C. perfringens type D strains are the leading cause of enterotoxaemia in ruminants such as goats, sheep, and cattle. However, there has been no prior research on the genomic characteristics of C. perfringens type D strains from various regions in China. Here, we investigated the antibiotic resistance, genomic characteristics, and phylogenetic relationship of C. perfringens type D isolates recovered from goat farms in Shaanxi, Gansu, and Ningxia provinces. The antibiotic resistance test indicated that the isolates displayed high minimum inhibitory concentration (MIC) values to sulfafurazole, whereas the other antibiotics tested, such as penicillin, enrofloxacin, and florfenicol, worked well on them. Additionally, only tetracycline resistance genes [tetA(P) and tetB(P)] were identified from the isolates. A collective of 13 toxin genes, including etx and cpe were detected among the isolates. Sequence comparison revealed that the etx and cpe genes shared high sequence identities, and they could coexist on a pCW3-like plasmid, representing a potential risk to both animal breeding and public health. Phylogenetic analysis using core genome multi-locus sequence typing (cgMLST) and core genome single nucleotide polymorphisms (SNPs) revealed the close genetic relationship and potential regional/transregional transmission of the C. perfringens type D isolates in Shaanxi and Gansu provinces. Furthermore, pan-genomic analysis suggested the functional differences at the protein-coding gene level, although isolates from the same source shared a close genetic relationship. In conclusion, this study indicated the antibiotic resistance, virulence markers, potential transregional transmission, and genomic diversity of C. perfringens type D strains from various regions in China, which could provide references for the prevention of C. perfringens foodborne diseases and further research.
BACKGROUND: The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro. METHODS: Six-week-old C57BL/6J mice were administered with D-galactose (200 mg/kg/day, intraperitoneally) for 8weeks, followed by daily subcutaneous injections of GLP-2 (300 or 600 µg/kg/day) for 4weeks. Skeletal muscle function and mass were evaluated using relative grip strength and muscle weight. The sizes and types of muscle fibers and apoptosis were assessed through histological analysis, immunofluorescence staining, and TUNEL staining, respectively. C2C12 myotubes were treated with D-galactose (40 mg/mL) and GLP-2. Protein expression of differentiation-related myogenic differentiation factor D (MyoD), myogenin (MyoG), and myosin heavy chain (Myhc), degradation-related Muscle RING finger 1 (MuRF-1), and muscle atrophy F-box (MAFbx)/Atrogin-1, and apoptosis-related B-cell leukemia/lymphoma 2 (Bcl-2) and Bax, were assessed using western blots. The Pi3k inhibitor LY294002 was applied to investigate whether GLP-2 regulated myogenesis and myotube aging via IGF-1/Pi3k/Akt/FoxO3a signaling pathway. RESULTS: The results demonstrated that GLP-2 significantly reversed the decline in muscles weight, relative grip strength, diameter, and cross-sectional area of muscle fibers induced by D-galactose in mice. Apart from suppressing the expressions of MuRF-1 and Atrogin-1 in the muscles and C2C12 myotubes, GLP-2 significantly increased the expressions of MyoD, MyoG, and Myhc compared to the D-galactose. GLP-2 significantly suppressed cell apoptosis. Western blot analysis indicated that the regulation of GLP-2 may be attributed to the activation of theIGF-1/Pi3k/Akt/FoxO3a phosphorylation pathway. CONCLUSIONS: This study suggested that GLP-2 ameliorated D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a pathway.
Concurrent readout of sequence and base modifications from long unamplified DNA templates by Pacific Biosciences of California (PacBio) single-molecule sequencing requires large amounts of input material. Here we adapt Tn5 transposition to introduce hairpin oligonucleotides and fragment (tagment) limiting quantities of DNA for generating PacBio-compatible circular molecules. We developed two methods that implement tagmentation and use 90-99% less input than current protocols: (1) single-molecule real-time sequencing by tagmentation (SMRT-Tag), which allows detection of genetic variation and CpG methylation; and (2) single-molecule adenine-methylated oligonucleosome sequencing assay by tagmentation (SAMOSA-Tag), which uses exogenous adenine methylation to add a third channel for probing chromatin accessibility. SMRT-Tag of 40 ng or more human DNA (approximately 7,000 cell equivalents) yielded data comparable to gold standard whole-genome and bisulfite sequencing. SAMOSA-Tag of 30,000-50,000 nuclei resolved single-fiber chromatin structure, CTCF binding and DNA methylation in patient-derived prostate cancer xenografts and uncovered metastasis-associated global epigenome disorganization. Tagmentation thus promises to enable sensitive, scalable and multimodal single-molecule genomics for diverse basic and clinical applications.
