Immune checkpoint receptors play a crucial role in steering tumor progression, prompting a focused investigation into the role of TIM3 in breast cancer. Analysis of TCGA BRCA data unveiled diverse correlations between TIM-3 expression and immune cell infiltration across subtypes. In our in-house cohort studied through IHC, significant changes in TIM3 expression with tumor grades were observed. Higher TIM3 expression correlated with increased disease-free survival in pan breast cancer, marking the first revelation of TIM3's positive role in pan BC prognosis. The study indicates that alluring TIM3 response, rather than suppression, may enhance breast cancer prognosis.

Purinergic signaling is that nucleotides (especially ATP) and adenosine are utilized as transmitter molecules, which play an important role in the immune system. In the extracellular ventricle, ATP plays a significant role of pro-inflammatory molecules mainly through activating P2 receptors, while adenosine plays the role as anti-inflammatory molecule mainly through activating P1 receptors. As we know，neutrophils are the most abundant immune cells in our circulation and have become an essential part of coordinating a series of complex events during inflammatory diseases. However, due to the destruction of inflammatory substances from neutrophils, the activation of neutrophils is fine-tuned, and purinergic signaling is associated with this process. As a matter of fact, altering the balance between P2 and P1 signals is of great importance for neutrophils to exert immune activities properly. Here, we review the role of purinergic signaling in regulatory function of neutrophils during inflammatory disease, and then discuss the potential contribution of targeted purinergic signals in the treatment of the neutrophil during inflammatory diseases.

An economic and business history approach is used to show the rise and relative failure of the Spanish wind industry during the period between 2004-2015, when Spain became the fourth country after China, the US and Germany in installed capacity of renewable energies and, in relative terms, the second country after Denmark. This study is unique in that it provides an integrated vision of the reasons for the relative fall of Spain in the world ranking of wind energy producers. The methodology of the economic analysis of industrial policies makes it possible to explain the fall in the relative importance of Spain in the international panorama of wind farms. There were no reasons related to technological obsolescence or inability of the CECRE managing renewable energies to explain the fall.

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.

Long non-coding RNA (lncRNA) aberrant expression have been found in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped in transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated in pediatric ALL and uc.112 expression was higher in T-ALL compared to patients with B-ALL and in patients with hyperdiploid karyotype. These findings suggest a potential role of this uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections.

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955 and 1990 and demonstrating their ability to transfer passive immunity from one animal or individual to another, often within 24 hours of inoculation. Such activity is potentially revolutionary both in making T cell vaccines readily manufacturable and also because the existence of transfer factors would undermine the basic assumptions of the clonal selection theory, which currently dominates immunological theory. Unfortunately, lack of the microanalytical and synthetic techniques required to properly identify transfer factors, combined with safety factors associated with it derivation from blood sources susceptible to HIV and prion infections, put an end to transfer factor research after 1990. This paper reviews the evidence supporting transfer factor activity and suggests that this potentially revolutionary concept be resurrected and subjected to renewed scrutiny in light of CRISPR-Cas mechanisms and because of its potential to make possible T cell vaccination and provide a novel basis for understanding immunological function.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no GE product has been approved, as opposed to 22 GT products that cost up to millions of dollars per dose. The FDA has recently added a guideline specific to gene editing that should be understood to enable faster development of GE products; at the same time, the FDA also needs to bring more clarification and make several amendments to this guideline to make it more rational.

Basic features of seed dormancy are illustrated. The seed overall regulatory network governs seed metabolism and development, and it is coordinated by plant hormones. A functional model focused on abscisic acid (ABA), the foremost plant hormone in dormancy, is used as a framework to critically discuss the literature. Gibberellins (GAs) have a main role in germination, and the ABA – GAs balance is a typical feature of the seed state: ABA dominates during dormancy and GAs prevail through germination. Thus, the literature converges toward envisaging the development switch between dormancy and germination as represented by the ABA/GAs ratio. The ABA – GAs antagonism is based on mutual inhibition, a feature of the regulatory network architecture that characterizes development trajectories based on a regulatory circuit with a bistable switch. Properties of such kind of regulatory architecture are introduced step by step, and it is shown that seed development – towards either dormancy or germination – is more properly represented by a tristable regulatory circuit, whose intermediate metastable states ultimately take one or the other development trajectory. Although the ABA/GAs ratio can conveniently represent the state of the seed overall regulatory network along the seed development trajectory, specific (unknown) dormancy factors are required to determine the development trajectory. The development landscape is shown to provide a well-suited representation of seed states travelling along developmental trajectories, particularly when the states are envisioned as regulatory circuits. Looking at seed dormancy in terms of regulatory circuits and development landscapes offers a valuable perspective to improve our understanding of this biological phenomenon.

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

In recent years, new treatments have been studied for relapsed-refractory multiple myeloma (RRMM), including two CAR-T products and a variety of non CAR-T agents. Since direct comparisons between these innovative treatments are not available, indirect comparisons can be of interest. Reconstruction of individual patient data from Kaplan-Meier graphs (Shiny method) has been employed in numerous reports that have validated its performance. In the present review, we evaluated six treatments proposed for RRMM including two CAR-T products (ciltacabtagene autoleucel and idecabtagene vicleucel) and four treatments not based on a CAR-T (melflufen plus dexamethasone, isatuximab plus dexamethasone, selinexor, and belantamab). The end-point was overall survival (OS); the Shiny method was used to generate reconstructed survival curves. Our results showed statistically significant differences in OS across these treatments. Compared with pharmacological treatments, CAR-T products significantly prolonged OS with an improvement of remarkable clinical relevance. In particular, ciltacabtagene autoleucel showed better OS than idecabtagene vicleucel. As regards non CAR-T treatments, the ranking in OS was headed by isatuximab plus dexamethasone, followed by belantamab, selinexor, and melflufen plus dexamethasone. In conclusion, while the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons have offered some original clues to better interpret the information on OS published in these studies.

Hamacher operation which is generalization of the Algebraic and Einstein operation, can widely provide a large number of arithmetical operation with respect to uncertainty information, and Heronian mean can deal with correlations of the input arguments or different criteria and don’t make calculation redundancy, meanwhile, the normal intuitionistic fuzzy numbers (NIFNs) can depict distinctively normal distribution information in practical decision making. In this paper, a multi-criteria group decision-making (MCGDM) problem is researched under the NIFNs environment, and a new MCGDM approach is introduced on the basis of the Hamacher operation. Firstly, according to Hamacher t-conorm and t-norm, some operational laws of NIFNs are presented. Secondly, it is noticed that Heronian mean can’t only once take into account mutual relation between attribute values once, but also consider the correlation between input argument and itself. Therefore, we develop some operators and study their properties in order to aggregate normal intuitionistic fuzzy numbers information, these operators include Hamacher Heronian mean (NIFHHM), Hamacher weighted Heronian mean (NIFHWHM), Hamacher geometric Heronian mean (NIFHGHM) and Hamacher weighted geometric Heronian mean (NIFHWGHM). Furthermore, we apply the proposed operators to the MCGDM problem and present a new method. The main characteristics of this new method involve that: (1) it is suitable to make decision under the normal intuitionistic fuzzy numbers environment and more reliable and reasonable to aggregate the normal distribution information. (2) it utilizes Hamacher operation which can provide more reliable and flexible decision-making results and offer an effective and powerful mathematic tool for the MAGDM under uncertainty. (3) it uses the Heronian mean operator which can considers relationships between the input arguments or the attributes and don’t brings subsequently about redundancy. Lastly, an application is given for showing the feasibility and effectiveness of the presented method in this paper.

Chimeric Antigen Receptor (CAR)-T cell immunotherapy revolutionized cancer treatment and consists of the genetic modification of T lymphocytes with a CAR gene, aiming to increase their ability to recognize and kill antigen-specific tumor cells. The dynamics of CAR-T cell responses in patients presents a multiphasic kinetics with distribution, expansion, contraction, and persistence phases. The characteristics and duration of each phase depend on the tumor type, the infused product, and on patient-specific characteristics. We present a mathematical model which describes the multiphasic CAR-T cell dynamics resulting from the interplay between CAR-T and tumor cells, considering patient and product heterogeneities. The CAR-T cell population is divided into functional (distributed and effector), memory, and exhausted CAR-T cell phenotypes. The model is able to describe the diversity of CAR-T cell dynamic behaviors in different patients and hematological cancers as well as their therapy outcomes. Our results indicate that the joint assessment of the area under the concentration-time curve in the first 28 days and the corresponding fraction of non-exhausted CAR-T cells may be considered as potential markers to classify therapy responses. Overall, the analysis of different CAR-T cell phenotypes can be a key aspect for a better understanding of the whole CAR-T cell dynamics.

Therapeutic vaccine studies should be designed to elicit durable, high magnitude, and efficacious T cell responses, all of which can be impacted by the choice of vaccination schedule. Here, we compare different prime-boost intervals (PBI) in a human papillomavirus (HPV) model using HPV16E6E7 Venezuelan equine encephalitis virus replicon particle (VRP) vaccination to address the optimal boosting schedule, quality of immune response, and overall in vivo efficacy. Six different vaccine regimens were tested with each group receiving booster vaccinations at different time intervals. Analysis of T-cell responses demonstrated a significant HPV16 E7 specific CD8+T cell response with minimally a one-week PBI between antigen re-exposure. Significant E7-specific in vivo cytotoxicity was also observed with longer PBIs. Additionally, longer PBIs led to an enhanced memory recall response to tumor challenge, which correlated with differential expansion of T cell memory subsets. Our findings imply that when using alphavirus vector platforms as a vaccination strategy, a one-week PBI is sufficient to induce high magnitude effector T cells with potent anti-tumor activity. However, longer PBIs lead to enhanced long-term protective anti-tumor immunity. These findings have implications for therapeutic vaccine clinical trials in which shorter intervals of prime-boost regimens may lead to suboptimal durable immune responses.

With the fintech industry growing at an unprecedented rate, it is critical to protect cybersecurity and ensure data privacy. The research presented here offers a thorough examination of the challenges faced by financial technology companies, highlighting the growing risks posed by malware, phishing, and network vulnerabilities. As essential components of a proactive defense plan, the report promotes strong cybersecurity measures like frequent security assessments, encryption, and stringent access controls. The findings highlight how important it is for fintech companies to give cybersecurity equal importance with open and honest data privacy policies in order to win over customers. In order to protect the industry from cybersecurity risks regulatory compliance, intrusion detection systems, and collaborative information sharing are considered essential components. The article advises businesses to include cybersecurity and data privacy into their core business operations and customer relations, highlighting the critical role these factors play in sustaining success in the rapidly evolving fintech industry.

