Mechanical properties of cardiomyocytes from different transmural regions are heterogeneous in the left ventricular wall. The cardiomyocyte mechanical environment affects this heterogeneity because of mechano-electric feedback mechanisms. In the present study, we investigated the effects of load upon transmural differences in contraction of subendocardial (ENDO) and subepicardial (EPI) single cells isolated from the murine left ventricle. Various loads were applied to the cells using carbon fiber techniques for single myocytes. To simulate experimentally obtained results and to predict mechanisms underlying the cellular response to change in load, our mathematical models of the ENDO and EPI cells were used. Extent of the transmural gradient in the time course of contractions was independent of the loading conditions where unloaded and heavy loaded (isometric) contractions were examined, but the regional gradient of the relaxation time characteristics tended to decrease when the load decreased. Under auxotonic contractions, time to peak contraction (T_max) was significantly longer in ENDO cells than in EPI cells at low preload. An increase in preload (axial stretch) prolonged T_max in both cell types; however, the prolongation was greater in EPI cells, resulting in a decrease in transmural gradient in T_max at high preload. The [Ca²⁺]_i transient decay time constant was consistent with the greater preload dependency in T_max of EPI cells. Our modified mathematical models reproduced experimental results, suggesting that differences in cooperativity of cross bridges and calcium troponin C complex interactions between the ENDO and EPI cardiomyocytes may contribute to the different cellular responses to stretch, which may provide a decrease in transmural dispersion of cellular shortening in the intact heart.

The proliferation of the Internet of Things (IoT) has revolutionized traditional services, giving rise to emerging smart infrastructures by connecting the physical and digital worlds. Sensory data is essential in IoT-based systems for providing context-aware and location-based services. Hence, the accurate localization of IoT devices is paramount. Anchor misplacement can significantly affect location information and coverage services in IoT. We study the effect of anchor misplacement in typical IoT settings where sensors are randomly deployed, can be mobile and may belong to multiple providers. We identify sensing coverage holes formed by anchor misplacement and analyze their presence and impact. To mitigate the impact of anchor misplacement on network reliability, we propose a framework to identify the affected sensor nodes and then identify and remove misplaced anchor nodes. The validity of our approach is verified, and its effectiveness is demonstrated by several experiments with different network topologies and parameters. Our results are promising and can be utilized in multiple coverage applications, such as smart agriculture systems and habitat monitoring, regardless of the sensors or deployment types. It also sheds light on best practices and methods for a reliable design of IoT-based systems.

Two monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2), trastuzumab and pertuzumab, were clinically approved. We previously developed a highly sensitive and specific anti-HER2 mAb, H2Mab-139 (mouse IgG1, kappa). In this study, we produced a defucosylated IgG2a version of anti‑HER2 mAb (H2Mab-139-mG2a-f) to enhance ADCC-mediated antitumor activity. H2Mab-139-mG2a-f exhibits a high binding affinity in flow cytometry with the dissociation constant (KD) determined to be 3.9 × 10‑9 M and 7.7 × 10‑9 M against HER2‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/HER2) and HER2-positive BT-474 cells, respectively. Moreover, we showed that H2Mab-139-mG2a-f exerted ADCC and complement-dependent cytotoxicity against CHO/HER2 and BT-474 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that H2Mab-139-mG2a-f exerts antitumor effects against HER2-positive human breast cancers and could be useful for an antibody treatment regimen for HER2-positive human cancers.

Background: In most cases, intra-labyrinthine schwannoma (ILS) occurs in patients with unilateral hearing deterioration or neurofibromatosis type II (NF II). The pattern of localization of these tumors is various but affects mostly the cochlea. Extirpation of the ILS, if hidden by the cochlea modiolus, is difficult under the aspect of complete removal. Therefore, a tissue removal device (TRD) was designed and tested in temporal bones. The principle of handling the new device is a pushing and pipe cleaner handling inside the cochlea. This present study aimed to describe the first in vivo experience with the newly developed TRD for removing cochlear intra-labyrinthine schwannoma. Methods: In three patients, the TRD was used for the tumor removal of ILS. In two patients with a cochlear schwannoma in combination with a cochlea implantation and one patient suffering from NF II, a cochlear schwannoma was removed with the TRD. The access was performed with a posterior tympanotomy, an enlarged round window approach, and an additional second-turn access. The device was inserted and extracted gradually from the second turn access until the rings were visible in the second turn access. By pushing and pipe cleaner handling, the tumors were removed. An MRI control was performed on the day postoperatively with a T1 GAD sequence. Results: Tumor removal with the TRD was performed in a 15-minute procedure. MRI control confirmed a complete removal on the postoperative day in both cases. Conclusion: In vivo handling of the device confirmed a straightforward handling for tumor removal. MRI scanning showed a complete removal of the tumor by the TRD.

Background: Visceral leishmaniasis affects approximately 12 million people worldwide. Current existing drugs cause several side effects and resistance, the identification of new therapeutic targets for the development of new drugs is necessary. The vesicular trafficking in the parasite flagellar pocket is essential for parasite survival and proliferation, but little is known about the proteins involved in the endocytic/secretory pathways. In this work, we are describing the characterization of a transporter cargo protein SFT-2/Got-1 like in Leishmania infantum. Material and Methods: Using bioinformatics tools, the putative Got-1 protein A4HSK3 was characterized structurally and phylogenetically. Molecular biology was used to clone and express the protein and confocal fluorescence to determine its subcellular localization. Results: The Got-1 like protein presents four alpha helix TM conserved domains (aa38-aa147) characteristics of the Got-1/SFT-2 family proteins and an important Pen-2 conserved motif LGDYXXF located in the extracellular loop. Confocal microscopy suggests that Got-1/SFT-2 like is localized in the flagellar pocket, and is partially co-localized with the L. infantum presenilin-like protein. Phylogenetically, the Leishmania sp Got-1 like is contained in a subgroup of proteins clearly detached from the other Trypanosomatidae, such as T. cruzi and T. brucei. Conclusions: Our data show the presence of an important transported proteins, and its colocalization with the presenilin aspartyl protease in the flagellar pocket of the L. infantum open new perspectives to identify novel targets, which can be an alternative therapeutic strategy against leishmaniasis.

Amyotrophic Lateral Sclerosis (ALS) stands as a debilitating neurodegenerative condition characterized by the progressive degeneration of motor neurons. Despite extensive research in various model animals, the cellular signal mechanisms of ALS remain elusive, impeding the development of efficacious treatments. Among these models, a well-characterized and diminutive organism, Caenorhabditis elegans (C. elegans), has arisen as a potent tool for investigating the molecular and cellular dimensions of ALS pathogenesis. This review summarizes the contributions of C. elegans models to our comprehension of ALS, emphasizing pivotal findings pertaining to genetics, protein aggregation, cellular pathways, and potential therapeutic strategies. We analyze both the merits and constraints of C. elegans system in the realm of ALS research, and point towards future investigations that could bridge the chasm between C. elegans foundational discoveries and clinical applications.

Introduction. Intra-abdominal cystic formations represent heterogeneous pathologies with varied localization and clinical manifestation. The first challenge of a giant intra-abdominal cystic lesion is identifying the organ of origin. The clinical presentation of intra-abdominal cystic lesions varies from acute manifestations to non-specific symptoms or accidental discovery. Case presentation: A 2-year-old girl presents to the emergency unit with a fever of 38.5 Celsius, loss of appetite, and apathy. The investigations showed a gigantic intra-abdominal mass whose organ belonging could not be specified. Postoperatively, a giant mesenteric lymphangioma was evident, which was completely excised. Discussions Giant cystic formations modify the anatomical reports and become space-replacing formations, and the starting point is even more challenging to assess preoperatively. Nevertheless, the careful evaluation of the characteristics of the formation, the effect on the adjacent organs, the age of the patient, and the clinical picture can provide elements of differential diagnosis.

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centers in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000-2009) and later (2010-2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 10,475 were allogeneic and 7,571 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post- transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada.

Lipid composition in the cellular membranes plays an important role in maintaining the struc-tural integrity of cells and in regulating cellular signaling that controls functions of both mem-brane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transport-ers, two integral membrane proteins, are known to contribute to lipid translocation across the li-pid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membrane in regulating cell signaling and how lipid transporters participate this process.

The epithelial cell adhesion molecule (EpCAM) is a stem cell and carcinoma antigen, which mediates cellular adhesion and proliferative signaling by the proteolytic cleavage. In contrast to low expression in normal epithelium, EpCAM is frequently overexpressed in various carcinomas, which correlates with poor prognosis. Therefore, EpCAM has been considered as a promising target for tumor diagnosis and therapy. Using the Cell-Based Immunization and Screening (CBIS) method, we previously established an anti‐EpCAM monoclonal antibody (EpMab-37; mouse IgG1, kappa). In this study, we investigated the antibody‐dependent cellular cytotoxicity (ADCC), complement‐dependent cytotoxicity (CDC), and an antitumor activity by a defucosylated mouse IgG2a-type of EpMab-37 (EpMab-37-mG2a-f) against an EpCAM‐expressing breast cancer cell line (BT-474). EpMab-37-mG2a-f recognized BT-474 cells with a moderate binding-affinity [a dissociation constant (KD): 2.9x10-8 M] by flow cytometry. EpMab-37-mG2a-f exhibited ADCC and CDC for BT-474 cells by murine splenocytes and complements, respectively. Furthermore, administration of EpMab-37-mG2a-f significantly suppressed the BT-474 xenograft tumor development compared with the control mouse IgG. These results indicated that EpMab-37-mG2a-f exerts antitumor activities against the BT-474 xenograft, and could provide valuable therapeutic regimen for the breast cancers.

In eastern part of Ethiopia groundnut is very commonly intercropped with sorghum. Even though intercropping of sorghum with groundnut is practiced in the eastern part of Ethiopia the population density at what ratio should not be known. Therefore determining the population ratio is found to be crucial to draw management options. The study was conducted at two locations at Fadis (on station) and Babile (sub- station). Sorghum variety (Teshale) and groundnut (Fetene) were used as planting materials. All agronomic data were collected and analyzed by using GenStat software. Significant different were obtained among the treatments. The research result showed that, there were significance difference for both sorghum and ground nut yield per hectare in the years (2014 and 2015) among treatments. The result over time(in 2014 and 2015) at Fadis and Erer showed that the highest sorghum and groundnut yield per hectare were obtained/harvested from the intra row spacing of 25cmx20cm and 30cmx20cm intercropping sorghum with ground nut system with (1.27 and 1.31) respectively. The highest LER (1.31) and highest GMV (10218.00 ETBr/ha) were obtained from the intercropping of 30cmx20cm (Sorghum & groundnut). Clearly showed that, with intercropping of sorghum and Groundnut, it is possible to produce additional yield of sorghum without significant reduction in groundnut yield. As a result of this, the intra spacing of the main crop (sorghum) 25cm and 30cm and for the subsidiary crop (groundnut) 20cm was recommended for further production in the study areas of eastern Harerghe zone and similar agro-ecologies.

Hepatitis D virus (HDV) infection represents the most severe form of chronic viral hepatitis. We have shown that the delivery of HDV replication-competent genomes to the hepatocytes using adenoassociated virus (AAV-HDV) as gene delivery vehicles offers a unique platform to investi-gate the molecular aspects of HDV and associated liver damage. Here, we generated HDV ge-nomes modified by site directed mutagenesis aimed to: i) prevent some post-translational modi-fications of HDV antigens (HDAgs) such as Large-HDAg (L-HDAg) isoprenylation or Short-HDAg (S-HDAg) phosphorylation ii) alter the localization of HDAgs within the subcellular compartments and iii) inhibit the right conformation of the delta ribozyme. First, the different HDV mutants were tested in vitro using plasmid-transfected Huh-7 cells and then in vivo in C57BL/6 mice using AAV vectors. We found that Ser 177 phosphorylation and the ribozymal ac-tivity are essential for HDV replication and HDAg expression. Mutation of the isoprenylation domain prevent the formation of infectious particles and increase cellular toxicity and liver dam-age. Finally, altering the intracellular localization od HDAg have a profound on viral replication in vivo but liver toxicity is maintained. Mutation in the nuclear export signal impair the for-mation of infectious viral particles. These findings contribute valuable insights into the intricate mechanisms of HDV biology and have implications for therapeutic considerations

