrix, and ability to encapsulate and deliver cells and therapeutics. However, traditional hydrogels have a few shortcomings, especially regarding their physical properties, thereby limiting their broad applicability. Recently, researchers have investigated the incorporation of nanoparticles (NPs) into hydrogels to improve and add to the physical and biochemical properties of hydrogels. This brief review focuses on papers that describe the use of nanoparticles to improve more than one property of hydrogels. Such multifunctional hydrogel nanocomposites have enhanced potential for various applications, including tissue engineering, drug delivery, wound healing, bioprinting and biowearable devices.

The recent legalization of Cannabis sativa L. in many regions has revealed a need for effective propagation and biotechnologies for the species. Micropropagation affords researchers and producers methods to rapidly propagate insect/disease/virus free clonal plants, store germplasm, and forms the basis for other biotechnologies. Despite this need, research in the area is limited due to the long history or prohibitions and restrictions. Existing literature has multiple limitation: many publications use hemp as a proxy for drug-type Cannabis when it is well established that there is significant genotype specificity, studies using drug-type cultivars are predominantly op-timized using a single cultivar, most protocols have not been replicated by independent groups, and some attempts demonstrate a lack of reproducibility across genotypes. Due to culture decline and other problems the multiplication phase of micropropagation (stage 2) has not been fully developed in many reports. This review will provide a brief background on the history and botany of Cannabis as well as a comprehensive and critical summary of Cannabis tissue culture. Special attention will be paid to current challenges faced by researchers, the limitations of existing Cannabis micropropagation studies, and recent developments and future directions of Cannabis tissue culture technologies.

Long-haul COVID-19 illness first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is mysterious as it affects COVID-19 survivors at all levels of disease severity, even younger adults and children. While the precise definition may be lacking, the defining symptoms are fatigue, dyspnea, and headache that last for months after hospital discharge. The less typical symptoms may include cognitive impairments, chest and joint pains, myalgia, smell and taste dysfunctions, cough, mood changes, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long-haul COVID-19, which the current review aims to address. In brief, long-haul COVID-19 may be driven by long-term lung and brain damage and unresolved inflammation from multiple sources. The associated risk factors may include female sex, more than five early symptoms, early dyspnea, and specific biomarkers like D-dimer. While only rehabilitation training has been useful for long-haul COVID-19, therapeutics repurposed from mast cell activation syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, and pulmonary fibrosis also hold potential. In sum, this review hopes to provide the current understanding of what is known about long-haul COVID-19.

Tissue engineering is an emerging field of research due to its growing impact on the regeneration of tissue injured from damage and organ failure. Small hydrogel microspheres containing regenerative cells and stimulators can be used as building blocks to regenerate tissue by injecting them into damaged areas; a microneedle is used to minimize the incision and any associated infections. To address the need for production of a large number of microspheres for use in tissue engineering, we developed a 3D coaxial multi-nozzle flow-focusing device fabricated via a simple 3D-printing method that demonstrates a high rate of microsphere production per nozzle. This device has six coaxial microscale nozzles that produce hydrogel microspheres. Two individual parts—the inlet and nozzle—can be made separately by a 3D printer and bonded together using uncured photo-curable resin as glue. The dimensions of the microspheres are between 100 μm and 1200 μm. They are produced by adjusting the flow rate ratio between the dispersed and continuous media. A flow rate ratio of 180 demonstrated the highest microsphere production rate of 2.12e+5 microspheres per sec (0.25 mL/min). This microsphere production rate per nozzle is four times higher than that of currently available devices.

Polyhydroxyalkanotes (PHA) are bio-based microbial biopolyesters with stiffness, elasticity, crystallinity and degradability tunable by the monomeric composition, bio-production strategy and post-synthetic processing; they display biological alternatives for diverse technomers of petrochemical origin. This, together with the fact that their monomeric and oligomeric in vivo degradation products do not exert any toxic or elsewhere negative effect to living cells or tissue of humans or animals, makes them highly stimulating for various applications in the medical field. The article provides an overview of PHA application in the therapeutic, surgical and tissue engineering area, and reviews strategies to produce PHA at purity levels high enough to be used in vivo. Tested applications of differently composed PHA and advanced follow-up products as carrier materials for controlled in vivo release of anti-cancer drugs or antibiotics, as scaffolds for tissue engineering, as guidance conduits for nerve repair or as enhanced sutures, implants or meshes are discussed from both a biotechnological and a material-scientific perspective. Particular attention is devoted to the adaptation of traditional polymer processing techniques for production of medicine-related devices based on PHA, such as melt-spinning, melt extrusion, or solvent evaporation, and to emerging processing techniques like 3D-printing, computer-aided wet-spinning, laser perforation, or electrospinning.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