The lining structures of tunnels are typically constructed using sprayed or cast concrete materials, and their performance and quality during tunnel excavation and blasting are crucial for the stability and safety of tunnels. Therefore, the safe distance between the lining structure and blasting source should be determined to avoid concrete damage caused by blasting vibrations. In this study, taking the subway tunnel of Danshan Station in Qingdao as an example, the JH-2 model is introduced as the constitutive model of the tunnel blasting simulation, and the JH-2 model parameters of the local surrounding rock are obtained by experiments, and finally the numerical simulation and theoretical verification are carried out to study the safety distance of shotcrete under various safety judgment standards. The results indicate that the JH-2 model can effectively simulate the propagation of stress waves under different media conditions, and the closer the strength parameters and pressure constant of the lining structure are to those of the surrounding rock, the safer the concrete-rock bonding interface. During tunnel blasting construction using the ring blasting method, the peak particle velocity (PPV) of the lining structure increases with an increase in the arch angle. Based on the numerical simulation results, we recommend that concrete lining be constructed at a distance of at least 62 m from the blasting source to avoid damage caused by vibrations. The effect of concrete tensile failure caused by longitudinal stress is much smaller than the damage to the bonding interface caused by the PPV and can be neglected.
The molecular weight (MW) of an enzyme is a critical parameter in enzyme-constrained models (ecModels). It is determined by two factors: the presence of subunits and the abundance of each subunit. Although the number of subunits (NS) can potentially be obtained from UniProt, this information is not readily available for most proteins. In this study, we addressed this gap by extracting and curating subunit information from the UniProt database to establish a robust benchmark dataset. Subsequently, we propose a novel model named DeepSub, which leverages the protein language model and Bi-directional Gated Recurrent Unit (GRU), to predict NS in homo-oligomers solely based on protein sequences. DeepSub demonstrates remarkable accuracy, achieving an accuracy rate as high as 0.967, surpassing the performance of QUEEN. To validate the effectiveness of DeepSub, we performed predictions for protein homo-oligomers that have been reported in the literature but are not documented in the UniProt database. Examples include homoserine dehydrogenase from Corynebacterium glutamicum, Matrilin-4 from Mus musculus and Homo sapiens, and the Multimerins protein family from M. musculus and H. sapiens. The predicted results align closely with the reported findings in the literature, underscoring the reliability and utility of DeepSub.
Databases, Protein , Deep Learning , Protein Subunits , Protein Subunits/chemistry , Protein Subunits/metabolism , Animals , Humans , Protein Multimerization , Mice , Computational Biology/methods
Bacteria-based therapies are powerful strategies for cancer therapy, yet their clinical application is limited by a lack of tunable genetic switches to safely regulate the local expression and release of therapeutic cargoes. Rapid advances in remote-control technologies have enabled precise control of biological processes in time and space. We developed therapeutically active engineered bacteria mediated by a sono-activatable integrated gene circuit based on the thermosensitive transcriptional repressor TlpA39. Through promoter engineering and ribosome binding site screening, we achieved ultrasound (US)-induced protein expression and secretion in engineered bacteria with minimal noise and high induction efficiency. Specifically, delivered either intratumorally or intravenously, engineered bacteria colonizing tumors suppressed tumor growth through US-irradiation-induced release of the apoptotic protein azurin and an immune checkpoint inhibitor, a nanobody targeting programmed death-ligand 1, in different tumor mouse models. Beyond developing safe and high-performance designer bacteria for tumor therapy, our study illustrates a sonogenetics-controlled therapeutic platform that can be harnessed for bacteria-based precision medicine.