Developmental modularity has long been viewed as a hierarchical organization that facilitates evolution over macro-evolutionary time through modification or co-option of preexisting modules. More recently, developmental modularity has been proposed as a micro-evolutionary mechanism capable of driving rapid evolution of novel color pattern phenotypes between closely related taxa. In this scenario, swapping allelic variants of modular cis-regulatory elements (CREs) via recombination generates novel phenotypes by shuffling preexisting color pattern modules into new arrangements. Recent evidence from Drosophila and butterflies, however, provides a series of examples in which pleiotropic CREs function in multiple developmental contexts. The potential prevalence of pleiotropy in CRE function is a major barrier to the proposed evolutionary role of CRE modules and encourages us to reconsider the relative importance of modularity for microevolutionary change. Here we first review the case for the apparent frequent exchange of modular color pattern phenotypes as a mechanism facilitating diversification. We then contrast this with recent evidence of CRE pleiotropy and argue that exchange of CRE modules should not be the default assumption, even when phenotypes look modular. Finally, we review experimental data on Heliconius butterfly wing patterns—which appear modular—and introduce the concept of evolutionary modularity as an alternative to developmental modularity. Evolutionary modularity reconciles the appearance of modularity in comparative genomic studies of Heliconius color patterns with experimental data supporting a non-modular architecture. We propose that evolutionary modularity provides a potentially important pathway for exchange of phenotypic elements between hybridizing taxa independent of the underlying developmental architecture.

Recently, a concept known as μTRISTAN, which involves the acceleration of μ+, has been proposed. This initiative has led to considerations of a new design for a neutrino factory. Additionally, leveraging the polarization of μ+, measurements of T violation in neutrino oscillations are also being explored. In this paper, we present analytical expressions for T violation in neutrino oscillations within the framework of standard three flavor neutrino oscillations, a scenario involving nonstandard interactions, and a case of unitarity violation. We point out that examining the energy spectrum of T violation may be useful for probing new physics effects.

Trichinella spp. are etiological zoonotic agents spread throughout the world affecting mammals, birds, and rep-tiles, involved in the evolution of the two cycles, domestic and sylvatic. The pine marten (Martes martes) is a mammal carnivorous nocturnal from the family Mustelidae. In Romania, this host is widespread in all the forests of the country. The pine marten has an extremely voracious appetite, feeding on fruit but also on a variety of small animals, including rodents such as mice or rats. The aim of the study was identification and molecular characterization of Trichinella larvae isolated from the muscles of tree martens from different counties of Romania. The muscle samples were examined by artificial digestion, and the larvae were processed by multiplex PCR. Trichinella britovi, a species frequently identified in wild carnivores in temperate zones, has been confirmed. Although T. britovi has been reported in Romania to several host animals, this study confirms for the first time its presence in the pine marten, a result which undoubtedly underlines the fact that the parasitic reserve in the sylvatic environment is maintained at a consistent level, and the knowledge of these vector hosts remains a permanent concern of the specialists.

The aim of this 9th expository article is to conclude a study on domination in two fuzzy models, including t−norm fuzzy graphs and fuzzy graphs. All parts are twofold even if we don’t men- tion, directly. I.e., all results depicts some properties about fuzzy graph and t−norm fuzzy graph.

Euler sums are alternating (or level two) extension of multiple zeta values (MZVs). Kaneko and Tsumura initiated the study of multiple T-values (MTVs), another level two generalization, by restricting the summation indices in the definition of MZVs to a fixed parity pattern. In this paper, we shall study finite MTVs and their alternating versions which are level two and level four variations of finite MZVs, respectively. We conjecture that all finite MZVs are in the Q-span of finite MTVs which in turn apparently lie in the span of finite Euler sums, and the inclusions are both proper. We shall first provide some structural results for Euler sums of small weights, guided by the author's previous conjecture that the finite Euler sum space of weight w is isomorphic to a quotient Euler sum space of weight w. Then, by utilizing some well-known properties of the classical alternating MTVs, we shall derive a few important Q-linear relations among the finite alternating MTVs, including the reversal, linear shuffle and sum relations. We then compute the upper bound for the dimension of the Q-span of weight w finite (alternating) MTVs for w<9, both rigorously using the newly discovered relations and numerically aided by computers.

There is scientific consensus that organismal aging did not evolve by natural selection (NS) because it lacks individual benefit. Nonetheless it exists, leading to much speculation about its origins, and when the diminishing force of selection begins. Both concepts are based upon two misconceptions; that aging occurs in and of itself and is caused by the declining strength of NS during the reproductive lifespan. Although lacking individual benefit, aging evolved by NS as a tradeoff of survival for reproduction. Based upon regulatory dynamics that participate in this tradeoff, aging begins once reproductive success has been achieved through offspring nurturing. Thereafter, the strength of NS wanes to exponentially accelerate aging, leading to death. Assumptions of the theory are that: (1) a life-long, “holistic” regulatory mechanism whose genic expression is modified epigenetically, originates in ontogenesis; (2) the regulatory mechanism of the last developmental stage becomes redundantly expressed during “morphostasis”, a non-aging, life interval of peak vitality to ensure completion of reproduction through nurturing, and (3) thereafter, loss of regulatory redundancy causes aging which reduces the strength of natural selection and allows accumulation of randomly occurring somatic damage.

Recently, many authors have been interested to introduce fuzzy implications over t-norms and t-conorms. In this paper, we introduce (S,N) and residuum fuzzy implication for Dubois t-norm and Hamacher's t-norm. Also, new concepts so-called (T,N) and residual fuzzy co-implication in dual Heyting Algebra are investigated. Some examples as well as application are discussed as well.

This article analyzes laws, normative reforms and regulations surrounding the practices and mechanisms of control over the consumption, cultivation and commercialization of cannabis. On the one hand, I investigate regulatory practices that deny rights for the consumption of cannabis classified as recreational. On the other hand, I study regulatory practices that extend rights for the production, consumption and commercialization of cannabis classified as medicinal and industrial. The empirical moment is composed of four stages and methodological tools. First, I conduct an analysis of state policies. Then, I analyze nine laws and codes on cannabis regulation from 1970 to the present. Next, I perform five semi-structured interviews. Finally, I develop two life stories of former people deprived of their liberty for cannabis cultivation and trade. In this way, I trace forms of regulation on multiple demands, knowledge, interests and beliefs. This research focuses on state regulation. Cannabis regulatory regimes are conceived as constructions of political, social and economic truths, meanings and rights. In sum, the answer to the question of how collective demands around cannabis are regulated in Ecuador stipulates that state action reinforces stigmatization and criminalization. In addition, it legitimizes moral entrepreneurs and counter-movements around cannabis.

Phospholipases are among the important elements involved in lipid-dependent cell signaling that lead to the induction of downstream pathways. In the current study, phospholipases D (PLDs) gene family was characterized and compared in two important oilseeds crops, Brassica napus and Camelina sativa. The results revealed that PLD has 33 members in Camelina sativa (CsPLD) and 41 members in Brassica napus (BnPLD). All studied PLDs showed a negative GRAVY value, indicating that PLDs are probably hydrophilic proteins. Phylogenetic analysis separated PLDs into five subfamilies; gamma, delta, beta, alpha, and zeta. According to evolution analysis, a different evolution process was observed between CsPLD and BnPLD. In addition, the results disclosed that the most of the PLD genes have been segmentally duplicated under purifying selection. Cis-regulatory elements related to ABA and auxin responsiveness were more found in upstream region of CsPLDs, while elements linked with MeJA responsiveness were more dis-tributed in promoter region of BnPLDs. Analysis of the expression data showed that PLD alpha genes have a wide expression and are expressed in most tissues. Quantitative expression analysis (qPCR) of CsPLD genes under salt stress, 200 mM of NaCl, was done in different time series. The results revealed that the CsPLD genes are involved in the response to salinity stress and their expression levels enhance with the increase of salinity stress time. The outcomes of this research will be useful for future molecular work related to lipid signaling in oilseed plants.

Contamination by microplastics (MP) in aquatic ecosystems is largely due to the release of millions of these particles from treated effluents from Wastewater Treatment Plants (WWTP). Due to the lack of policies and regulations that establish criteria for the control and elimination of MP from WWTP effluents, this research evaluated the presence of MP for particle sizes of 38 and 150 µm in influents and effluents from three WWTP in the port of Acapulco, Mexico. Using optical microscopy and Fourier transform infrared spectroscopy (FTIR) techniques, the MP detected were polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET) and polyvinyl chloride (PVC). MP removal efficiencies of 82.5 to 98.7% (38 µm) and 86.8 to 97.5% (150µm) were obtained; the MP average daily emissions to the receiving bodies of these three WWTPs were in the ranges of 9.5 x 106 - 4.70 x 108 particles and the annual emissions in the range of 3.05 x 109 - 1.72 x 1011 particles. This work reveals the urgency of implementing regulatory policies to avoid the continuous emission of MP to aquatic ecosystems from WWTPs in Acapulco, Mexico.

The COVID-19 pandemic has exerted a significant impact on mental health globally. The uncertainty, fear, and stress associated with this crisis have contributed to a heightened prevalence of anxiety, depression, and various other mental health disorders. In this scenario, the present study aimed at investigating the relationship between locomotion regulatory mode, resilience, and COVID-19 anxiety. It is worth noting that previous extensive research has established a significant correlation between high levels of locomotion and diverse positive psychological conditions, such as optimism, reduced hopelessness, and positive affect. A total of 243 participants completed measures of locomotion regulatory mode, resilience, and COVID-19 anxiety. In line with our hypotheses, individuals' locomotion regulatory mode was negatively, although non significatively, associated with COVID-19 anxiety. Furthermore, resilience was found to mediate the relationship between locomotion regulatory mode and COVID-19 anxiety, indicating that individuals displaying high locomotion may be better equipped to cope with the stress and uncertainty of the COVID-19 pandemic due to their greater levels of resilience. Taken together, these findings highlight the importance of considering both locomotion and resilience in managing anxiety related to COVID-19 and suggest that interventions aimed at enhancing resilience may be beneficial particularly for individuals with low locomotion regulatory mode.

Epicatechin has been described as a polyphenol compound that promotes skeletal muscle restructuring, by expressing muscle regulation factors, activation of satellite cells and modulation of the main pathways associated with catabolism. However, the literature shows contrasting results of therapeutic effects and treatment protocols. Thus, the aim of this systematic review was to analyze the current literature addressing the molecular mechanism and clinical protocol of epicatechin on skeletal muscular atrophy in humans and animals. A search was conducted in PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library databases. The qualitative analysis showed a prevalence of the inhibitory action of epicatechin in myostatin expression and atrogenes FOXO, MAFbx and MuRF1. Epicatechin showed positive effects on increased follistatin and on the activation of the myogenic regulatory factors (Myf5, MyoD and myogenin). In addition, the studies evidenced the impact of epicatechin on the mitochondrias' biosynthesis in muscle fibers, activation of the signaling pathway of AKT/mTOR protein synthesis, and improvement of skeletal musculature performance, particularly when associated with physical training. Epicatechin showed promising clinical applicability through beneficial results under conditions that negatively affect the skeletal musculature. However, there is no protocol standardization allowing to draw more specific conclusions on its therapeutic use.