The theory says that the first things to exist in the universe and the current moment were driven by an imperative need; that is, the intensities of the physical concept specify influence the existence of elements and facts based on the countless observations in physical spaces in relation to elements and facts. The existence of mandatory elements in space is motivated by the characteristics of the spaces that offer conditions for such an obligation. The theory states that the universe did not arise by chance; that is, the universe emerged through determination influenced by its surroundings. The objective of the study is to help explain the elements and facts of the universe from its origins to the present.

This study employs molecular docking simulations using Autodock Vina with the Pyrx program to investigate the binding interactions between Human prostate-specific antigen (PSA) and natural compounds, namely Amentoflavone, Ginketin, Rutin, and Hypericin. The evaluation reveals excellent binding energy values, averaging around -10 kcal/mol, suggesting robust and favorable interactions between the selected compounds and PSA. The results provide valuable insights into the potential therapeutic applications of these natural compounds in the context of prostate cancer treatment or management. Further experimental validation is warranted to confirm these findings and explore the viability of these compounds as promising candidates for innovative therapeutic strategies. This research contributes to the growing body of knowledge in the field of molecular docking and its applications in drug discovery and bioinformatics.

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.

The fishmeal production industry is essential for providing protein for animal feed in the aquaculture sector. However, the industry faces challenges related to energy consumption and environmental sustainability. This study evaluates the energy efficiency and environmental benefits of waste heat recovery (WHR) technologies in a fishmeal production plant in Vietnam. Data were collected from the plant between 2016 and 2022, and a specific energy consumption (SEC) indicator and a comprehensive methodology were utilized. Implementing an economizer as a WHR technology resulted in a 55.5% decrease in SEC compared to the state before installation. The enhanced energy efficiency also translated to reduced energy consumption per output unit. Moreover, the economizer contributed to annual energy savings of 4,537.57 GJ/year and cost savings of $26,474.49. Additionally, carbon dioxide (CO2) emissions associated with producing one ton of fishmeal decreased by 58.37%. These findings highlight the potential for WHR technologies to improve energy efficiency and reduce the environmental footprint of fishmeal production. The study's results provide valuable insights for practitioners and policymakers in promoting energy efficiency practices and reducing environmental impact in the industry.

In recent years, the number of open preservation surgeries for treatment of laryngeal Cancer has increased. The purpose of this surgery is to avoid the highly mutilating intervention of a total laryngectomy (TL) and to maintain laryngeal function while ensuring oncological radicality. The aim of this study was to assess the oncologic results of OPHL I and II and to identify prognostic factors that could impact patient survival and local failure rates. This study was conducted on 182 patients with laryngeal squamous cell carcinoma treated with OPHLs between 2005 and 2015. The survival rates of a group of patients treated with TL between 2004 and 2014 were taken into con-sideration to compare survival outcomes. The DSS in pT2 and pT3 tumors in relation to the type of surgery showed no statistically significant difference between OPHLs and TL (p=0.54 and p=0.63 respectively). The 5-years T-recurrence free survival showed that pT4 tumors, perineural/vascular positive invasion and OPHL IIb + ARY treated tumors were associated with a higher risk of tumor recurrence (p<0.0001, p=0.0005 and p=0.016 respectively). OPHLs represent an excellent alterna-tive to TL considering the characteristics of the tumor and the general conditions of the patient.