The COVID-19 pandemic stimulated attention to the medicinal applications of messenger RNA (mRNA). mRNA is expected to be applied not only to vaccines but also to regenerative medicines. The purity of mRNA is important for its medicinal application. However, the current mRNA synthesis techniques have problems, e.g., contamination of undesired 5’-uncapped mRNA and double-stranded RNAs. Recently, our group developed a completely capped mRNA synthesis technology that contributed to the progress of mRNA research. The introduction of chemically modified nucleosides, e.g., N1-methylpseudouridine and 5-methylcytidine, have been demonstrated by Dr. Karikó and Dr. Weissman which opened the practical application of mRNA for vaccines and regenerative medicines. Dr. Yamanaka reported the production of Induced Pluripotent Stem Cells (iPSCs) by the introduction of 4 types of genes using a retrovirus vector. iPSCs are widely used for research about regenerative medicines and the preparation of disease models to screen new drug candidates. Of the Yamanaka factors, Klf4 and c-Myc are oncogenes, and there is a tumor development risk if these are integrated into genomic DNA. Therefore, regenerative medicines using mRNA, which has no risk of genome insertion, have attracted attention. In this review, we summarized the synthesis of mRNA and its application for regenerative medicine.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent world-wide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBP) is a family of secreted proteins involved in senescence and scarring mainly synthetized in the liver. Here we aimed to study the association of IGFBP and its induced senescence with the progression of NAFLD and liver fibrosis. Materials and Methods: 16 weeks old male C57BL/6 mice weighing 23 ± 3 g were fed either Methionine-Choline Deficient or control diet for 2, 8 or 12 weeks. Blood and liver samples were collected; histological assessment of NAFLD and fibrosis was performed. Fat contents were measured. Cellular senescence was evaluated in the liver. IGFBP levels were assessed in liver and serum. Data was expressed as Mean ± SD and analyzed by one-way ANOVA followed Tukey’s test. Lineal regression models were applied for NAFLD and fibrosis progression. p

Epidemiological and clinical evidence have extensively documented the role of obesity in the develop-ment of endometrial cancer. However, the effect of fatty acids on cell growth in endometrial cancer has not been widely studied. Here we reported that palmitic acid significantly inhibited cell proliferation of endometrial cancer cells and primary cultures of endometrial cancer, and reduced tumor growth in a transgenic mouse model of endometrial cancer, in parallel with increased cellular stress and apoptosis and decreased cellular adhesion and invasion. Inhibition of cellular stress by N-acetyl-L-cysteine effec-tively reversed the effects of palmitic acid on cell proliferation, apoptosis and invasive capacity in the endometrial cancer cells. Palmitic acid increased the intracellular formation of lipid droplets in a time- and dose-dependent manner. Depletion of lipid droplets by blocking DGAT1 and DGAT2 effectively increased the ability of palmitic acid to inhibit cell proliferation and induce cleaved caspase 3 activity. Collectively, this study provides new insight into the effect of palmitic acid on cell proliferation, inva-sion and the formation of lipid droplets that may have potential clinical relevance in the treatment of obesity-driven endometrial cancer

Bayesian nonlinear mixed effects models for data in the form of continuous, repeated measurements from a population, also known as Bayesian hierarchical nonlinear models, are a popular platform for analysis when interest focuses on individual specific characteristics and relevant uncertainty quantification. Due to the limitation of computational power, this framework was relatively dormant until the late 1980s, but in recent years, the statistical research community saw vigorous development of new methodological and computational techniques for these models, the emergence of software, and wide application of the models in numerous industrial and academic fields. This article presents an overview of the formulation, interpretation, and implementation of Bayesian nonlinear mixed effects models and surveys recent advances and applications.

One of the hallmarks of microgravity-induced effects in several cellular models is represented by the alteration of oxidative balance with the consequent accumulation of Reactive Oxygen Species (ROS). It is well known that male germ cells are sensitive to oxidative stress and to changes of gravitational force even if published data on germ cell models are scarce. To gain more insights into the mechanisms of male germ cell response to altered gravity, a 3D cell culture model has been established from TCam-2 cells, a seminoma-derived cell line considered the only human cell line available to study in vitro mitotically active human male germ cells. TCam-2 cell spheroids were cultured for 24 hours under unitary gravity (Ctr) or simulated microgravity (s-microgravity) conditions, these last ones were obtained using the Random Positioning Machine (RPM). A significant increase in intracellular ROS and mitochondria superoxide anion levels has been observed after RPM exposure. In line with these results a trend of protein and lipid oxidation increase, and increased pCAMKII expression levels were observed after RPM exposure. The ultrastructural analysis by Transmission Electron Microscopy revealed that RPM-exposed mitochondria appeared enlarged and, even if seldom, disrupted. Notably, even the expression of the main enzymes involved in the redox homeostasis appears modulated by RPM exposure in a compensatory way, being GPX1, NCF1, and CYBB downregulated, whereas NOX4 and HMOX1 upregulated. Interestingly, HMOX1 is involved in the heme catabolism of mitochondria cytochromes, and therefore the positive modulation of this marker can be associated to the observed mitochondria alteration. All together, these data demonstrate TCam-2 spheroid sensitivity to acute SM exposure and indicate the capability of these cells to trigger compensatory mechanisms that allow to overcome the exposure to altered gravitational force.

Although, promotion of urbanization culture in recent decades has made inevitable development of cities in the world, however, the development can be guided in a direction that leave, to the extent possible, minimum socioeconomic and environmental impacts. For this, it is required to first forecast auto-spreading orientation of cities and suburbs in rural areas over time and then avoid shapeless growth of cities. This paper is an attempt to develop a dynamic hybrid model based on logistic regression (LR), Markov chain (MC), and cellular automata (CA) for prediction of future urban sprawl in fast-growing cities. The model was developed using 12 widely-used urban development criteria, whose significant coefficient was determined by logistic regression, and validated by relative operating characteristic (ROC) analysis. The validated model was run in Guilan, a tourist province in northern Iran with a very high rate of urban development. For this, changes in the area of urban land use were detected over the period of 1989 to 2013 and then, future sprawl of the province was forecasted by the years 2025 and 2037. The analysis results revealed that the area of urban land use was increased by more than 1.7 % from 36012.5 ha in 1989 to 59754.8 ha in 2013, and the area of Caspian Hyrcanian forestland was reduced by 31628 ha. The results also predicted an alarming increase in the rate of urban development in the province by the years 2025 and 2037, during which urban land use is predicted to develop 0.9 % and 1.38 %, respectively. The development pattern is expected to be uneven and scattered, without following any particular direction. The development will occur close to the existing or newly-formed urban basements as well as around major roads and commercial areas. This development, if not controlled, will lead to the loss of 13863 ha of Hyrcanian forests and if the trend continues, 21013 ha of Hyrcanian forests and 20208 ha of Barren/open lands are expected to be destroyed by the year 2037. In general, the proposed model is an efficient tool for the support of urban planning decisions and facilitates the process of sustainable development of cities by providing decision-makers with an overview on future development of cities where the growth rate is very fast.

Human keratinocytes and melanoma can stick together to form clusters after eight days in co-culture. As in dynamic system concepts, one can consider cluster formation as the system attractor, cell seeding as the initial condition, and density change over time as a path within the basin of attraction. Herein, Cellular Automata, which is a class of Agent-Based Models, and Boolean Networks are discrete modeling methods used in population dynamics such that running the dynamics of cellular automata backward reveals an underlying network in terms of basin of attraction, also known as global dynamics. Thus, we hypothesize that one can estimate the local dynamic of an agent-based model from the basin of attraction of a boolean network. Here, we propose an approach to estimating these agent-based model rules, which consists of comparing the density states within each state transition and reaching a consensus among state transitions belonging to a basin of attraction of a boolean network. The objectives of this study are: (1) to infer a boolean network from the co-culture growth curve; (2) to estimate the rules of agent-based models; and (3) to implement spatial dynamics simulations. The binarization of the growth curve shows high population density after four days; the estimated agent-based model rules were compatible with cell proliferation and migration in agreement with literature, so we had to propose individual rules for survival and death. Spatial dynamics shows that (1) keratinocytes exhibit a higher density in neighborhoods where melanoma is present; (2) the chance of keratinocyte migration increases until the fourth day, then decreases, and the probability of survival increases substantially after four days; and (3) cells with low proliferation capacity die and free space for those with high ones. Our approach suggests that the attractor state of cell co-culture is induced mainly by an increase in keratinocyte migration and survival. Our approach has the potential to offer valuable clues about microenvironmental interactions or configurations that drive population dynamics.

Most studies on vaccines of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on antibody, but cellular immunities are also critical. We aimed to evaluate the immune reactions of hemodialysis (HD) patients after the administration of the booster dose from the perspective of both humoral and cellular immunities. Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (control group) receiving three doses of BNT162b2 vaccine were measured for anti-SARS-CoV-2 immunoglobulin (IgG) and T-SPOTⓇ.COVID test (T-SPOT) before, 3 weeks, and 3 months after the booster dose. The HD group had significantly higher SARS-CoV-2 IgG levels 3 weeks and 3 months after the booster dose than the control group, although both groups had no difference in SARS-CoV-2 IgG levels before the booster dose. Moreover, the HD group had significantly higher T-SPOT levels before and 3 weeks after the booster dose than the control group, but the difference was not significantly different 3 months after the booster dose. Furthermore, the incidence rates of local and systemic adverse reactions were significantly higher in the HD group than in the control group. HD patients obtained higher SARS-CoV-2 IgG levels and SARS-COV-2-specific T-cell responses after the booster dose than control.

We previously developed a highly sensitive and specific anti-PDPN mAb, LpMab-23 (mouse IgG1, kappa). In this study, we produced a humanized IgG1 version (humLpMab-23) and its defucosylated form (humLpMab-23-f) of an anti‑PDPN mAb to potentiate the ADCC activity. The humLpMab-23 could recognize PDPN‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/PDPN) and PDPN-positive PC-10 and LN319 cells by flow cytometry. Furthermore, we found that humLpMab-23-f exerted ADCC and complement-dependent cytotoxicity against CHO/PDPN, PC-10 and LN319 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that humLpMab-23-f could be useful for an antibody treatment regimen for PDPN-positive human cancers.

Cartilage degeneration is a characteristic of osteoarthritis (OA) which is often observed in aging populations. This degeneration is due to the breakdown of articular cartilage (AC) mechanical and tribological properties, primarily attributed to lubrication failure. Understanding the reasons behind these failures and identifying potential solutions could have significant economic and societal implications, ultimately enhancing the quality of life. This review provides an overview of developments in the field of AC, focusing on its mechanical and tribological properties. The emphasis is on the role of lubrication in degraded AC, offering insights into its structure and function relationship. Further it explores the fundamental connection between AC mechano-tribological properties and the advancement of its degradation and puts forth recommendations for strategies to boost its lubrication efficiency.

Chorioamnionitis (CA) at term of pregnancy can have infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (Intrauterine Inflammation, Infection or both, TI) has been proposed to reduce the overdiagnosis of infection and the neonatal overtreatment. The aim of the study is to identify clinical and histological variables predicting adverse outcomes when TI has been suspected and/or confirmed. This retrospective cohort study included 404 pregnancies ≥37 g.a. that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to NICHD definition of 2015 and it could be confirmed (TI+) or not (TI-) by histological examination. Signs of infection/inflammation not respecting the definition of TI were classified as “Clinical suspicion”, supported (CS+) or not (CS-) by histology. Histological chorioamnionitis (HCA) without clinical manifestation represented fifth group. Whole Placental Involvement (WPLI), was defined as a histological inflammation involving maternal and fetal side. There were 113 TI+, 30 TI-, 186 CS+, 35 CS- and 40 isolated HCA. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). TI+ compared to CS+ was more predictive of CNO (p=0.001), CMO (p<0.001) and WPLI (p=0.005). WPLI was related both to CNO (p<0.001) and CMO (p=0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p=0.001) and by WPLI (OR 2.23; p=0.001). TI, compared to CS, is a better predictor of CNO and can be useful for the identification of newborns at risk.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Cancer stem cells play a crucial role in tumor initiation, metastasis and therapy resistance. Cellular heterogeneity and plasticity challenge the isolation of cancer stem cells. The impact of intratumoral cellular heterogeneity in the context of treatment resistance using a label-free approach remains understudied. Here, we use the sedimentation field-flow fractionation technique to separate, without labeling, cell subpopulations of colorectal cancer cell lines and primary cultures according to their biophysical properties. One of the three cell subpopulations sorted by SdFFF exhibits cancer stem cell traits, including high tumorigenicity in vivo, and a higher frequency of tumor-initiating cells compared to the other subpopulations. In vitro two- and three-dimensional chemosensitivity assays emphasize the therapeutic relevance of this cancer stem cell-like subpopulation due to its chemoresistance. Therefore, our findings highlight a label-free cell sorting approach to reveal intratumoral cellular heterogeneity and its implication in therapy resistance. This approach enables the study of the individualized response of each sorted cell subpopulation by breaking down the tumor, thus offering new perspectives for personalized therapy.

Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed-refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything, considering only around 30% of patients show a response but with consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. This review first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. Next, recent single cell sequencing data for AML to assess somatically acquired alterations at the DNA, epigenetic, RNA and protein levels are discussed to give a perspective on cellular heterogeneity, intercellular hierarchies, and the cellular ecosystem. Finally, promising novel strategies are summarized, including more sophisticated next-generation CAR T, TCR-T and CAR-NK therapies; approaches to tailor the microenvironment and target neoantigens; and allogeneic approaches.

