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Based on our data, we propose the protein PRMT5 as a regulatory factor to develop strategies to fight against an excessive activity of the MAPK pathway, which could be of use in chronic diseases and cancer.While initial approaches to adoptive T cell therapy relied on the identification and expansion of rare tumour-reactive T cells, genetic engineering has transformed cancer immunotherapy by enabling the modification of primary T cells to increase their therapeutic potential. Specifically, gene editing technologies have been utilized to create T cell populations with improved responses to antigens, lower rates of exhaustion, and potential for use in allogeneic applications. In this review, we provide an overview of T cell therapy gene editing strategies and the delivery technologies utilized to genetically engineer T cells. We also discuss recent investigations and clinical trials that have utilized gene editing to enhance the efficacy of T cells and broaden the application of cancer immunotherapies.

genetic susceptibility to infection is mediated by numerous host factors, including the highly diverse, classical human leukocyte antigen (HLA) genes, which are critical genetic determinants of immunity. We systematically evaluated the effect of HLA alleles and haplotypes on susceptibility to 12 common enteric infections in children during the first year of life in an urban slum of Dhaka, Bangladesh.

a birth cohort of 601 Bangladeshi infants was prospectively monitored for diarrhoeal disease. Each diarrhoeal stool sample was analyzed for enteric pathogens by multiplex TaqMan Array Card (TAC). High resolution genotyping of HLA class I (A and B) and II (DRB1, DQA1, and DQB1) genes was performed by next-generation sequencing. We compared the frequency of HLA alleles and haplotypes between infected and uninfected children.

we identified six individual allele associations and one five-locus haplotype association. One allele was associated with protection A*2402 - EAEC. Five alleles were associated with increased risk A*2417 - typical EPEC, B*1501 - astrovirus, B*3802 - astrovirus, B*3802 - Cryptosporidium and DQA1*0101 - Cryptosporidium. A single five-locus haplotype was associated with protection A*1101~B*1502~DRB1*1202~DQA1*0601~DQB1*0301- adenovirus 40/41.

our findings suggest a role for HLA in susceptibility to early enteric infection for five pathogens. Understanding the genetic contribution of HLA in susceptibility has important implications in vaccine design and understanding regional differences in incidence of enteric infection.

this research was supported by the National Institute of Health (NIH) and the Bill and Melinda Gates Foundation.

this research was supported by the National Institute of Health (NIH) and the Bill and Melinda Gates Foundation.The effect of aerobic/anoxic duration on the performance, microbial community and enzymatic activity of sequencing batch biofilm reactor (SBBR) were investigated in treating mariculture wastewater. The microbial oxygen uptake rate and nitrifying rate gradually decreased with the aerobic/anoxic duration from 120/210 to 30/300 min, whereas the nitrite reducing rate and nitrate reducing rate had the opposite results. The activities of dehydrogenase, ammonia monooxygenase and nitrite oxidoreductase gradually decreased with the aerobic/anoxic duration from 120/210 to 30/300 min, but the activities of nitrate reductase and nitrite reductase had a gradual increment. The microbial nitrogen removal rates had similar changing trends to their corresponding enzymatic activities at different aerobic/anoxic duration. The variation of aerobic/anoxic duration obviously affected the microbial richness and diversity of SBBR. The co-occurrence, keystone taxa and significant difference of microbial community had some changes with the aerobic/anoxic duration from 120/210 to 30/300 min.Rigorous process models provide a reliable basis for model-based monitoring and control of anaerobic digestion plants. Due to the complex model structure and non-linear system characteristics, the established Anaerobic Digestion Model No. 1 (ADM1) is rarely applied in industrial plant operation. The present investigation proposes a systematic procedure for successive model simplification and presents the description of five model variants of a mass-based ADM1. Individual model structures greatly differ in their number of implemented process phases, characteristic components and required parameters. Simplified model variants combine nutrient degradation and biogas formation based on first-order sum reactions, whereas complex model structures describe individual degradation pathways and intermediates during acido- and acetogenesis. Characteristic features of the derived model structures as well as the stoichiometric methane potentials and microbial biomass yields of the underlying degradation pathways of individual model variations are evaluated and discussed in detail.The impact of wastewater cultivation was studied on pollutant removal, biomass production, and biosynthesis of high-value metabolites by newly isolated cyanobacteria namely Acaryochloris marina BERC03, Oscillatoria sp. BERC04, and Pleurocapsa sp. BERC06. During cultivation in urabn wastewater, its pH used to adjust from pH 8.0 to 11, offering contamination-free cultivation, and flotation-based easy harvesting. Besides, wastewater cultivation improved biomass production by 1.3-fold when compared to control along with 3.54-4.2 gL-1 of CO2 fixation, concomitantly removing suspended organic matter, total nitrogen, and phosphorus by 100%, 53%, and 88%, respectively. Biomass accumulated 26-36% carbohydrates, 15-28% proteins, 38-43% lipids, and 6.3-9.5% phycobilins, where phycobilin yield was improved by 1.6-fold when compared to control. Lipids extracted from the pigment-free biomass were trans-esterified to biodiesel where pigment extraction showed no negative impact on quality of the biodiesel. These strains demonstrated the potential to become feedstock of an integrated biorefinery using urban wastewater as low-cost growth media.