Prostate-specific membrane antigen (PSMA) is a well validated prostate cancer marker, but reported PSMA-targeted tracers derived from the Lys-urea-Glu pharmacophore including the clinically validated [99mTc]Tc-EDDA/HYNIC-iPSMA have high off-target uptake in kidneys, spleen and salivary glands. In this study, we synthesized and evaluated three novel 99mTc-labeled PSMA-targeted tracers and investigated if the tracers derived from the Lys-urea-Aad pharmacophore could have minimized uptake in off-target organs/tissues. In vitro competition binding assays showed that compared with HYNIC-iPSMA, the three novel ligands had slightly weaker PSMA binding affinity (average Ki = 3.11 vs 8.96 - 11.6 nM). Imaging and ex vivo biodistribution studies in LNCaP tumor-bearing mice showed that [99mTc]Tc-EDDA/HYNIC-iPSMA and the three novel tracers successfully visualized LNCaP tumor xenografts in SPECT images and were excreted mainly via the renal pathway. The average tumor uptake at 1 h post-injection varied from 5.40 to 18.8 %ID/g, and the tracers derived from the Lys-urea-Aad pharmacophore had much lower uptake in spleen and salivary glands. Compared with the clinical tracer [99mTc]Tc-EDDA/HYNIC-iPSMA, the Lys-urea-Aad derived [99mTc]Tc-EDDA-KL01127 had lower background uptake and superior tumor-to-background contrast ratios, and is therefore promising for clinical translation to detect prostate cancer lesions with SPECT.

Malignancy is a fatal disease with an increasing incidence with each passing year, and the early diagnosis of malignancy can significantly improve the cure rate of patients, which has profound implications for saving patients' lives. The changes of miRNA are closely related to the occurrence of malignant tumors. The expression of miRNA in many malignant tumors is obviously different and unique from that in normal tissues. In this study, a strategy for amplifying microRNA (miRNA) signal was designed using duplex specific nuclease (DSN), which was then combined with Peptide nucleic acid (PNA) probe hybridization technology to prepare a sensitive and efficient paper-based lateral flow biosensor (LFB) for the detection of pancreatic cancer (PC) associated microRNA-10b. The performance evaluation results of the LFB showed that the detection limit of miR-NA-10b is 5 nM/mL, and carries demonstrated well specificity, stability, reproducibility. The biosensor prepared in this paper can provide accurate and rapid detection of miRNA-10b. The detection results play a guiding role in the early diagnosis of PC. Meeting the clinical need for largescale screening of individuals at high risk of PC. Providing new avenues to achieve early mass screening in individuals at high risk of PC.

SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase of systemic antibodies, being higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose 3 occurred and boosted antibody levels in the salivary compartment. These results lead to rethink the current vaccination strategies against COVID-19 and the use of salivary anti-SARS-CoV-2 antibodies for disease surveillance and vaccination follow-up.

Takotsubo syndrome (TTS), recognized as stress’s cardiomyopathy, or better as left ventricular apical balloon syndrome in the recent years, is a rare pathology, described for the first time by Japanese researchers in 1990. TTS is characterized by an interindividual heterogeneity in onset and progression, and by the strong predominance in postmenopausal women. The clear causes of these TTS features are uncertain, given the reduced understanding of this intriguing syndrome until now. However, the increasing frequency of TTS cases in the last years, and particularly correlated to SARS-CoV-2 pandemic, leads us to imperative necessity both of a complete knowledge of TTS pathophysiology for identifying biomarkers facilitating its management, and targets for specific and effective treatments. The suspect of a genetic basis in TTS pathogenesis has been evidenced. Accordingly, familial form of TTS has been described. But a systematic and comprehensive characterization of the genetic or epigenetic factors significantly associated with TTS is lacking. Thus, we, here, conducted a systematic review of literature before June 2021, to contribute to identify potential genetic and epigenetic factors associated with TTS. Interesting data were evidenced, but of reduced number and with diverse limitations. Consequently, we concluded further work is needed to address the gaps discussed, and probably a clear evidence may arrive using multi-omics investigations.