Does cell clustering influence intrinsic and acquired multi-drug resistance (MDR) differently? To address this question, we studied cultured monolayers (representing individual cells) and cultured spheroids (representing clusters) formed by drug-naïve (intrinsic MDR) and drug-exposed (acquired MDR) lines of ovarian cancer A2780 cells by cytometry of reaction rate constant (CRRC). MDR efflux was characterized by accurate and robust “cell number vs. MDR efflux rate constant (kMDR)” histograms. Both drug-naïve and drug-exposed monolayer cells presented unimodal histograms; the histogram of drug-exposed cells was shifted towards higher kMDR value suggesting greater MDR activity. Spheroids of drug-naïve cells presented a bimodal histogram indicating the presence of two subpopulations with different MDR activity. In contrast, spheroids of drug-exposed cells presented a unimodal histogram qualitatively similar to that of the monolayers of drug-exposed cells but with a moderate shift towards greater MDR activity. The observed greater effect of cell clustering on intrinsic than on acquired MDR can help guide the development of new therapeutic strategies targeting clusters of circulating tumor cells.

Abstract: (1) Background: Minimally-invasive sacroiliac joint (SIJ) fusion is the preferred surgical intervention to treat chronically severe pain associated with SIJ degeneration and dysfunction. (2) Methods: This paper details the ten-step surgical procedure associated with the postero-inferior approach using the PsiF™DNA Sacroiliac Joint Fusion System. (3) Results: The posterior surgical approach with an inferior operative trajectory (postero-inferior) utilizes easily identifiable landmarks to provide the safest, most direct access to the articular joint space for transfixing device placement. Implanting the device through the subchondral bone, provides maximum fixation and stabilization of the joint by utilizing an optimal amount of cortical bone-implant interface. Approaching the joint from the inferior trajectory also places the implant perpendicular to the S1 endplate at a “pivot point” near the sacral axis of rotation, which addresses the most significant motion of the joint. (4) Conclusions: Further observational data from real-world clinical use are encouraged to further validate this procedure as the surgical preference for minimally-invasive SIJ fusion.

Cellular agriculture is defined as the production of agricultural products from cell cultures rather than from whole plants or animals. With growing interest in cellular agriculture as a means to address the public health, environmental, and animal welfare challenges of animal agriculture, the concept of producing seafood from fish cell- and tissue-cultures is emerging as a means to address similar challenges with industrial aquaculture systems and marine capture. Cell-based seafood - as opposed to animal-based seafood - can combine developments in biomedical engineering with modern aquaculture techniques. Biomedical engineering developments such as closed-system bioreactor production of land animal cells create a basis for large scale production of marine animal cells. Aquaculture techniques such as genetic modification and closed system aquaculture have achieved marked gains in production that can pave the way for innovations in cell-based seafood production. Here, we present the current state of innovation relevant to the development of cell-based seafood across multiple species as well as specific opportunities and challenges that exist for advancing this science. The authors find that the physiological properties of fish cell- and tissue- culture may be uniquely suited to cultivation in vitro. These physiological properties, including hypoxia tolerance, high buffering capacity, and low-temperature growth conditions, make marine cell culture an attractive opportunity for scale production of cell-based seafood; perhaps even more so than mammalian and avian cell cultures for cell-based meats. This, coupled with the unique capabilities of crustacean tissue-friendly scaffolding such as chitosan, a common seafood waste product and mushroom derivative, presents great promise for cell-based seafood production via bioreactor cultivation. To become fully realized, cell-based seafood research will require more understanding of fish muscle culture and cultivation; more investigation into serum-free media formulations optimized for fish cell culture; and bioreactor designs tuned to the needs of fish cells for large scale production.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

Intra-abdominal pressure (IAP) elevation during capnoperitoneum can cause adverse cardiovascular and respiratory effects. This study aimed to determine if a sequentially increased IAP affects cardiovascular and respiratory variables in anesthetized dogs and evaluate the effects of constant rate infusion of dexmedetomidine (Dex) on cardiovascular and respiratory variables with increased IAP. Five dogs were anesthetized, instrumented, and the Veress needle was equipped to adjust the IAP using a carbonic anhydrase insufflator. Stabilization was conducted for 1 h, and physiological variables were measured in IAPs of 0, 5, 10, 15, and 20 mmHg and after desufflation. After the washout period, the dogs underwent similar procedures along with constant rate infusion of dexmedetomidine. Cardiovascular effects of increased IAP up to 20 mmHg were not significant in healthy beagle dogs and those administered with dexmedetomidine. In the control group, the arterial pressure slightly increased, but not statistically significant, at an IAP of 20 mmHg compared with that at baseline (mean arterial blood pressure, p = 0.399; systolic arterial blood pressure, p = 0.293; diastolic arterial blood pressure, p = 0.141). When comparing the control and dexmedetomidine groups, overall significant effects of dexmedetomidine were noted on heart rate, cardiac output, and systemic vascular resistance during the experiment. Respiratory effects were not affected by abdominal insufflation when compared between different IAPs and between the two groups. Overall, an increased IAP of until 20 mmHg did not significantly affect cardiovascular and respiratory variables in both control and dexmedetomidine groups. This study suggests that dexmedetomidine infusion administration is applicable in laparoscopic procedures in healthy dogs.

Deficient wound healing is frequently observed in patients diagnosed with diabetes, a clinical complication that compromises mobility and leads to limb amputation, decreasing patient autonomy and family lifestyle. Fibroblasts are crucial for secreting the extracellular matrix to pave the wound site for endothelial and keratinocyte regeneration. The biosynthetic pathways for collagen production are one of the main components of the extracellular matrix, as the crosslinking of extracellular collagen fibers is intimately related to fibroblast redox homeostasis. In this study, human dermic fibroblasts were cultured with 1 mM sodium selenite (inorganic) and 1 mM of two selenium amino acids (organic), Se-cysteine and Se-methionine. This concentration was compatible with long-term exposure necessary for extracellular matrix production and allowed us to examine the impact of these three compounds on the state and response of the thiol-based HyPer biosensor expressed in the cytoplasm. In addition, the abundance of extracellular matrix and ultrastructural properties were evaluated by Picrus Sirius red staining and scanning electronic microscopy, respectively. We also evaluated whether these selenium compounds effectively ameliorated the perturbations induced by culturing fibroblasts at high glucose levels (25 mM) regarding cytoplasmic redox, extracellular matrix, and glycation on collagen fibers. Our results indicate that cytoplasm protein oxidation was sensitive to selenium compound supplementation. Selenium amino acids increased the sensitivity to protein oxidation, and only Se-cysteine increased the disulfide bond reduction in fibroblasts maintained in high glucose. Despite the lack of effect of selenium compounds on the glu-cose-induced increase in matrix fiber thickness, we found that endothelial migration improved in the matrix generated by high glucose-cultured fibroblasts.

Understanding the evolutionary role of environmentally-induced phenotypic variation (i.e., environmental plasticity) is an important issue in developmental evolution. One of the major physiological responses to environmental changes is cellular stress, which is counteracted by a generic stress reaction that detoxifies the cell, refolds proteins, and repairs DNA damage. In this paper, we elaborate on a previous finding suggesting that the cell differentiation cascade of human decidual stromal cells, a cell type critical for embryo implantation and the maintenance of pregnancy, evolved from a cellular stress reaction. We hypothesize that the stress reaction in these cells was elicited ancestrally through the inflammation caused by embryo attachment and invasion. We describe a model, Stress-Induced Evolutionary Innovation (SIEI), whereby ancestral stress reactions and their corresponding pathways can be transformed into novel structural components of body plans, such as new cell types. After reviewing similarities and differences between SIEI and the “plasticity first hypothesis” (PFH) of evolution, we argue that SIEI is a distinct form of plasticity-based evolutionary change because it leads to the origin of novel structures rather than the adaptive transformation of a pre-existing character.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

Feline panleukopenia (FPL), a highly contagious and frequently fatal disease of cats, is caused by Feline parvovirus (FPV) and Canine parvovirus (CPV). We characterized the diversity of these Carnivore protoparvovirus 1 variants in 18 faecal samples collected from domestic cats with FPL during an outbreak, using targeted parvoviral DNA metagenomics to a mean depth of >10,000 X coverage per site. All samples comprised FPV alone. Compared to the reference FPV genome, isolated in 1967, 44 mutations were detected. Ten of these were non-synonymous, including 9 in non-structural genes and one in VP1/VP2 (Val232Ile), which was the only one to exhibit inter-host diversity, being present in five sequences. There were five other polymorphic nucleotide positions, all with synonymous mutations. Intra-host diversity at all polymorphic positions was low with sub-consensus variant frequencies (SVF) of >1% except for two positions (2108 and 3208) in two samples with SVF of 1.1 – 1.3%. Intra-host nucleotide diversity was measured across the whole genome (0.7 - 1.5%) and for each gene, and was highest in the NS2 gene of four samples (1.2 – 1.9%). Overall, intra-host viral genetic diversity was limited and most mutations observed were synonymous, indicative of a low background mutation rate and strong selective constraints.

The most important predictors for outcomes after ischemic stroke, that is, for health deterioration and death, are chronological age and stroke severity; gender, genetics and lifestyle / environmental factors also play a role. Of all these, only the latter can be influenced after the event, even though recurrent stroke may be prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, and treatment of cardiovascular risk factors. Moreover, blood cell composition and protein biomarkers such as C-reactive protein or interleukins in serum are frequently considered as biomarkers of outcome. We surveyed protein biomarkers that were reported to be predictive for outcome after ischemic stroke, specifically considering biomarkers that predict long-term outcome (≥3 months) and that are measured over the first days following the event. We classified the protein biomarkers as immune‑inflammatory, coagulation-related, and adhesion-related biomarkers. Some of these biomarkers are closely related to cellular senescence and, in particular, to the inflammatory processes that can be triggered by senescent cells. Moreover, the processes that underlie inflammation, hypercoagulation and cellular senescence connect stroke to cancer, and biomarkers of cancer-associated thromboembolism, as well as of sarcopenia, overlap strongly with the biomarkers discussed here. Finally, we demonstrate that most of the outcome-predicting protein biomarkers form a close-meshed functional interaction network, suggesting that the outcome after stroke is partially determined by an interplay of molecular processes relating to inflammation, coagulation, cell adhesion and cellular senescence.

Bacteria participate in a wide diversity of symbiotic associations with eukaryotic hosts that require precise interactions for bacterial recognition and persistence. Most commonly, host-associated bacteria interfere with host gene expression to modulate the immune response to the infection. However, many of these bacteria also interfere with host cellular differentiation pathways to create a hospitable niche, resulting in the formation of novel cell types, tissues, and organs. In both of these situations, bacterial symbionts must interact with eukaryotic regulatory pathways. Here, we detail what is known about how bacterial symbionts, from pathogens to mutualists, control host cellular differentiation across the central dogma, from epigenetic chromatin modifications, to transcription and mRNA processing, to translation and protein modifications. We identify four main trends from this survey. First, mechanisms for controlling host gene expression appear to evolve from symbionts co-opting cross-talk between host signalling pathways. Second, symbiont regulatory capacity is constrained by the processes that drive reductive genome evolution in host-associated bacteria. Third, the regulatory mechanisms symbionts exhibit correlate with the cost/benefit nature of the association. And, fourth symbiont mechanisms for interacting with host genetic regulatory elements are not bound by native bacterial capabilities. Using this knowledge, we explore how the ubiquitous intracellular Wolbachia symbiont of arthropods and nematodes may modulate host cellular differentiation to manipulate host reproduction. Our survey of the literature on how infection alters gene expression in Wolbachia and its hosts revealed that, despite their intermediate-sized genomes, different strains appear capable of a wide diversity of regulatory manipulations. Given this and Wolbachia’s diversity of phenotypes and eukaryotic-like proteins, we expect that many symbiont-induced host differentiation mechanisms will be discovered in this system.

Purpose: The aim of present study was to compare the treatment results of daily cisplatin (CDDP), weekly docetaxel (DOC) intra-arterial infusion chemotherapy combined with radiotherapy (DIACRT) regimen and weekly CDDP intra-arterial infusion chemotherapy combined with radiotherapy (WIACRT) for patients with tongue cancer. Materials and Methods: Between January 2007 and December 2016, a total of 11 patients treated with WIACRT and 45 patients treated with DIACRT were enrolled in present study. In DIACRT group, 25 patients had T2, 20 patients had T3. A total of 9 patients had T2 and 2 had T3 in WIACRT (p = NS). In DIACRT, the treatment schedule consisted of intra-arterial chemotherapy (DOC, total 60 mg/m²; CDDP, total 150 mg/m²) and daily concurrent radiotherapy (RT) (total, 60 Gy). In WIACRT, the treatment schedule consisted of intra-arterial chemotherapy (CDDP, total 360 mg/m²) and daily concurrent RT (total, 60 Gy). Results: The median follow-up periods for DIACRT and WIACRT were 61 and 66 months respectively. The 5-year local control (LC) and overall survival (OS) rate were 94.5% and 89.6% for DIACRT group, 60.6% and 63.6% for WIACRT group respectively. The LC rate and OS of DIACRT group were significantly higher than that of WIACRT group. As regards toxicities, no treatment-related deaths were observed during the follow-up periods both in two groups. Conclusions: DIACRT was found to be feasible and effective for patients with tongue cancer and could become a new treatment modality.