Background: The Ibizan Hound is a canine breed native to the Mediterranean region, where leishmaniasis is an endemic zoonosis. Several studies indicate a low prevalence of this disease in dogs, whereas other canine breeds present a high prevalence. However, the molecular underlaying mechanisms yet remains unknown. Methods: In this study, we analyze the haplotypes of genes encode cytokines related to immune response of Leishmania infantum infection in twenty-four Boxer and twenty-four Ibizan hound apparently healthy using CanineHD DNA Analysis BeadChip including 165,480 mapped positions. Results: The results show that several haplotypes of genes encoding Interleukin 6 (IL6) and Interferon gamma (IFNG) are related to Interferon gamma (IFN-γ), and Interleukins (IL) 2 and 18 serum levels. Our results indicate that the regulation of immune response is different in the two canine breeds analyzed and are related to the haplotype compositions of the genes encoding these cytokines. Conclusions: Future studies are needed to elucidate whether these differences and haplotypes are related to different phenotypes in immune response and expression gene regulation to L. infantum infection in dogs.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders related to aging. Though several risk factors are shared between these two diseases, the exact relationship between these two diseases is still unknown. In this paper, we analyzed how these diseases relate to each other from a genomics viewpoint. Using an extensive literature search, we accumulated the list of genes from the major genome-wide association (GWAS) studies. However, we found only one gene (HLA-DRB5) reported in these GWAS studies that are common between AD and PD. We also listed all the miRNAs that have been previously reported for AD and PD. Here we found 15 different miRNAs that were reported in both diseases. In order to get better insights, we predicted the gene coexpression network for both AD and PD. Network analysis on these networks show six clusters of genes related to AD and four clusters of genes related to PD.

Legionella pneumophila RpoS (LpRpoS) is an alternative sigma factor of RNA polymerase (RNAP) essential for virulence and stress resistance. To investigate the mechanism of RpoS in the intracellular pathogen L. pneumophila, we determined the high-resolution crystal structure of the LpRpoS (residues 95-194) containing a partial region 1.2 and region 2. The structure of LpRpoS (residues 95-194) reveals that the conserved residues are critical for promoter melting, DNA and core RNAP binding. The differences in regulatory factor binding site between Escherichia coli RpoS and LpRpoS suggest that LpRpoS may employ a distinct mechanism to recruit alternative regulatory factors controlling transcription initiation.

Extracellular vesicles (EV) are a very heterogeneous group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular communication, both locally and systemically, since they induce signals and transfer their contents (proteins, lipids, RNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. How-ever, cell surface receptor-induced EV release is limited to cells from the immune system, includ-ing T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptor for antigen and several bioactive molecules, including proapoptotic proteins. These EV are thus specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy. In this review we discuss the generation of EV by T lymphocytes and some potential therapeutic approaches of these EV.

C-C Chemokine receptor type 5 (CCR5) is expressed on the CD4 T cell surface where CXCR4 and CCR5 expressions are controlled differently during the activation of T cells and with the binding of interleukin type-2 (IL-2). IL-2 can upregulate CCR1 and CCR2 in CD45R01 T cells and increase the T lymphocyte chemotaxis toward CC-chemokines. CD4+ T cells are either apart of the T helper 1 or Th1 lymphocytes that release interferon gamma (IFNγ) and lymphotoxin that provide cellular immunity to internal pathogens and T helper cells type 2 (Th2), which secrete interleukins 4 and 5 (IL-4 and IL-5). IL-4 and IL-5 cause an allergic and humoral immune response to parasites. Th2 lymphocytes use CCR3 chemokine receptors. CCR5 and CXCR3 chemokine receptors are specific for CD4+ Th1 and Th2 lymphocytes. CCR5Δ32 is a 32-base-pair deletion of the CCR5 gene. CCR5 is a co-receptor for the entrance of the human immunodeficiency virus-1 (HIV-1). CCR5Δ32 creates a malfunction of the CCR5 protein that can prevent HIV-1 infection. However, the CCR5Δ32 32-base-pair deletion is not prevalent and predominant in many populations worldwide and there also exist more genetic variations of CCR5 known as CCR5-SNPs. An alternative polymorphism was identified based on the CCR5 gene that was identified as a A to G (A/G) point mutation. This point mutation is located at the 59029 locus on the promoter that lowers the expression rate of CCR5. Gurdol et al. found activity at the promoter of CCR5/590029G was 45% lesser than the CCR5/59029A. The genetic variations of CCR5 SNPs also include: 2459G>SNP of CCR5, C101X, CCR5 gene position at -2273, and the A to G SNP mutation found in two South African blacks. Therefore, more studies are needed to find more and varied chemokine polymorphisms that are present in many diverse populations in the world. The aim of this literature review is to describe the immense impact of CCR5 SNP mutations on viral infection susceptibility, on the pathogenesis of chronic conditions, to endorse the increased discovery of more novel CCR5 SNPs, and to show the significant potential of anti-CCR5 therapies to treat multiple diseased conditions.

Maternal-derived immunity is a critical component for survival and success of offspring in pigs to protect from circulating pathogens like Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study was to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (TRT 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2- and 4-wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In lungs, CD8 T cells were the primary and CD4 T cells the secondary IFN-γ producers including a novel subset of porcine CD8α-CCR7- CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets; and it introduces two novel immune cell subsets in pigs – IFN-γ producing CD21α+ B cells and CD8α-CCR7- CD4 T cells.

Introduction: Obstructive sleep apnea (OSA) is the most common sleep-breathing disorder. OSA is associated with cardiovascular diseases such as coronary artery disease (CAD) and arrhythmias with an increased risk of sudden cardiac death. Some changes in ECG markers are seen as an indicator of arrhythmogenicity, especially ventricular arrhythmias. The goal of this study was to investigate if OSA patients with CAD have QT dispersion and T peak to T end (TpTe) changes as a surrogate of arrhythmogenicity. Methods: We studied 75 patients with CAD who underwent polysomnographic studies. Patients were categorized into mild, moderate, and severe OSA according to the Apnea hypopnea index (AHI). Baseline ECG and echocardiography for assessing LV function and valvular heart disease were done for all of them. Results: Results showed that in patients with moderate and severe sleep apnea QT dispersion was higher in a group with more involvement of coronary artery disease, reduced ejection fraction, and a history of old MI. However, we didn’t find any significant statistical relationship between OSA and TpTe marker. Conclusion: Our results showed a positive relation between ECG arrhythmic indices such as QT dispersion and OSA severity in patients with CAD.

The α(1,2)fucosyltransferase (Se enzyme) encoded by FUT2 is involved in the secretor status of ABH(O) blood group antigens. The sedel2 allele is one of the non-functional FUT2 (se) alleles in which 9.3 kb containing the entire coding region of FUT2 is deleted by Alu-mediated nonhomologous recombination. In addition to this allele, three SNPs of FUT2, c.375A>G, c.385A>T, and c.571C>T, appear to be prevalent in certain Oceanian populations such as Polynesians. Recently, we developed an endpoint genotyping assay to determine the sedel2 zygosity, using a FAM-labeled probe for detection of the sedel2 allele and a VIC-labeled probe for detection of FUT2. In this study, instead of the VIC probe, a HEX-labeled probe covering both c.375A>G and c.385A>T and a Cy5-labeled probe covering c.571C>T were added to the sedel2 allele assay mixture to allow simultaneous detection of these four variations by endpoint genotyping for the sedel2 zygosity and fluorescence melting curve analysis for c.375A>G, c.385A>T, and c.571C>T genotyping. The results obtained from 24 Samoan subjects with this method were identical to those obtained with previous methods. Therefore, it appears that present method can accurately determine these four variations simultaneously.

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens increasing tumor elimination efficiency. In the last years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate on patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable to be mathematically modeled. In this work, we developed a three population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities were considered as uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on some specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reduce and optimize the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such in silico laboratory was made available in a Shiny R-based platform called CARTmath. It is an open-source, easy to run simulator, available at github.com/tmglncc/CARTmath or directly on the webpage cartmath.lncc.br, containing this manuscript results as examples and documentation. The developed model, together with the CARTmath platform, provides potential use for assessing different CAR-T cell immunotherapy protocols and associated efficacy, becoming an accessory towards in silico trials.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGene database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined using Mendelian randomization. A total of 169 genes that exerted trans-regulatory impacts on 692 genes were identified. 90% of the genes (N=749) aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. The identified network displayed the scale-free topology. This provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and ALDH2 overexpression contributes to obesity. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The network identified in this study showed scale-free topology indicating the hub genes of a GRN could be targeted to prevent disease outcomes.

This comprehensive article explores the intricate responsibilities of executives leading AI projects within the framework of Federal Directives, specifically Executive Order 14110 and Executive Order 14091. The executive role is dissected, covering aspects such as defining leadership in the AI context, historical perspectives, current trends, and challenges in AI project leadership. The article delves into the significance of Federal Directives, particularly Executive Order 14110, which emphasizes safe, secure, and trustworthy AI development, and Executive Order 14091, focusing on racial equity and support for underserved communities. Key provisions of these orders are outlined, including safe AI development, secure AI implementation, trustworthy AI use, and commitments to racial equity. The article also highlights steps that should guide documenting case studies that align with successful AI projects, showcasing compliance with Executive Orders and positive impacts on communities and organizations. The future outlook focuses on anticipating regulatory changes, adapting to evolving ethical standards, and promoting a culture of continuous improvement within AI projects. The conclusion summarizes executive responsibilities, emphasizing the call to action for ethical and inclusive AI leadership, contributing to the positive evolution of AI technologies for societal well-being.

Several effective online and offline inference tools offer an interactive platform for inference, visualization, and analysis of gene regulatory networks. However, a tool currently needs to offer a scalable, lightweight, integrated online platform for carrying out inference, visualization, benchmarking, and extensive network analysis in an integrated manner. We introduce NetRA (Network Reconstruction and Analysis for Gene Regulatory Network), a comprehensive web tool for network analysis, visualization, and inference of large expression networks. Additionally, a platform for benchmarking and evaluation is provided. In order to deliver a highly scalable, lightweight, and rich user interface, the tool is created using the most recent technologies. We incorporate the original code of eleven (11) inference algorithms (not limited to) from Bioconductor in the current version. We also report a qualitative comparison of 11 candidate methods regarding prediction accuracy and network characteristics which will shed light on their performance against 4000 sizes synthetic DREAM network. We believe the tool will significantly aid biologists' downstream system biology research. NetRA tool can be extensible to different kinds of complex network analyses. Availability: On request (sroy01@cus.ac.in).