The ubiquitin-specific protease 2 (USP) belongs to the family of deubiquitinases and plays a critical role in tumors cells’ survival and therefore signifies an important therapeutic target. Previous studies have indicated promising efficacies of potent human USP2 inhibitors including, thiopurine analogues against SARS-CoV papain-like proteases (PLpro). The PLpro have significant functional implications in the innate immune response during SARS-CoV-2 infection and considered an important antiviral target. Both proteases share strikingly similar USP fold with right-handed thumb–palm–fingers structural scaffold and conserved catalytic triad Cys-His-Asp/Asn. In this urgency situation of COVID-19 outbreak, there is a lack of in-vitro facilities readily available to test SARS-CoV-2 inhibitors in whole-cell assays. Therefore, we adopted an alternate route to identify potential USP2 inhibitor through integrated structure-based virtual screening efforts. After a subsequent virtual screening protocol, the best compounds were selected and tested. The compound Z93 showed significant IC₅₀ value against Jurkat (9.67 µM) and MOTL-4 cells (11.8 µM). The binding mode of Z93 was extensively analyzed through molecular docking, followed by MD simulations, and molecular interactions were compared with SARS-CoV-2. The relative binding poses of Z93 fitted well in the binding site of both proteases and showed consensus π-π stacking and H-bond interactions with histidine and aspartate/asparagine residues of the catalytic triad. These results led us to speculate that compound Z93 might be the first potential chemical lead against SARS-CoV-2 PLpro, which warrants in-vitro evaluations.

Research in various fields of evolutionary biology has shown that divergence in gene expression is a key driver for phenotypic variation. An exceptional contribution of cis-regulatory evolution has for instance been found to contribute to morphological diversification. In the light of these findings, the analysis of genome-wide expression data has become one of the central tools to link genotype and phenotype information on a more mechanistic level. However, in many studies, especially if general conclusions are drawn from such data, a key feature of gene regulation is often neglected. With our article, we want to raise awareness that gene regulation and thus gene expression is highly context dependent. Genes show tissue- and developmental stage-specific expression. We argue that the regulatory context must be considered when studying evolution of gene expression.

Types of DNA recombination include homologous recombination and nonhomologous recombination. Homologous DNA recombination is a general term that includes exchange of information between chromatids: (reciprocal) crossing-over, gene conversion, and post-meiotic segregation. Gene conversion is now thought to be a type of non-Mendelian segregation of heterozygous markers near the recombination initiation site. Thus, it includes both gene conversion and post-meiotic segregation previously described. DNA non-HR including transpositional recombination and site-specific recombination. Our understanding of the molecular mechanism by which DNA recombination occurs has significantly increased in the past decades. Currently The synthesis-dependent strand annealing model is now thought to give rise to most or all noncrossovers, with the double-strand-break repair model forming mainly crossovers. The Shapiro model proposed by Dr. J. Shapiro explains the molecular mechanism of transpositional recombination. Site-specific recombination results from another distinct model. We previously proposed a novel theory which can provide a more reasonable and simpler explanation accounting for DNA HR including the 3 classes of recombinogenic events described above. In the new supplementedly molecular model, DNA meiotic recombination can be initiated by a copy choice mechanism, that is, copying part of 1 single-stranded DNA template, followed by DNA polymerase switching to another single-stranded DNA template, and then resuming the following DNA synthesis along the new template. The current review suggests that transpositional recombination and site-specific recombination should be initiated by copy choice during DNA synthesis rather than break/join mechanism. The work indicates that review of DNA nonhomologous recombination are very necessary. The novel theory would challenge earlier models accounting for transpositional recombination and site-specific recombination and would be critical to the understanding of the mechanisms. We hope copy choice initiating DNA nonhomologous recombination will be one of the concepts that are explored. Proper and specific experiments are required to reconstruct the detailed mechanism described here.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. It may be the case that lipofuscin accumulation is the main issue with regard to current age-related disease. Degradation in situ may be an insurmountable task currently. However, a method of systemic lipofuscin removal is discussed herein.

Intraoperative load sensors have been developed with the aim of balancing the soft tissue in the knee during Total Knee Replacements (TKRs). Literature has shown success in soft tissue bal-ancing however, concerns regarding the accuracy of these sensors remain. For this reason, pre-vious research has attempted to create robust sensors for intraoperative use. The design of the sensor in this research has aimed to address the concerns outlined in the literature to create a new and novel smart-sensor for soft-tissue balancing. This new intraoperative load sensor included design features to increase accuracy while artificial intelligence allowed for comprehensive sensing across the entirety of the sensor, providing unparalleled insight during the operation. Notably, the sensor was designed to withstand loads of at least 450 N, ensuring robust perfor-mance of the sensor. To optimize the design process while minimizing cost, Finite Element Analysis was employed. This approach ensured the design features fulfilled their function while maintaining structural integrity to withstand loads. Moreover, the novelty of using training data from simulated data will reduce the iterative process of the labor-intensive collection of training data for the artificial intelligence while reducing human error associated with it. Results from the evaluation demonstrated the ability of this design to successfully bridge the current gap in the market by fulfilling all essential design criteria established within the literature. This innovative smart-sensing tool will in turn enhance patient outcomes and alleviate financial burdens to pa-tients and the healthcare systems by reducing the need for early revision surgeries associated with improper joint tension.

