Cancer is a leading cause of morbidity and mortality worldwide, yet much is still unknown about its mechanism of establishment and destruction. Recently, studies had shown that tumor cells cannot survive under the high temperature conditions. This treatment technique is called Hyperthermia. This report presents the case of radiative microwave heating of hyperthermia therapy on breast cancer in a porous medium. In this study, the steady state is solved analytically while unsteady state is solved using semi-implicit finite difference to get a more accurate prediction of blood temperature distributions within the breast tissues. A moderate temperature hyperthermia treatment is apply which results into cell death due to an increase in the level of cell sensitivity to radiation therapy and blood flow in tumor and oxygen. The results show that by applying metabolic heat generation rate of $3.97 X 10^{5}Wm^{-3}$, it takes upto 2 minutes for the tumor cells to get the require therapeutic temperature point.

Both fibrosis and cirrhosis of the liver are the end results of most kinds of chronic liver damage and present a common but difficult clinical challenge throughout the world. The inhibition of the fibrogenic, proliferative, and migratory effects of hepatic stellate cells (HSCs) has become an experimental therapy for preventing and even reversing hepatic fibrosis. Furthermore, a complete understanding of the function of non-coding RNA-mediated epigenetic mechanisms in HSC activation may improve our perception of liver fibrosis pathogenesis. This review focuses on an evolving view of molecular mechanisms in which HSC activation by miR-29a signaling may moderate their profibrogenic phenotype, thus supporting the use of miR-29a agonists as a potential therapy for treating liver fibrosis in the future.

The interaction between endocannabinoid (eCB) system with in key brain structures such as hippocampus, amygdala and prefrontal cortex and sleep deprivation (SD)-induced psychosis has been less studied. The present hypothesis revolves around the question whether altered chemical dynamics within the eCB system with the resultant impact on cannabinoid receptors in key cortical hubs would impact SD-induced psychosis-like symptoms. Having this investigated research is expected to pave the path towards identifying newer drug targets namely for schizophrenia.

The misfolding and aggregation of proteins is the neuropathological hallmark of numerous diseases including Alzheimer’s disease, Parkinson’s disease, and prion diseases. It is believed that misfolded and abnormal -sheets forms of wild-type proteins are the vectors of these diseases by acting as seeds for the aggregation of endogenous proteins. Cellular prion protein (PrPC) is a glycosyl-phosphatidyl-inositol (GPI) anchored glycoprotein which is able to misfold to a pathogenic isoform PrPSc, the causative agent of prion diseases which present as sporadic, dominantly inherited and transmissible infectious disorders. Increasing evidence highlight the importance of prion-like seeding as a mechanism for pathological spread in Alzheimer’s disease and tauophaty, as well as other neurodegenerative disorders. Here, we report the latest findings on the mechanisms controlling protein folding, focusing on the ER quality control of GPI-anchored proteins and describe the “prion-like” properties of amyloid- and tau assemblies. Furthermore, we highlight the importance of pathogenic assemblies interactions with protein and lipid membrane components and their implications in both prion and Alzheimer’s diseases.

Currently, the clinical impact of cell therapy after a myocardial infarction (MI) is limited by low cell engraftment due to significant cell death, including apoptosis, in an infarcted, inflammatory, poor angiogenic environment, low cell retention and secondary migration. Cells interact with their environment through integrin mechanoreceptors that control their survival/apoptosis/differentiation/migration/proliferation. Optimizing these interactions may be a way of improving outcomes. The association of free cells with a 3D-scaffold may be a way to target their integrins. Collagen is the most abundant structural component of the extracellular matrix (ECM) and the best contractility levels are achieved with cellular preparations containing collagen, fibrin, or Matrigel (i.e. tumor extract). In the interactions between cells and ECM, 3 main proteins are recognised: collagen, laminin and RGD (Arg-Gly-Asp) peptide. The RGD plays a key role in heart development, after MI, and on cardiac cells. Cardiomyocytes secrete their own laminin on collagen. The collagen has a non-functional cryptic RGD and is thus suboptimal for interactions with associated cells. The use of a collagen functionalized with RGD may help to improve collagen biofunctionality. It may help in the delivery of paracrine cells, whether or not they are contractile, and in assisting tissue engineering a safe contractile tissue.

: Glioblastoma (GBM) is the most common and most aggressive primary brain tumor with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evi-dence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infil-trative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the ex-pression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show using in vitro limiting dilution assays, quantita-tive real-time PCR and ex vivo adult organotypic brain slice transplantation cultures that thera-peutic doses of calcitriol, the hormonally active form of vitamin D3, reduces stemness to varying extent in a panel of investigated GSC lines and effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to com-pletely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in fol-low-up studies.

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.

Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer Disease will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed focussing on Alzheimer Disease pathogenesis.

One method of creating a brass coating is through electrodeposition, which is most often completed in cyanide galvanic baths. Because of the toxicity of cyanides, many are working on the development of cyanide-free baths, which are promising but not satisfactory to replace the classic methods. The purpose of the study was to explore a new generation of non-aqueous cyanide-free baths based on 1-ethyl-3-methylimidazolium acetate ionic liquids. The study involved the formation of copper, zinc, and brass coatings. The influence of the bath composition, cathodic current density, and temperature was determined. The obtained coatings were characterized by their morphology, chemical composition, roughness, and corrosion resistance. It was found that the structure of the obtained coatings is strongly dependent on the process parameters. The three main structures observed were fine-grained, porous, and olive-like. To the best knowledge of the authors, it is the first time the olive-like structure was observed in the case of an electrodeposited coating. The Cu-Zn coatings consisted of 19–96 at.% copper and exhibited relatively strong corrosion resistance. High improvement of corrosion properties was found in the case of copper and brass coatings with an olive-like structure.

Tissue engineering and regenerative medicine has gradually evolved as a promising therapeutic strategy to the modern healthcare of the aging and diseased population. In this study, we developed a novel nano-fibrous scaffold and verified its application in the critical bone defect regeneration. The metformin-incorporated nano-gelatin/hydroxyapatite fibers (NGF) was produced by electrospinning, cross-linked, and then characterized by XRD and FTIR. Cytotoxicity, cells adhesion, cell differentiation, and quantitative osteogenic gene and protein expression were analyzed by bone marrow stem cells from rat. Rat forearm critical bone defect model was performed for the in vivo study. The nano-gelatin/hydroxyapatite fibers (NGF) were characterized by their porous structures with proper interconnectivity without significant cytotoxic effects; the adhesion of bone marrow stem cells on the nano-gelatin/hydroxyapatite fibers (NGF) could be enhanced. The osteogenic gene and protein expression were upregulated. Post implantation, the new regenerated bone in bone defect was well demonstrated in the NGF samples. We demonstrated that the metformin-incorporated nano-gelatin-hydroxyapatite fibers greatly improved healing potential on the critical sized bone defect. Although metformin-incorporated nano-gelatin/hydroxyapatite fibers had advantageous effectiveness during bone regeneration, further validation is required before it can be applied to clinical applications.

Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate (NHP) models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimage analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.

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.

To examine the role of RNA silencing in defense against viroid, a Dicer-like 2 and 4 (DCL2&4)—double knockdown transgenic tomato line 72E was created. The expression of endogenous DCL2 and DCL4 in line 72E decreased to about a half of the empty cassette line EC. When challenged with potato spindle tuber viroid (PSTVd), 72E allowed significantly higher level of PSTVd accumulation early in infection and showed lethal systemic necrosis. The size distribution of PSTVd-derived small RNA was significantly changed: the numbers of 21 and 22 nucleotides (nt) species in line 72E was approximately 66.7% and 5% of those in line EC, respectively. Conversely, the numbers of 24-nt species increased by 1100%. Furthermore, expression of miR398a-3p and miR398 increased 770–868% in the PSTVd-infected 72E, compared to the PSTVd-infected EC. In parallel, superoxide dismutase (SOD1) in PSTVd-infected 72E showed higher expression levels. In concert with miR398a-3p, SOD1 controls detoxification of reactive oxygen species (ROS) generated in cells. Since high levels of ROS production and its scavenging activity were observed in PSTVd-infected 72E, the lack of full-activity of DCLs was thought to have made the plant incapable to control excessive ROS production and thus resulted in to develop lethal systemic necrosis.

We present the mathematical model of cooperative functioning of unconscious and consciousness. The model is based on the theory of open quantum systems. Unconscious and consciousness are treated as bio-information systems. The latter plays the role a measurement apparatus for the former. States of both systems are represented in Hilbert spaces. Consciousness performs measurements on the states which are generated in unconscious. This process of unconscious-conscious interaction is described by the scheme of indirect measurements. This scheme is widely used in quantum information theory and it leads to the theory of quantum instruments (Davis-Lewis-Ozawa). Our approach is known as quantum-like modeling. It should be sharply distinguished from modeling of genuine quantum physical processes in biosystems, in particular, in the brain. In the quantum-like framework, the brain is a black box processing information in the accordance with the laws of quantum theory. During the last 10-15 years this framework has been actively used in cognition, psychology, decision making, social and political sciences. The quantum-like scheme of unconscious-consciousness functioning has already been explored for sensation-perception modeling.

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Here, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model is built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellular-ized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2-3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal com-partments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular Doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diag-nosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

Background. Sarcopenia, defined as the loss of skeletal muscle mass and function, is a major clinical problem in many chronic illnesses, in cancer and in the elderly. Exercise and adequate nutrition, peculiarly dependents on availability of essential amino acids, considered the primary strategies for prevention and treatment of protein synthetic deficits, affect both the efficient scavenging of aged and overused protein molecules and the renewal, by maintaining muscular protein synthesis. Many questions still remain about the regulation of protein syntheses and degradation. Degradation of inefficient proteins or organelles is performed by the sum of micro and macro-autophagy plus ubiquitin-proteasome system, activities known as proteostasis, necessary to preserve and promote protein masses and consequently, the body’s reserves. However, how protein synthesis is regulated, and how activation of the mTOR complex may modulate and transduce the flow of information provided by exercise and nutrition to balance proteostasis and syntheses, is far from being fully understood. We suggest that energy production and availability, thus also mitochondria, may have a pivotal role in synchronizing activity and functional outcomes of protein syntheses, and that those syntheses, since higly energy demanding, are main effectors of AMPK dependent autophagy activation by consuming ATP and producing AMP. Conclusion. While in normal conditions protein syntheses drive autophagy activation by decreasing ATP to AMP ratio, conversely autophagy may be inefficiently activated when chronic both low production and consumption of ATP would result in lowest concentrations of AMP, and therefore both blunted rates of protein syntheses and autophagy would be observed. We suggest that this functional hypothesis may explain sarcopenia in many pathological conditions , as in cancer or in aging muscles.

The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision. Pluripotent stem cells, retinal progenitor cells and somatic stem cells are the main cell sources used for cell transplantation therapies. The success of retinal transplantation based on cell suspension injection is hindered by limited cell survival and lack of cellular integration. Recent advances in material science helped to develop strategies to grow cells as intact monolayers or as sheets on biomaterial scaffolds for transplantation into the eyes. Such implants are found to be more promising than the bolus injection approach. Tissue engineering techniques are specifically designed to construct biodegradable or non-degradable polymer scaffolds to grow cells as a monolayer and construct implantable grafts. The engineered cell construct along with the extracellular matrix formed, can hold the cells in place to enable easy survival, better integration and improved visual function. This article reviews the advances in the use of scaffolds for transplantation studies in animal models and its application in current clinical trials.