Due to their excellent physicochemical properties, fluorinated greenhouse gases (F-gases), including hydrofluorocarbons (HFCs), perfluorocarbons (PFCs), sulfur hexafluoride (SF6), and nitrogen trifluoride (NF3), are used in a variety of applications, but they are potent greenhouse gases. Therefore, they have been blanketed into the list of phase-out under the international protocols or treaties. In this work, the updated statistics of the Taiwan’s national inventory report (NIR) were used to analyze the trends of F-gases (i.e., HFCs, PFCs, SF6 and NF3) emissions during the period of 2000-2020. Furthermore, the regulatory strategies and measures for reducing the emissions of the four F-gases will be summarized to be in accordance with the national and international regulations. With the progressive efforts by the regulatory requirements and the industry’s voluntary reduction, the total F-gases emissions indicated a significant increase from 2,462 kilotons of carbon dioxide equivalents (CO2eq) in 2000 to the peak value (i.e., 12,643 kilotons) of CO2eq in 2004, but sharply decreased from 10,284 kilotons of CO2eq in 2005 to 3,906 kilotons of CO2eq in 2020. It was also found that the most commonly used method for controlling the emissions of F-gases from the semiconductor and optoelectronic industries was based on the thermal destruction-local scrubbing technology.

This study introduces and demonstrates a comprehensive, accurate, unbiased approach to robust quantitative comparison of Electronic Nicotine Delivery Systems (ENDS) appropriate for establishing substantial equivalence (or lack thereof) between tobacco products. The approach is demonstrated across a family of thirteen pen- and pod-style ENDS products. Methods employed consist of formulating a robust emissions surface regression model, quantifying the empirical accuracy of the model as applied to each product, evaluating relationships between product design characteristics and maximum emissions characteristics, and presenting results in formats useful to researchers, regulators, and consumers. Results provide a response surface to characterize emissions (total particulate matter and constituents thereof) from each ENDS appropriate for use in a computer model and for conducting quantitative exposure comparisons between products. Results demonstrate that emissions vary as a function of puff duration, flow rate, E-Liquid composition, and device operating power. Further, results indicate that regulating design characteristics of ENDS devices and consumables may not achieve desired public health outcomes; it is more effective to regulate maximum permissible emissions directly. Three emissions outcome measures (yield per puff, mass concentration and constituent mass ratio) are recommended for adoption as standard quantities for reporting by manufacturers and research laboratories. The approach provides a means of (a) quantifying and comparing maximal emissions from ENDS products spanning their entire operating envelope, (b) comparative evaluation of ENDS devices and consumable design characteristics, and (c) establishing comparative equivalence of maximal emissions from ENDS. A consumer-oriented product emissions dashboard is proposed for comparative evaluation of ENDS exposure potential. Maximum achievable power dissipated in the coil of ENDS is identified as a potentially effective regulatory parameter.

Circular RNAs (circRNAs), which are a class of non-coding RNA with covalently closed loops, play important roles in epigenetics regulation of gene expression at both the transcriptional and post-transcriptional level. Accumulating evidence demonstrated that numerous circRNAs were abnormally expressed in tumors and their dysregulation was involved in the tumorigenesis and metastasis of cancer. Although the functional mechanisms of many circRNAs have been revealed, why circRNAs are dysregulated in cancer remains elusive. CircRNAs are generated by a “backsplicing” process, which is regulated by different cis-regulatory elements and trans-acting proteins. Therefore, how these cis- and trans-elements change during tumorigenesis and how they regulate the biogenesis of circRNAs in cancer are two questions that interest us. In this review, we summarized the pathways for the biogenesis of circRNAs; and then illustrated why circRNAs dysregulated in cancer by discussing the changes of cis-regulatory elements and trans-acting proteins that related to circRNA splicing and maturation in cancer.

We study a minimal model of the stress-driven p53 regulatory network that includes competition between active and mutant forms of the tumor-suppressor gene p53. Depending on the nature of the external stress signal, four distinct dynamical states are observed. These states can be distinguished by dierent dynamical properties and correspond to active, apoptotic, pre-malignant and cancer states. Transitions between any two of these states are found to be unidirectional and irreversible if the stress signal is either oscillatory or constant. When the signal decays exponentially, the apoptotic state vanishes, and for low stress the pre-malignant state is bounded by two critical points, allowing the system to transition reversibly from the active to the pre-malignant state. For signicantly large stress, the range of the pre-malignant state expands and the system moves to the cancerous state which is a stable attractor. This suggests that identification of the pre-malignant state may be important both for therapeutic intervention as well as for drug discovery.

Although Cucurbita pepo is one of the most variable species of the plant kingdom, Zucchini morphotype has undergone intensive breeding that has led to a narrow genetic base making the crop vulnerable to pest and diseases. This vulnerability makes the knowledge of resistance genes of utmost importance. In this study, a data mining search of Zucchini summer squash genome database was conducted to identify and annotate members of the NBS-encoding gene family. In order to characterize the retrieved genes in detail, they have been studied in the bases of phylogenetic relationships, structural diversity, conserved protein motifs, gene duplications and promoter region analysis. Our study shows that the NBS-encoding gene family is relatively small in Zucchini (34 members, which are separated into non-TIR- and TIR-NBS-LRR subfamilies) with a significantly lower number of R-genes than in other species. Duplications have not played a major role in the expansion of this type of genes in C. pepo. Among the cis-regulatory elements presented in these sequences, six motifs are over-represented. These elements were reported to be involved in pathogens or plant stress induced responses. These results will contribute to the identification, isolation and characterization of candidate R-genes, thereby providing insight into NBS gene family evolution in the species.

Computational simulation using mathematical models is a useful method for understanding the complex behavior of a living system. The majority of studies using mathematical models to reveal biological mechanisms uses one of the two main approaches: the bottom-up or the top-down approach. When we aim to analyze a large-scale network, such as a comprehensive knowledge-integrated model of a target phenomenon, for example a whole-cell model, the variation of analyses is limited to particular kind of analysis because of the size and complexity of the model. To analyze a large-scale regulatory network of neural differentiation, we developed a hybrid method that combines both approaches. To construct a mathematical model, we extracted network motifs, subgraph structures that recur more often in a metabolic network or gene regulatory network than in a random network, from a large-scale regulatory network, detected regulatory motifs among them, and combined these motifs. We confirmed that the model reproduced the known dynamics of HES1 and ASCL1 before and after differentiation, including oscillation and equilibrium of their concentrations. The model also reproduced the effects of overexpression and knockdown of the Id2 gene. Our model suggests that the characteristic change in HES1 and ASCL1 expression in the large-scale regulatory network is controlled by a combination of four feedback loops, including a large loop which has not been focused on. The model extracted by our hybrid method has the potential to reveal the critical mechanisms of neural differentiation. The hybrid method is applicable to other biological events.

Based on a large sample of publicly listed and non-listed US commercial banks from 1996 to 2011, we find robust evidence consistent with banks using realized available for sale (AFS) securities gains and losses to smooth earnings and increase low regulatory capital. We also find that (i) banks with positive earnings smooth earnings, and banks with negative earnings generally take big baths; (ii) regulatory capital constrains big baths; (iii) banks with more negative earnings and more unrealized beginning-of-quarter losses (gains) take big baths (smooth earnings); and (iv) banks with low regulatory capital and more unrealized gains realize more gains. Also, banks with negative earnings tak big baths (avoid or reduce the earnings loss) if their unrealized gains are insufficient (sufficient) to offset the negative earnings. Our inferences apply to listed and non-listed banks, which indicates that the earnings management incentives do not derive solely from public capital markets. Our findings reveal that the accounting for AFS securities gains and losses enables banks to manage regulatory capital and earnings in a variety of ways.

Data generation using high throughput technologies has led to the accumulation of diverse types of molecular data.These data have different types (discrete,real,string etc.) and occur in various formats and sizes. Datasets including gene expression, miRNA expression, protein-DNA binding data (ChIP-Seq/ChIP-ChIP), mutation data(copy number variation, single nucleotide polymorphisms), GO annotations, protein-protein interaction and disease-gene association data are some of the commonly used genomic datasets to study biological processes. Each of them provides a unique, complementary and partly independent view of the genome and hence embed essential information about their regulatory mechanisms. In order to understand the functions of genes, proteins and analyze mechanisms arising out of their interactions, information provided by each of these datasets individually may not be sufficient. Therefore integrating these multi-omic data and inferring regulatory interactions from the integrated dataset provides a system level biological insights in predicting gene functions and their phenotypic outcomes. To study genome functionality through interaction networks, different methods have been proposed for collective mining of information from an integrated dataset. We survey here data integration approaches using state-of-the-art techniques such as network integration, Bayesian networks, regularized regression (LASSO) and multiple kernel learning methods.

In chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

We propose that the coexistence of gapless Fermi arcs with the metal-insulator crossover of in-plane resistivity in strongly underdoped cuprates can be explained by the FL* fractionalized Fermi liquid nature of these systems and it is not due simply to disorder effects. The particle excitations of this FL* system derived from variants of the t-J model are: the gapless holon carrying charge with small Fermi momentum proportional to the doping, the gapful spinon carrying spin 1/2, gauge fluctuations coupling them and the hole as a spinon-holon bound state or resonance due to gauge binding with a Fermi surface respecting the topological Luttinger theorem. In our proposal Fermi arcs are determined by the hole resonance, whereas the metal-insulator crossover is dominated by spinon-spinon (with subleading holon-holon) gauge interactions and this dichotomy is able to explain their coexistence.

The oncogenicity of the human cytomegalovirus (CMV) is debated to this day. In recent years, mounting evidence addresses an anti-cancer effect via T cell-mediated CMV-targeted tumor de-struction. However, the data mostly comes from single-center studies and in vitro experiments. Broad geographic coverage is required to offer a global perspective. This study examined the correlation between country-specific CMV seroprevalence (n=73) and age-standardized inci-dence rates for 34 tumors using data obtained from the International Agency for Research on Cancer of the World Health Organization. The association between CMV and cancer incidences in 10-year age increments was also analyzed. The study revealed a worldwide inverse correlation between CMV seroprevalence and incidences of 88.2% tumors. Notably, this inverse link persists for all cancers combined (Spearman’s ρ= -0.732, p= 0.001). An antithetical and significant correlation is also observed in particular age groups for the vast majority of tumors. Our results corroborate the conclusions of previous studies and indicate that this phenomenon holds true on a global scale. It applies to a wide spectrum of cancer histologies, suggesting a common under-lying mechanism – CMV-stimulated T cell tumor targeting. Although these results further advance the notion of CMV-based therapies, further in-depth investigation of host-virus interactions is warranted.

The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (PNE), eosinophil to lymphocyte ratio (ELR) and eosinophil to neutrophil to lymphocytes ratio (ENLR) before and after can-nabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were includ-ed in the study. T. gondii, PNE, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest PNE (p = .02), ELR (p = .03) and ENLR levels (p = .031) and highest increase of PNE (p = .044), and ENLR (p = .036) levels were found in patients after cannabis cessation only in the Toxo+ group. At four weeks, significant interactions between cannabis and T. gondii status for PNE (p = .038), and for ENLR (p = .043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = .049). After cannabis cessation, we found a positive correlation between negative symptoms and PNE levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patient after cannabis cessation.