Organophosphate esters (OPEs) are a class of flame retardants in common use. OPEs can easily leach from materials, resulting in human exposure. Increasing concentrations have been reported in human populations over the past decade. Recent studies have linked prenatal OPE exposure to hyperactivity and attention problems in children. Such behaviors are often found among children with attention-deficit hyperactivity disorder (ADHD), however, no study has investigated OPEs in relation to clinically assessed ADHD.

To evaluate prenatal exposure to OPEs as risk factors for clinically assessed ADHD using a case-cohort study nested within the Norwegian Mother, Father, and Child Cohort Study (MoBa).

We included in the case group 295 ADHD cases obtained via linkage with the Norwegian Patient Registry, and the sub-cohort group 555 children sampled at baseline, irrespective of their ADHD case status. Prenatal concentrations of OPE metabolites were measured in maternal urine collected at 17weeks of gestation, and inc88 [0.62, 1.26]) or BBOEP (1.03 [0.73, 1.46]) during pregnancy. Simultaneously decreasing all constituents of common-detect OPE-phthalate mixture, specifically DPHP, DNBP, and 6 phthalate metabolites, by a quartile resulted in an ADHD risk ratio of 0.68 [0.64, 0.72].

Prenatal exposure to DPHP and BDCIPP may increase the risk of ADHD. For DPHP, we observed potential modification by child sex and maternal PON1 Q192R genotype and partial mediation through maternal thyroid hormone imbalance at 17weeks gestation.

Prenatal exposure to DPHP and BDCIPP may increase the risk of ADHD. For DPHP, we observed potential modification by child sex and maternal PON1 Q192R genotype and partial mediation through maternal thyroid hormone imbalance at 17 weeks gestation.Experimental evidence has demonstrated the ability of transient pulses of electric fields to alter mammalian cell behavior. Strategies with these pulsed electric fields (PEFs) have been developed for clinical applications in cancer therapeutics, in-vivo decellularization, and tissue regeneration. Successful implementation of these strategies involve understanding how PEFs impact the cellular structures and, hence, cell behavior. Fosbretabulin The caveat, however, is that the PEF parameter space (i.e., comprising different pulse widths, amplitudes, number of pulses) is large, and design of experiments to explore all possible combinations of pulse parameters is prohibitive from a cost and time standpoint. In this study, a scaling law based on the Ising model is introduced to understand the impact of PEFs on the outer cell lipid membrane so that an understanding developed in one PEF pulse regime may be extended to another. Combining non-Markovian Monte Carlo techniques to determine density-of-states with a novel non-equilibrium thermodynamic framework based on the principle of steepest entropy ascent, the applicability of this scaling model to predict the behavior of both thermally quenched and electrically perturbed lipid membranes is demonstrated. A comparison of the predictions made by the steepest-entropy-ascent quantum thermodynamic (SEAQT) framework to experimental data is performed to validate the robustness of this computational methodology and the resulting scaling law.

Clinical training for new graduate nurses has a positive impact on their clinical competence; however, there is limited evidence on the impact of this training at the organizational level and on the processes that mediate these impacts.

To identify the individual and organizational impacts of a clinical training system and the mechanism that produces them by exploring nurses' perceptions of the changes in health facilities after the introduction of a standardized clinical training system in Vietnam.

Qualitative research using an ethnographic approach; photovoice was used to obtain insights into nurses' perceptions.

Health facilities of four provinces and one city in Vietnam participated in the Project for Strengthening of the Clinical Training System for New Graduate Nurses.

New graduate nurses, preceptors, and managers who engaged in the clinical training program.

Qualitative data, including photographs, were collected through photovoice sessions and inductively analyzed using thematic analysis.

health outcome.

The novel clinical training system for new graduate nurses could strengthen nurses' competencies and facilitate organizational changes to actualize a positive impact on nursing care and nurses' status. These findings could facilitate the design of an effective training program to stimulate organizational learning to produce better health outcome.The most dangerous form of leishmaniasis is Visceral leishmaniasis (VL). The elimination of VL depends not only on agent treatments but also on effective vaccines against Leishmania parasites. Epitope-based vaccines composed of alternative short antigenic epitopes have the advantages of MHC epitope easy designing, which has broad application prospects. In a previous study, we analyzed Leishmania Gp63, Kmp-11 and Amastin protein sequence in silico, and found that the amino acid fragments of Gp63 (138-360aa), Kmp-11 (1-91aa) and Amastin (1-72aa) were rich in dominant epitopes. In this study, we used the three amino acid fragments as multi-epitope vaccine candidates to construct DNA and protein vaccines. BALB/c mice were vaccinated with the DNA and protein vaccines by DNA prime-protein boost strategy and challenged with Leishmania promastigotes. To evaluate vaccine immunogenicity and immunoprotection, serum specific antibody titers and cytokines were detected using ELISA, splenic CD3+, CD4+ and CD8+ cells were analyzed by flow cytometry, livers were made into pathological sections to observe pathological changes, and splenic parasitic loads were quantified using qPCR.