Background: Anxiety and depression are prevalent mental disorders. As modern society continues to face mounting pressures, the incidence of anxiety and depression is on the rise. In recent years, there has been an increasing breadth of research exploring the relationship between anxiety, depression, and physical activity (PA). However, the current research progress and future development trends are unclear. The purpose of this study is to explore the research hotspots and development trends in this field, and to provide guidance for future studies and to provide some reference for clinicians. Methods: We searched the relevant literature of Web of Science Core Collection from the establishment of the database to August 15, 2023. CiteSpace, VOSviewer and Bibliometrix Packages based on the R language were used to analyze the number of publications, countries, institutions, journals, authors, references, and keywords. Results: A total of 1,591 studies were included in the analysis, and the research in the field of PA on anxiety or depression has consistently expanded. The USA (304 publications), Harvard University (93 publications), and the journal of affective disorders (97 publications) were the countries, institutions, and journals that published the highest number of articles, respectively. According to the keywords, students and pregnant women, adult neurogenesis, and Tai Chi were the groups of concern, physiological and pathological mechanisms, and the type of PA of interest, respectively. Conclusion: The study of PA on anxiety or depression is experiencing ongoing expansion. Clinicians can consider advising patients to take mind-body exercise to improve mood. In addition, future researchers can explore the mind-body exercise and its impact on anxiety or depression, PA and anxiety or depression in specific populations, and adult neurogenesis of various exercise in anxiety or depression.
INTRODUCTION: Considering the increasing incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI) worldwide, there is an urgent need to identify efficacious, safe and convenient treatments. Numerous investigations have been conducted on the use of supplements in this domain, with oral supplementation emerging as a viable therapeutic approach for AD or MCI. Nevertheless, given the multitude of available supplements, it becomes imperative to identify the optimal treatment regimen. METHODS AND ANALYSIS: Eight academic databases and three clinical trial registries will be searched from their inception to 1 June 2023. To identify randomised controlled trials investigating the effects of supplements on patients with AD or MCI, two independent reviewers (X-YZ and Y-QL) will extract relevant information from eligible articles, while the risk of bias in the included studies will be assessed using the Rob 2.0 tool developed by the Cochrane Collaboration. The primary outcome of interest is the overall cognitive function. Pair-wise meta-analysis will be conducted using RevMan V.5.3, while network meta-analysis will be carried out using Stata 17.0 and ADDIS 1.16.8. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The GRADE system will be employed to assess the quality of evidence. This study is scheduled to commence on 1 June 2023 and conclude on 1 October 2023. ETHICS AND DISSEMINATION: Ethics approval is not required for systematic review and network meta-analysis. The results will be submitted to a peer-reviewed journal or at a conference. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42023414700).
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/drug therapy , Network Meta-Analysis , Systematic Reviews as Topic , Cognitive Dysfunction/therapy , Cognition , Dietary Supplements , Meta-Analysis as Topic
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy, largely due to the paucity of reliable biomarkers for early detection and therapeutic targeting. Existing blood protein biomarkers for PDAC often suffer from replicability issues, arising from inherent limitations such as unmeasured confounding factors in conventional epidemiologic study designs. To circumvent these limitations, we use genetic instruments to identify proteins with genetically predicted levels to be associated with PDAC risk. Leveraging genome and plasma proteome data from the INTERVAL study, we established and validated models to predict protein levels using genetic variants. By examining 8,275 PDAC cases and 6,723 controls, we identified 40 associated proteins, of which 16 are novel. Functionally validating these candidates by focusing on 2 selected novel protein-encoding genes, GOLM1 and B4GALT1, we demonstrated their pivotal roles in driving PDAC cell proliferation, migration, and invasion. Furthermore, we also identified potential drug repurposing opportunities for treating PDAC. SIGNIFICANCE: PDAC is a notoriously difficult-to-treat malignancy, and our limited understanding of causal protein markers hampers progress in developing effective early detection strategies and treatments. Our study identifies novel causal proteins using genetic instruments and subsequently functionally validates selected novel proteins. This dual approach enhances our understanding of PDAC etiology and potentially opens new avenues for therapeutic interventions.