Recent research efforts in bone tissue engineering have been primarily directed towards manufacture-viable synthesis of biomaterials that can significantly enhance the biocompatibilities and osteogenic capabilities on the new biomaterials. This paper presents a straightforward, cost-effective, optimized, and well-controlled hydrothermal synthesis of Nb-doped potassium titanate nanofibers in high-purity. Characterization data revealed that the Nb-doping potassium titanate maintained the crystal structure, showing great promise for applications in bone tissue engineering.

The majority of contemporary total hip arthroplasty (THA) implants are constructed from Ti-alloys, which are generally believed to generate fewer adverse local tissue reactions (ALTR) compared to CoCr-alloys. This study presents a case of unusual primary THA failure where a substantial release of Ti-alloy debris was observed. A 52-year-old active male underwent THA after posttraumatic aseptic necrosis of the femoral head in 2006. Seventeen years after the procedure, the patient presented with groin pain and restricted range of motion. X-rays revealed protrusion of the alumina ceramic head through the Ti6Al4V acetabular cup. Trace element analysis indicated significantly elevated levels of serum Ti, Al and V. CT and MRI confirmed Ti-alloy cup failure and severe ALTR. During revision surgery, the worn-out ceramic head was in direct contact with the acetabular cup, having protruded through the central hole it created over time. Histological analysis of tissue samples showed wear-induced synovitis with areas of multinucleated foreign-body giant cells and accumulation of numerous metal particles but no acute inflammatory response. Six months after the revision THA, the patient has experienced favourable outcomes. This case provides an instructive illustration for studying the consequences of substantial release of Ti-alloy debris from orthopaedic implants.

The development of new medical monitoring applications requires precise modeling of the human body effects as well as simulating and emulating realistic scenarios and conditions. The first aim of this paper is to develop realistic and adjustable human body 3D emulation platforms which could be used for evaluating emerging microwave-based medical monitoring/sensing applications such as the detection of brain tumors, strokes, breast cancers as well as for capsule endoscopy studies. The new phantom recipes are developed for microwave ranges for the realistic shaped phantom molds. The second aim is to validate the feasibility and reliability of the phantoms for practical scenarios with electromagnetic simulations using tissue layer models and biomedical antennas. The third aim is to investigate the impact of the water temperature in the phantom cooking phase on the dielectric properties of the stabilized phantom. The evaluations show that the dielectric properties of the developed phantoms correspond closely to those of real human tissue. The error in dielectric properties varies between 0.5-8%. In the practical scenario simulations, the differences obtained with phantoms-based simulations in S21 parameters are 0.1-13dB. However, the differences are smaller in the frequency ranges targeted for medical applications.

Eryngium foetidum L., a biennial herb with diverse applications in food and traditional medicine, holds economic and pharmacological significance. Given its growing commercial interest, implementing biotechnological approaches like plant tissue culture is vital for sustainable propagation and metabolite production. In this study, we investigated the in vitro photoautotrophic potential of E. foetidum, examining growth, chlorophyll a fluorescence, photosynthetic pigments, and anatomical features under different sucrose concentrations and gas exchange rates. Acclimatization and survival rates of plants after ex vitro transfer were also assessed. E. foetidum exhibited robust growth in both photoautotrophic and photomixotrophic conditions, with natural ventilation significantly enhancing plant development. Chlorophyll a fluorescence and photosynthetic performance were influenced by sucrose and gas exchange, highlighting the importance of these factors in plant micropropagation. Moreover, the species demonstrated remarkable plasticity during acclimatization, with high survival rates and rapid inflorescence emission. The research provides valuable insights into optimizing in vitro cultivation conditions for E. foetidum, emphasizing the potential for large-scale clonal propagation and exploring secondary metabolites. The observed phenotypic plasticity underscores the adaptability of the species to diverse environments. These biotechnological strategies open avenues for future studies, including the application of elicitors for enhanced secondary metabolite production.