In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis.Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections.Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy.As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combatting viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

As technology and multimedia production have advanced, there has been a significant rise in attacks on digital media, resulting in duplicated, fraudulent, and altered data and the infringement of copyright laws. This paper presents a robust and secure digital image watermarking technique that has been implemented in the spatial domain and exploits the erratic and chaotic behaviour of the powerful elementary cellular automata rule-30. The crucial characteristics of the watermarking system, i.e., imperceptibility, capacity, and robustness, have been perfectly balanced by the suggested blind watermarking technique. In this approach, prior to embedding, the grayscale watermark image is downsized to its two Most Significant Bits (MSBs). Then, the 2-MSBs watermark is encrypted using an ECA rule-30 so as to level up the security attribute of the system. Then, the host image is scrambled using ECA rule-30 to distribute the watermark pixels throughout the host image and thus achieve the highest robustness against geometrical attacks. Finally, the encrypted watermark data is embedded into the scrambled host image using the ECA rule-30-based embedding key. The proposed method performs better in terms of imperceptibility, capacity, and robustness when compared to several systems with similar competencies. The simulation's findings demonstrate strong imperceptibility as evaluated by the Peak Signal-to-Noise Ratio (PSNR), which has an average value of 58.3735 dB and a high payload. The experimental outcomes, observed across a diverse range of standardized attack scenarios, unequivocally establish the ascendancy of the proposed algorithm over competing methodologies in the realm of image watermarking.

Foam concrete is a highly cellularized cementitious material that undergoes extensive plastic deformation when loaded to failure. Under compression, the foam structure gets progressively crushed at a steady stress stage such that a substantial amount of energy is dissipated. Understanding foam concrete crushing behavior is of special importance for its engineering applications such as energy absorber, but the current studies are insufficient to define material properties for design of field applications. This study characterizes the crushing strength and foam modulus of samples with penetration test and resonant frequency test, respectively. A four-phase crushing behavior is observed. The yield strength and plateau strength are identified to characterize the foam crushing. Using the experimental inputs, the modulus-strength constitutive equations are then established. These findings are useful for expanding the knowledge of normal concrete to studies on foam concrete, as well as design of applications.Foam concrete is a highly cellularized cementitious material that undergoes extensive plastic deformation when loaded to failure. Under compression, the foam structure gets progressively crushed at a steady stress stage such that a substantial amount of energy is dissipated. Understanding foam concrete crushing behavior is of special importance for its engineering applications such as energy absorber, but the current studies are insufficient to define material properties for design of field applications. This study characterizes the crushing strength and foam modulus of samples with penetration test and resonant frequency test, respectively. A four-phase crushing behavior is observed. The yield strength and plateau strength are identified to characterize the foam crushing. Using the experimental inputs, the modulus-strength constitutive equations are then established. These findings are useful for expanding the knowledge of normal concrete to studies on foam concrete, as well as design of applications.

Purpose: To evaluate seasonal variation in intra-ocular pressure (IOP) with and without short tear break-up time (SBUT, BUT ≤ 5 s). Methods: This study enrolled 176 patients who visited one of six eye clinics in Japan for IOP measurement at every season. The mean patient age was 67.9 years, including 79 males. We compared the seasonal variation in IOP (mean ± SD) across spring (Mar-May), summer (Jun-Aug), fall (Sep-Nov), and winter (Dec-Feb). Results: The IOP (mmHg) in winter and summer, respectively, was 12.8 ± 3.7 and 12.8 ± 3.1 for non-glaucoma patients without SBUT (n = 47, P = 0.964), 14.8 ± 3.4 and 13.3 ± 3.4 for non-glaucoma patients with SBUT (n = 57, P < 0.001), 14.3 ± 3.2 and 14.1 ± 3.4 for glaucoma patients without SBUT (n = 36, P = 0.489), and 13.3 ± 3.0 and 11.6 ± 2.9 for glaucoma with SBUT (n = 36, P < 0.001). Seasonal variation was largest across the seasons in the glaucoma with SBUT group, and the magnitude of seasonal variation correlated with BUT (β = 0.228, P = 0.003). Conclusions: Seasonal variation tended to be larger in patients with SBUT than those without SBUT.

Fluid flow in human body is generally known to influence a variety of cellular behaviors. Different nanoparticle properties as well as cell type, interaction with other cells and cellular environments also show significant effect on nanoparticle uptake and drug efficacy. The aim of this study was to evaluate the effect of shear stress on cellular behaviors of biocompatible and biodegradable nanoparticles to cancer cells (A549 cell lines) in a biomimetic microfluidic system. We prepared a gelatin-oleic conjugate (GOC) as an amphiphilic biomaterial to prepare self-assembled gelatin-oleic nanoparticles (GON). Coumarin-6 and paclitaxel were used as the fluorescence marker and model drug, respectively, and were loaded into GONs by incubation (C-GONs; PTX-GONs). Additionally, we evaluated the cellular uptake of fluorescence labeled C-GONs and the drug efficacy of PTX-GONs. The cellular uptake of C-GONs by A549 cells in the absence of shear stress revealed that the mean fluorescence intensity was slightly decreased compared to that in the presence of shear stress. The results also indicated that negatively charged PTX-GONs had a lower cancer killing effect under dynamic conditions than that under static conditions. It also suggested that fluidic shear stress did not significantly affect drug uptake and efficiency in case of PTX-GONs. The cellular interactions between nanoparticles and cells in drug delivery should be carefully examined according to the physicochemical properties of nanoparticles such as the type of materials, size and mainly surface charge in a biomimetic microfluidic condition.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

Background: Elevated fasting plasma glucose and visceral fat area (VFA) is highly prevalent in obese adults. This study investigated the associations between systemic arterial hypertension (SAH) and laboratory, anthropometric, heart rate variability (HRV), and obstructive sleep apnea markers. Methods: Cross-sectional study with 95 obese patients treated at Obesity Treatment and Surgery Center, located in Salvador, BA, Brazil. SAH data were obtained from electronic medical records of patients. To evaluate the association of SAH with the predictor variables, the sample was stratified in Normotense Group (NG) and Hypertensive Group (HG), and laboratory markers, body composition, polysomnography data, and HRV were measured. Results: The average age of the NG was 36.3 ± 10.1 and HG 40.4 ± 10.6 years, 73.7% were women in the NG and 57.9% in HG; 82.4% in HG had insulin resistance. In the multivarious logistics regression model with adjustments age, sex, height, and oxyhemoglobin saturation, SAH was inversely associated with fasting plasma glucose mg/dL (odds ratio [OR] = 0.96; 95% interval confidence [CI] = 0.92 - 0.99) and VFA cm² (OR = 0.98; 95% CI = 0.97 - 0.99). The area under curve the VFA was 0.728; CI 95% (0.620 - 0.836) and fasting plasma glucose 0.693; CI 95% (0.582 - 0.804). Conclusions: Lower VFA and fasting plasma glucose concentrations were inversely associated with SAH. These results indicate opportunities to improve the outcome in obese patients through counseling and clinical interventions.

Phagocytosis (and endocytosis) is an unusual cellular process which results in the formation of a novel subcellular organelle, the phagosome. This phagosome contains not only the internalised target of phagocytosis, but also the external medium, creating a new border between extracellular and intracellular environments. The boundary at the plasma membrane is, of course, tightly controlled and exploited in ionic cell signalling events. Although there has been much work on the control of phagocytosis by ions, notable Ca2+ ions influxing across the plasma membrane, increasing our understanding of the mechanism enormously, very little work has been done exploring the phagosome/cytosol boundary. In this paper, we have explored the changes in the intra-phagosomal Ca2+ ion content which occur during phagocytosis and phagosome formation in human neutrophils. Measuring Ca2+ ion concentration in the phagosome is potentially prone to artefacts as the intra-phagosomal environment experiences changes in pH and oxidation. However, by excluding such artefacts, we conclude that there are open Ca2+ channels on the phagosome, which allow Ca2+ ions to ‘drain’ into the surrounding cytosol. This conclusion was confirmed by monitoring the translocation of intracellularly expressed YFP-tagged C2 domain of PKC-γ. This approach marked regions of membrane at which Ca2+ influx occurred, the earliest being the phagocytic cup, and then the whole cell. This paper therefore presents data which has novel implications for understanding phagocytic Ca2+ signalling events, such as peri-phagosomal Ca2+ hotspots, and other phenomena.

Climate change is an issue that is the order of the day, and among the many consequences it has on the environment one is its influence on the amount and frequency of rainfall on our planet, since our water supply depends on them. Therefore, in order to quantify these effects, a rainfall analysis has been carried out using data collected in Bilbao over the last 150 years. Thanks to this, it has been possible to observe that, although the total annual amount seems to suffer a slight decrease, hardly quantifiable with certainty, it is true that the intra-annual patterns are more concentrated at certain times of the year, with greater imbalances between one month and another than in previous years. However, taking into account the capacity of the reservoirs that supply the Greater Bilbao area, it can be concluded that this does not pose any problem for Bilbao's supply, at least at present.

In this study, our goal was to research land-use change by combining spatio–temporal land use/land cover monitoring (LULC (1989–2019) and urban growth modeling (1999–2039) in Benslimane, Morocco, to determine the effect of urban growth on different groups based on cellular automata (CA) and geospatial methods. A further goal was to test the reliability of the AC algorithm for urban expansion modeling. To do this, four years of satellite data were used at the same time as population density, downtown distance, slope, and ground road distance. The LULC satellite reported a rise of 3.8 km2 (318% variation) during 1989–2019. Spatial transformation analysis reveals a good classification similarity ranging from 89% to 91% with the main component analysis (PCA) technique. The statistical accuracy between the satellite scale and the replicated built region of 2019 gave 97.23 %t of the confusion matrix overall accuracy, and the region under the receiver operational characteristics (ROC) curve to 0.94, suggesting the model's high accuracy. Although the constructed area remains low relative to the total area of the municipality's territory, the LULC project shows that the urban area will extend to 5,044 km2 in 2019, principally in the western and southwestern sections. In 2019–2039, urban development is expected to lead to a transformation of the other class (loss of 1,364 km2), followed by vegetation cover (loss of 0.345 km2). In spatial modeling and statistical calculations, the GDAL and NumPy Python 3.8 libraries were successful.

The significance of diversity, composition, and functional attributes of the gut microbiota is recognized in human health and disease. Studies have also shown that the gut microbiota is related to human aging, and a causal relationship between gut microflora dysbiosis and chronic age-related disorders is also becoming apparent. Further, emerging evidence indicates that age-associated changes in the gut microbiome are predictors of human survival and longevity. Recent advances in our understanding of the cellular and molecular aspects of biological aging have revealed a cellular senescence-centric view of the aging process. However, the association between gut microbiome and cellular senescence is only beginning to be understood. The present review provides an integrative view of the emerging relationship between the gut microbiome and cellular senescence in aging and disease. Evidence relating to microbiome-mediated modulation of senescent cells, as well as senescent cells-mediated changes in intestinal homeostasis have been discussed. Unanswered questions and future research directions have also been deliberated to truly ascertain the relationship of the gut microbiome and cellular senescence for developing microbiome-based age-delaying and longevity promoting therapies.

Silicon is an essential trace nutrient for plant growth and is frequently employed to remediate soils contaminated with heavy metals in agriculture. However, silicon’s role and mechanism in reducing heavy metal toxicity have not been well understood, especially for multi-heavy metals. In this study, the effects of silicon-rich materials (silicate, rice husk biochar (RHB), and bentonite) on growth trait, antioxidant response, and heavy metal accumulation and distribution of wheat grown in two soils polluted by multiple heavy metals (Cd, Zn, Pb, and As) were investigated. The results revealed that the addition of silicon-rich materials enhanced plant growth, improved the photosynthetic attributes in leaf tissues, and decreased the contents of Cd, Zn, Pb, and As in wheat shoots and grains. The examination of the subcellular distribution of heavy metals in plants implied that silicon-rich materials transferred heavy metals as intracellular soluble fractions to the cell walls, indicating the reduction of mobility and toxicity of heavy metals in the plants. In addition, the application of the silicon-rich materials reduced oxidative damage in plants by downregulating plant antioxidant response systems and decreasing the production of malondialdehyde (MDA), ascorbic acid (AsA), and glutathione (GSH). Moreover, fractionation analysis of soil heavy metals showed that silicon-rich amendments could convert bioavailable heavy metals into immobilized forms. The results indicated that silicon-rich materials could remediate multi-heavy metal-polluted soils and promote wheat production.

:Pulmonary fibrosis is a chronic and fatal lung disease that significantly impacts the aging population globally. To date, anti-fibrotic, immunosuppressive, and other adjunct therapy demonstrate a limited efficacy. Advancing our understanding of pathogenic mechanisms of lung fibrosis provides a future path for the cure. Cellular senescence has gained substantial interest in the past decades due to the increased incidence of fibroproliferative lung diseases in the older age group. Furthermore, the pathologic state of cellular senescence that includes maladaptive tissue repair, decreased regeneration, and chronic inflammation resembles key features of progressive lung fibrosis. This review describes regulatory pathways of cellular senescence and discusses the current knowledge on the senescence of critical cellular players of lung fibrosis, including epithelial cells (alveolar type 2 cells, basal cells, etc.), fibroblasts, and immune cells, their phenotypic changes, and the cellular and molecular mechanisms by which these cells contribute to the pathogenesis of pulmonary fibrosis. A few challenges in the field include establishing appropriate in vivo experimental models and identifying senescence targeted signaling molecules and specific therapy to target senescent cells, known collectively as "senolytic" or “senotherapeutic” agents.