Human Rhinovirus (HRV) is the most common cause of upper respiratory infections and exacerbations of asthma. In this work, we selected 14 peptides (6 from HRV A and 8 from HRV C) encompassing potential CD4 T cell epitopes. Peptides were selected for being highly conserved in HRV A and C serotypes and predicted to bind to multiple HLA II molecules. We found positive T cell recall responses by IFNγ-ELISPOT assays to 8 peptides, validating 7 of them (3 from HRV A and 4 from HRV C) as CD4 T cell epitopes through intracellular cytokine staining assays. Additionally, we verified their promiscuous binding to multiple HLA II molecules by quantitative binding assays. According to their experimental HLA II binding profile, the combination of all these 7 epitopes could be presented and recognized by > 95 % of the world population. We actually determined IFNγ responses to a pool encompassing these CD4 T cell epitopes by intracellular cytokine staining, finding positive responses in 29 out of 30 donors. The CD4 T cell epitopes identified in this study could be key to monitor HRV infections and to develop peptide-based vaccines against most HRV A and C serotypes.

When swine flu vaccines and circulating influenza A virus (IAV) strains are poorly matched, vaccine-induced antibodies may not protect from infection. Highly conserved T cell epitopes may, however, have a disease-mitigating effect. The degree of T cell epitope conservation among circulating strains and vaccine strains can vary, which may also explain differences in vaccine efficacy. Here, we evaluate a previously developed conserved T cell epitope-based vaccine and determine the persistence of T cell epitope conservation over time. We used a pair-wise homology score to define conservation between the vaccine’s swine leukocyte antigen (SLA) class I and II-restricted epitopes and T cell epitopes found in 1,272 swine IAV strains sequenced between 2013 and 2017. Twenty-four of the 48 total T cell epitopes included in the epitope-based vaccine were highly conserved and found in >1,000 circulating swine IAV strains over the five-year period. In contrast, commercial swine IAV vaccines developed in 2013 exhibited declining conservation with the circulating IAV strains over the same five-year period. Conserved T cell epitope vaccines may be useful adjunct for commercial swine flu vaccines and to improve protection against influenza when antibodies are not cross-reactive.

For several years, drugs bearing reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving drug-protein target spectrum. Studies on natural electrophilic molecules have indicated that in many instances natural electrophiles use similar mechanisms to alter signaling pathways. However, natural reactive species are also endowed with other important mechanisms to hone signaling properties that are uncommon in drug design. These include ability to be active at low occupancy and elevated inhibitor kinetics. Here we discuss how we have begun to harness these properties in inhibitor design.

Chimeric antigen receptors (CARs) is one of the curative immunotherapeutic approaches that exploit the antigen specificity and cytotoxicity function of potent immune cells against cancers. Neuroblastoma, the most common extracranial pediatric solid tumors with diverse comportment, could be a promising candidate for using CARs therapies. Several methods harness CARs modified cells in neuroblastoma to increase therapeutic efficiency, albeit the assessment has still been less successful. Regarding the improvement of CARs, various trials have been launched to overcome insufficient capacity. However, the reason behind the inadequate response against neuroblastoma of CARs modified cells are still not well understood. It is essential to update the present reveal of comprehension of CARs to improve the efficiency of CARs therapies. This review summarizes the crucial features of CARs and its design for neuroblastoma, discusses challenges that impact the outcomes of the immunotherapeutic competence, and focuses on devising strategies currently investigated to improve the efficacy of CARs for neuroblastoma immunotherapy.

The article presents tests aimed to verify the possibility of making T-joints in TMCP steel using laser. The tests involved the use of 10 mm thick high yield point steel S700MC obtained in an industrial manufacturing process. The joints made in the tests were single and double-sided. Subsequent non-destructive tests revealed that the joints obtained in the tests represented quality level B in accordance with PN-EN ISO 13919-1. Single-sided welding performed using the laser beam having a power of 11 kW enabled the obtainment of 8 mm deep penetration without visibly deforming the web of the joint. The double-sided welded joints were characterised by proper geometry and the presence of gas pores in the welds not compromising the requirements of quality level B (strict requirements). The weld structure was bainitic-ferritic. The weld hardness was by approximately 60 HV1 higher than that of the base material (280 HV1). The HAZ area was slightly softer than the base material. The tests of thin foils performed using a high-resolution scanning transmission electron microscope revealed that, during welding, an increase in the content of the base material in the weld was accompanied by an increase in contents of alloying microagents Ti and Nb, particularly near the fusion line. The above-named alloying microagents, in the form of fine-dispersive (Ti,Nb)(C,N) type precipitates, could reduce plastic properties of joints.

Keywords: Agrobacterium 1; Xenorhabdus 2; NR-AMP 3 T-DNA keyword 4; TI-plasmid 5; Intact/Cured/T-DNA Deleted 6 Sensitive/Resistant 7; EMA_PF2 8; HPLC 9

The aim of this article is introduced the concept of double framed T-soft fuzzy set (DFT-soft fuzzy set) which is the combination of soft set and fuzzy set. We also defined the notions and apply this concept in BCK/BCI-algebras. By using example, we also discussed the concept of double framed T-soft fuzzy algebra (DFT-soft fuzzy algebra) and double framed B-soft fuzzy algebra (DFB-soft fuzzy algebra) and also investigated their properties. Each double framed T-soft fuzzy algebra is double framed B-soft fuzzy algebra but by using example, we proved that converse may or may not be possible.

Transcription factors (TFs) are crucial in modulating gene expression and sculpting cellular and organismal phenotypes. The identification of TF-target gene interactions is pivotal for comprehending molecular pathways and disease etiologies but has been hindered by the demanding nature of traditional experimental approaches. This paper introduces a novel web application, utilizing the R programming language, which predicts TF-target gene relationships and vice versa. Our application integrates the predictive power of various bioinformatic tools, leveraging their combined strengths to provide robust predictions. It merges databases for enhanced precision, incorporates gene expression correlation for accuracy, and employs pan-tissue correlation analysis for context-specific insights. The application also enables the integration of user data with established resources to analyze TF-target gene networks. Despite its current limitation to human data, it provides a platform for exploring gene regulatory mechanisms comprehensively. This integrated, systematic approach offers researchers an invaluable tool for dissecting the complexities of gene regulation, with the potential for future expansions to include a broader range of species.

The implementation of residential distributed generation (DG) in South America has shown significant growth in the last decade, driven by increased research on photovoltaics and renewable energy sources. Regulatory policies and business models have been crucial in fostering the adoption of DG in the region, with residential self-supply being the most receptive sector for implementing the concept. This article presents a literature review on DG as applied to residential self-supply in South America by comprehensively analyzing documents published between 2013 and 2023, applying the PRISMA methodology. In total, 37 literature resources have been systematically selected and reviewed to contribute to the identification of trends and developments in the field of DG in the residential sector, as well as highlighting areas that require further research and attention from stakeholders, including policymakers, investors, technology providers and consumers in the South American context.

The optimization of the energy grid is a critical task for ensuring a sustainable and efficient energy future. Deep machine learning techniques have the potential to improve energy grid optimization by predicting energy demands and supplies, optimizing energy production and distribution, and detecting and preventing fraud. However, there are also several challenges associated with the use of deep machine learning in energy grid optimization. These include the lack of standardized datasets and data quality issues, interpretability and explain-ability of machine learning models, ethical and social implications of using machine learning, and integration with existing energy infrastructure and regulatory frameworks. Having a clear understanding that continued research and developments in deep learning applications to energy field are crucial for achieving a sustainable and efficient energy future. This paper therefore reviewed existing literature for challenges and opportunities associated with deep machine learning in energy grid optimization; and highlights the importance of continued research and development in the field. The paper found out that opportunities for future research in deep machine learning for energy grid optimization include advancements in machine learning algorithms and techniques, development of new datasets and data collection methods, integration of machine learning with other emerging technologies. It also established needs for collaborative research and public-private partnerships.

Sulfate transporters (SULTRs) are responsible for the uptake of the sulfate (SO42−) ions in the rhizosphere by the roots and their distribution in plant organs. In this study, SULTR family members in the genome of the two oilseed crops, Camelina sativa, and Brassica napus, were identified and characterized based on their sequence structure, duplication events, phylogenetic relationships, phosphorylation sites, and expression levels. Herein, 36 and 45 putative SULTR genes were recognized from the genome of C. sativa, and B. napus, respectively. SULTR proteins were predicted as basophilic proteins with low hydrophilicity in both studied species. According to phylogenetic relationships, we divided SULTRs into five groups, in which SULTRs 3 showed highest variation. Besides, several duplication events were observed between SULTRs. The first duplication event was predicted approximately five million years ago between three SULTRs 3.1 in C. sativa. Two subunits were indicated in the 3D structure of SULTRs that the active binding sites differed between C. sativa and B. napus. According to available RNA-seq data, SULTRs showed diverse expression in tissues and response to stimuli. SULTRs 3 showed an expression in all tissues. SULTRs 3.1 were more upregulated in response to abiotic stresses in C. sativa, while SULTRs 3.3, and SULTRs 2.1 showed an upregulation in B. napus. Furthermore, SULTRs 3 and SULTRs 4.1 showed an upregulation in response to biotic stresses in B. napus. Based on the distribution of cis-regulatory elements in the promoter region, we speculated that SULTRs might be controlled by phytohormones such as ABA, and MeJA. Therefore, it seems that SULTR genes in C. sativa have been more influenced by evolutionary processes and have acquired more diversity.

Integration of battery energy storage in photovoltaic (PV) systems can reduce the electricity costs and provide desirable flexibility and reliability to these systems decreasing renewable energy fluctuations. This paper presents a review of the PV-battery application in Brazil, highlighting the challenges and prospects based on the state-of-art. A PV-battery systems description is presented in this work, as well as the most applied battery technology and its comparison. The paper also describes the set of applications such as voltage and frequency regulation, renewable energy integration, power quality, etc. In the Brazilian scenario, there are applications of PV-battery systems, most of them part of research and development projects (R&amp;D’s), and some real cases are shown, including its goals, applied equipment, operation modes, strategies, and perspectives. Additionally, this work evaluates the Brazilian scenario regarding the energy storage systems implementation challenges, such as regulatory barriers, business models, and opportunities for R&amp;D in the energy market. In conclusion, it is need develop proper regulatory models to expand PV-battery systems and make them visible to the agents in the electricity sector.

Interleukin-33 (IL-33), a member of the IL-1 cytokine family has been recently associated with the development of autoimmune diseases, including SLE. IL-33 is an alarmin and a pleiotropic cytokine that affects various types of immune cells via binding to its receptor, ST2. In this study, we determine the impact of intraperitoneal IL-33 treatments in young lupus, NZB/W F1 mice. Mice were treated from the age of 6 to 11 weeks. We then assessed the proteinuria level, renal damage, survival rate, and anti-dsDNA antibodies. The induction of regulatory B (Breg) cells and changes in gene expression were also examined. In comparison to the control group, young NZB/W F1 mice administered with IL-33 had a better survival rate as well as reduced proteinuria level and lupus nephritis. IL-33 treatments significantly induced IgM anti-dsDNA antibody, IL-10 expressing Breg cells, and alternatively induced M2 macrophage gene signatures. These results imply that IL-33 exhibit regulatory roles during lupus onset via the expansion of protective IgM anti-dsDNA as well as regulatory cells such as Bregs and M2 macrophages.