Recent evidences support a role of menthol, a TRPM8 agonist, in enhanced energy expenditure, thermogenesis and BAT-like activity in classical WAT depots in TRPM8 dependent and independent manner. The present study was designed to analyze whether oral and topical administration of menthol is bioavailable at subcutaneous adipose tissue and is sufficient to induce desired energy expenditure effects directly. GC-FID was performed to study menthol bioavailability in serum and subcutaneous white adipose tissue following oral and topical administration. Further, 3T3L1 adipocytes were treated with bioavailable menthol doses and different parameters (lipid accumulation, “browning/brite” and energy expenditure gene expression, metal analysis, mitochondrial complex’s gene expression) were studied. No difference was observed in serum levels but significant difference was seen in the menthol concentration on subcutaneous adipose tissues after oral and topical application. Menthol administration at bioavailable doses significantly increased “browning/brite” and energy expenditure phenotype, enhanced mitochondrial activity related gene expression, increased metal concentration but didn’t alter the lipid accumulation. Further, we used pharmacological antagonism based approach to study the TRPM8 involvement in menthol effect. In conclusion, the present study provides an evidence that bioavailable menthol after single oral and topical administration is sufficient to induce “brite” phenotype in subcutaneous adipose tissue.

Background: This study aimed to describe the frequency and duration of sedentary bouts and assess the bidirectional cross-sectional associations between these characteristics and adiposity in elderly women. Methods: Data from 314 elderly community-dwelling women (mean age 66.6±6.5 years) from Czech Republic, Poland, and Slovakia were analyzed. Measures were collected in 2008–2017. Fat mass percentage (FM%) was used as an indicator of adiposity. The patterns of sedentary behaviour were monitored using an accelerometer, and ≥5, ≥10, ≥20, ≥30, ≥40, and ≥60 minute bouts were analyzed. The exponent alpha was also calculated to express the accumulation of sedentary time in bouts. We performed a multiple linear regression analysis to assess the bidirectional causal association between variables. Results: There was a significant association of FM% with time spent in bouts with a duration ≥5, ≥10, ≥20min (β ranging 0.11–0.28, p≤0.01) and the frequency of bouts with a length ≥5, ≥10, ≥20, and ≥30min (β ranging 0.03–0.74, p≤0.05) in fully-adjusted models. In contrast, a strong negative association was observed between FM% and alpha (bout distribution) in both directions (p≤0.001). Conclusions: Our results suggest that the sedentary characteristics such as bout duration, bout frequency, and distribution (alpha) are bidirectionally associated with adiposity and they should be considered in further research in older adults.

Tissue engineering has the potential for repairing large bone defects, which impose a heavy financial burden on the public health. However, difficulties with O₂ delivery to the cells residing in the interior of tissue engineering scaffolds make it challenging to grow artificial tissues of clinically-relevant sizes. This study uses image-based simulation in order to provide insight into how to better optimize the scaffold manufacturing parameters, and the culturing conditions, in order to resolve the O₂ bottleneck. To do this, high resolution 3D X-ray images of two common scaffold types (salt leached foam and non-woven fiber mesh) are fed into a Lattice Boltzmann Method fluid dynamics and reactive Lagrangian Scalar Tracking mass transfer solvers. The obtained findings indicate that the scaffolds should have maximal surface area-to-solid volume ratios, for higher chances of the molecular collisions with the cells. Furthermore, the cell culture media should be flown through the scaffold pores as fast as practically possible (without detaching or killing the cells). Finally, we have provided a parametric sweep that maps how the molecular transport within the scaffolds is affected by variations in rates of O₂ consumption by the cells. Ultimately, the results of this study are expected to benefit the computer-assisted design of tissue engineering scaffolds and culturing experiments.

Abstract : This paper presents the investigation of biomechanical behaviour of sheep heart fibre using uniaxial tests in various samples. Non-linear Finite Element models (FEA) that are utilised in understanding mechanisms of different diseases may not be developed without the accurate material properties. This paper presents uniaxial mechanical testing data of the sheep heart fibre. The mechanical uniaxial data of the heart fibre was then used in fitting four constitutive models including the Fung model, Polynomial (Anisotropic), Holzapfel (2005) model, Holzapfel (2000) model and the Four-fibre Family model. Even though the constitutive models for soft tissues including heart myocardium have been presented over several decades, there is still a need for accurate material parameters from reliable hyperelastic constitutive models. Therefore, the aim of this research paper is to select five hyperelastic constitutive models and fit experimental data in the uniaxial experimental data of the sheep heart fibre. A fitting algorithm was made used to optimally fitting and determination of the material parameters based on selected hyperelastic constitutive model. In this study, the evaluation index (EI) was used to measure the performance and capability of each selected anisotropic hyperelatic model. It was observed that the best predictive capability of the mechanical behaviour of sheep heart fibre the Polynomial (anisotropic) model has the EI of 100 and this means that it is the best performance when compared to all the other models.

HIV-1 is a complicated and perplexing virus. It infects T cells, reverse transcribes its RNA into DNA, utilizes its host DNA machinery to replicate its HIV-DNA, translates the HIV-DNA into proteins, assembles itself for a budding escape from the T cell, and rapidly mutates its conformation. Partially, due to its complexity, there remains no cure for HIV or AIDs. However, recently with the discovery of TALENs, the use of zinc fingers, and most of all the applications of CRISPR-Cas9 technology, has given researchers new hope in finding alternative gene therapies and treatments for diseases. With more focus on CRISPR-Cas9, this new and novel technology uses a guiding RNA, sgRNA, to lead a Cas9 nuclease to its target for deletion or to change that DNA site. CRISPR-Cas9 can delete point mutations and multiple DNA sites. Because CRISPR can alter DNA sequences, several scientists have conducted research into CRISPR, possibly treating more diseases such as cancer, diabetes, and even HIV. HIV-1 drew the focus of a researcher named Dr. Ebina in 2013 when he was the first to design and apply CRISPR-Cas9 to genes found in the binding sites of HIV-1, inhibiting HIV-1 gene expression. Since 2013, several other researchers have blocked HIV replication and infection through CRISPR-Cas9 targeting the receptors of T cells called the CC chemokine receptor 5 or CCR5. HIV-1 binds to the CD4 receptor of T cells, which consists of co-receptors CCR5 and CXCR4. If CCR5 expression can be removed, the HIV virus cannot bind to T-cells, blocking the initial attachment stage, and discontinuing the infection. However, there remain obstacles and issues for the CRISPR deletion of CCR5 for treating HIV-1. The issues include: 1) finding new and safe methods of CRISPR-Cas9 delivery, 2) clearing the latent HIV reservoirs, 3) improving the sgRNA design to avoid off-target mutations or deletions, and 4) effectively analyze the viral escape of HIV from CRISPR-Cas9 modifications. Therefore, the purpose of this review is to discuss possible techniques for removing the obstacles that can lessen the potential of CRISPR to delete CCR5, repressing HIV-1 into long-term remission or a functional cure.

Dental pulp tissue engineering (TE) quests to regenerate dentin/pulp complex by combining a suitable supporting matrix, stem cells, and biochemical stimuli. Such procedures foresee a matrix that can be easily introduced into the root canal system (RCS) and tightly adhere to dentin walls to assure the dentin surface's proper colonization with progenitor cells capable of restoring the dentin/pulp complex. Herein was investigated an injectable self-setting hyaluronic acid-based (HA) hydrogel system, formed by aldehyde-modified (a-HA) with hydrazide-modified (ADH), enriched with platelet lysate (PL), for endodontic regeneration. The hydrogels' working (wT) and setting (sT) times, the adhesion to the dentine walls, the hydrogel's microstructure, and the delivery of human Dental Pulp Cells (DPCs) were studied in vitro. Hydrogels incorporating PL showed a suitable wT and sT and a porous microstructure. The tensile tests showed that the breaking point occurs after 4.13 mm deformation. While in the indentation test after 1.3 mm deformation. Both breaking points occur in the hydrogel extension. The HA/PL hydrogels exhibited supportive properties and promoted cell migration toward dentin surfaces in vitro. Overall, these results support using PL-laden HA injectable hydrogels (HA/PL) as a biomaterial for DPCs encapsulation, thereby displaying great clinical potential towards endodontic regenerative therapies.

Background: PRAME, NY-ESO-1 and SSX2 are cancer testis antigens (CTAs), which in normal tissues are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterized cohort soft tissue sarcomas (STS). Methods: On protein level, we examined PRAME, NY-ESO-1 and SSX2 expression in tumour tissues of 249 STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including Tumour-infiltrating lymphocyte (TIL) counts, grading and long- term survival. Results: Expression of PRAME, NY-ESO-1 and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo subtypes. Expression of PRAME was associated with shorter patient survival (p=0.005) and higher grade (G2 vs G3, p=0.001) while NY-ESO-1 expression was correlated with more favourable survival (p=0.037) and low grade (G2 vs G3, p=0.029). Both PRAME and NY-ESO-1 expression was more frequent in STS with low TILs counts. Conclusions: CTAs PRAME, NY-ESO-1 and SSX2 show distinct expression patterns in different STS subtypes. These results may guide future immunotherapeutic approaches in STS.

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.

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.

Bufadienolides-like chemicals, which mostly composed the active ingredient of Chansu, had been widely discovered to possess anti-inflammatory, tumor-suppressing and antipain activity, but the mechanisms of action were not clearly illuminated. In this research, in order to explore the potential mechanism of bufadienolides-like chemicals on breast cancer, a serious of bioinformatics analysis, included (1) differentially expressed genes identification combined with gene set variation analysis, (2) tissue specific co-expression network construction, (3) differentially regulated sub-networks detection with disease phenome, (4) hub gene selection and it’s relation to survival probability, and (5) similar small molecule detection were performed with gene expression profiles of bufadienolides-like chemicals. Results indicated bufadienolides-like chemicals had the most same target with valproic, estradiol and etc, could disturbed the pathways in RNA splicing, apoptotic process, cell migration, extracellular matrix organization, adherens junction organization, synaptic transmission, Wnt signaling, AK-STAT signaling, BMP signaling pathway and unfolded protein response, and had the potential ability to be used as anticancer, hormones and vasoprotectives agents.

Polydopamine (PDA) deposition, obtained from the oxidation of dopamine and other catecholamines is an universal way to coat all known materials with a conformal coating which can subsequently be functionalyzed at will. The structural analogies between polydopamine and eumelanin, the black-brown pigment of the skin, incited to produce stable polydopamine nanoparticles in solution instead of amorphous precipitates obtained from the oxidation of dopamine. Herein, we demonstrate that size controlled and colloidally stable PDA based nanoparticles can be obtained in acidic conditions, where spontaneous auto-oxidation of dopamine is suppressed, using sodium periodate as the oxidant and a protein like alkaline phosphatase as a templating agent. The size of the PDA@Alp nanoparticles depends on the dopamine/enzyme ratio and the obtained particles display the enzymatic activity of alkaline phosphatase with an activity extending up to two weeks after particle synthesis. The PDA@ alkaline phosphatase (Alp) nanoparticles can be engineered in polyelectrolyte multilayered films to potentially design model biosensors.