Neuromonitoring of the efferent nerve impulses transmission in the spinal cord tracts during surgical scoliosis treatment makes it possible to assess whether the functional status is deteriorating, affecting the procedure's safety. Is there any relationship between pre- and intraoperative motor evoked potentials recordings and does idiopathic scoliosis (IS) surgical correction improve directly the spinal efferent transmission? This study aimed to compare the results of surface recorded electromyography (EMG), electroneurography (ENG, M and F-waves), and especially motor evoked potentials (MEP) from tibialis anterior (TA) muscle bilaterally in 353 girls with the right idiopathic scoliosis (types 1A-4C according to Lenke classification). It has not yet been documented whether the results of MEPs recordings induced by transcranial single magnetic stimulus (TMS, pre – and postoperatively) and trains of electrical stimuli (TES; intraoperatively in T0-before surgery, T1 – after pedicle screws implantation, T2 – after scoliosis curvature distraction and derotation following two rods implantation) can be compared for diagnostic verification of improvement of the spinal neural transmission. The study also attempted to determine whether the constant level of optimal anesthesia during the certain surgical steps of scoliosis treatment affects the parameters of MEPs recorded during neuromonitoring procedures. No neurological deficits have been observed postoperatively. Values of amplitudes but not latencies in MEPs recordings evoked with TMS in IS patients compared before and after surgery indicated a slight improvement in the efferent transmission of neural impulses within the fibers of the spinal tracts postoperatively. Results of all neurophysiological studies in IS patients were significantly asymmetrical and recorded worse on the concave side, suggesting greater neurological motor deficits at p=0.04. This asymmetry had been significantly reduced following IS surgery. The surgeries in IS patients brought significant improvement (p=0.04) in parameters of amplitudes of sEMG recordings, however reflecting still the consequences of the neurogenic injury of TA muscle motor units. ENG studies results indicated the symptoms of the axonal type injury in peroneal motor fibers improved only on the concave side at p=0.04 in parallel with the significant improvement of F-waves parameters, which suggests that surgeries might result in the lumbar ventral roots decompression. There were not detected significant differences in amplitudes or latencies of MEPs induced with TMS or TES comparing the parameters recorded preoperatively (one day before surgery) and intraoperatively in T0. The amplitudes of TES evoked MEPs increased gradually at p=0.04 in the subsequent periods (T1 and T2) of observation. The significant reduction of MEPs latency at p=0.05 was observed only at the end of the IS surgery. Studies on the possible connections between the level of anesthesia fluctuations and the required TMS stimulus strength, as well as the MEPs amplitude changes measured in T0-T2 revealed lack of relationships. It is not likely that they could be the factors influencing the efferent transmission in spinal pathways beside the surgical procedures. Considering that MEPs amplitude parameter reflects the number of axons excited from the motor cortex and transmitting the efferent impulses via spinal descending tracts in the white matter, pre- (TMS evoked) and intraoperative (TES evoked) recordings are reliable for evaluating the patient’s neurological status before and during surgical scoliosis correction procedures. The results of this study indicate an agreement between preoperative and early-intraoperative evaluations with these both diagnostic methods. An increase of MEPs amplitude parameters recorded on both sides after scoliosis surgery proves immediate improvement of the total efferent spinal cord transmission. Considering comparative pre- and postoperative sEMG and ENG recordings it can be concluded that surgeries might directly result in the additional lumbar ventral roots decompression. Our results of the tests on the possible variability of the anesthesia level on the parameters of intraoperative recorded MEPs show no clear relationships. We can conclude that MEPs parameters changes are determined by the surgery procedures during neuromonitoring, not the anesthesia conditions if they are kept stable, which influences a decrease in the number of false-positive neuromonitoring warnings. Further studies on a larger population of patients with long-lasting observation postoperatively are required to confirm the presented conclusions on the direct influences of scoliosis surgery on improvement of the motor function in patients with IS.

Foam concrete is a construction material with controllable low strength and untraditional physical properties. Its highly crushable nature leaves it a niche as an engineered energy-absorbing material in many value-added applications; however, fundamental understanding of the material properties is crucial. As foam concrete is highly cellularized and ductile, conventional concrete testing methods such as compression test are insufficient to characterize the key material attributes of foam concrete, especially when the foam density is low. The resonant frequency test (ASTM C215) is specified for evaluating dynamic Young’s modulus of normal concrete. Inspired by the non-destructive feature of this test, we investigate the possibility of using the resonant frequency test to continuously monitor the modulus build-up of foam concrete with age. For the representativeness of the samples, three variables are considered in material design—bulk density ranging from 0.4 to 1.2 g/cm3, water to cementitious materials ratio of 0.42 and 0.47, and fly ash replacement of 10 and 30% by weight of cement. After examining the different vibration modes, the fundamental transverse frequency is determined most suitable for interpreting the foam modulus. The experimental results demonstrate good accuracy of using this approach for the measurement of different samples. It is also confirmed that, for a given foam concrete, the foam modulus can be predicted by knowing the foam density and solid modulus of its base cement paste, which provides an important insight for the further studies and real applications of foam concrete.

Repetitive nature of the ribosomal DNA (rDNA) gene makes the sequencing of hundreds copies of mammalian 45S rDNA (about 45-kb per copy) extremely difficult and its assembly is often excluded. Increasing evidence shows that 45S rDNA variations (copy number or single nucleotide), structural ribosomal RNA (rRNA) transcript variants, and non-structural rRNA transcripts (sense and anti-sense long noncoding rRNAs that include promoter rRNAs, and rRNA-derived fragments) play essential roles in mammalian development and diseases. Complete pictures of the hundreds copies of 45S rDNA and their rRNA transcripts require further innovation in sequencing techniques that include bioinformatics. The advancements in mammalian rDNA and rRNA sequencings and the discoveries of novel functions of the rDNA variants and rRNA transcripts are discussed here.

The field of human microbiome and gut microbial diversity research has witnessed a profound transformation, driven by advances in omics technologies. These advancements have unveiled essential connections between microbiome alterations and severe conditions, spurring the development of new frameworks through epidemiological studies. Traditionally, each individual was thought to harbor unique microbial communities acquired early in life, but recent research challenges this belief. The neonatal microbiome's onset, influenced by factors like delivery mode and maternal health, remains a subject of intense debate, hinting at potential intrauterine microbial processes. In-depth research reveals associations between microbiome profiles and specific health outcomes, ranging from obesity to neurodevelopmental disorders. Understanding these diverse microbiome profiles is essential for unraveling the intricate relationships between the microbiome and health outcomes.

Rainfall is a major climate parameter whose variation in space and time influences activities in different weather sensitive sectors such as agriculture, transport, and energy among others. Therefore, accurately forecasting rainfall is of paramount importance to the development of these sectors. In this regard, this study sought to contribute to quantitative forecasting of rainfall over Eastern Uganda through assessing the Weather Research and Forecasting model’s ability to simulate the intra–seasonal characteristics of the September to December rain season. These were: onset and cessation dates; wet days and lengths of the wet spells. The data used in the study included daily ground rainfall observations and lateral and boundary conditions data from the National Centers for Environmental Prediction (NCEP) final analysis at 1 0 horizontal resolution and at a temporal resolution of 6 hours for the entire study period were used to initialize the Weather Research and Forecasting (WRF) model. The study considered four weather synoptic weather stations namely; Jinja, Serere, Soroti and Tororo. The results show that the WRF model generally simulated fewer wet days at each station except for Tororo. Also, the WRF model simulated earlier onset and cessation dates of the rainfall season and overestimated the length of the wet spells.

Abstract: The purpose of this review is to summarize recent knowledge on the main processes that occur during wound healing, including the responses of various cell types and the molecular mechanisms involved. Particular attention is also dedicated to new therapies often involved in the resolution of wounds, whether acute or chronic. Awareness of these dynamics is important for the various professional figures who are confronted with these kinds of problem daily. However, the study of the healing mechanisms has yet to be defined in detail, in fact there are alterations of variously coordinated events which lead to a delayed resolution or, as in the case of keloids, to pathological states consisting in the excessive formation of scars with consequences yet to be seen. to define. Therefore, it is necessary to know the most feasible approaches and the most effective therapies.

Gliomas are one of the most aggressive and treatment-resistant types of human cancer. One of the most promising field in gliomas cancer therapy is identification and evaluation of anticancer properties of compounds found in plants i.a. naringenin (N) and 8-prenylnaringenin (8PN). The prenyl group seem to be crucial to the anticancer activity of flavones, which may lead to enhanced cell membrane targeting and thus increased intracellular activity. Unfortunately, 8PN content in hop cones is from 10 to 100 times lower compared to other flavonoids i.e. xanthohumol. In this study we used a simple method for the synthesis of 8PN from isoxanthohumol, via O-demethylation with high, 97% of the isolated yield. Cellular accumulation and cytotoxicity of naringenin and 8-prenylnaringenin in normal (BJ) and cancer cells (U-118 MG) were also examined. Obtained data indicated that 8-prenylnaringenin exhibited higher toxicity against used cell lines than naringenin and both flavones inhibited stronger glioblastoma U-118 MG cells than normal fibroblasts. The anticancer properties of 8PN correlated with its significantly greater (37%), accumulation in glioblastoma cells than in normal fibroblasts. Additionally, naringenin indicated higher selectivity for glioblastoma as it was over 6 times more toxic for cancer than normal cells. Our results provide evidence that examined prenylated and non-prenylated flavanones have different biological activity against normal and cancer cell lines and this phenomenon may be useful in clinical practice to construct new, anticancer drugs for glioblastoma.

The accurate virus detection, strain discrimination, and source attribution of contaminated food items remains a persistent challenge because of the high mutation rates anticipated to occur in foodborne RNA viruses, such as Hepatitis A virus (HAV). This has led to predictions of the existence of more than one sequence variant between the hosts (inter-host) or within an individual host (intra-host). However, there have been no reports of intra-host variants from an infected single individual, and little is known about the accuracy of the single nucleotide variations (SNVs) calling with various methods. In this study, the presence and identity of viral SNVs, either between HAV clinical specimens or among a series of samples derived from HAV clone1-infected FRhK4 cells, were determined following analyses of nucleotide sequences generated using next-generation sequencing (NGS) and pyrosequencing methods. The results demonstrate the co-existence of inter- and intra-host variants both in the clinical specimens and the cultured samples. The discovery and confirmation of multi-viral RNAs in an infected individual is dependent on the strain discrimination at the SNV level, and critical for successful outbreak traceback and source attribution investigations. The detection of SNVs in a time series of HAV infected FRhK4 cells improved our understanding on the mutation dynamics determined probably by different selective pressures. Additionally, it demonstrated that NGS could potentially provide a valuable investigative approach toward SNV detection and identification for other RNA viruses.

We hypothesise that anti-inflammatory macrolides can alleviate both the NLRP3 inflammasome activation and accelerated senescence in alveolar macrophages in COPD and/or response to cigarette smoke. Lung tissues from COPD patients and mice chronically exposed to cigarette smoke, cultures of human primary alveolar macrophages and macrophages derived from blood (MDM) or THP-1 monocytes were analysed for markers of macrophage NLRP3 inflammasome activation and accelerated senescence using multifluorescence quantitative confocal microscopy, Western blot, flow cytometry and histochemistry. Cultured macrophages were stimulated with 10% cigarette smoke extract (CSE), with or without presence of non-antibiotic macrolides 2'-desoxy-9-(S)-erythromycylamine and azithromycin-based 2'-desoxy molecule. Cigarette smoke and CSE induced in macrophages significant (p

Metastasis is a systemic condition and the major challenge among cancer types, as it can lead to multiorgan vulnerability. Recently, attention has been drawn to cellular senescence, a complex stress response condition, as a factor implicated in metastatic dissemination and outgrowth. Here, we examine the current knowledge of the features required for cells to invade and colonize secondary organs and how senescent cells can contribute to this process. First, we described the role of senescence in placentation, itself an invasive process which has been linked to higher rates of invasive cancers. Second, we describe how senescent cells can contribute to metastatic dissemination and colonization. Third, we discuss several metabolic adaptations by which senescent cells could promote cancer survival along the metastatic journey. In conclusion, we posit that targeting cellular senescence may have a potential therapeutic efficacy to limit metastasis formation.

The ultrasound guided viscosupplementation of the hip joint with hyaluronic acid(HA)is considered a standard procedure among the conservative treatments for hip arthritis.The aim of the study was to evaluate the clinical benefit and the incidence of adverse events of the technique in a obseravtional study at one year follow up. We evaluated a consecutive series of 85 patients with a diagnosis of symptomatic arthritis that performed intra-articular ultrasound-guided hyaluronic acid injections. The scales used for evaluation were modified Harris Hip Score(mHHS),WOMAC (Western Ontario and McMaster University),Hip Outcome Score (HOOS) with subscale Sport (HOOSs), for pain the Visual Analogic Scale (VAS).The patients were classified according to Tonnis’ radiological classification of arthrosis (range 0-3):20 patients(grade 0),32(grade 1),18(grade 2),15(grade 3).At last follow up all the scales increased:mHHS from 59.35 to 82.1,HOOS from 69.45 to 78.53,HOS Sport from 47.4 to 58.11,VAS from 6.09 to 3.97,WOMAC from 33.2 to 31.5 (p<0.05 for all the parameters);13/85 requested arthroplasty. Based on our findings, indication for use of hyaluronic acid is limited to patients with mild to moderate arthritis.Patients in advanced arthritis refusing replacement surgery and asking for this treatment should be informed about the poor results of the technique even in the short term follow up.