Small non-coding RNAs (sRNAs) are ubiquitously found in the three domains of life playing large-scale roles in gene regulation, transposable element silencing, and defense against foreign elements. While a substantial body of experimental work has been done to uncover function of sRNAs in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are still poorly understood. Recently, high throughput studies using RNA-sequencing revealed that sRNAs are broadly expressed in the Archaea, comprising thousands of transcripts within the transcriptome during non-challenged and stressed conditions. Antisense sRNAs, which overlap a portion of a gene on the opposite strand (cis-acting), are the most abundantly expressed non-coding RNAs and they can be classified based on their binding patterns to mRNAs (3’ UTR, 5’ UTR, CDS-binding). These antisense sRNAs target many genes and pathways, suggesting extensive roles in gene regulation. Intergenic sRNAs are less abundantly expressed and their targets are difficult to find because of a lack of complete overlap between sRNAs and target mRNAs (trans-acting). While many sRNAs have been validated experimentally, a regulatory role has only been reported for very few of them. Further work is needed to elucidate sRNA-RNA binding mechanisms, the molecular determinants of sRNA-mediated regulation, whether protein components are involved, and how sRNAs integrate with complex regulatory networks.

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.

To elucidate the cellular immune response to coronavirus disease (COVID-19) among children, we assessed cellular immunity in 8 children post-vaccination for COVID-19 and 11 children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, using the T-SPOT®.COVID assay for both the spike (S) and nucleocapsid (N) proteins. In the vaccinated group, the T-SPOT®.COVID assay for the S protein yielded positive results in all eight children. In contrast, in the post-infection group, the assay for the N protein was positive in 5 of 11 children, with 3 of these 5 children requiring hospital admission, including 2 who needed mechanical ventilation. Therefore, the T-SPOT®.COVID assay is valuable for assessing cellular immunity against COVID-19, and most children infected with COVID-19 may not develop such immunity unless the disease severity is significant.

A Friedmann-Lemaitre-Robertson-Walker space-time model with all curvatures k=0,±1 is explored in f(R,T) gravity. The solutions are obtained via the parametrization of the scale factor that leads to a model transiting from a decelerated universe to an accelerating one. The physical features of the model are discussed and analysed.

Oak woodlands are a keystone ecosystem that may not be sustainable under ongoing fire management regimes and climate change. For example, in 2014, sassafras saplings started to emerge in degraded woodlands at the 1200 ha Drury Conservation Area as part of research at the Bull Shoals Field Station in Taney County, Missouri where burning was initiated in 1999. After Spring (March) 2021 burnt, we examined trend in the potential community and ecosystem effects, we assessed sapling density, height, and specific leave weigh (SLW) of white oak and sassafras (<1.0 m) from fall 2021 through fall 2022. In fall 2021, sassafras density was 560/0.1ha with mean height of 25.42cm and SLW of 0.00436g/cm² while white Oak density was 171/0.1ha with mean height of 10.2cm and SLW of 0.00680g/cm. However, in fall 2022, Sassafras density was 582/0.1ha with mean height of 71.689cm and SLW of 0.00366 g/cm² meanwhile, white Oak density was 213/0.1ha with mean height of 50.544cm and SLW of 0.00563 g/cm². We analyzed mass loss for sassafras and white oak after buried for 198 days. The weight loss for sassafras was 0.857g while oak was 0.790g for 61 days of buried. Subsequent sassafras weight loss was 1.942g, 3.343g, 4.222g and 4.82g while that of white Oak was 1.877g, 2.862g, 3.344g and 4.28g for day 105, 153 and 198 respectively. The nutrients composition and carbon sequestration of sassafras and white oak species need to be determined to better understand the effect of their dominance in fire management regime of degraded oak woodland in Southwest Missouri Ozarks.

The solar heat pump system based on photovoltaic photothermal (PV/T) modules is a new technology that integrates photovoltaics and heat reutilization. It can improve the efficiency of photovoltaic conversion and recovery the remaining heat generated during the photoelectric conversion process, thereby improving the comprehensive efficiency of the whole system. Simulink software is a visual simulation tool, which has the advantages of strong applicability, clear simulation structure and calculation process. The design of its graphical programming greatly simplifies the user modeling process and allows for direct viewing of results, therefore improving the simulation efficiency. At present, there is little research on simulation of solar heat pump systems with PV/T modules based on Simulink software. In this paper, the mathematical models of each component contained in the PV/T solar heat pump system were established based on the system working principle, energy conservation equations and some empirical formulas, and then the operation of the system was simulated by the Simulink software. Due to the operation characteristic of PV/T modules is the key influencing factor for the whole system performance, the model and simulation process for PV/T modules were introduced in detail. The results showed that the surface temperature of PV/T modules under different operating conditions was significantly lower than that of ordinary photovoltaic panels, and the temperature change amplitude was lower. As results, the power generation and photovoltaic conversion efficiency were significantly improved.

CD8 T cells and Natural Killer (NK) cells are cytotoxic lymphocytes important in the response to intracellular pathogens and cancer. Their activity depends on the integration of a large set of intracellular and environmental cues, including antigenic signal, cytokine stimulation and nutrients availability. This integration is achieved by signaling hubs such as the mechanistic target of Rapamycin (mTOR). mTOR is a conserved protein kinase, controlling cellular growth and metabolism in eukaryotic cells and therefore is essential for lymphocyte development and maturation. However, our current understanding of mTOR signaling comes mostly from studies performed in transformed cell lines, which constitute a poor model to comprehend metabolic pathway regulation. Therefore, it is only quite recently that the regulation of mTOR in primary cells has been assessed. Here we review the signaling pathways leading to mTOR activation in CD8 T and NK cells, focusing on activation by cytokines. We also discussed how this knowledge can contribute to immunotherapy development for intracellular pathogen and cancer treatment.

Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells' mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells’ biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironment, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The patients' reactions to radiation are varied, ranging from a complete response to even cancer progression during treatment. This concept illustrates how different levels of mitochondrial metabolism might contribute to this heterogeneity. Considering this notion can help to improve personalized oncological treatments. This article outlines the importance of mitochondrial metabolism in cancer biology and personalized treatments.

In this paper, the concept of fuzzy locally convex spaces generated by a family of fuzzy seminorms is introduced. We prove that a Minkowski functional of zero neighborhoods generates a seminorm and finally deduce that the topology generated by the family of seminorms coincides with that of the Minkowski functional.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

During their complex life cycles, the Apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii employ several genetic switches to regulate their gene expression. One such switch is mediated at the level of translation through upstream Open Reading Frames (uORFs). As uORFs are found in the upstream regions of a majority of genes in both the parasites, it is essential that their roles in translational regulation be appreciated to a greater extent. This review provides a comprehensive summary of studies that show uORF-mediated gene regulation in these parasites and highlights examples of clinically and physiologically relevant proteins that exhibit uORF-mediated regulation. In addition to these examples, several studies that use bioinformatics, transcriptomics, proteomics, and ribosome profiling also indicate the possibility of widespread translational regulation by uORFs. Further analysis of genome-wide datasets will reveal novel genes involved in key biological pathways such as cell-cycle progression, stress-response, and pathogenicity. The cumulative evidence from studies presented in this review suggests that uORFs will play crucial roles in regulating gene expression during clinical disease caused by these important human pathogens.

Synthesis of zeolite T with a variety of desired characteristics necessitate extensive work in the formulation and practical experiments either by conventional hydrothermal methods or aided with different approaches and synthesis techniques such as secondary growth or microwave irradiation. The objectives of this review are to adduce the potential work in zeolite T (Offretite-Erionite) synthesis evaluating determining factors affecting the synthesis and quality of the zeolite T crystals. Attention is given to the extensive studies that interconnect with other significant findings.

It was once thought that high QoS (Quality of Service) performance solves recurrent problems of low-quality multimedia services. Since then, solutions have been proposed to ensure a high level of QoE (Quality of Experience). In this document, the authors attempt to outline their understanding of an accurate meaning of quality of multimedia services. Starting from QoS and passing through generalised QoE, the authors focus on aspects of subjective and objective quality modelling and optimisation of visual performance for TRV (Target Recognition Video) applications (such as video surveillance), outlining the path of ITU-T standardisation in this area. The authors revised the ITU-T Recommendation P.912 to reflect improved subjective test techniques developed since this Recommendation was approved. The authors also attempt to predict at least some existing errors of reasoning, which are likely to become evident for the industry in the next decade.

Although Mast cells are known as key drivers of type I allergic reactions, there is increasing evidence for their critical role in host defense. MCs do not only play an important role in initiating innate immune responses, but also influence the onset, kinetic and amplitude of the adaptive arm of immunity, or fine-tune the mode of the adaptive reaction. Intriguingly, MCs have been shown to affect T cell activation by direct interaction or indirectly by modifying properties of antigen-presenting cells, and can even modulate lymph node-borne adaptive responses remotely from the periphery. In this review, we provide a summary of recent findings that explain how MCs act as a link between the innate and the adaptive immunity, all the way from sensing inflammatory insult to orchestrating the final outcome of the immune response.

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T-cells for targeted cancer therapy. CAR T-cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T-cell therapies were approved by the U. S Food and Drug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T-cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B-cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T-cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This Commentary summarizes the current state of knowledge on CAR T-cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

Inflammatory bowel disease (IBD) has evoked a significant interest in human immunobiology given its tactical immune evasion methodologies resulting in acute immune destabilization. IBD comprising of Crohn’s disease and Ulcerative colitis manifest as chronic inflammation in the gut mucosa, leading to complexities involving immune dysregulation in the T helper lymphocyte arm effecting disease pathogenicity. The mucosa of the alimentary canal is constantly exposed to a myriad of food antigens and luminal microorganisms for which a consistent host-protective mechanism is operative in healthy people. Lowered mucosal immune expression which allows penetration of the epithelial barrier by infective pathogenic microbes, elicits both innate and adaptive immune responses in the gut culminating in aberrant intestinal inflammation. Interestingly, IBD leukocyte repertoire is significantly entwined with chemokine assisted chemotactic navigation into the sites of inflammation which is also thought to generate favourable immune suppressive responses. The functions of the cognate chemokine receptor, CCR6, which binds with its unique ligand CCL20, are expected to tilt the balance between upregulation of homeostatic tolerance and inflammatory pathophysiology. This review aims at critically examining the CCR6 driven immune pathways; T_H1/T_H2, T_H1/T_H17, T_H17/ T_reg, IL-23/IL-17, Akt/ERK-1 /2, ILC3 for systematic investigation of its underlying mechanisms in the future and to underpin its importance in resolving IBD aetiopathology. Thus, CCR6 occupies an exclusive position in gut immunology which renders it an invaluable therapeutic tool for the production of novel medicaments to treat IBD.