The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathways regulated in cachexia. Matched rectus abdominis muscle and subcutaneous adipose tissue were obtained at surgery from patients with benign conditions (n=11) and patients with PDAC (n=24). Self-reported weight loss and body composition measurements defined cachexia status. Gene profiling was done using Ion proton sequencing. Results were queried against external datasets for validation. 961 DE genes were identified from muscle and 2000 from adipose tissue, demonstrating greater response of adipose than muscle. In addition to known cachexia genes such as FOXO1, novel genes from muscle, including PPP1R8 and AEN correlated with cancer weight loss. All the adipose correlated genes including SCGN and EDR17 are novel for PDAC cachexia. Pathway analysis demonstrated shared pathways but largely non-overlapping genes in both tissues. Age related muscle loss predominantly had a distinct gene profiles compared to cachexia. This analysis of matched, externally validate gene expression points to novel targets in cachexia.

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.

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

Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (MECP2), which alter the functions of domains to either bind to methylated DNA or interact with a transcriptional co-repressor complex. It has been established that alterations in cyclin-dependent kinase-like 5 (CDKL5) or forkhead box protein G1 (FOXG1) correspond to distinct neurodevelopmental disorders, given that a series of studies have indicated that RTT is also caused by alterations in either one of these genes. We tried to elucidate RTT through evolution and structure assessment of MeCP2, CDKL5, and FOXG1, by focusing on their binding partners and disordered structures. Here, we provide insight into the similarities of the FOXG1 and MECP2 binding partners evolution and function. On the other hand, we suggest that CDKL5 could be a potential candidate for a classical RTT treatment, particularly based on its disordered structure that spans after the catalytic domain to the C-terminus, which shows abundant linear motifs that can bind to molecules with divergent structures of similar affinity. Additionally, we provide insight into the relationship between disordered structure and disease.

The occurrence of bone-related disorders and diseases has increased dramatically in recent years around the world. Demineralized bone matrix (DBM) has been widely used as a bone implant due to its osteoinduction and bioactivity. However, the use of DBM is limited because it is a particulate material, which makes it difficult to manipulate and implant with precision, in addition, these particles are susceptible to migrate to other sites. To address this situation, DBM is commonly incorporated into a variety of carriers. An injectable scaffold has advantages over bone grafts or preformed scaffolds, such as the ability to flow and fill the bone defect. The aim of this research is to develop a DBM carrier with such viscoelastic properties to obtain an injectable bone substitute (IBS). The DBM carrier developed consisted of a PVA/glycerol network cross-linked with borax and reinforced with CaCO3 as a pH neutralizer, porosity generator, and source of Ca. The physicochemical properties were determined by the injectability test, FTIR, SEM, and TGA. Porosity, degradation, bioactivity, possible cytotoxic effect, and proliferation in osteoblasts were also determined. The results show that the developed material has great potential to be used in bone tissue regeneration

Restricted feeding is well known to affect expression profiles of both clock and metabolic genes. However, it is unknown whether these changes in metabolic gene expression result from changes in the molecular clock or in feeding behavior. Here we eliminated the daily rhythm in feeding behavior by providing 6-meals evenly distributed over the light/dark-cycle. Animals on this 6-meals-a-day feeding schedule retained the normal day/night difference in physiological parameters including body temperature and locomotor activity. The daily rhythm in respiratory exchange ratio (RER), however, was significantly phase-shifted through increased utilization of carbohydrates during the light phase and increased lipid oxidation during the dark phase. This 6-meals-a-day feeding schedule did not have a major impact on the clock gene expression rhythms in the master clock but did have mild effects on peripheral clocks. By contrast, genes involved in glucose and lipid metabolism showed differential expression. Concluding, eliminating the daily rhythm in feeding behavior in rats does not affect the master clock and only mildly affects peripheral clocks, but disturbs metabolic rhythms in liver, skeletal muscle and brown adipose tissue in a tissue-dependent manner. Thereby a clear daily rhythm in feeding behavior strongly regulates timing of peripheral metabolism, separately from circadian clocks.

Lack of reliable information on PTC industry in Sri Lanka is hampering the advancement of the technology. Hence, this study attempted to assess the current status of PTC industry in Sri Lanka in order to ascertain the type and the level of interventions needed to broaden the horizons of the industry. Data of last 05 years were collected through qualitative research methods including a questionnaire-based survey, personal interviews, etc. and personal interviews to identify product diversity, R&D, available facilities, production capacity, and markets. Information was analyzed qualitatively using descriptive statistical software to assess the current status, and identify gaps, challenges and opportunities. COVID pandemic and the economic crisis had a heavy toll on the PTC industry. Six major challenges experienced by business owners were identified as increasing capacity, opportunities to build market linkages, demand fluctuations, issues relating to awareness and insufficient support given by the government. Proper identification and screening of mother plants, determining the production capacities and marketing, knowledgeable and skilled human resources, were identified as important contributory factors for success. Development strategies identified mainly include instinctive decision making and government support. Embracing the significant trade achievements through resource reallocation, prioritization and improvisation processes at individual, family group, inter-organizational levels and across these levels need to be regulated through a responsible authority. These interpretations and recommendations of this research can be utilized both by the policy makers and public and private sector organizations for decision making purposes targeting commercial scale advancements.

Premature ovarian insufficiency (POI) is a highly prevalent disorder, characterized by the development of menopause before age of 40. Most cases are idiopathic; however, in some women the cause of this condition (e.g. anticancer treatment, genetic disorders, and enzymatic defects) may be identified. Although hormone replacement therapy, the principal therapeutic approach for POI, helps to alleviate the related symptoms, this does not effectively solve the issue of fertility. Assisted reproductive techniques also lack efficacy in these women. Thus, the effective approach to manage the patients with POI is highly warranted. Several mechanisms, associated with POI, have been identified, including lack of FSH receptor functioning, alterations in the apoptosis control, mutations in Sal-like 4 genes, thymulin or basonuclin-1 deficiency etc. The above-mentioned may be good targets for gene therapy in order to correct defects, leading to POI. The goal of this review is to summarize the current experience on the POI studies, that employed gene therapy, and to discuss the possible future directions in this field.

The cell’s capacity to integrate and respond to spatial information is a crucial feature of morphogenesis and development. The Planar Cell Polarity (PCP) pathway is a signaling mechanism, widely conserved across metazoans, providing spatial orientation along the plane of an epithelium in morphogenic processes ranging from insect wing patterning to mammalian cochleae. Although the core genes involved in the PCP pathway have been molecularly identified in the 1990s, the PCP signaling mechanism remains controversial. In this article I discuss the main players and previous models of PCP signaling reported in the literature, and propose a new model. According to it PCP is established through an homophobic signal by transmembrane protein Frizzled (Fz): 1) a Fz signal in one cell repeals Fz itself in the adjacent cell, thereby generating symmetry breaking; 2) the instructive PCP signal is conveyed through Fz interaction with atypical cadherin Flamingo (Fmi). More broadly, homophobic signaling may represent a novel mechanism for cell-cell signaling of spatial information through modulation of cell adhesion rather than canonical ligand-receptor binding.

Cannabis has developed into a multi-billion dollar industry that relies on clonal propagation of elite genetics with desirable agronomic and chemical phenotypes. While the goal of clonal propagation is to produce genetically uniform plants, somatic mutations can accumulate during growth and compromise long-term genetic fidelity. Cryopreservation is a process in which tissues are stored at cryogenic temperatures, halting cell division and metabolic processes to facilitate high fidelity germplasm preservation. In this study, a series of experiments were conducted to optimize various stages of cryopreservation and develop a protocol for long-term germplasm storage of Cannabis sativa. The resulting protocol uses a standard vitrification procedure to cryopreserve nodal explants from in vitro shoots as follows: Nodes were cultured for 17 hours in a pre-culture solution (PCS), followed by a 20 minute treatment in a loading solution (LS), and a 60 minute incubation in plant vitrification solution 2 (PVS2). The nodes were then flash frozen in liquid nitrogen, re-warmed in an unloading solution at 40°C, and cultured on basal MS culture medium in the dark for 5 days followed by transfer to standard culture conditions. This protocol was tested across 13 genotypes to assess the genotypic variability. The protocol was successful across all 13 genotypes, but significant variation was observed in tissue survival (43.3-80%) and regrowth of shoots (26.7-66.7%). Plants grown from cryopreserved samples were morphologically and chemically similar to control plants for most major traits, but some differences were observed in the minor cannabinoid and terpene profiles. While further improvements are likely possible, this study provides a functional cryopreservation system that works across multiple commercial genotypes for long-term germplasm preservation.

Ebola Virus Disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and caused by members of the Filoviridae family. The recent large outbreak of EVD in West Africa (2013-2016), highlighted the worldwide danger of this disease and its impact on global public health and economy. The development of highly needed anti-Filoviridae antivirals has been so far hampered by the shortage of tools to study their life cycle in vitro, and therefore screen for potential active compounds outside a biosafety level-4 (BSL-4) containment. Importantly, the development of surrogate models to in vitro study of Filoviridae entry in a BSL-2 setting, such as viral pseudotypes and Ebola virus like particles, tremendously boosted both our knowledge on viral life cycle and the identification of promising anti-Filoviridae compounds interfering with viral entry. In this context, the combination of such surrogate systems with large-scale small molecule compounds and haploid genetic screenings, as well as rational drug design and drug repurposing approaches will prove priceless in our quest for the development of a treatment for EVD.

The musculoskeletal system consisting of bones and muscles have been recognized as endocrine organs secreting hormones that are involved in regulating metabolic and inflammatory pathways. Obesity and type 2 diabetes (T2D) are associated with several musculoskeletal system complications. We hypothesized that an interaction exists between adipomyokines namely, irisin and METRNL, and various bone markers in individuals with obesity and T2D. A total of 228 individuals were enrolled in this study, including 124 non-diabetic and 104 T2D. A Multiplex assay was used to assess the level of various bone markers namely Osteoactivin, Syndecan, osteoprotegerin (OPG) and osteonectin/SPARC. Our data shows elevated levels of Osteoactivin, Syndecan, OPG and SPARC in T2D as compared to non-T2D individuals (p ≤ 0.05). Using Spearman’s correlation, irisin was positively correlated only with Osteoactivin and OPG (p &lt; 0.05). Similarly, a positive association was observed between METRNL and Osteoactivin (p &lt; 0.05). The strong positive association shown in our study between irisin, METRNL and various bone markers emphasises the strong interaction between these organs. This suggests that a dysregulation in the functional interaction between these molecules could play a possible role in the development of bone and muscle related complications that are associated with obesity and T2D.

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.