The polymerase chain reaction (PCR) is a widely used technique in the biosciences and has become increasingly popular in recent years. One of the key elements of this technique is the use of a DNA polymerase that is heat-stable and retains fidelity during the process. To this end, archaeal Fam-ily-B DNA polymerases are preferred due to their high thermostability and fidelity. In particular, the DNA polymerase from Thermus aquaticus (Taq DNApol) is widely utilized in PCR procedures. In this work, a novel in-silico structure-based methodology was employed to examine the most heat-tolerant DNA polymerase available. In spite of this, Thermococcus kodakarensis and Geobacillus stearothermophilus DNApol are more stable and heat-tolerant DNApols due to their high number of intra-protein interactions. Variations in the content of polar amino acids also played a significant role in the increase in heat stability. A further factor contributing to the stability of proteins is the stabilization of helix in secondary structure through the use of charged amino acids. DNApol from these organisms has been shown to be suitable for use in PCR, as well as in other biological processes able to withstand high temperatures. In this study, it has been demonstrated that im-provements in PCR performance can be easily obtained by blending elements from closely related archaeal polymerases, a strategy that may, in the future, be extended to other archaeal polymer-ases. This approach allowed for a comprehensive analysis of the enzyme's thermal stability and fidelity, leading to an improved understanding of the polymerase's properties and potential ap-plications

The interpretation of the local microenvironment of extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (PLLA and PCL) and collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter of (Nuclear/Cytoplasm) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity (IC₅₀) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

We explores the relational, dynamic elements of Complex Buildings, a type of architecture designed to incubate uses, located in urban areas with high housing density. The uses of Complex Buildings concern different elements, including the network of agents using or managing them, the environment, and the activities and functions that take place occasionally, temporarily or permanently. Data was gathered through ethnographic research lasting 6 months and a chronotopian approach was used to describe time and space. We analyzed and discussed the interaction of the elements of Complex Buildings through a cellular automaton model, a computational method that simulates the growth of complex systems. It was used here to generate patterns that suggest configurations of uses that can optimize management and therefore increase economic and social capital. The cellular automaton model was also used to develop an abstraction of the Centquatre, a public cultural center in Paris. This center is a good example of a Complex Building, being based on a public-private partnership and having an architectural configuration designed to host a wide range of art, social and productive activities. The building includes a large central space used as an urban public area open to different types of people. The importance of this case study lies in its capacity to produce economic value by combining different uses, and also by welcoming different people to the public space. Regarding the building as a living organism, the cellular automaton model reveals the determinant nature of the concepts of configuration, compatibility of uses and economic value generated by the presence of people. We argue that this approach makes it possible to show that the space-time design and public space dimensions are determinant factors in Complex Buildings.

Abstract: Interrupted-sampling repeater jamming (ISRJ) is a kind of intra-pulse coherent decep-tion jamming that can generate false target peaks in the range profile and interfere with the de-tection and tracking of real targets. In this paper, an anti-ISRJ method based on the intra-pulse orthogonal waveform is proposed, which can recognize common interference signals by com-paring sub-signal matched filtering results. For some special scenes where real targets cannot be directly differentiated from false targets, a new recognition method based on the energy discon-tinuity of the interference signal in the time domain is proposed in this paper. The method pro-posed in this paper can recognize real and false targets in all ISRJ modes without any prior in-formation, such as jammer parameters, with a small amount of calculation, which is suitable for actual radar systems. Simulation experiments using different interference parameters show that although this method has a 3dB loss of pulse compression gain, it can completely suppress dif-ferent kinds of ISRJ interference when the SNR before pulse compression is higher than -20dB, with 100 % target detection probability.

Cancer is one of the leading causes of death and morbidity with a complex pathophysiology. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Nanoparticles (1-100nm) can be used in the treatment of cancer owing to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. Nanoparticles are classified into several main categories. The nanoparticle drug delivery system is particular and utilizes tumor and tumor environment characteristics. Nanoparticles not only solve the limitations of conventional cancer treatment but also overcome multidrug resistance. Additionally, as new multidrug resistance mechanisms are unraveled and studied, nanoparticles are being investigated more vigorously. Various therapeutic implications of nano-formulations have created brand new perspectives for cancer treatment. However, a majority of the research is limited to in vivo and in vitro studies, and the number of nano-drugs that are approved has not much amplified over the years. In this review, we discuss numerous types of nanoparticles, targeting mechanisms along with approved nanotherapeutics for oncological implications in cancer treatment. Further, we also summarize the current perspective, advantages, and challenges in clinical translation.

(1) Background: The purpose of this study is to evaluate the full arch scan accuracy (precision and trueness) of nine digital intra-oral scanners and four lab scanners. Previous studies have compared the accuracy of some intra-oral scanners, but as this is a field of quickly developing technologies, a more up-to-date study was needed to assess the capabilities of currently available models.; (2) Methods: The present in vitro study compared nine different intraoral scanners (Omnicam 4.6; Omnicam 5.1; Primescan; CS 3600; Trios 3; Trios 4; Runyes; i500 and DL206) as well as four lab light scanners (Einscan SE; 300e; E2 and Ineos X5) to investigate the accuracy of each scanner by examining the overall trueness and precision. Ten aligned and cut scans from each of the intra-oral and lab scanners in the in vitro study were brought into CloudCompare. A comparison was made with the master STL using the CloudCompare 3D analysis best-fit algorithm. The results were recorded along with individual standard deviation and a colorimetric map of the deviation across the surface of the STL mesh; a comparison was made to the master STL, quantified at specific points. ; (3) Results: In the present study, the Primescan had the best overall trueness (17.3 ± 4.9). Followed by (in order of increasing deviation) the Trios 4 (20.8 ± 6.2), i500 (25.2 ± 7.3), CS3600 (26.9 ± 15.9), Trios 3 (27.7 ± 6.8), Runyes (47.2 ± 5.4), Omnicam 5.1 (55.1 ± 9.5), Omnicam 4.6 (57.5 ± 3.2) and Launca DL206 (58.5 ± 22.0). Regarding the lab light scanners, the Ineos X5 had the best overall trueness with (0.0 ± 1.9). Followed by (in order of increasing deviation) the 3Shape E2 (3.6 ± 2.2), Up3D 300E (12.8 ± 2.7), and Einscan SE (14.9 ± 9.5); (4) Conclusions: This study confirms that all current generations of intra-oral digital scanners can capture a reliable, reproducible full arch scan in dentate patients. Out of the intra-oral scanners tested, no scanner produced results significantly similar in trueness to the Ineos X5. However, the Primescan was the only one to be statistically of a similar level of trueness to the 3Shape E2 lab scanner. All scanners in the study had mean trueness of under 60-micron deviation. While this study can compare the scanning accuracy of this sample in a dentate arch, the scanning of a fully edentulous arch is more challenging. The accuracy of these scanners in edentulous cases should be examined in further studies.

Facial expression recognition is crucial for understanding human emotions and nonverbal communication. With the growing prevalence of facial recognition technology and its various applications, accurate and efficient facial expression recognition has become a significant research area. However, most previous methods have focused on designing unique deep-learning architectures while overlooking the loss function. This study presents a new loss function that allows simultaneous consideration of inter- and intra-class variations to be applied to CNN architecture for facial expression recognition. More concretely, this loss function reduces the intra-class variations by minimizing the distances between the deep features and their corresponding class centers. It also increases the inter-class variations by maximizing the distances between deep features and their non-corresponding class centers, and the distances between different class centers. Numerical results from several benchmark facial expression databases, such as Cohn-Kanade Plus, Oulu-Casia, MMI, and FER2013, are provided to prove the capability of the proposed loss function compared with existing ones.

During the COVID-19 pandemic, immunosuppressed patients showed prolonged SARS-CoV-2 infections, with several studies reporting the accumulation of mutations in the viral genome. The weakened immune system present in these individuals, along with the effect of antiviral thera-pies, are thought to create a favourable environment for intra-host viral evolution and have been linked to the emergence of new viral variants, which strongly challenged the containment measures and some therapeutic treatments. To assess whether an impaired immunity could lead to an increased instability of viral genomes, longitudinal nasopharyngeal swabs were collected from eight immunocompromised patients and fourteen non-immunocompromised subjects, all undergoing SARS-CoV-2 infection. Intra-host viral evolution was compared between the two groups through deep sequencing, exploiting a probe-based enrichment method to minimize the possibility of artefactual mutations commonly generated in amplicon-based methods, which heavily rely on PCR amplification. Although, as expected, immunocompromised patients expe-rienced significantly longer infections, the acquisition of novel intra-host viral mutations was similar between the two groups. Moreover, a thorough analysis of viral quasispecies showed that the variability of viral populations in the two groups is comparable not only at the consensus level, but also when considering low frequency mutations. This study suggests that a compro-mised immune system alone does not affect SARS-CoV-2 within-host genomic variability.

Autologous micrografting technology (AMT®) involves the use of autologous micrografts to stimulate/enhance the repair of damaged tissue. This study assessed the efficacy and safety of the AMT® procedure in patients with early stages of knee osteoarthritis. Briefly, the AMT® procedure involved extraction of auricular cartilage, disaggregation using the Rigeneracons® SRT in 4.0 mL of saline solution and injection of the disaggregated micrografts into the external femorotibial compartment area of the affected knee. Ten patients (4 men, 6 women; age range: 37─84 years) were included in the study. In all patients, there was a steady improvement in knee instability, pain, swelling, mechanical locking, stair climbing and squatting at 1- and 6-months post-procedure. Improvement in mobility was observed as early as 3 weeks post-procedure in 2 patients. Significant improvements were seen in mean scores of all five subscales of Knee Injury and Osteoarthritis Outcome Score (KOOS [KOOS symptoms, KOOS pain, KOOS ADL, KOOS sport and recreation, and KOOS quality-of-life]) between pre-procedure and 1- and 6-months post-procedure (all p≤0.05). Autologous auricular cartilage micrografts obtained by AMT® procedure (using Rigenera® technology) is an effective and safe protocol in the treatment of early-stage knee osteoarthritis. These encouraging findings need to be validated in a larger patient population.

The free energy principle (FEP) is a mathematical and scientific principle that describes the relationship between the physical behavior of a dynamical system and the interpretation of such behavior as carrying out inference. It blurs the boundary between the ontological mode of the system of interest and the epistemological significance it acquires through its dynamic interaction with the environment. New materialism (or neo-materialism), despite lacking a single definition, refers to a range of emerging perspectives that attempt to dismantle the long-held divisions between ontology, epistemology, and even ethics, with the aim of achieving a comprehensive transformation of naturalized thinking. In this context, new materialism provides powerful tools to reframe some of the conceptual foundations of the FEP. This paper is the first in a series that aims to systematically construct a neo-materialistic perspective for the FEP, exploring its wide-ranging implications. It serves as an introduction to the series, arguing for the justification of deploying new materialism to reframe the FEP and introducing some essential concepts to be utilized in developing a neo-materialistic account of the FEP.

Cluster-based routing in Mobile Ad-Hoc Networks is considered one of the convenient methods of routing. The existence of Cluster Head (CH) in a group of nodes for data forwarding improves the performance of routing in terms of routing overhead and power consumption. In this paper, a clustering algorithm using hierarchical routing for mobile ad hoc networks is proposed. In the proposed method, first, clusters are formed by the FLOC clustering method with low overlapping. Then, according to the most important network criteria, including hop count, noise ratio, distance, remaining energy, and link expiration time, head clusters are selected based on the weighting algorithm. To transfer data in the proposed method, two types of communication are used, e.g., inter-cluster communication and intra-cluster communication in which the shortest path to the target cluster is selected. The proposed P-METHOD technique is based on hierarchy and clustering as well as using a weighted algorithm that reduces delay in data transmission on the network. Moreover, P-METHOD is evaluated here via extensive simulations carried out in NS-2. The simulation results indicate that the MANET network performance metrics are improved in terms of average throughput, Packet Delivery Ratio (PDR), delay, residual energy, and lifetime.

OVOL proteins (OVOL1 and OVOL2), vertebrate homologs of Drosophila OVO, are critical regulators of epithelial lineage determination and differentiation during embryonic development in tissues such as kidney, skin, mammary epithelia, testis. OVOL inhibits EMT and can promote MET; moreover, they can regulate the stemness of cancer cells, thus playing an important role during cancer cell metastasis. Due to their central role in differentiation and maintenance of epithelial lineage, OVOL overexpression has been shown to be capable of reprogramming fibroblasts to epithelial cells. Here, we review the roles of OVOL mediated epithelial differentiation across multiple contexts – embryonic development, cancer progression, and cellular reprogramming.