During the past two decades there has been a major shift in the choice of agents to treat multiple myeloma, whether newly diagnosed or in the relapsed/refractory stage. The introduction of new drug classes, such as proteasome inhibitors, immunomodulators, and anti-CD38 and anti-SLAMF7 monoclonal antibodies, coupled with autologous stem cell transplantation, have approximately doubled the disease’s five-year survival rate. However, this positive news is tempered by the realization that these measures are not curative and patients eventually relapse and/or become resistant to the drug’s effects. Thus, there is a need to discover newer myeloma-driving molecular markers and develop innovative drugs designed to precisely regulate the actions of such putative targets. B cell maturation antigen (BCMA), which is found almost exclusively on the surfaces of malignant plasma cells to the exclusion of other cell types, including their normal counterparts, has emerged as a specific target of interest in this regard. Immunotherapeutic agents have been at the forefront of research designed to block BCMA activity. These agents encompass monoclonal antibodies, such as the drug conjugate belantamab mafodotin; bispecific T-cell engager strategies exemplified by AMG 420; and chimeric antigen receptor (CAR) T-cell therapeutics that include idecabtagene vicleucel (bb2121) and JNJ-68284528.

Background: Nodal peripheral T-cell lymphomas (nPTCLs) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in the clinical practice. Accurate biomarkers to refine the different subtypes of nPTCLs and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA3 gene expression, and its capability to discriminate the different subtypes of nPTCLs. Patients and Methods: From 2000 to 2017, 80 patients with nPTCLs were eligible for GATA3 gene expression analysis that was assessed retrospectively by quantitative real time PCR (qRT-PCR) of neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE). Results: Median age was 49 years old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years. Of them, 36.3% were classified as PTCL/NOS, 31.2% ALK-negative ALCL, 21.2% ALK-positive ALCL and 11.3% AITL. The majority of cases had advanced stage (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA3 gene expression level was 0.49% (range 0 – 7.07) in all cohort, it was 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL/NOS and 0.67% for AITL. The difference of GATA3 gene expression among distinct variants of nPTCLs was statistically significant (p < 0.001). GATA3 gene expression levels ≥ 0.71% discriminate PTCL/NOS from ALK-negative ALCL and AITL with sensitivity of 62% and specificity of 80.3%. GATA3 gene expression levels ≥ median was associated with poor 2-year OS for PTCL/NOS (46.7% x 21.4%, p=0.04) and for ALK-negative ALCL (85.7% x 54.5%, p=0.04). Conclusion: Despite the relative small and heterogeneous group of patients with nPTCLs, GATA3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL/NOS and ALK-negative ALCL. Moreover it may also discriminate different subtypes of nPTCLs. Further studies with larger series of patients should confirm our findings.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

This review paper presents a comprehensive synthesis of current knowledge on the contamination of water systems by polycyclic aromatic hydrocarbons (PAHs). PAHs, organic contaminants characterized by two or more fused aromatic rings, are notably problematic due to their persistence, bioaccumulation, and significant health risks. The review commences with an examination of various sources of PAHs in aquatic environments, encompassing both anthropogenic activities, such as industrial discharges, urban runoff, and oil spills, and natural phenomena including volcanic eruptions and wildfires. Subsequently, the discussion shifts to the distribution patterns of PAHs within different aquatic ecosystems, with an analysis of factors that influence their transport. Considerable focus is placed on the entry mechanisms of PAHs into water systems and their interactions with diverse environmental matrices. Additionally, the ecotoxicological effects of PAHs on aquatic life are scrutinized, with particular emphasis on molecular, individual, and ecosystemic impacts. This includes an exploration of PAH bioaccumulation in aquatic organisms and their potential mutagenic and carcinogenic consequences. The review further addresses the challenges associated with detecting and quantifying PAHs in aquatic settings, reflecting on the advancements in analytical methodologies and the complexities introduced by their varied physicochemical properties. The paper concludes with a summary of existing regulatory frameworks and guidelines governing PAH contamination in water systems, underscoring the imperative for global collaboration in the monitoring and management of PAH pollution.

Cancer diagnosis stands at the cusp of a profound transformation, driven by the burgeoning capabilities of Artificial Intelligence (AI) and Machine Learning (ML). This comprehensive review illuminates the extraordinary impact of AI and ML in the field, unraveling their multifaceted roles in the realm of oncology. In the arena of cancer diagnosis, AI and ML serve as invaluable allies, empowering healthcare professionals with unparalleled tools for precision and efficiency. Notably, AI's prowess in analyzing medical images, including radiological scans and pathology slides, elevates the early detection of malignancies to new heights. Coupled with its ability to dissect genomic data, AI tailors therapeutic strategies to the individual, promising optimized treatment outcomes. However, the incorporation of AI and ML into clinical practice necessitates a careful navigation of ethical considerations, data privacy, and regulatory landscapes. Safeguarding patient data, ensuring transparency, and addressing algorithmic biases emerge as pivotal challenges that require vigilant attention. Yet, the future of AI and ML in cancer diagnosis is brimming with promise. The integration of multi-modal data, real-time monitoring, and Explainable AI (XAI) methods holds the potential to enrich diagnostic capabilities and engender patient trust. Global collaboration and data sharing initiatives are fostering the development of robust AI models. Furthermore, AI's role in cancer prevention, identifying high-risk individuals and enabling targeted preventive strategies, is poised to revolutionize healthcare. AI and ML are forging a path toward an era of unparalleled accuracy, efficiency, and personalization in cancer diagnosis. Challenges notwithstanding, these technologies bear the promise of fundamentally reshaping patient care, elevating outcomes, and advancing the fight against cancer. The ongoing exploration and responsible implementation of AI and ML in oncology will be pivotal in harnessing their full potential and paving the way for a brighter future for cancer patients.

NADPH is an indispensable cofactor in a wide range of physiological processes which is generated by a family of NADPH-dehydrogenases, where the NADP-dependent malic enzyme (NADP-ME) is one member of these enzymes. Pepper (Capsicum annuum L.) fruit is a horticultural product worldwide consumed which has great nutritional and economic relevance. Besides the phenotypical changes that undergo pepper fruit during ripening, there are many associated modifications at transcriptomic, proteome ic, biochemical, and metabolic levels. Nitric oxide (NO) is a recognized signal molecule that can exert regulatory functions in diverse plant processes. To our knowledge, there is very scarce information about the number of genes encoding for NADP-ME in pepper plants and their expression during the ripening of sweet pepper fruit. Based on a data-mining approach on the pepper plant genome and fruit transcriptome (RNA-seq), five NADP-ME genes were identified, and four of them, namely CaNADP-ME2 to CaNADP-ME5, were expressed in fruit. The time-course expression analysis of these genes during different fruit ripening stages including green immature (G), breaking point (BP), and red ripe (R) showed that they were differentially modulated. Thus, while CaNADP-ME3 and CaNADP-ME5 were upregulated, CaNADP-ME2 and CaNADP-ME4 were downregulated. Exogenous NO treatment of fruit triggered the downregulation of CaNADP-ME4. Furthermore, the analysis of the cis-regulatory elements showed that CaNADP-ME2 and CaNADP-ME5 were positively regulated by the light-responsive element Box4 whereas CaNADP-ME4 was by ABRE (ACGT-containing abscisic acid response element), which is involved in the abscisic acid (ABA) responsiveness. To get deeper knowledge on this enzyme system from fruits, we obtained the 50-75% ammonium-sulfate-enriched protein fraction containing CaNADP-ME enzyme activity, and this was assayed by non-denaturing polyacrylamide gel electrophoresis (PAGE). The results allowed identifying four isozymes designated CaNADP-ME I to CaNADP-ME IV. Taken together, the data provide new pieces of information on the CaNADP-ME system with the identification of five CaNADP-ME genes and how the four genes expressed in pepper fruits are modulated during ripening and by exogenous NO gas treatment.

In recent years, the ecological and economic values of forest plants have been gradually recognized worldwide. However, the growing global demand for new forest plant varieties with higher wood production capacity and better stress tolerance cannot be satisfied by conventional phenotype-based breeding, marker-assisted selection, and genomic selection. In the recent past, diverse omics technologies, including genomics, transcriptomics, epigenomics, proteomics, and metabolomics, have been developed rapidly, providing powerful tools for the precision genetic breeding of forest plants. Genomics lays a solid foundation for understanding complex biological regulatory networks, while other omics technologies provide different perspectives at different levels. Multi-omics integration has combined the different omics technologies, becoming a powerful tool for genome-wide functional element identification in forest plant breeding. This review summarizes the recent progress of omics technologies and their applications in the genetic studies of forest plants. It will provide forest plant breeders with an elementary knowledge of multi-omics techniques for future breeding programs.

As with every new technology, safety demonstration is a critical component of bringing products to market and gaining public acceptance for cultured meat and seafood. This manuscript develops research priorities from the findings from a series of interviews and workshops with governmental scientists and regulators from food safety agencies in fifteen jurisdictions globally.  The interviews and workshops aimed to identify the key safety questions and priority areas of research. Participants raised questions about which aspects of cultured meat and seafood production are novel, and the implications of the paucity of public information on the topic. Novel parameters and targets may require the development of new analytical methods or adaptation and validation of existing ones, including for a diversity of product types and processes. Participants emphasized that data sharing of these efforts would be valuable, similar to those already developed and used in the food and pharmaceutical fields. Contributions to such databases from the private and public sectors would speed general understanding as well as efforts to make evaluations more efficient. In turn, these resources, combined with transparent risk assessment, will be critical elements of building consumer trust in cultured meat and seafood products.

A large variety of fermentation products are used in food and feed production, but also in other industries, and many of these products are produced with genetically modified microorganisms (GMMs). In food and feed production, prominent examples are amino acids, vitamins, food and feed enzymes, colorants, non-caloric sweeteners and human milk oligosaccharides. From a regulatory perspective, fermentation products are typically produced under containment. This means that premises, equipment and work processes need to be designed to prevent or at least minimize release of GMMs into the environment. The fermentation products themselves should not contain any live cells of the GMM. Over the past years, there have been concerning developments, particularly in the European Union, stipulating that also absence of recombinant DNA might be interpreted as a regulatory requirement for fermentation products produced with GMMs. In this paper, we (i) attempt to place these developments into the historical context, (ii) sketch the potential negative repercussions for the food and feed industries, (iii) elaborate on the safety of recombinant DNA, and (iv) postulate that recombinant DNA should remain an integral part of the safety assessment of fermentation products but should not be misconstrued as a criterion for regulatory classification of products of biotechnology.