In bone tissue engineering, ceramics have been the choice due to their excellent biological properties. But the paradigm changed with the discovery of bioactive glasses (BGs) in 1969 by Larry Hench and co-workers, due to their ability to bond to living tissues through the formation of an interfacial bone-like hydroxyapatite layer when the bioglass was put in contact with biological fluids in vivo. Among a number of tested compositions, the one exhibiting the highest bioactivity index is the well-known trademarked 45S5 Bioglass®. The topic received increasing attention particularly after 1985 when this material entered in the market of biomedical devices, inspiring many other investigations aiming at further exploring the in vitro and in vivo performances of this BG, or developing other related BG compositions. The research efforts gradually revealed a number of shortcomings of 45S5 Bioglass®, mostly derived from its high sodium content, initially intended to decrease the melting temperature and accelerating the degradation of the silicate network over time. But the extensive release of sodium from 45S5 Bioglass® in the biological fluids creates a high pH cytotoxic environment. Other serious drawbacks include a fast degradation rate, and a poor sintering ability, which hinders the reliable fabrication of porous scaffolds. Therefore, sol-gel was regarded as an attractive alternative to prepare alkali-free BG compositions. The process uses inorganic and/or organic precursors, which undergo hydrolysis and condensation at room-temperature, being less costly. When properly conducted, the sol-gel process might result in amorphous structures with all the components intimately mixed at the atomic scale. Moreover, developing new better performing materials for bone tissue engineering is a growing concern, as the ageing of the world’s population leads to lower bone density and osteoporosis. This work describes the sol-gel synthesis of a novel quaternary silicate-based BG with the composition 60 SiO2 – 34 CaO – 4 MgO – 2 P2O5 (mol%) was prepared using acidified distilled water as single solvent. By controlling the kinetics of the hydrolysis and condensation steps, an amorphous glass structure could be obtained. The results of XRD of samples calcined within the temperature range from 600-900 ºC demonstrated that amorphous nature was maintained until 800 ºC, followed by partial crystallization at 900 ºC. The specific surface area, an important factor in osteoconduction, was also evaluated over different temperatures, ranging from 160.6 ± 0.8 m2/g at 600 ºC down to 2.2 ± 0.1 m2/g at 900 ºC, being accompanied consistent changes in average pore size and agreeing pore size distribution. The immersion of the BG particles in simulated body fluid (SBF) led to the formation of an extensive apatite layer on its surface. These overall results indicate the proposed material is very promising for biomedical applications in bone regeneration and tissue engineering.

Biphasic bone substitutes (BBS) are nowadays established biomaterials. Through their constant development even natural components like hyaluronic acid (HY) are added to improve both their handling and also their regenerative properties. However, low knowledge exists regarding the consequences of the HY addition for their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY) combined with a BBS on the in vitro biocompatibility and the in vivo tissue reaction. Established in vitro procedures using L929 cells were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo study part, calvarial defects were created in 20 Wistar rats and subsequently filled with the BBS and the BBS combined with two different HMWHY amounts, i.e., BBS+HY(L) and BBS+HY(H). As controls empty defects were used. Established histological, immunohistochemical and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damages to the L929 cells and can considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of proinflammatory macrophages (* p < 0.05) comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to the BBS while improving the material handling properties.

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.

Pulse oximetry is the current standard for detecting drops in arterial blood oxygen saturation (SpO₂) associated with obstructive sleep apnea and hypopnea events in polysomnographic (PSG) testing. In cases of hypoxic challenge, such as occurs during apneic events, regulatory mechanisms restrict blood flow to the skin to preferentially maintain SpO₂ for more vital organs. As a result, a measure related to skin tissue oxygenation is likely to be more sensitive to inadequate breathing during sleep than pulse oximetry. Energy Conversion Monitoring (ECM) provides a method for measuring skin tissue oxygen-dependent energy conversion and, as such, is promising for more sensitively detecting sleep disordered breathing (SDB) events compared to pulse oximetry. We hypothesized that ECM would detect hypoxia occurring with SDB events associated with drops in SpO₂ but also would detect hypoxic challenge occurring with SDB events not associated with drops in SpO₂ (hypopneas defined by a drop in nasal pressure occurring in conjunction with an arousal, respiratory-related arousals, and primary snoring). Primary snoring is of particular interest with respect to the potential of ECM because it is statistically associated with co-morbidities of SDB, such as hypertension, but is not considered pathological because of the lack of a proximal measure of pathology occurring with PSG. In this article we review ECM technology and methodology, present preliminary data indicating that it detects hypoxia occurring in the skin during SDB events that is not detected as blood desaturation by pulse oximetry, and make the case that it is a promising tool for identifying pathology occurring at the mild end of the SDB spectrum.

Adipose tissue (AT) is a remarkably plastic and active organ with functional pleiot-ropism and high remodeling capacity. Although the expansion of fat mass, by defini-tion, represents the hallmark of obesity, the dysregulation of the adipose organ emerges as the forefront of the link between adiposity and its associated metabolic and cardio-vascular complications. The dysfunctional fat displays distinct biological signatures, which include enlarged fat cells (i.e., adipocyte hypertrophy), low-grade inflammation, impaired redox homeostasis, and cellular senescence. While these events are orches-trated in a cell-type, context-dependent and temporal manner, the failure of the adipose precursor cells to form new mature adipocytes appears the main instigator of the adi-pose dysregulation, which, ultimately, poses a deleterious milieu either by promoting ectopic lipid overspill in non-adipose targets (i.e., lipotoxicity) or by inducing an al-tered secretion of different adipose-derived hormones (i.e., adipokines and lipokines). This novel paradigm (“expandability hypothesis”) challenges and extends previous “adipocentric view”, which implies a reduced plasticity of the adipose organ at the nexus between “unhealthy” fat expansion and the development of obesity-associated comorbidities. In this review, we will briefly summarize the potential mechanisms by which adaptive changes to variations of energy balance may impair adipose plasticity and promote fat organ dysfunction. We will also highlight the conundrum with the perturbation of the adipose microenvironment and the development of cardio-metabolic complications by focusing on adipose lipoxidation and cellular senescence. Finally, we discuss the sci-entific rationale for proposing adipose organ plasticity as a target to curb/prevent adi-posity-linked cardio-metabolic complications.

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.

Objective: Diabetes is associated with increased cardiovascular and cerebrovascular disease-related mortality. We investigated the association between carotid intima-media thickness (CIMT) with clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), total and active glucagon-like peptide-1 (GLP-1) levels, and dipeptidyl peptidase-4 (DPP-4) in type 2 diabetes mellitus (T2DM) individuals with or without coronary artery disease (CAD). Methods: This study consisted of four groups in Medicine Hospital between April- October, 2017: Control group (mean ages: 50.3 ± 10.7 years, 20 females and 15 males), diabetic group (DM) (mean ages: 53.9 ± 11.1, 14 females and 23 males), CAD group (mean ages: 62.6 ± 11.8, 17 females and 17 males) and CAD+ DM group: (mean ages: 62.6 ± 11.8 years, 18 females and 18 males). Results: Both CAD and CAD+DM groups have higher CIMT levels than controls. CAD+DM group have also significantly higher CIMT levels than DM group. Left external carotid artery (ECA) was only found different in DM group from controls. When compared with controls, DM, CAD groups have low DPP-4 and GLP-1_total concentration. Control group have significantly lower SFRP-4 levels than DM, CAD and CAD+DM (p<0.001) groups. Serum GLP-1_total levels were found to be significantly low in CAD+DM group when compared to control group. Conclusion: DPP-4 and SFRP-4 levels are predictive marker for atherosclerosis in diabetes, correlates well with HOMA-IR particularly in diabetes. CIMT has the potential to be a clinically useful predictor of vascular risk in diabetic patients with CAD. Large cohorts and at-risk populations are needed to confirm the predictive value of these findings.

COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets’ inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.

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.

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.

Leucokinins (LKs) constitute a family of neuropeptides identified in numerous insects and many other invertebrates. The LKs act on G-protein coupled receptors that display only distant relations to other known receptors. In adult Drosophila, 26 neurons/neurosecretory cells of three main types express LK. The four brain interneurons are of two types, and these are implicated in several important functions in the fly’s behavior and physiology, including feeding, sleep-metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. The 22 neurosecretory cells (ABLKs) of the abdominal neuromeres coexpress LK and a diuretic hormone (DH44), and together these regulate water and ion homeostasis and associated stress, as well as food intake. In Drosophila larvae, LK neurons modulate locomotion, escape responses, and aspects of ecdysis behavior. A set of lateral neurosecretory cells, ALKs, in the brain express LK in larvae, but inconsistently so in adults. These ALKs coexpress three other neuropeptides and regulate water and ion homeostasis, feeding and drinking, but the specific role of LK is not yet known. This review summarizes Drosophila data on embryonic lineages of LK neurons, functional roles of individual LK neuron types, interactions with other peptidergic systems, and orchestrating functions of LK.

Rapid progress in gene editing based on clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) has revolutionized the study of gene and genome function and genetic disease correction. While numerous genetically modified cellular and animal models have been created to understand biological processes, the clinical application of CRISPR/Cas tools has been impeded by off-targeting and delivery problems. It is generally accepted that the delivery of CRISPR in the form of a ribonucleoprotein complex (RNP) substantially reduces the time of DNA exposure to the effector nuclease, minimizing off-target effects and facilitating clinical usage. This review focuses on CRISPR/Cas RNP delivery with retro/lentiviral particles and exosomes, whose parallel production by cells transfected with viral vectors is underestimated. We critically evaluate specific mechanisms of extracellular particle formation and loading with CRISPR/Cas for each system. Additionally, the details of Cas-nanoparticle entry and uncoating, previously unappreciated in the context of gene editing efficiency, are discussed. Based on existing knowledge about the consequences of intervention in retroviral assembly, entry, or exosome formation, we outline the potential problems with CRISPR/Cas delivery using extracellular nanoparticles and ways to address them.

Urolithiasis is a painful experience associated with hematuria, damage to kidney tissue and renal failure. It is a multi-factorial disorder while in India, its prevalence is rapidly increasing imposing a large burden for both healthcare and economy globally. In this article, we aimed to evaluate the association between genetic defects in SPP1 gene and urolithiasis from East Indian patients.75 urolithiasis patients were recruited from SSKM Hospital & Institute of Post Graduate Medical Education & Research (IPGME&R), Kolkata, India while 75 healthy controls were recruited from the same community. SNPs based areas of SPP1 gene were analyzed by direct sequencing to identify genetic defects.We identified 3 polymorphisms one synonymous and two 3’UTR variants rs1126616: p.Ala250Ala, rs1126772: 7315 a>g, rs9138: 7471 a>c in SPP1 gene in study individuals. Genotype and allele frequency analysis of these SNPs revealed that, rs9138 SNP was significantly associated with urolithiasis risk in East Indian patients. To our knowledge this is the first study reporting the role of the gene with urolithiasis in the population of West Bengal, India.