The subject of the research are materials formed as a result of hydrothermal treatment, in this case cellular concretes, both traditional and modified with plastics (HIPS). There are two types of materials resulting from hydrothermal treatment: autoclaved sand-lime bricks and autoclaved concrete. Both in the case of ABK and silicates, the basic stubstrates used during their production are: lime, sand and water (cement is also added to cellular concrete). The article presents the methodology of testing the porous structure of autoclaved materials with the use of computed tomography. Aerated concrete (light autoclaved concrete) has a compressive strength of 2-6 MPa. The tests included aerated concrete modified with high-impact polystyrene, commonly known as HIPS. HIPS high-impact polystyrene is a thermoplastic polymer that is obtained by block-suspension polymerization of styrene with the addition of synthetic rubber. As a result of polymerization, small particles of polybutadiene remain in the polystyrene male, changing its physical and mechanical properties. The results from the content of air voids in the autoclaved concrete sample with HIPS were on average: 52.53%.

Our target point within this following steps, is prostate cancer. Phosphatases are implicated in differents cell alterations, including proliferation, differentiation and carcinogenesis. In specific life circumstances, proteins are regulators with implications in intracellular signaling pathways. Alterations in phosphatases functionality represent a key point in malignancy development. We try within our description, to focus on an important process refering to dysregulation of phosphatase activity. More than, we will discuss therapeutic key points refering to compounds that inhibits phosphatase proteins with implications in carcinogenesis. So finally after folowing describtion steps, purposed aim is to conclude on prostate cancer and different key points abordation.

Blood-derived products (BP) like citrate-platelet-rich plasma (CPRP) or hyperacute serum (HAS) are known to contain many growth factors. Combined mitogenic and DNA damaging stimuli might lead to increased senescent cell burden and altered senescence-associated secretory pheno-type (SASP). Therefore, the senescent state was extensively tested by γH2AX staining, p21 Q-PCR and western blot, growth curves and senescence associated ß-galactosidase staining. Two main treatments with BP were performed early (immediately after etoposide) and late (after addition-al 11days). Effects of the BP treatment was evaluated by IL-6 and IL-8 measurement as well as collagen (COL1) and p21 mRNA expression. Additionally, XTT assays, cell size measurements, viability assays, and cell number calculations were performed. HAS treated cells in early treat-ment had the lowest observed IL-6 and IL-8. In contrast, there was a clear inflammatory response for IL-8 on HAS and CPRP treated cells in late treatment. For COL1 expression an upregulation in early treatment could be shown, meanwhile cells in the late treatment group remained unaf-fected. In CPRP treated cells, the COL1 expression decreased. All in all, BP treatment seems to have slightly positive effects regarding skin rejuvenation.

All fundamental Planck scale symmetries are restored on a global level when a new charge is postulated in a finite, closed, Euclidean discrete space. Gravity emerges as a residual effect of the electromagnetic force in this scenario, resulting in a deterministic toy universe driven by a single input parameter. The model is developed using a constructive approach. Randomness is identified using a Chaintin argument. Aleph0 definite value is tied to the size of the universe. This is not an interpretation of Quantum Mechanics, but a deeper attempt to describe nature.

All fundamental Planck scale symmetries are restored on a global level when a new charge is postulated in a finite, closed, Euclidean discrete space. Gravity emerges as a residual effect of the electromagnetic force in this scenario, resulting in a deterministic toy universe driven by a single input parameter. Randomness is identified using a Chaintin argument. Aleph0 definite value is tied to the size of the universe. This is not an interpretation of Quantum Mechanics, but a deeper attempt to describe nature.

This paper shows that the percolation clusters from elementary cellular automata {30, 45, 60, 86, 99, 105, 129, 150, 153, 169, 182, 183, 184, 195 and 225 exhibit strong power law behavior, either under random initial conditions, a single occupied cell, or both. Most of the tail exponents are less than unity, implying diverging means and variances of cluster sizes. The analysis presented here is admittedly coarse in an effort to expedite its dissemination.

The disproportionate incidences of COVID-19-related hospitalization and mortality for different age groups and various underlying health conditions is a result of a complex social predisposition to the exposure, resistance, and tolerance for the infection. Based on the observed data as well as the molecular mechanisms for viral entry and replication, cellular senescence related to aging, obesity, hypertension, and diabetes appears to be strongly correlated with the SARS-CoV-2 infections resulting in higher COVID-19 related complications and mortality. Establishing such a correlation may allow us to better explain the pathobiology as well as the differential nature of the SARS-CoV-2 infections and consider targeted control and therapeutic strategies to combat the disease.

Models of consciousness are usually developed within physical monist or dualistic frameworks, in which the structure and dynamics of the mind derive from the workings of the physical world (in particular, the brain). Little attention has been given to modeling within a mental monist framework, deriving the structure and dynamics of the mental world from primitive mental constituents only. Mental monism is gaining attention as a candidate solution to Chalmers’ Hard Problem, and it is therefore timely to examine possible formal models of consciousness within it. Here, we propose a minimal set of hypotheses that any credible model of consciousness (within mental monism) should respect. From those hypotheses, it is feasible to construct many formal models that permit universal computation in the mental world, through cellular automata. We need further hypotheses to define transition rules for particular models, and we propose a transition rule with the unusual property of deep copying in the time dimension. In conclusion, we hope to dispel the notion that mental monism requires a deus ex machina, by showing that a parsimonious set of assumptions can yield a naturalistic and computationally potent mental world.

BACKGROUND Relaxin (RLX), a hormone-like molecule with pleiotropic effects, has been found to reduce matrix deposition and mediate collagen degradation in animal models of chronic liver injuries and might be considered as an adjuvant therapeutic agent for progressive liver diseases. AIMS In the present study, we evaluated whether RLX affects the development of liver fibrosis in an experimental mouse model of NASH in C57BL6 male mice fed with a methionine-choline deficient diet (MCD). Methods Mice were treated per os as we intended to assess the enteric absorption and bioavailability of orally administered RLX (RLX purified from pig ovaries, IBSA SA, Lugano, Switzerland). Mice were fed the MCD diet for 6 weeks. After the initial 3 weeks, one group received drinking water supplemented with RLX (25 mcg/ml) whereas the other continued to receive regular water. A third group of mice fed a regular diet served as control. After 3 additional weeks mice were anesthetized and sacrificed. Results A significant, reduced expression of the pro-inflammatory cytokines TNF-α and of relevant markers of active fibrogenesis and extracellular matrix deposition, Col1A1 and α-SMA, was observed in mice treated with RLX vs controls. RLX also induced a significant decrease of TIMP1 and an increase of both MMP 2 and 9 when evaluated by zymographic analysis in liver extracts. Conclusions Although preliminary pharmacokinetics experiments showed barely detectable amounts of RLX in the blood of mice treated per os, these data support the absorption of orally administered RLX and confirm its potential therapeutic use in the management of liver fibrosis.

Antisense oligonucleotides (ASONs) have proven potential for the treatment of various diseases. However, their limited bioavailability restricts their clinical application. New structures with improved enzyme resistance stability and efficient drug delivery are needed. In this work, we propose a novel category of ASONs bearing anisamide conjugation at phosphorothioate sites for oncotherapy. ASONs can be conjugated with the ligand anisamide very efficiently and flexibly in solution. The conjugation sites and ligand amount both influence anti-enzymatic stability and cellular uptake, resulting in changes in antitumor activity that are detectable by cytotoxicity assay. T6 (with double end AA-conjugation) was identified as the optimal conjugate, and its antitumor activity and the underlying mechanism were examined further in vitro and in vivo. This paper presents a new strategy for the design of nucleic acid–based therapeutics with improved drug delivery and biophysical and biological efficacy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus, is responsible for coronavirus disease 2019 (COVID-19) pandemic of 2020. Experimental evidence suggests that microRNA can mediate an intracellular defence mechanism against some RNA viruses. The purpose of this study was to identify microRNA with predicted binding sites in the SARS-CoV-2 genome, compare these to their microRNA expression profiles in lung epithelial tissue and make inference towards possible roles for microRNA in mitigating coronavirus infection. We hypothesize that high expression of specific coronavirus-targeting microRNA in lung epithelia may protect against infection and viral propagation, conversely low expression may confer susceptibility to infection. We have identified 128 human microRNA with potential to target the SARS-CoV-2 genome, most of which have very low expression in lung epithelia. Six of these 128 microRNA are differentially expressed upon in vitro infection of SARS-CoV-2. Twenty-eight and 23 microRNA also target the SARS-CoV and MERS-CoV, respectively. In addition, 48 and 32 microRNA are commonly identified in two other studies. Further research into identifying bona fide coronavirus targeting microRNA will be useful in understanding the importance of microRNA as cellular defence mechanism against pathogenic coronavirus infections.

Angiogenesis, the sprout and growth of new blood vessels from existing vasculature, is an important process of tumor development for the supply of oxygen and nutrition to cancer cells. Endothelial cell is a critical player in angiogenic process by modulating cell proliferation, cell motility, and cell morphology in the response to pro-angiogenic factors and environments provided by tumor and cancer cells. Recent in vivo and in vitro studies have revealed that gap junction of endothelial cells also participates in the promotion of angiogenesis. Pro-angiogenic factors modulate gap junction function and connexins expression in endothelial cells, whereas endothelial connexins involve in angiogenic tube formation and cell migration of endothelial cells via both gap junction channel function dependent or independent mechanisms. In particular, connexin might have the potential to regulate cell mechanics such as cell morphology, cell migration, and cellular stiffness that are dynamically changed during angiogenic processes. Here, we review the implication for endothelial gap junction and cellular mechanics in vascular angiogenesis.

Past epigenetic information refers to the epigenetic modifications that have occurred in the past have since been updated. These modifications may no longer be present and not actively influencing on cellular functions. When past epigenetic modifications disappear, the precise records of those modifications typically may be vanish. If it is indeed true, a critical question arises: Can an organism sustain continuous survival and evolution without the information about past epigenetic modifications up to the present? It is reasonable to assume that among the information about past modifications, there could be crucial data essential for survival and evolution. If all these experiences were to vanish, rendering them unknowable in the present, it would undoubtedly pose significant challenges to survival and evolution. Therefore, the argument that such epigenetic information has been securely stored somewhere within the cell is not merely speculative but likely a factual reality.In this study, a new term “Epigenetic Archive”, is introduced in biology. It refers to a data repository that encompasses all experience data on past epigenetic modifications. The argument presented here underscores the importance of Epigenetic Archive and the need for its secure preservation. According to the argument, the information that cells experience should be continuously and securely stored, and any distortion of this information is said to be inconsistent with the principles of evolution and survival. This information is seen as evidence of a cell's successful existence up to the present, and it is emphasized that this successful record must be preserved. From this perspective, Epigenetic Archive should be designed to safely store past biological experiences and link this information securely to the present data. This study proposes that the data architecture in Epigenetic Archive is indeed akin to the principles of blockchain technology, particularly in terms of immutability and a distributed ledger securely preserving information across generations and ensuring that all cells possess consistent epigenetic information across a biological organism.The applications and implications of such an analogy of blockchain to Epigenetics could be an original contribution for future research on biology and genetics.

TiC–high Mn steel-bonded carbide with a cellular structure was designed and fabricated by powder metallurgy techniques using coarse and fine TiC particles as the hard phase. This preparation process was carefully investigated and optimized. The microstructure of the TiC steel-bonded carbide was observed using a scanning electron microscope. Results showed that there are two types of microstructures in the TiC steel-bonded carbide: the coarse-grained TiC and fine-grained TiC. The transverse rupture strength and impact toughness of the alloy reach maximum values 2231 MPa and 12.87 J/cm2, respectively when the starting weight ratio of MP-A (containing coarse TiC particles) to MP-B (containing fine TiC particles) is 60:40. Hence, this study serves as a feasible example of how to prepare a high-strength and high-toughness TiC–high Mn steel-bonded carbide.

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b compared to IgG1. Furthermore, we found that immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicates that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

Vaccination has proven highly effective against severe acute res-piratory syndrome coronavirus 2 (SARS-CoV-2), but the long-term immunogenicity and the functional preserved im-mune responses of vaccines are needed to inform evolving evi-dence-based guidelines for boosting schedules. We enrolled 205 healthcare workers into a cohort study; all had received three doses of BBIBP-CorV (China Sinopharm Bio-Beijing Company) inactivated vaccine. We assessed SARS-CoV-2 specific binding antibodies, neutralizing antibody, and peripheral T and B cell responses. We demonstrated that more robust antibody re-sponses to SARS-CoV-2 were elicited by booster immunization compared to primary vaccination. Neutralizing antibody titers to SARS-CoV-2 Omicron variant were also efficiently elevated post homologous vaccine booster despite in a lower titer compared to the prototype stain. In addition to S specific humoral and cellular immunity, BBIBP-CorV also induced N-specific antibody and ef-fector T cell responses. The third-dose vaccination led to further expansion of critical polyfunctional T cell responses, likely an essential element for vaccine protection. In particular, a func-tional role for Tfh cell subsets in immunity was suggested by the correlation between both CD4+Tfh and CD8+Tfh with total anti-body, IgG, B cell responses and neutralizing antibodies. Our study details the humoral and cellular responses generated by the BBIBP-CorV booster vaccination in a seven-month follow up study. There is a clear immunologic boosting value of homolo-gous inactivated SARS-CoV-2 vaccine boosters, a consideration for future vaccine strategies.