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.

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.

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.

Background: Functional restoration of abdominal wall defects represent one of the fundamental challenges of reconstructive surgery. Synthetic grafts or crosslinked animal-derived biological grafts are characterized by significant adverse reactions, which are mostly observed after their implantation. The aim of this study was to evaluate the efficacy of the decellularization protocol to produce a completely acellular full-thickness abdominal wall scaffold. Methods: Full-thickness abdominal wall samples were harvested from Wistar rats and submitted to a 3 cylce decellularization process. Histological, biochemical and DNA quantification analyses were applied to evaluate the effect of the decellularization protocol. Mechanical testing and immunogenicity assessment were also performed. Results: Histological, biochemical and DNA analysis results showed the efficient decellularization abdominal wall samples after the 3rd cycle. Decellularized abdominal wall scaffolds were characterized by good biochemical and mechanical properties Conclusion: The data presented herein confirm the effective production of rat-derived full-thickness abdominal wall scaffold. Expanding this approach will allow the exploitation of the capacity of the proposed decellularization protocol in producing acellular abdominal wall scaffolds from larger animal models or human cadaveric donors. In this way, the utility of biological scaffolds with preserved in vivo remodelling properties may be one step closer to its application in clinical studies.

In recent years, bone tissue engineering (BTE) has made significant progress in promoting the direct and functional connection between bone and graft, including osseointegration and osteoconduction, to facilitate the healing of damaged bone tissues. Herein, we introduce a new, environmentally friendly, and cost-effective method for synthesizing reduced graphene oxide (rGO) and hydroxyapatite (HAp). The method uses epigallocatechin-3-O-gallate (EGCG) as a reducing agent to synthesize rGO (E-rGO), and HAp powder is obtained from Atlantic bluefin tuna (Thunnus thynnus). The physicochemical analysis indicated that the E-rGO/HAp composites had exceptional properties for use as BTE scaffolds, as well as high purity. Moreover, we discovered that E-rGO/HAp composites facilitated not only proliferation, but also early and late osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our work suggests that E-rGO/HAp composites may play a significant role in promoting the spontaneous osteogenic differentiation of hMSCs, and we envision that the E-rGO/HAp composites could serve as promising candidates for BTE scaffolds, stem cell differentiation stimulators, and implantable device components due to their biocompatible and bioactive properties. Overall, we suggest a new approach for developing cost-effective and environmentally friendly E-rGO/HAp composite materials for BTE application.

E2F4 was initially described as a transcription factor with a key function in the regulation of cell quiescence. Nevertheless, a number of recent studies have established that E2F4 can also play a relevant role in cell and tissue homeostasis as well as tissue regeneration. For these non-canonical functions, E2F4 can also act in the cytoplasm, where it is able to interact with many homeostatic and synaptic regulators. Since E2F4 is expressed in the nervous system, it may fulfill a crucial role in brain function and homeostasis, being a promising multifactorial target for neurodegenerative diseases and brain aging. The regulation of E2F4 is complex as it can be chemically modified through acetylation, from which we present evidence in the brain, as well as methylation, and phosphorylation. The phosphorylation of E2F4 within a conserved threonine motif induces cell cycle re-entry in neurons, while a dominant negative form of E2F4 (E2F4DN), in which the conserved threonines have been substituted by alanines, has been shown to act as a multifactorial therapeutic agent for Alzheimer’s disease (AD). We have generated transgenic mice neuronally expressing E2F4DN. We have recently shown using this mouse strain that expression of E2F4DN in 5xFAD mice, a known murine model of AD, improved cognitive function, reduced neuronal tetraploidization, and induced a transcriptional program consistent with modulation of amyloid-beta (Abeta) peptide proteostasis and brain homeostasis recovery. 5xFAD/E2F4DN mice also showed reduced microgliosis and astrogliosis in both cerebral cortex and hippocampus at 3-6 months of age. Here we have analyzed the immune response in 1 year-old 5xFAD/E2F4DN mice, concluding that reduced microgliosis and astrogliosis is maintained at this late stage. In addition, the expression of E2F4DN also reduced age-associated microgliosis in wild-type mice, thus stressing its role as a brain homeostatic agent. We conclude that E2F4DN transgenic mice represent a promising tool for the evaluation of E2F4 as a therapeutic target in neuropathology and brain aging.