Jumping side volley has created breathtaking moments and cherished memories for us. Regrettably, a scientific study on the skill has not been found in literature. Relying on talent of athletes to improvise on the fly can hardly be considered a viable learning strategy. This study targets to fill the gap by quantifying factors contributing to develop its coaching method. Using 3D motion capture (12-cameras, 200Hz) and full-body biomechanical modeling, our study aimed to identify elements that govern entrainment of the skill by examining jumping, kicking and falling phases of its execution. Given the rarity of players who have acquired this skill, we found five subjects for the study. Twenty-three trials were captured and quantified. The results unveil the following key elements: 1) the control of trunk rotation during the jumping, 2) the angle between thighs upon take-off, 3) the whip-like control of the kicking leg during airborne, 4) timing between ball motion and limbs’ coordination, and 5) damping mechanism during falling. An accurate kick can only be achieved through repetitive training. This underlines the need for athletes to master a safe landing technique that minimizes risk of injury during practice. Therefore, training should begin with learning a safe falling technique.

Angiotensin converting enzyme 2 (ACE2) is a key entry point of SARS-CoV-2 virus known to induce COVID-19. We have recently outlined the concept to reduce ACE2 expression by the administration of glycyrrhizin, a component of Glycyrrhiza glabra extract, via its inhibitory activity on 11beta hydroxysteroid dehydrogenase type 2 (11betaHSD2) and resulting activation of mineralocorticoid receptor (MR). We hypothesized that in organs, such as the intestine, which co-express 11betaHSD2, MR and ACE2, the expression of ACE2 would be suppressed. We studied organ tissues from an experiment originally designed to address the effects of Glycyrrhiza glabra extract on the stress response. Male Sprague Dawley rats were left undisturbed or exposed to chronic mild stress for five weeks. For the last two weeks, animals continued with a placebo diet or received a diet containing extract of Glycyrrhiza glabra root at a dose of 150 mg/kg of body weight/day. Quantitative PCR measurements showed a significant decrease in gene expression of ACE2 in the small intestine of rats fed with diet containing Glycyrrhiza glabra extract. This effect was independent of the stress condition and failed to be observed in non-target tissues, namely the heart and the brain cortex. In the small intestine we confirmed the reduction of ACE2 also at the protein level. Present findings provide first evidence to support the hypothesis that Glycyrrhiza glabra extract may reduce an entry point of SARS-CoV-2. Whether this phenomenon, when confirmed in additional studies, is linked to the susceptibility of cells to the virus requires further studies.

Bioglasses are highly adoptable bone substitute materials, which can be combined with so-called therapeutic ions. These ions have shown to influence underlying molecular processes of the bone regeneration cascade. Moreover, it is known that bone substitutes induce an immune reaction within their implantation area involving macrophages and their pro- and anti-inflammatory subtypes dependent on their chemical composition. However, only poor knowledge exists regarding the influence of therapeutic ions onto the immune reactions and the associated bone healing. Thus, the aim of this work was to investigate the influence of strontium- and copper-doped bioglasses on the induction of M1- and M2-macrophages as well as the implant bed vascularization. (2) Methods: For this study, two alkali glasses were produced on basis of ICIE-16 bioglass via the melt-quench route with the addition of 5 wt% copper or strontium (ICIE16-Cu and ICIE16-Sr). Pure ICIE16 and 45S5 bioglasses were used as control materials. The bioactivity (ion release), chemical composition and the surface pattern were investigated, as well as an in vivo experiment was performed using the subcutaneous implantation model in rats. (3) Results: SEM imaging showed different formations of hydroxyapatite on the surfaces of the bioglass systems after submersion in simulated body fluid. EDX analysis confirmed the doping process by showing the release kinetics. Copper-doped bioglass exhibited a higher ion release than strontium-doped bioglass. Copper induced both a low immune cell migration and triggered a low number of M1- and M2-macrophages but also of blood vessels. The strontium-containing bioactive glass induced higher numbers of M1-macrophages after 30 days. Both copper- and strontium-doped bioglasses induced comparable numbers of M2-macrophages as found in the control groups. (4) Conclusions: Bioglass doping with copper and strontium did not exhibit significant influence on the foreign body response or the implantation bed vascularization in vivo. However, the prepared bioglass systems seemed to be biocompatible.

Acne vulgaris is a chronic skin disease, which occurs due to inflammation of the hair follicles and sebum producing (sebaceous) glands of the skin called pilosebaceous unit and the anaerobic propionic acne bacterium, P.acne. Human sebum is dominantly made up of 57.5% of triglycerides and fatty acids, 26%wax esters, 12% Squalene and 4.5% Cholesterol. The increased level Androgen hormone, sebum lipid composition, P.acne over growth which induces monocytes and pro inflammatory cytokines attracts neutrophils, basophils, and T cells to the pilosebaceous unit and drive epithelial hyper proliferation i.e., Acne vulgaris. The actual biomolecular changes due to acne vulgaris disease are present in the blood, in the sebum, and in the noninvasive sample of human scalp hair follicles. The main objectives of the present study are to analyze human scalp hair follicles samples using FTIR-ATR spectroscopy to compare and discriminate the spectral signatures of acne vulgaris and healthy scalp hair tissue samples through acne biomarkers Protein, Amide I, Amide II and Squalene (LDL), using the method of internal ratio parameters. This work represents a first step in the development of an analytical tool for future drug development.

Biological micro-dissection has a wide range of applications in the field of molecular pathology. The current laser-assisted dissection technology is expensive, and laser radiation can lead to sample contamination. As an economical and pollution-free micro-dissection method, piezoelectric ultrasonic micro-dissection has a wide application prospect. However, the performance of the current piezoelectric ultrasonic micro-dissection technology is unsatisfactory. In this paper, a novel piezoelectric ultrasonic micro-dissection device based on a flexure mechanism is proposed in order to solve the problems of low dissecting precision and excessive wear of the dissecting needle caused by the harmful lateral vibration of the current piezoelectric ultrasonic micro-dissection device. By analyzing the flexibility of flexure hinge, the type of flexure beam and the optimal design parameters are determined. Through comparing the harmonic response simulation analysis of the micro-dissection device based on a flexure mechanism and the traditional micro-dissection device without the flexure mechanism, the newly designed micro-dissection device achieves the best vibration effect when the driving frequency is 28kHz, compared with the traditional micro-dissection device, the lateral vibration suppression effect is improved by 68%. Then, based on the 3D printing technology, a prototype of a novel micro-dissection device was produced, and its performance was tested. It was found that the flexure mechanism did indeed suppress the lateral vibration of the needle tip. Finally, the experiments of 5μm thick paraffin-embedded rat liver sections were carried out, and the effects of different dissecting parameters on the dissecting effect were analyzed, and the optimal dissecting parameters were obtained. By comparing the dissecting effects of the tissue sample and the wear condition of the needle tip between the novel micro-dissection device and the traditional micro-dissection device under their optimal dissecting parameters, it is proved that the suppression of harmful lateral vibration not only significantly improves the dissecting effect, but also improves the service life and durability of the dissecting needle, which is beneficial to reduce the equipment costs.

In this paper, we study the weak gravitational deflection angle of relativistic massive particles by the Kerr-like black hole in the bumblebee gravity model. In particular, we focus on weak field limits and calculate the deflection angle for a receiver and source at a finite distance from the lens. To this end, we use the Gauss-Bonnet theorem of a two-dimensional surface defined by a generalized Jacobi metric. The spacetime is asymptotically non-flat due to the existence of a bumblebee vector field. Thus the deflection angle is modified and can be divided into three parts: the surface integral of the Gaussian curvature, the path integral of a geodesic curvature of the particle ray and the change in the coordinate angle. In addition, we also obtain the same results by defining the deflection angle. The effects of the Lorentz breaking constant on the gravitational lensing are analyzed. We then consider the finite-distance correction for the deflection angle of massive particles.

Tissue engineering, also called “regenerative medicine”, refers to attempt to create functional human tissue from cells in laboratory. This is a field that uses living cells, biocompatible materials, suitable biochemical and physical factors and their combinations, to create tissue-like structures.. To date, no tissue engineered skeletal muscle implants have been developed for clinical use, but it may represent a valid alternative to treat volumetric muscle loss in the near future. Herein, we reviewed the literature and showed different techniques to produce synthetic tissues with the same architectural, structural and functional properties of native tissues.

Three-dimensional (3D) bioprinting promises to be essential in tissue engineering for solving the rising demand for organs and tissues. Some bioprinters are commercially available, but their impact on the field of TE is still limited due to their cost or difficulty to tune. Herein, we present a low-cost easy-to-build printhead for microextrusion-based bioprinting (MEBB) that can be installed in many desktop 3D printers to transform them into 3D bioprinters. We can extrude bioinks with precise control of print temperature between 2 - 60 ºC. We validated the versatility of the printhead, by assembling it in three low-cost open-source desktop 3D printers. Multiple units of the printhead can also be easily put together in a single printer carriage for building a multi-material 3D bioprinter. Print resolution was evaluated by creating representative calibration models at different temperatures using natural hydrogels such as gelatin and alginate, and synthetic ones like poloxamer. Using one of the three modified low-cost 3D printers, we successfully printed cell-laden lattice constructs with cell viabilities higher than 90% after 24h post printing. Controlling temperature and pressure according to the rheological properties of the bioinks was essential in achieving optimal printability and great cell viability. The cost per unit of our device, which can be used with syringes of different volume, is less expensive than any other commercially available product. These data demonstrate an affordable open-source printhead with the potential to become a reliable alternative to commercial bioprinters for any laboratory.

CoO-ZnO-based composites have attracted considerable attention for the development of energy storage devices because of their multifunctional characterization and ease of integration with existing components. This paper reports the synthesis of CoO@ZnO (CZ) nanostructures on Ni foam by the CBD method for facile and eco-friendly supercapacitor applications. The formation of a CoO@ZnO electrode functioned with cobalt, zinc, nickel and oxygen groups was confirmed by X-ray diffraction, X-ray photoelectron spectroscopy, low and high-resolution of scanning electron microscopy, and transmission electron microscopy. The as-synthesized hierarchical nanocorn skeleton-like structure of CoO@ZnO-3h (CZ3h) electrode delivered a higher specific capacitance of 1136 F/g at a current density of 3 A/g with outstanding cycling stability, showing 98.3% capacitance retention over 3000 cycles in an aqueous 2 M KOH electrolyte solution. This retention was significantly better than that of other prepared electrodes, such as CoO (CO), ZnO (ZO), CoO@ZnO-1h (CZ1h), and CoO@ZnO-7h (CZ7h) (274, 383, 240 and 537 F/g, respectively). This superior capacitance was attributed to the ideal surface morphology of CZ3h, which is responsible for the rapid electron/ion transfer between the electrolyte and electrode surface area. The enhanced features of the CZ3h electrode highlight potential applications in high performance supercapacitors, solar cells, photocatalysis, and electrocatalysis.

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.

Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nethertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continous hydrogen release. In this context, the hydrogen release and the related (micro-) milieu conditions pretend to strictly follow in vitro standards based on ISO 10993-5/-12. Thus, special adaptions for the testing of Mg materials are necessary, which have been described in a previous study from our group. Based on these adaptions, further developments of a test procedure allowing rapid and effective in vitro cytocompatibility analyses of Mg-based materials based on ISO 10993-5/-12 are necessary. The following study introduces a new two-step test scheme for rapid and effective testing of Mg. Specimens with different surface characteristcis were produced by means of plasma electrolytic oxidation (PEO) using silicate-based and phosphate-based electrolytes. The test samples were evaluated for corrosion behavior, cytocompatibility and their mechanical and ostogenic properties. Thereby, two PEO ceramics could be identified for further in vivo evaluations.