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Proteome , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/genetics , Glycosyltransferases , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Biomarkers , Membrane Proteins
The aim of this study was to investigate if the supplementation of folic acid and taurine can relieve the adverse effects of different levels of heat stress (HS) on growth performance, physiological indices, antioxidative capacity, immunity, rumen fermentation and microbiota. A total of 24 Dorper × Hu crossbred lambs (27.51 ± 0.96 kg) were divided into four groups: control group (C, 25 °C), moderate HS group (MHS, 35 °C), severe HS group (SHS, 40 °C), and the treatment group, under severe HS (RHS, 40 °C, 4 and 40 mg/kg BW/d coated folic acid and taurine, respectively). Results showed that, compared with Group C, HS significantly decreased the ADG of lambs (p < 0.05), and the ADG in the RHS group was markedly higher than in the MHS and SHS group (p < 0.05). HS had significant detrimental effects on physiological indices, antioxidative indices and immune status on the 4th day (p < 0.05). The physiological indices, such as RR and ST, increased significantly (p < 0.05) with the HS level and were significantly decreased in the RHS group, compared to the SHS group (p < 0.05). HS induced the significant increase of MDA, TNF-α, and IL-ß, and the decrease of T-AOC, SOD, GPx, IL-10, IL-13, IgA, IgG, and IgM (p < 0.05). However, there was a significant improvement in these indices after the supplementation of folic acid and taurine under HS. Moreover, there were a significant increase in Quinella and Succinivibrio, and an evident decrease of the genera Rikenellaceae_RC9_gut_group and Asteroleplasma under HS (p < 0.05). The LEfSe analysis showed that the genera Butyrivibrio, Eubacterium_ventriosum_group, and f_Bifidobacteriaceae were enriched in the MHS, SHS and RHS groups, respectively. Correlated analysis indicated that the genus Rikenellaceae_RC9_gut_group was positively associated with MDA, while it was negatively involved in IL-10, IgA, IgM, and SOD (p < 0.05); The genus Anaeroplasma was positively associated with the propionate and valerate, while the genus Succinivibrio was negatively involved in TNF-α (p < 0.05). In conclusion, folic acid and taurine may alleviate the adverse effects of HS on antioxidant capacity, immunomodulation, and rumen fermentation of lambs by inducing changes in the microbiome that improve animal growth performance.
The death of coronavirus disease 2019 (COVID-19) is primarily due to from critically ill patients, especially from ARDS complications caused by SARS-CoV-2. Therefore, it is essential to contribute an in-depth understanding of the pathogenesis of the disease and to identify biomarkers for predicting critically ill patients at the molecular level. Immunogenic cell death (ICD), as a specific variant of regulatory cell death driven by stress, can induce adaptive immune responses against cell death antigens in the host. Studies have confirmed that both innate and adaptive immune pathways are involved in the pathogenesis of SARS-CoV-2 infection. However, the role of ICD in the pathogenesis of severe COVID-19 has rarely been explored. In this study, we systematically evaluated the role of ICD-related genes in COVID-19. We conducted consensus clustering, immune infiltration analysis, and functional enrichment analysis based on ICD differentially expressed genes. The results showed that immune infiltration characteristics were altered in severe and non-severe COVID-19. In addition, we used multiple machine learning methods to screen for five risk genes (KLF5, NSUN7, APH1B, GRB10 and CD4), which are used to predict COVID-19 severity. Finally, we constructed a nomogram to predict the risk of severe COVID-19 based on the classification and recognition model, and validated the model with external data sets. This study provides a valuable direction for the exploration of the pathogenesis and progress of COVID-19, and helps in the early identification of severe cases of COVID-19 to reduce mortality.