Blockchain technology can achieve decentralization, multi-party verification, anti-tampering, anonymity, traceability of transactions, and the application of distributed ledger. Countries around the world continue to seek the blockchain business models, technologies and applications, and have different visions and policies for the development of blockchain. This study conducts a comparative policy framework of theoretical analysis of the blockchain technology between the USA and China. Using the innovative policy tools proposed by Rothwell and Zegveld, the above mentioned governments are analyzed from the viewpoint of twelve policy tools. The results show that the USA and China all prefer to use “Environmental-side” policy. The USA has paid more attention to “Legal and regulatory”, “Public services” and “Procurement”. China has the highest proportion of policies in “Political tools”, followed by “Legal & regulatory”, while “Scientific and technical”, “Education” and “Overseas agent” come in third . The blockchain technology has developed vigorously among industries and its applications have gradually diversified. The results are provided to various stakeholders as a reference for policy planning.

Inflammatory bowel disease (IBD) is a CC chemokine receptor 6 (CCR6) - associated immune mediated disorder which has attracted an extensive superfluity of experimental analyses. IBD has come to the fore of varied scrutinizing owing to its complexity by nature for comprising of two synergistic sub phenotypes; Crohn’s disease (CD) and Ulcerative colitis (UC). Both these disease entities cause potent immune dysregulation followed by intense tissue damage within the gut mucosal system, initiating symptoms which are severely debilitating. Multiple causative factors are said to be responsible for IBD but direct immune dysfunction is kindled by overplay of innate and adaptive immune responses produced against a pathogenic microbial attack through the weakened or leaky gut epithelial barrier. Once immune homeostasis is not achieved by tolerating agents, the self-assertive adaptive immunity mobilize its various T and B cell cohorts initializing their allied immune mechanisms by vigorously deploying them towards the site of infection. CCR6 and its unique solitary ligand CC-chemokine ligand 20 (CCL20) are small protein molecules which are abundantly expressed by T and B lymphocytes and act as chemotactic immune-modulatory envoys that help in the deployment of the effector lymphocyte arm of the immune system, producing two directly opposing outcomes in IBD. This dichotomous immunity consists of either immune tolerance or inflammation which then develops into a chronic state, remaining catatonic to inherent immunity or targeted clinical therapy. In this review, we have chronologically identified a plethora of experimental studies radiating into 14 different compartments highlighted in the visual depiction which have employed both mouse models and clinical subjects spanning a period of nearly two decades. In doing so, we expect the research community would further benefit by tracing through the history, thereby understanding the CCR6 –CCL20 axis in IBD and identifying the gaps in literature which can be fortuitously filled in the future.

The self-organisation of a fertilised egg to form a blastocyst structure, which consists of three distinct cell lineages (trophoblast, epiblast and hypoblast) arranged around an off-centre cavity, is unique to mammals. While the starting point (the zygote) and endpoint (the blastocyst) are similar in all mammals, the intervening events have diverged. This review examines and compares the descriptive and functional data surrounding embryonic gene activation, symmetry-breaking, first and second lineage establishment, and fate commitment in a wide range of mammalian orders. The exquisite detail known from mouse embryogenesis, embryonic stem cell studies and the wealth of recent single cell transcriptomic experiments are used to highlight the building principles underlying early mammalian embryonic development.

Over the last decades, cellular immunotherapy has revealed its curative potential. However, the inherent physiological characteristics of immune cells can limit the potency of this approach. Best defined in T cells, dysfunction associated with terminal differentiation, exhaustion, senescence, and activation-induced cell death undermine adoptive cell therapies. In this review, we concentrate on how the multiple mechanisms that articulate the various forms of immune dysfunction impact cellular therapies primarily involving conventional T cells, but also other lymphoid subtypes, in addition to the various strategies put in place to circumvent these effects. The repercussions of immune cell dysfunction across the full life cycle of cell therapy, from the source material, during manufacturing, and after adoptive transfer are discussed. Applicable to cellular products prepared from native and unmodified immune cells, as well as genetically engineered therapeutics, the understanding and potential modulation of dysfunctional features is key to the development of improved cellular immunotherapies.

The Cav3.2 T-type calcium channel is implicated in various pathological conditions, including cardiac hypertrophy, epilepsy, autism, and chronic pain. Phosphorylation of Cav3.2 by multiple kinases plays a pivotal role in regulating its calcium channel function. The calcium/calmodulin-dependent serine/threonine phosphatase, calcineurin, interacts physically with Cav3.2 and modulates its activity. However, it remains unclear whether calcineurin dephosphorylates Cav3.2, the specific spatial regions on Cav3.2 involved, and the extent of the quantitative impact. In this study, we elucidated the serine/threonine residues on Cav3.2 targeted by calcineurin using quantitative mass spectrometry. We identified six serine residues in the N-terminus, II-III loop, and C-terminus of Cav3.2 that were dephosphorylated by calcineurin. Notably, a higher level of dephosphorylation was observed in the Cav3.2 C-terminus, where calcineurin binds to this channel. Additionally, a previously known CaMKII-phosphorylated site, S1198, was found to be dephosphorylated by calcineurin. Furthermore, we also discovered that a novel CaMKII-phosphorylated site, S2137, underwent dephosphorylation by calcineurin. In CAD cells, a mouse central nervous system cell line, membrane depolarization led to an increase in the phosphorylation of endogenous Cav3.2 at S2137. Mutation of S2137 affected the calcium channel function of Cav3.2. Our findings advance the understanding of Cav3.2 regulation not only through kinase phosphorylation but also via calcineurin phosphatase dephosphorylation.

CD4+ T cells orchestrate and regulate immunity within jawed vertebrates, yet our understanding of their evolution, development, and cellular physiology has only begun to be unearthed in the past few decades. Discoveries of genetic diseases that ablate this cellular population have provided insight into their critical functions while transcriptomics, proteomics, and highresolution microscopy have recently revealed new insights into CD4+ T cell anatomy and physiology. This article compiles historical, microscopic, and multi omics data which can be used as a reference atlas to dissect cellular physiology within these influential cells and further understand pathologies like HIV infection that inflict human CD4+ T cells.

The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of tumor microenvironment, Nor-Adrenaline (NA) is poured-in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surface of cancer and immune cells and are often involved in activation of pro-tumoral signaling pathways. β2-adrenergic receptor (β2-AR) is an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate the regulatory immune cells and inhibit the effector immune cells. Blocking β2-AR increases activation, proliferation and cytokine release of T lymphocytes. Moreover β2-AR deficiency during metabolic reprograming of T cells increases mitochondrial membrane potential and biogenesis. In the view of available research data, immunosuppressive role of β2-AR in T cells presents it a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged contemporary knowledge about adrenergic stress mediated β2-AR activation on T lymphocytes inside tumor milieu.

Background: Hepatic interstitial T-lymphocytes (T-Li), Natural Killer (NK) and NK-T cells play an important role in both innate and adaptive immunity and contribute to the regulation of ischemia/reperfusion injury (IRI) after transplantation of abdominal organ. Methods: The cellular concentrations and phenotypes of NK, T-Li, NK-T were analyzed retrospectively in a consecutive series of hepatic perfusates after surgical removal of whole livers on the bench previously collected from adult multi-organ donors after brain death. (DBD), and compared with the demographic and pathological characteristics of the patients transplanted at our Institute with kidneys taken from the same donors. The liver interstitial cells were purified from the perfusate by density gradient centrifugation and the phenotype was determined by flow cytometric investigation using the following immunological markers: CD3, CD4, CD8 and CD56 in order to determine the relative percentage of T-Li, NK-T and NK cells. Results: The perfusates of 42 DBDs, and the related clinical outcome of kidney transplant recipients from 2010 to 2020, were analyzed. T-Li were significantly associated with the time in days of delayed functional recovery of transplanted kidneys (DGF) (p = 0.02), to onset of secondary infection from Cytomegalovirus (p = 0.03). On COX analysis, percent cell concentration of T-Li and time to DGF were significantly associated with an increased relative risk (HR) of organ survival (HR = 1.038, p = 0.04; and HR = 1.029, p = 0.01, respectively). The specificity of the NK and NK-T cell proportions were not associated with any relevant clinical outcomes in kidney transplant patients. Conclusions: The present study points to a new potential role of T-Li cells detected in the context of liver perfusate DBD, and could detect potential impacts in organ allocation, surgical harvesting techniques and in the analysis of IRI pathophysiological events after kidney transplants from multi-organ DBDs.

We analyze the behavior of relativistic spherical objects within the context of modified $f(R,T)$ gravity considering Tolman VI spacetime, where gravitational lagrangian is a function of Ricci scalar(R) and trace of energy momentum tensor(T) i.e,$ f(R,T)= R+ 2\beta T$, for some arbitrary constant $\beta$. For developing our model, we have chosen $\pounds_{m} = -p$, where $ \pounds_{m}$ represents matter lagrangian. For this investigation, we have chosen three compact stars namely PSR J1614-2230 [Mass=(1.97$\pm$ 0.4)M$_\odot$; Radius= 9.69$_{-0.02} ^{+0.02}$ Km] ,Vela X-1 [Mass=(1.77$\pm$ 0.08)M$_\odot$; Radius= 9.560$_{-0.08} ^{+0.08}$ Km] and 4U 1538-52 [Mass=(9.69)M$_\odot$; Radius= 1.97 Km]. In this theory the equation of pressure isotropy is identical to standard Einstein's theory. So all known metric potential solving Einstein's equations are also valid here. In this paper, we have investigated the effort of coupling parameter ($\beta$) on the local matter distribution. Sound of speed and adiabatic index are higher with grater values of $\beta$ while on contrary mass function and gravitational redshift are lower with higher values of $\beta$ . For supporting the theoretical results, graphical representation are also employed to analyze the physical viability of the compact stars.

Novel Cellular Immunotherapy with engineered T cells has improved cancer treatment and established therapeutic promises to prevent tumor formation in clinical studies. Due to certain restrictions and difficulties, CAR and TCR T cells therapies were inadequate at points. CRISPR Cas9 genome-editing tool has a significant potential for these two cell-based therapies. As a specialized gene-editing technique, CRISPR Cas9 is used to repair genetic alternation with minimum damage. It is used as an adjunct to Immunotherapy to stimulate a more robust immune response. CRISPR has long outpaced other target-specific genome editing methods such as ZFNs and TALEN due to its high efficiency, competence in targeting, and stable operating condition. CRISPR can overcome the two major drawbacks of universal CAR T cells: allorejection and graft-vs-host disease. TCR-based T cell treatment can reduce inappropriate binding between endogenous and transgenic TCR, resulting in a reduction of severe toxicity. The CAR and TCR T based cell therapies uphold an excellent future for tumor malignancies This article has elucidated the administration of CRISPR Cas9 in Novel Cellular Immunotherapy, CAR, and TCR T cell therapy. However, this article did not fail to observe this technology's ethical concerns, limitations, and challenges. Furthermore, the article compares CRISPR-mediated allogeneic CAR T cell to TCR-T cell therapy.