Scaffolds are widely used in tissue engineering because their manufacture is based on natural and synthetic polymers, which allows them to have properties such as biocompatibility and biodegradability, creating an ideal environment for cell growth on their surface. In this context, among the polymers studied in Tissue Engineering are Chitosan (CH) and Polyvinyl Alcohol (PVA). CH is a versatile polymer obtained from de-acetylation of chitin, which is used for its high biodegradability and biocompatibility, although its mechanical properties must be improved. It has been found that one of the ways to improve the mechanical properties of CH is to mix it with other synthetic polymers such as PVA. PVA is known for its biocompatibility, biodegradability, zero toxicity and ease of preparation due to its solubility in water and excellent mechanical properties, such as tensile strength and ease in the formation of films and barriers. In this study we evaluated the capacity of scaffolds made with CH and PVA in different concentrations (2: 1, 1: 1, 1: 2, respectively) as a possible application in bone regeneration. This was made through different characterization tests such as Infrared Spectroscopy, AFM, Swelling test and Porosity test, where we obtained information about its structural and physicochemical properties. Additionally, a cellular quality control was performed on the material through the MTT assay. The Fourier transform infrared spectroscopy (FTIR) study showed that there are strong intermolecular hydrogen bonds between the chitosan and polyvinyl alcohol molecules. The Swelling and Porosity tests showed favorable results, obtaining maximum values ​​of 5519% and 72.17% respectively. MTT tests determined that the prepared materials are not cytotoxic. These findings suggest that scaffolds possess properties suitable for use in Tissue Engineering.

Manipulating cloth-like deformable objects (CDOs) is a long-standing problem in the robotics community. CDOs are flexible (non-rigid) objects that do not show a detectable level of com- pression strength while two points on the article are pushed towards each otherand include objects such as ropes (1D), fabrics (2D) and bags (3D). In general, CDOs’ many degrees of freedom (DoF) introduce severe self-occlusion and complex state-action dynamics as significant obstacles for perception and manipulation systems. These challenges exacerbate existing issues of modern robotic control methods such as imitation learning (IL) and reinforcement learning (RL). This review focuses on the application details of data-driven control methods on four major task families in this domain: cloth-shaping, rope manipulation, dressing and bag manip- ulation. Furthermore, we identify specific inductive biases in these four domains that present challenges for more general IL and RL algorithms, and summarise the future direction for the development of the field.

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.

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.

Temperature and pH can expedite the ability of pathogens to cause diseases in cold-water corals (CWCs). The present study employed a combination of histology and polymerase chain reaction diagnostic techniques to investigate potential pathogens present in the CWCs Lophelia pertusa and Madrepora oculata in the Porcupine Bank Canyon (PBC), NE Atlantic. No pathogen was observed in the Madrepora samples. Neither histology nor standard PCR detected Vibrio spp. in the corals, although using Illumina technology, V. shilonii was observed in some L. pertusa samples in low abundances (0.22%). A Rickettsiales-like organisms (RLOs) occurred at a prevalence of 8.0% and at a low infection intensity of 1 - 4. Lophelia showed a few RLOs infection from the PBC canyon head (2.7%) and high infections in the south branch (5.3%). Similarly, unidentified cells observed in L. pertusa from the south branch (4.0%) were more common than those found in the canyon head (1.3%) with a prevalence of 5.3%. Although the route of pathogen infection is unclear, a likely mode of entry could be associated with particulate availability and the feeding strategies of the scleractinian corals. This suggest that L. pertusa invests energy into an enhanced immune function and reduced susceptibility to global pathogens despite a changing ocean environment.

This study aimed to investigate Coll-I, III, IV and elastin in canine normal prostate and PC, using Picrosirius red (PSR) and Immunohistochemical (IHC) analysis. Eight normal prostates and 10 PC from formalin-fixed, paraffin-embedded samples were used. Collagen fibers area was analyzed with ImageJ software. The distribution of Coll-I and Coll-III was approximately 80% around prostatic ducts and acini, 15% among smooth muscle and 5% surrounding blood vessels, in both normal prostate and PC. There was a higher median area of Coll-III in PC, when compared to normal prostatic tissue (p=0.001 for PSR and p= 0.05 for IHC). Immunostaining for Coll-IV was observed in the basal membrane of prostate acini, smooth muscle, blood vessels, and nerve fibers of normal and PC samples. Although there was no difference in Coll-IV area between normal tissue and PC, tumors with Gleason score 10 showed absence of Coll-IV, when compared to scores 6 and 8 (p=0.0095). Elastic fibers were found in the septa dividing the lobules and around the prostatic acini of normal samples, and was statistically higher in PC, compared to normal tissue (p=0.00229). Investigation of ECM components brings new information and should be correlated with prognosis in future studies.

Poly(2-methoxyethyl acrylate) (PMEA) and poly(ethylene oxide) (PEO) have protein-antifouling properties and blood compatibility. ABA triblock copolymers (PMEAn-PEO11340-PMEAn (MEOMn)) were prepared using single-electron transfer-living radical polymerization (SET-LRP) using a bi-functional PEO macroinitiator. Two types of MEOMn composed of PMEA blocks with a degree of polymerization (DP = n) of 85 and 777 were prepared using the same PEO macroinitiator. MEOMn formed flower micelles with a hydrophobic PMEA (A) core and hydrophilic PEO (B) loop shells in diluted water with a similar appearance to petals. The hydrodynamic radii of MEOM85 and MEOM777 were 151 and 108 nm, respectively. The PMEA block with a large DP formed a tightly packed core. The aggregation number (Nagg) of the PMEA block in a single flower micelle for MEOM85 and MEOM777 was 156 and 164, respectively, which were estimated using a light scat-tering technique. The critical micelle concentrations (CMCs) for MEOM85 and MEOM777 were 0.01 and 0.002 g/L, respectively, as determined by the light scattering intensity and fluorescence probe techniques. The size, Nagg, and CMC for MEOM85 and MEOM777 were almost the same inde-pendent of hydrophobic DP of the PMEA block.

The use of mixed-state ionic beams in collision dynamics investigations is examined. Using high resolution Auger projectile spectroscopy involving He-like ($1s^2\thinspace^1\!S, 1s2s\thinspace^{3,1}\!S$) mixed-state beams, the spectrum contributions of the $1s2s\thinspace^3\!S$ metastable beam component is effectively separated and clearly identified. This is performed with a technique that exploits two independent spectrum measurements under the same collision conditions, but with ions having quite different metastable fractions, judiciously selected by varying the ion beam charge-stripping conditions. Details of the technique are presented together with characteristic examples. In collisions of 4 MeV B$^{3+}$ with H$_2$ targets, the Auger electron spectrum of the separated $1s2s\thinspace^{3}S$ boron beam component allows for a detailed analysis of the formation of the $1s2s(^3\!S)nl \thinspace^2\!L$ states by direct $nl$ transfer. In addition, the production of hollow $2s2p\thinspace^{1,3}\!P$ doubly- and $2s2p^2\thinspace^2\!D$ triply-excited states, by direct excitation and transfer-excitation processes, respectively, can also be independently studied. In similar mixed-state beam collisions of 15 MeV C$^{4+}$ with H$_2$, He, Ne and Ar targets, the contributions of the $1s^2$, $1s2s\thinspace^{3,1}S$ beam components to the formation of the $2s2p\thinspace^{3,1}\!P$ states by double-excitation, $1s\rightarrow2p$ excitation and transfer-loss processes can be clearly identified, facilitating comparisons with theoretical calculations.

We continue to analyze basic constraints on human's decision making from the viewpoint of quantum measurement theory (QMT). As has been found, the conventional QMT based on the projection postulate cannot account for combination of the question order effect (QOE) and the response replicability effect (RRE). This was an alarm signal for quantum-like modeling of decision making. Recently, it was shown that this objection to quantum-like modeling can be removed on the basis of the general QMT based on quantum instruments. In the present paper we analyse the problem of combination of QOE, RRE, and the famous QQ-equality (QQE). This equality was derived by Busemeyer and Wang and it was shown (in the joint paper with Solloway and Shiffrin) that statistical data from many social opinion polls satisfies it. Now, we construct quantum instruments satisfying QOE, RRE, and QQE. The general features of our approach are formalized with postulates which generalize {\it Wang-Busemeyer} postulates for quantum-like modeling of decision making. Moreover, we show that our model closely reproduces the statistics of the famous Clinton-Gore Poll data with a prior belief state independent of the question order. This model successfully removes the order effect from the data to determine the genuine distribution of the opinions in the Poll. The paper also provides a psychologist-friendly introduction to the theory of quantum instruments - the most general mathematical framework for quantum measurements. We hope that this theory will attract attention of psychologists and will stimulate further applications.

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

Papillary thyroid carcinoma (PTC) has two main histologic variants: classical-PTC (CL-PTC) and follicular variant PTC (FV-PTC). Recently, due to its similar features to benign lesions, the encapsulated FV-PTC variant was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Nonetheless, specific molecular signatures are not yet available. It is well known that telomere-related genome instability is caused by inappropriate DNA repair of dysfunctional telomeres and that mechanisms involved in the damaged telomere repair processing may led to detrimental outcomes, altering the 3D nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples and telomere length overlaps in NIFTP and FTA. There was no association between BRAF expression and telomere length in all tested samples. Our data showing that 3D nuclear telomere organization is altered differently in thyroid cancer variants, suggest that this parameter might guide clinical management of NIFTP. Although further investigations in a larger cohort of patients are necessary to corroborate our observations, telomere-related genomic instability might be of value in the diagnosis of NIFTP and allow for a more appropriate selection of the correct treatment.

Purpose: to assess the effect of photobiomodulation (PBM) on human gingival fibroblast proliferation. Methods: The study was conducted using the primary cell cultures of human fibroblasts collected from systemically healthy donors. Three different laser types: Nd:YAG (1064nm), infrared diode laser (980nm) and prototype led laser emitting 405, 450 and 635nm were used to irradiate fibroblasts. Thanks to the patented structure of that laser, it was possible to irradiate fibroblasts with a beam combining two or three wavelengths. The energy density was 3 J/cm², 25 J/cm², 64 J/cm². The viability and proliferation of cells were determined using the MTT test conducted 24, 48 and 72 hours after laser irradiation. Results: The highest percentage of mitochondrial activity (MA=122.1%) was observed in the group irradiated with the 635nm laser, with an energy density of 64 J/cm² after 48 hours. The lowest percentage of MA (94.0%) was observed in the group simultaneously irradiated with three wavelengths (405 + 450 + 635 nm). The use of the 405nm laser at 25 J/cm² gave similar results to the 635 nm laser. Conclusions: The application of the 635nm and 405nm irradiation caused a statistically significant increase in the proliferation of gingival fibroblasts.