Xenorhabdus nematophila and Photorhabdus luminescens are entomopathogenic symbionts that produce several toxic proteins that can interfere with the immune system of insects. Here, we showed that outer membrane proteins (OMPs) could be involved as virulence factors during bacterial symbiont pathogenesis. Purified OMPs from bacterial culture were injected fifth instar larvae of Spodoptera exigua Hübner. Larvae were surveyed for fluctuations in total haemocyte counts (THC), granulocyte percentage (cellular defence), protease, phospholipase A2 (PLA₂), and phenoloxidase (PO) activities (humoral defence) at specific time intervals. Changes in the expression of the three antimicrobial peptides (AMPs), cecropin, attacin, and spodoptericin, were also measured. Larvae treated with both types of OMPs had more haemocytes than did the negative controls. OMPs of X. nematophila caused more haemocyte destruction than did the OMPs of P. luminescens. The OMPs of both bacterial species initially activated insect defensive enzymes post-injection, their activating fluctuated in different ways. Attacin, cecropin and spodoptericin were up-regulated by OMP injections more than in normal larvae. The expression of these three AMPs was maximal at four hpi with P. luminescens OMPs treatment. Expression of the three AMPs in X. nematophila treatment was irregular and lower than in the P. luminescens OMPs treatment. These findings provide insights into the role of OMPs of entomopathogenic nematode bacterial symbionts in countering the physiological defenses of insects.

Despite being well established phenomena, solidification principles are experiencing tough challenges in their application to explain microscale transport phenomena in additive manufacturing melt pool. The problem becomes even more complicated when applied to multicomponent bulk metallic glass matrix composites (BMGMC) whose behavior is dubious and still not fully understood. The aim of the present study is to highlight pathways to overcome these challenges. A comprehensive nucleation and growth model based on original KGT theory and Rappaz modification is proposed encompassing actual transient thermophysical BMGMC data to predict evolving microstructure during additive manufacturing. The model is aimed at pictorial representation of in-situ ductile phase dendrite evolution from melt pool during solidification using two-dimensional cellular automaton (CA) methods. It is proposed to be coded in MATLAB® using commercial simulation code ABAQUS® at back end for macroscopic heat transfer model. The results will be compared with experimental values for validation.

Two strongly curved areas of the Carpathians in Romania are earthquake-prone: Vrancea - in the South-Eastern Carpathians, and Danubian – in the western edge of the Southern Carpathians. By far the highest seismicity episode in 2023 was recorded in the Southern Carpathians, near Targu Jiu city, of more than 4000 earthquakes. A first ML 5.2 mainshock was recorded on 13 February, followed by a second one, ML 5.7, on 14 February. Our purpose is to provide a first analysis of this sequence in order to explain its extent and unusual development, in time. The possible role of fluids in the middle crust, is discussed in connection with the rather unusual character of the space-time distribution of aftershocks. A large and high-quality dataset is provided by the dense array of seismic stations which has been gradually improved by adding new stations in the epicentral area. The thorough revision of the phase picking and location reveals a few interesting and intriguing features of seismicity that still remain worthy to be further investigated. The database built within this paper provides excellent information not only for Targu Jiu area, but for any other investigation in intra-continental regions characterized by diffuse and sporadic seismic activity.

Physical exercise favorably affects visceral adipose tissue (VAT) which is a risk factor for cardiometabolic diseases. However, many people are unable or unwilling to conduct frequent and intensive exercise programs that have favorable effects on VAT. The present study aimed to determine the effect of the time-efficient and joint-friendly whole-body electromyostimulation (WB-EMS) technology on VAT volume in overweight to obese adults with osteoarthritis of the knee. In total 72 women and men 40-70 years old with femuro-tibial knee osteoarthritis were randomly allocated to WB-EMS (n=36) with 1.5 sessions of 20 min/week for 29 weeks or a usual care control group (CG: n=36) with 6 sessions of physiotherapy. Magnetic Resonance Imaging (MRI) using a non-contrast enhanced 2-point Dixon Gradient Echo Volumetric Interpolated Breath-hold Examination determined VAT. Twelve slices covered a total length of approximately 5 cm from mid L2 to mid L3. In summary, VAT volume increased non-significantly in the CG (p=.261) and decreased non-significantly in the WB-EMS group (p=.160). We failed to determine significant WB-EMS-induced effects i.e. group differences for absolute changes on VAT volume (p=.097). Due to the low application volume, present WB-EMS protocols might not be the perfect tool for decreasing VAT in overweight to obese adults.

Alzheimer’s disease (AD) is an age-related neuropsychiatric disorder and a common cause of progressive dementia. Diltiazem (DTZ), the non-dihydropyridine benzothiazepine class of calcium channel blocker (CCB), used clinically in angina and other cardiovascular disorders have proven neurological benefits. In the present study, the neuroprotective anti-dementia effects of DTZ against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced sporadic AD (SAD)-type rat model was investigated. ICV-STZ-induced cognitive impairments were measured by passive avoidance and Morris water maze tasks. Anti-oxidative enzyme status, pro-inflammatory markers, and amyloid-beta (Aβ) protein expression in rat brain tissues were measured by ELISA kits, Western blotting, and immunostaining techniques. Data revealed that ICV-STZ injection in rats significantly induced cognitive deficits and altered the levels of oxidative and pro-inflammatory markers (p &lt; 0.05 ~ p &lt; 0.001). Treatment with DTZ (10 mg/kg, 20 mg/kg, and 40 mg/kg. p.o.) daily for twenty-one days, 1 h before a single ICV-STZ (3 mg/kg) injection, significantly improved cognitive impairments, ameliorated the ICV-STZ-induced altered nitrite, pro-inflammatory cytokines (TNF-α, and IL-1β) and anti-oxidative enzyme levels (superoxide dismutase, lipid peroxidation, and glutathione). Further, DTZ restored the increased Aβ protein expression in ICV-STZ-induced brain tissue Considering the data obtained, DTZ exhibited a potential neuroprotective anti-dementia role in ICV-STZ-induced SAD-type conditions in rats and might be repurposed as a potential therapeutic agent in the treatment and management of AD and related dementia pathologies.

Intra-articular fractures are a major cause of post-traumatic osteoarthritis (PTOA). Despite adequate surgical treatment, the long-term risk for PTOA is high. Previous studies reported that joint injuries initiate an inflammatory cascade characterized by elevation of synovial pro-inflammatory cytokines, which can lead to cartilage degradation and PTOA development. This review summarizes the literature on the post-injury regulation of pro-inflammatory cytokines and the markers of cartilage destruction in patients suffering from intra-articular fractures. METHODS We searched Medline, Embase, and Cochrane databases (1960–February 2020) and included studies that were performed on human participants and included control groups. Two investigators assessed the quality of the included studies using Covidence and the Newcastle-Ottawa Scale. RESULTS Based on the surveyed literature, several synovial pro-inflammatory cytokines, including interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-12p70, interferon-y, and tumor necrosis factor-α, were significantly elevated in patients suffering from intra-articular fractures compared to control. A simultaneous elevation of anti-inflammatory cytokines such as IL-10 and IL-1RA was also observed. In contrast, IL-13, CTX-II, and aggrecan concentrations did not differ significantly between the compared cohorts. CONCLUSIONS Overall, intra-articular fractures are associated with an increase in inflammation-related synovial cytokines. However, more standardized studies which focus on the ratio of pro- and anti-inflammatory cytokines at different time points are needed.

Total Hip Arthroplasty is one of the most successful surgery. However, due to the worldwide growing population life expectancy and the related incidence of age-dependent bone diseases, a growing number of cases of intra-operative fractures lead to revision surgery with high rates of morbidity and mortality. Surgeons choose the type of the implant, either cemented or cementless prosthesis, on the basis of the age, the quality of the bone and the general medical conditions of the patients. Generally, no quantitative measures are available to assess the intra-operative fracture risk. Consequently, the decision-making process is mainly based on medical operators’ expertise and qualitative information obtained by imaging. Motivated by this scenario, we here propose a mechanical-supported strategy to assist surgeons in their decisions, by giving intelligible maps of the risk fracture which take into account the interplay between actual strength distribution inside the bone tissue and its response to the forces exerted by the implant. To this end, we produce charts and patient-specific synthetic “traffic-light” indicators of fracture risk, by making use of ad hoc analytical solutions to predict the stress levels in the bone by means of CT-based mechanical and geometrical parameters of the patient. We felt that, if implemented in a friendly software or proposed as an app, the strategy could constitute a practical tool to help the medical decision-making process, in particular with respect to the choice of adopting cemented or cementless implant

The paper presents new data on mineralogical-geochemical peculiarities of the granites and pegmatites of the Baikal area (Olkhon Region) with implications for the age, generation conditions and geodynamic settings of magmatism. The early Paleozoic granitoids of the Olkhon region are syncollisional formations produced from the gneiss-schistose substratum of the Olkhon metamorphic sequences. Pegmatoid granites and pegmatites of the Region were generated within a wide age range (458-390 Ma) and include different mineralogical and geochemical types. Amongst the Early Paleozoic granitoids, pegmatoid rocks are products of the collisional magmatism evolution and are similar to granites in terms of the mineral composition and distribution patterns of rare and rare earth elements. On the Olkhon island (Baikal lake) the pegmatite of the Tashkiney vein belong to the Be-Nb-Ta mineralogical-geochemical type demonstrating high contents of W, Sn U, Th and very low concentrations of Li and volatile components (F, B). In the Pryolkhonye area, vein pegmatite Iliksin is with Li, Be, Nb, Ta mineralization (lepidolite, vorobyevite, samarskite et al). The studied pegmatite veins are similar both by the profound negative Ba, Sr, Eu, and Zr anomalies. The zircons from the Tashkiney vein (390±5.0 Ma) and of the Iliksin vein (430.1±2.2 Ma, U-Pb isotope LA ICP MS metod) indicate the formation of pegmatite at the late post-collisional stage of magmatism in the Olkhon Region. As regard to mineralogical and geochemical characteristics, vein pegmatites with amazonite (Ainsky and Ulan-Nur) belong to the Li-F type. The tantalum mineralization, represented by microlites and minerals of the columbite-tantalite group is associated with the Ainsky amazonite pegmatite. As opposed to the Early Paleozoic syncollisional granitoids and pegmatoid formations, the middle Paleozoic vein bodies of pegmatites (Tashkiney, Iliksin, Ainsky, Ulan-Nur) are regarded as rare-metal pegmatites. In terms of geochemical characteristics, they are similar to the rare-metal pegmatoid granites and pegmatites of the intra-plate setting widespread in Mongolia and Transbaikalia. The rare-metal mineralization in the Olkhon region may be genetically related to the evolution of Be-Nb-Ta and Li-F types of the post-collisional granites and pegmatites.

Abstract: Intra-abdominal abscesses (IAA) may commonly arise following complicated gastrointestinal tract infections and, on occasion, from infections within the urinary system. Many of these IAA are initiated as a consequence of post-surgical complications. These abscesses have a substantial risk of morbidity and mortality. As a result, it is crucial to diagnose and treat them promptly to minimise these adverse outcomes. Therefore, radiological modalities play a vital role in diagnosing, localising, and detecting associated complications of IAA, as sometimes other investigations could be less reliable and non-specific. Radiological modalities are pivotal in achieving an accurate diagnosis, localising the abscesses, and identifying associated complications. This is especially important since alternative investigative methods may be misleading in certain situations. Radiological techniques such as ultrasound scans (USS), contrast-enhanced computed tomography (CECT), and even magnetic resonance imaging (MRI) are immensely helpful in diagnosing these conditions. These imaging tools guide clinicians in determining the most appropriate patient management strategies. In this article, we compile a case series involving tubo-ovarian abscess, appendicular abscess, diverticular abscess and infected walled-off pancreatic necrosis, paying particular attention to radiological features in the diagnosis. Furthermore, we reviewed the existing literature to delineate characteristic radiological features related to the cases we discussed.

Here, we found higher percentage of CD8+ T cells in piglets immunized with CVC1302-adjuvanted inactivated FMDV vaccine. We wonder whether promoted cellular immunity induced by CVC1302-adjuvanted inactivated FMDV vaccine due to the promoted antigen cross-presentation efficiency of OVA by DC mainly via the cytosolic pathways, demonstrated by enhanced levels of lysosomal escape of OVA in DC, loaded with OVA and CVC1302. Higher levels of ROS and significant enhanced elevated lysosomal pH in DC facilitated the lysosomal escape of OVA. Significant enhanced CTL activities were observed in mice immunized with OVA-CVC1302. Overall, CVC1302 increased the cross-presentation of exogenous antigens and the cross-priming of CD8+ T cells by alkalizing the lysosomal pH and facilitating the lysosomal escape of antigen. These studies shed new light on the development of immunopotentiators to improve the cellular immunity induced by vaccine.