COVID-19 , Humans , COVID-19/genetics , SARS-CoV-2/genetics , Critical Illness , Immunogenic Cell Death , Machine Learning
Purpose: Chinese herbal medicine and electroacupuncture (EA) have been used to control pain for many decades in China. We aim to explore the efficacy of intervening patients whose discogenic sciatica symptoms lasting longer than 3 months with these conservative treatments. Patients and Methods: This is a single-center, parallel-group, patient-unblinded Randomized Controlled Trial (RCT) with blinded outcome assessment and statistician. One hundred and twenty-four patients will be assigned randomly into 2 groups including conservative treatment group (Shenxie Zhitong capsule combined with EA treatment) and Nonsteroidal Anti-inflammatory Drugs (Nonsteroidal Anti-inflammatory Drugs, NSAIDs) control group (Celecoxib) in a 1:1 ratio. The trial involves a 4-week treatment along with follow-up for 6 months. The primary outcome is the leg pain intensity measured by the visual analogue scale (VAS) at 6 months after randomization. Secondary outcomes include leg pain intensity at other time points, back pain intensity, leg pain and back pain frequency, functional status, quality of life, return to work status and satisfaction of patients. Adverse events will also be recorded. Strengths and Limitations of This Study: Through this study, we want to observe the efficacy of electroacupuncture combined with Chinese herbal medicine on pain intensity for chronic sciatica secondary to Lumbar Disc Herniation. If the final results are favorable, it is expected to be a safe, economical, and effective treatment for patients. The study design has the following limitations: the setup of control group was less than perfect; patients and doctors could not be blinded in this trial; we skipped the feasibility study. We have tried our best to minimize adverse impacts. Trial Registration: ChiCTR2300070884 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 25th April 2023).
Genome-scale metabolic models (GEMs) have been widely employed to predict microorganism behaviors. However, GEMs only consider stoichiometric constraints, leading to a linear increase in simulated growth and product yields as substrate uptake rates rise. This divergence from experimental measurements prompted the creation of enzyme-constrained models (ecModels) for various species, successfully enhancing chemical production. Building upon studies that allocate macromolecule resources, we developed a Python-based workflow (ECMpy) that constructs an enzyme-constrained model. This involves directly imposing an enzyme amount constraint in GEM and accounting for protein subunit composition in reactions. However, this procedure demands manual collection of enzyme kinetic parameter information and subunit composition details, making it rather user-unfriendly. In this work, we've enhanced the ECMpy toolbox to version 2.0, broadening its scope to automatically generate ecGEMs for a wider array of organisms. ECMpy 2.0 automates the retrieval of enzyme kinetic parameters and employs machine learning for predicting these parameters, which significantly enhances parameter coverage. Additionally, ECMpy 2.0 introduces common analytical and visualization features for ecModels, rendering computational results more user accessible. Furthermore, ECMpy 2.0 seamlessly integrates three published algorithms that exploit ecModels to uncover potential targets for metabolic engineering. ECMpy 2.0 is available at https://github.com/tibbdc/ECMpy or as a pip package (https://pypi.org/project/ECMpy/).
Backgrounds: Glioma is a highly aggressive type of brain tumor, and its prognosis is still poor despite recent progress in treatment strategies. G protein-coupled receptor 27 (GPR27) is a member of the G protein-coupled receptor family and has been reported to be involved in various cellular processes, including tumor progression. Nevertheless, the clinical potential and tumor-related role of GPR27 in glioma remain unknown. Here we aimed to explore the function and role of GPR27 in gliomas. Methods: In the current study, we evaluated the expression and clinical significance of GPR27 in gliomas using data from The Cancer Genome Atlas (TCGA) datasets. We also conducted cellular experiments to evaluate the functional role of GPR27 in glioma cell growth. Results: We found that GPR27 expression level was closely associated with disease status of glioma. Of note, GPR27 was negatively correlated with WHO grade, with grade IV samples showing the lowest GPR27 levels, while grade II samples showed the highest levels. Patients with IDH mutation or 1p/19q co-deletion exhibited higher GPR27 levels. In addition, lower GPR27 levels were correlated with higher death possibilities. In cellular experiments, we confirmed that GPR27 inhibited glioma cell growth. Conclusions: Our results indicate that GPR27 may function as a potential prognostic biomarker and therapeutic target in gliomas. Further studies are needed to illustrate the signaling mechanism and clinical implications of GPR27 in gliomas.