Rett syndrome (RTT) is mainly caused by mutations in methyl CpG-binding protein 2, cyclin-dependent kinase-like 5, or forkhead box protein G1. These RTT-causing proteins harbor an intrinsically disordered region (IDR) whose conformation exhibits spatiotemporal heterogeneity, which not only confer versatility to the protein, but also implicates them in diseases. The IDR generally evolves more rapidly than an ordered structure. In this study, we examined the relationship between pathogenic RTT-associated point mutations in RTT-causing proteins and the evolutionary dynamics of sequence features including structural order–disorder, phosphorylation sites, and evolutionary rates. We also analyzed the molecular properties and evolution of proteins that interact with RTT-causing proteins in terms of phylogenetic profiles, tissue specificity, subcellular localization, expression level, and functions. The results indicate that constrained IDRs may function by forming contacts with other regions in the protein sequence causing pathogenic missense mutations likely to arise in the rapidly evolving IDR and affect molecular networks, leading to disease. The results also provide novel insights into the genetic basis for RTT and the evolution of the neocortex in higher vertebrates.

RNA interference (RNAi) is one of the main mechanisms for disease resistance and small RNA production in plants. The main proteins involved in RNAi include Dicer-like (DCL), RNA-dependent RNA polymerase (RDR), double-stranded RNA-binding (DRB), and Argonaute (AGO). Juglandaceae contains a variety of important woody plants, and walnuts are one of the four major woody plant groups and one of the four major dried fruits in the world. To clarify the evolution and functional differentiation of RNAi-related proteins in the walnut (Juglans regia) genome, this study integrated various web resources from gene family acquisition to structural analysis and transcriptome data to correlate walnuts and their congeners. The walnut genome has 5 DCL, 13 RDR, 15 DRB and 15 AGO genes, similar genes encoding conserved protein structural domains and conserved motifs with similar subcellular localization. Walnut AGO proteins are classified into three classes and seven subclasses. The DCL is divided into four categories, while RDR is mainly divided into four categories, and DRB can be divided into six categories. The exception is that the copy number of walnut RDR1 is 9, in which seven RDR1 are distributed in clusters on chromosome 16. Purifying selection drove the formation of walnut genes, but protein classes were subjected to varying degrees of purifying selection. Additionally, these results showed some similarity in other plants of the walnut family. Moreover, different RNAi-related genes of walnut produced abundant selective expression in response to different tissues and stresses. In this study, DCL, RDR, DRB and AGO gene families were identified and analysed in the genome of the walnut family for the first time and preliminarily examined the evolution, structure and expression characteristics of these families to provide a preliminary basis for the evolution of the walnut RNAi pathway and breeding research.

The asymptotic dynamics of the classes of rational difference equations (RDEs) of third order defined over the positive real-line as $$\displaystyle{x_{n+1}=\frac{x_{n}}{ax_n+bx_{n-1}+cx_{n-2}}}, \displaystyle{x_{n+1}=\frac{x_{n-1}}{ax_n+bx_{n-1}+cx_{n-2}}}, \displaystyle{x_{n+1}=\frac{x_{n-2}}{ax_n+bx_{n-1}+cx_{n-2}}}$$ and $$\displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n}}}, \displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n-1}}}, \displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n-2}}}$$ is investigated computationally with theoretical discussions and examples. It is noted that all the parameters $a, b, c$ and the initial values $x_{-2}, x_{-1}$ and $x_0$ are all positive real numbers such that the denominator is always positive. Several periodic solutions with high periods of the RDEs as well as their inter-intra dynamical behaviours are studied.

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.

Cholinergic innervation in pancreas controls both the release of digestive enzymes to support the intestinal digestion and absorption, as well as insulin release to promote nutrient use in the cells of the body. The effects of muscarinic receptor stimulation are described in detail for endocrine beta cells and exocrine acinar cells separately. Here we describe morphological and functional criteria to separate these two cell types in situ in tissue slices and simultaneously measure their response to ACh stimulation on cytosolic Ca2+ oscillations [Ca2+]c in stimulatory glucose conditions. Our results show that both cell types respond to glucose directly in the concentration range compatible with the glucose transporters they express. The physiological ACh concentration increases the frequency of glucose stimulated [Ca2+]c oscillations in both cell types and synchronizes [Ca2+]c oscillations in acinar cells. The pharmacological ACh concentration further increases the oscillation frequency on the level of individual beta cells, inhibits the synchronization between these cells, and abolishes oscillatory activity in acinar cells. We discuss possible mechanisms leading to the observed phenomena.

The repurposing of licenced drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given the approximately 8,000 licenced compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially-available ex vivo/3D airway and alveolar tissue models. These models are a closer representation of in vivo studies compared to in vitro models, but retain the benefits of rapid in vitro screening for drug efficacy. We demonstrate that several existing drugs appear to show anti-SARS-CoV-2 activity against both Delta and Omicron Variants of Concern in the airway model. In particular, fluvoxamine, as well as aprepitant, everolimus, and sirolimus have virus reduction efficacy comparable to the current standard of care (remdesivir, molnupiravir, nirmatrelvir). Whilst these results are encouraging, further testing and efficacy studies are required before clinical use can be considered.

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) family that identify pathogen-associated molecular patterns derived from microbes and activate immune cell response. Following TLRs ligation, different adaptor and transcription molecules such as myeloid differentiation primary response gene 88 (MyD88) and nuclear factor kappa B (NF-kB) are recruited that initiate inflammatory signaling pathways. The human Toll-like receptor 10 (hTLR10) is a novel member of the PRRs family with a regulatory function of immune responses because of unique cytoplasmic domains which lead to induction of both inflammatory and anti-inflammatory properties. Recent studies have reported the association of TLR10 polymorphisms with many inflammatory diseases and human cancer. Engagement of TLR10 on the surface of the epithelium and macrophages leads to the production of proinflammatory cytokines and chemokines, while other studies have proven an anti-inflammatory role of TLR10. Accordingly, TLR10 suppresses proinflammatory cytokine production via negative regulation of MyD88 and the Akt (protein kinase B) and MAPK (mitogen-activated protein kinase) signaling pathways. This review aimed to provide answers for these conflicting findings (Inflammatory and anti-inflammatory properties of TLR10) to further identify distinct biological functions of TLR10.

Adiposity is associated with adverse health conditions such as obesity, cardiovascular disease and type 2 diabetes. The combination of resistance exercise and creatine supplementation has been shown to decrease body fat % in adults ≥ 50 years of age. However, the effects in adults < 50 years of age is unknown. To address this limitation, we systematically reviewed the literature and performed several meta-analyses comparing studies that included resistance exercise and creatine supplementation to resistance exercise and placebo. Twelve studies were included involving 266 participants. Adults (< 50 years of age) that supplemented with creatine and performed resistance exercise experienced a significant reduction in body fat % (-1.19%, p=0.006) and a non-significant reduction in absolute fat mass (-0.09 kg, p=0.88). Collectively, the combination of resistance exercise and creatine supplementation produces a very small reduction in body fat % in adults < 50 years of age.

Posterior capsule opacification (PCO) is the most common complication of cataract surgery. It causes a gradual deterioration of visual acuity, which would otherwise remain improved after a successful procedure. Despite recent advances in ophthalmology, this complication has not been eradicated and the incidence of PCO can be as high as 10%. This article reviews the literature concerning the pathomechanism of PCO and examines the biochemical pathways involved in its formation and methods to prevent this complication. We also review the reported tests performed in cell cultures under laboratory conditions, in experimental animal models, and in ex vivo human lens capsules. Finally, we describe research involving human eyes in the clinical setting and pharmacological methods that may reduce the frequency of PCO. Due to the multifactorial eti-ology of PCO, in vitro studies make it possible to assess the factors contributing to its complica-tions and search for new therapeutic targets. Not all pathways involved in cell proliferation, mi-gration, and contraction of the lens capsule are reproducible in laboratory conditions; moreover, PCO in humans and laboratory animals may be additionally stimulated by various degrees of postoperative reactions depending on the course of surgery. Therefore, further studies are necessary.

Fusarium wilt of banana is a devastating disease that has decimated banana production worldwide. Host resistance to Fusarium oxysporum f. sp. cubense (Foc), the causal agent of this disease, is genetically dissected in this study using two Musa acuminata ssp. malaccensis segregating populations segregating for Foc Tropical (TR4) and Subtropical (STR4) race 4 resistance. Marker loci and trait association using 11 SNP-based PCR markers allowed the candidate region to be delimited to a 12.9 cM genetic interval corresponding to a 959 kb region on Chromosome 3 of ‘DH-Pahang’ reference assembly v4. Within this region, there is a cluster of pattern recognition receptors, namely leucine rich repeat ectodomain containing receptor-like protein kinases, cysteine-rich cell wall associated protein kinases, and leaf rust 10 disease-resistance locus receptor-like proteins positioned in an interspersed arrangement. Their transcript levels were rapidly upregulated in the resistant but not in susceptible F2 progenies at the onset of infection. This suggests that one or several of these genes may control resistance at this locus. To confirm the segregation of single-gene resistance, we generated an inter-cross between the resistant parent ‘Ma850’ and a susceptible line ‘Ma848’, to show that the STR4 resistance co-segregated with marker ‘28820’ at this locus. Finally, an informative SNP marker 29730 allowed the locus specific resistance to be assessed in a collection of diploid and polyploid banana plants. Out of the 60 lines screened, 22 lines were predicted to carry resistance at this locus, including lines known to be TR4 resistant, such as ‘Pahang’, ‘SH-3362’, ‘SH-3217’, ‘Ma-ITC0250’, and ‘DH-Pahang/CIRAD 930’. Additional screening in the International Institute for Tropical Agriculture’s collection suggests that the dominant allele is common among in the elite ‘Matooke’ NARITA hybrids, as well as in other triploid or tetraploid hybrids derived from East African highland bananas. Fine-mapping and candidate gene identification will allow characterization of molecular mechanisms underlying TR4 resistance. The markers developed in this study can now aid the marker-assisted selection of TR4 resistance in breeding programs around the world.

The concerning worldwide increase of obesity and chronic metabolic diseases such as T2D, dyslipidemia, and cardiovascular disease motivates further investigations into preventive and alternative therapeutic approaches. Over the past decade, there is growing evidence that the formation and activation of thermogenic adipocytes (brown and beige) may serve as therapy to treat obesity and its associated diseases owing to its capacity to increase energy expenditure and to modulate circulating lipids and glucose levels. Thus, understanding the molecular mechanism of brown and beige adipocytes formation and activation will facilitate the development of strategies to combat metabolic disorders. Here, we provide a comprehensive overview of pathways and players involved in the development of brown and beige fat as well as the role of thermogenic adipocytes in energy homeostasis and metabolism. Also, we discuss the alterations in brown and beige adipose tissue function during obesity and, explore the therapeutic potential of thermogenic activation to treat metabolic syndrome.