Background: The course of obesity and type 2 diabetes (T2D) development is highly dependent on adipose tissue (AT) angiogenesis. Moreover, angiogenic microRNAs (miRNAs) play pivotal role in AT functionality. The aim of this study was to analyze the relationship of the human AT miR-221-3p/222-3p cluster and their regulatory network with obesity and T2D. Methods: miR-221-3p/222-3p and their target genes (TG) expression levels were measured in visceral and subcutaneous ATs from patients classified according to their BMI and to their glycemic status with a high degree of insulin resistance (IR) and T2D. In silico analyses of miR-221-3p/222-3p and their TGs were performed to identify relevant signaling pathways. Results: A multivariate analysis, including the simultaneous expression of miR-221-3p and miR-222-3p as dependent variables, showed significant differences considering the variables; tissue depot, obesity, IR and T2D altogether as independent variables. In addition, miRNAs and their TGs were differentially expressed according to obesity degree, glycemic status, and AT depot type. Our in silico analysis showed that miR-221-3p/222-3p cluster TGs are mostly involved in angiogenesis, WNT signaling pathway and apoptosis. Conclusion: These findings suggest that the miR-221-3p/222-3p cluster and their related regulatory networks could represent tangible targets for the management of obesity and associated metabolic disorders

Bone tissue engineering has been developed in the past decades, with the engineering of bone substitutes on the vanguard of this regenerative approach. PCL based scaffolds are fairly applied for bone regeneration, and several composites have been incorporated, as to improve the devices’ mechanical properties and tissue ingrowth. In this study, HA was incorporated on PCL based scaffolds with two different proportions, 80:20 and 60:40. Devices were produced with two different techniques, SC and MB, and further investigated with regards to their mechanical characteristics and in vitro cytocompatibility. Results show the MB devices to present more promising mechanical properties, along with the incorporation of HA. The latter is also related to an increase in osteogenic activity and promotion. Overall, this study suggest PCL:HA scaffolds to be promising candidates for bone tissue engineering, particularly when produced by the MB method.

Heart myocardia are critical to the facilitation of heart pumping and blood circulating around the body. The biaxial mechanical testing of the Left Ventricle (RV) is utilised to build the computa-tional model of the whole heart with little importance given to the unique mechanical properties of Right Ventricle (RV) and Mid-wall (MDW). Most of those studies focussed on the LV of the heart, and then apply the obtained characteristics with a few modifications to the right side of the heart. However, that view has been contested over time with the realisation that the right side of the heart possesses its own unique mechanical properties that are widely distinct from that of the left side of the heart. This paper is aimed at reporting and evaluating the passive mechanical property dif-ferences in the three main walls of the rat heart based on biaxial tensile test data. Fifteen mature Wistar rats weighing 225 ± 25 g were euthanised by inhalation of 5 % halothane. The hearts were excised after which all the top chambers comprising the two atria, pulmonary and vena cava trunks, aorta and valves are all dissected out. Then 5 x 5 mm sections from the middle of each wall were carefully dissected with a surgical knife to avoid over-prestraining the specimens. The specimens were subjected tensile test. The elastic moduli, peak stresses in the toe region and stresses at 40 % strain, anisotropy indices as well as the stored strain energy in the toe and linear region up to 40 % strain are used for statistical significance tests. The following are the main findings of this study: (1) LV and MDW tissues have relatively shorter toe regions of 10 - 15 % strain as compared to RV tissue whose toe region extends up to twice as much as that (2) LV tissues have higher strain energy storage in the linear region despite being lower in stiffness than the RV (3) the MDW has the highest strain energy storage along both directions which might be directly related to its high level of anisotropy. These findings, though for a specific animal species at similar age and around the same body mass, emphasize the importance of application of wall specific material parameters to obtain accurate ventricular hyperelastic models. The findings further enhance our understanding of the desired mechanical behaviour of the different ventricle walls.