Glaucoma is a blinding disease largely caused by increased resistance to drainage of fluid from the eye’s anterior chamber, resulting in elevated intraocular pressure (IOP). A major site of fluid outflow regulation and pathology is the trabecular meshwork (TM) at the entrance of the eye’s drainage system. We aimed to characterize the structural and functional properties of a newly developed tissue-engineered anterior segment eye culture model. We hypothesized that repopulation of a decellularized TM with non-native TM cells could restore aspects of normal TM. The decellularization protocol removed all cells and debris while preserving the ECM. Seeded cells localized to the TM region and progressively infiltrated the meshwork ECM. Cells reached a distribution comparable to control TM after four days of perfusion culture. After a perfusion rate increase challenge, tissue-engineered cultures reestablished normal IOPs (reseeded = 13.7±0.4 mmHg, decellularized = 35.2±2.2 mmHg, p < 0.0001). eGFP expressing CrFK control cells caused a high and unstable IOP (27.0±6.2 mmHg). In conclusion, we describe a readily available, storable, and biocompatible scaffold for anterior segment perfusion culture of non-native cells. Tissue-engineered organs demonstrated similarities to native tissues and may reduce the need for scarce donor globes in outflow research.

There is an overarching need to find alternative treatment options for malaria and this quest is more pressing in current times due to the morbidity and mortality data arising from most endemic countries and partially owing to the fact that the SARS-Cov-2 pandemic has diverted much public health attention. Additionally, the therapeutic options available for malaria has been severely threatened with the emergence of resistance to almost all existing drugs by the human malaria parasite. The Artemisinin Combination Therapies (ACTs) which hitherto have been the mainstay for malaria have encountered resistance in South East Asia, a notorious ground zero for the emergence of antimalarial drug resistance. This review analyses few key druggable targets of the parasite and the potential to leverage strategic inhibitors to mitigate the scourge of malaria by providing a concise assessment of the essential proteins of the malaria parasite that could serve as targets. Furthermore, this work provides a summary of the advances made in malaria parasite biology and the potential to leverage such findings for antimalarial drug production.

Staphylococcus aureus is a Gram-positive bacterium causing a range of mild to life-threatening infections including bone infections such as osteomyelitis. S. aureus is able to invade and persist within non-professional phagocytic cells such as osteoblasts. In the present study four different S. aureus strains, 2SA-ST239-III, 5SA-ST5-II, 10SA-ST228-I, and 14SA-ST22-IVh were tested for their ability to modulate cell viability in MG-63 osteoblast-like cells following a successful invasion and persistence. Methicillin-sensitive S. aureus (MSSA) ATCC-12598-ST30 was used as control. Despite the demonstrated similar abilities of internalization and persistence of ATCC-12598-ST30, 2SA-ST239-III, and 14SA-ST22-IVh strains in MG-63 osteoblast-like cells under our experimental conditions, we demonstrated that the decrease in cell viability was due to the different behavior of the considered strains, with the number of intracellular bacteria playing a limited role. We focused our attention on different cellular biochemical functions related to inflammation, cell metabolism, and oxidative stress during osteoblast infections. We were able to show that: 1) ATCC-12598-ST30 and 2SA-ST239-III were the only two clones able to persist and maintain their number into the cellular hostile environment during the entire period of infection; 2) 2SA-ST239-III was the only clone able to significantly increase the gene expression (3 and 24 h) and protein secretion (24 h) of both interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in MG-63 osteoblast-like cells; 3) the same clone determined a significant up-regulation of transforming growth factor-β1 (TGF-β1) and the metabolic marker glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNAs at 24 h post infection; 3) neither the MSSA nor the four MRSA strains induced oxidative stress phenomena in MG-63 cells, although a very different expression pattern towards nuclear factor E2-related factor 2 (Nrf2) and its downstream gene heme oxygenase 1 (HO-1) activation was observed among the different clones. Our results can open a new way of considering therapies, going in the direction of an individualized therapeutic strategy that should take into account the difference existing between MSSA and MRSA as well as the distinctive features of the different clones. Not only, therefore, a different antibiotic approach but also a starting point for considering different host factors, i.e. the modulation of specific cytokines such as IL-6, TNF-α, and TGF-β1.

Viruses are the most abundant biological entities in aquatic ecosystems and harbor an enormous genetic diversity. While their great influence on the marine ecosystems is widely acknowledged, current information about their diversity remains scarce. A viral metagenomic analysis of three water samples was conducted from sites on the South Scotia Ridge (SSR) near the Antarctic Peninsula, during the austral summer 2016. The taxonomic composition and diversity of the viral communities were investigated and a functional assessment of the sequences was determined. Phylotypic analysis showed that most viruses belonging to the order Caudovirales, especially the family Podoviridae (41.92-48.7%), similar to the viromes from the Pacific Ocean. Functional analysis revealed a relatively high frequency of phage-associated and metabolism genes. Phylogenetic analyses of phage TerL and Capsid_NCLDV (nucleocytoplasmic large DNA viruses) marker genes indicated that many sequences associated with Caudovirales and NCLDV were novel and distinct from known phage genomes. High Phaeocystis globosa virus virophage (Pgvv) signatures were found in SSR area and complete and partial Pgvv-like were obtained which may have an influence on host-virus interactions. Our study expands the existing knowledge of viral communities and their diversities from the Antarctic region and provides basic data for further exploring polar microbiomes.

In this paper, we study the third order semilocal convergence of the Newton-like method for finding the approximate solution of nonlinear operator equations in the setting of Banach spaces. First, we discuss the convergence analysis under ω-continuity condition, which is weaker than the Lipschitz and Hölder continuity conditions. Second, we apply our approach to solve Fredholm integral equations, where the first derivative of involved operator not necessarily satisfy the Hölder and Lipschitz continuity conditions. Finally, we also prove that the R-order of the method is 2p + 1 for any p $\in$ (0,1].

We set a feasible method to produce tailored collagen scaffolds and analyzed its potential for corneal engineering. Collagen-vitrigel membranes (CVM) were produced with a 1:1 ratio of Dulbecco’s Modified Eagle’s medium (DMEM), 1% antibiotics and 8% fetal bovine serum, and 5mg/mL collagen type I. Three volumes of collagen were used: 1X (2.8 L/mm2 of collagen), 2X, and 3X. Vitrification was done at 40% relative humidity (RH), 40° C, and 30 rpm using a matryoshka system set with a shaking-oven and a desiccator with a saturated K2CO3 solution. The CVM was characterized for width, microstructure, transparency, and biocompatibility using NIH3T3 cells. Surgical manipulation was assessed in an ex vivo corneal model. Constructs of corneal endothelial cells (CECs) and 2X-CVM were transplanted into five 18-month-old White New Zealand rabbits. CVM exhibited homogeneous surface and laminar organization. Membrane width increased with gel volume from 3.65µm to 7.2µm. 1X and 2X-CVM exhibited a 99% transmittance. NIH3T3 cells concentration increased 3-fold within 48 h with no significant difference among the 3 CVM (p = 0.323). The 2X-CVM was surgically manipulable. Transplantation of corneal endothelial cells (CECs) seeded over 2X-CVM restored corneal endothelium. The matrioshka system is a feasible method that yields CVM suitable for corneal engineering.

RNAi technology is a versatile, effective, safe, and eco-friendly alternative for crop protection. There is plenty of evidence of its use through host-induced gene silencing (HIGS) and spray-induced gene silencing (SIGS) techniques to control viruses, bacteria, fungi, insects, and nematodes. For SIGS, its most significant challenge is achieving stability and avoiding premature degradation of RNAi in the environment or during its absorption by the target organism. One alternative is encapsulation in liposomes, virus-like particles, polyplex nanoparticles, and bioclay, which can be obtained through the recombinant production of RNAi in vectors, transgenesis, and micro/nanoencapsulation. The materials must be safe, biodegradable, and stable in multiple chemical environments, favoring the controlled release of RNAi. Most of the current research on encapsulated RNAi focuses primarily on oral delivery to control insects by silencing essential genes. The regulation of RNAi technology focuses on risk assessment using different approaches; however, this technology has positive economic, environmental, and human health implications for its use in agriculture. The emergence of alternatives combining RNAi gene silencing with the induction of resistance in crops by elicitation and metabolic control is expected, as well as multiple silencing and biotechnological optimization of its large-scale production.

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.

The Particle-In-Cell (PIC) method has been developed in order to investigate microscopic phenomena, and with the advances of computing power, newly developed codes have been used for several fields such as astrophysical, magnetospheric, and solar plasmas. PIC applications have grown extensively with large computing powers available on supercomputers such as Pleiades and Blue Waters in the US. For astrophysical plasma research PIC methods have been utilized for several topics such as reconnection, pulsar dynamics, non-relativistic shocks, relativistic shocks, relativistic jets, etc. PIC simulations of relativistic jets have been reviewed with the emphasis on the physics involved in the simulations. This review summarizes PIC simulations, starting with the Weibel instability in slab models of jets, and then focuses on global jet evolution in helical magnetic field geometry. In particular we address kinetic Kelvin-Helmholtz instabilities and mushroom instabilities.

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Contributing pathophysiologic factors include endothelial dysfunction caused by excessive production of reactive oxygen species (ROS), increased activity of nuclear factor kB (NFkB), altered macrophage polarization, and reduced synthesis of endothelial progenitor cells (EPC). Consequently, there can be a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque, leading to increased cardiovascular mortality. Management is aimed at prevention, early diagnosis, and treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial function, inflammatory markers, markers of oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of trials that evaluated the cardiovascular safety of these drugs and found them to be safe from the CV standpoint.

We propose a non-invasive approach to control the quality of spheroids and their fusion into a complex bioconstruct. The proposed method is based on the union of the nutrient concentration change calculated using Fick's law and the "reaction-diffusion" equations, taking into account absorption coefficient with specifying the exact fusion geometry using implicit Function Repre-sentation (FRep) functions. The proposed approach allows us to analyze the viability of cells within the spheroid, predict the fusion of spheroids, and accurately model complex heteroge-neous biostructures as a future task for our research. These results will significantly accelerate the development of such a promising field of additive biotechnologies as 3D bioprinting.

Background: The ageing process starts in the center of the face, in the periocular region and around the mouth, with a combination of volume loss and tissue descent, wrinkles deepen, and loss of skin structure and quality. Recently, several studies proved the efficacy of therapies based on the autologous adipose tissue grafting that leverages the properties of stromal vascular fraction (SVF) and adipose derived mesenchymal stem cells (ADSCs) to accelerate the regenerative processes of the skin. This study aimed to verify the ability of the guided Superficial Enhanced Fluid Fat Injection (SEFFI) in the facial area to correct volume loss and skin aging and proved the very low rate of complications of this standardized procedure . Methods: we retrospectively collected data from 2,365 procedures performed in Italian centers between 2019 and 2021. Guided SEFFI was performed alone or combined with cosmetic treatments, including the use of hyaluronic acid filler, suspension threads, synthetic calcium hydroxylapatite, botulin toxin, and microneedling. Results: SEFFI was used alone in more than 60% of the patients, and in all face areas. In about one tenth of patients SEFFI was combined with botulin toxin treatment or hyaluronic acid filling. Other procedures were used more rarely. Ecchymosis in the donor or injection sites was the most frequent event, and yet observed in only 14.2% and 38.6% of patients, respectively. Conclusions: The SEFFI technique is standardized and minimally invasive, leading to very few complications. It can be a promising antiaging medical treatment that combines effectiveness, safety, and simplicity.