Brain Neoplasms , Glioma , Humans , Brain Neoplasms/genetics , Chromosome Aberrations , Glioma/genetics , Mutation , Neoplastic Processes , Receptors, G-Protein-Coupled/genetics
OBJECTIVE: To analyze the clinical phenotype and genetic characteristics of a patient with Isidor-Toutain spinal epiphyseal dysplasia (SEMD) due to variant of RPL13 gene. METHODS: A pregnant woman at 18 weeks of gestation who had presented at Quzhou Maternal and Child Health Care Hospital on January 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the patient, and candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The woman was 37 years old with extremely short stature (135 cm) and "O" shaped legs. WES revealed that she has harbored a c.548G>C (p.Arg183Pro) missense variant of the RPL13 gene (NM_000977.4). The same variant was not found in her fetus. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4). CONCLUSION: Isidor-Toutain type SEMD due to variants of the RPL13 gene may have variable expressivity and diverse clinical phenotypes. Above finding has facilitated the differential diagnosis and genetic counseling for this family.
Ribosomal Proteins , Humans , Female , Adult , Ribosomal Proteins/genetics , Pregnancy , Exome Sequencing , Phenotype , Osteochondrodysplasias/genetics , Dwarfism/genetics , Mutation, Missense , Genetic Testing
Metamaterials hold significant promise for enhancing the imaging capabilities of magnetic resonance imaging (MRI) machines as an additive technology, due to their unique ability to enhance local magnetic fields. However, despite their potential, the metamaterials reported in the context of MRI applications have often been impractical. This impracticality arises from their predominantly flat configurations and their susceptibility to shifts in resonance frequencies, preventing them from realizing their optimal performance. Here, a computational method for designing wearable and tunable metamaterials via freeform auxetics is introduced. The proposed computational-design tools yield an approach to solving the complex circle packing problems in an interactive and efficient manner, thus facilitating the development of deployable metamaterials configured in freeform shapes. With such tools, the developed metamaterials may readily conform to a patient's knee, ankle, head, or any part of the body in need of imaging, and while ensuring an optimal resonance frequency, thereby paving the way for the widespread adoption of metamaterials in clinical MRI applications.
Type 2 diabetic osteoporosis (T2DOP) has received increasing attention from researchers. In this study, a total of 453 publications related to T2DOP from 2013 to 2022 were analyzed using bibliometric and visual analysis to identify the research trends and research hotspots in the field of T2DOP. PURPOSE: The objective of this study was to conduct a comprehensive bibliometric analysis of T2DOP-related publications from 2013 to 2022 to determine global research trends in T2DOP in terms of number of publications, countries/regions, institutions, authors, journals, funding agencies, and keywords. METHODS: All data were collected from the Web of Science Core Collection (WoSCC). All original research publications regarding T2DOP from 2013 to 2022 were retrieved. VOSviewer and Microsoft Office Excel were used to conduct the bibliometric and visual analysis. RESULTS: From 2013 to 2022, 515 relevant publications were published, with a peak in 2022 in the annual number of publications. The countries leading the research were USA and China. Sugimoto was the most influential authors. Capital Medical University and Nanjing Medical University were the most prolific institutions. Osteoporosis International was the most productive journal concerning T2DOP research. National Natural Science Foundation of China was the primary funding source for this research area. "Bone-mineral density", "fracture risk", and "postmenopausal women" were the most high-frequency keywords over the past 10 years. CONCLUSION: This was the first bibliometric study of diabetes mellitus and osteoporosis to exclusively examine type 2 diabetes mellitus. Our findings would provide guidance to understand the research frontiers and hot directions in the near future.
Bibliometrics , Diabetes Mellitus, Type 2 , Osteoporosis , Humans , Diabetes Mellitus, Type 2/epidemiology , Osteoporosis/epidemiology , Biomedical Research/statistics & numerical data
A copper-catalyzed efficient regioselective silylation reaction of chloro-substituted allenyl-Bdan was developed. Under mild reaction conditions, allenyl and propargyl silane compounds can be selectively obtained in moderate to high yields by adjusting the bases and solvents used in the reactions. This study offers direct and efficient methods for synthesizing multifunctionalized allenyl and propargyl silane compounds from the same initial material of chloro-substituted allenyl-Bdan.
BACKGROUND: Glutamine is crucial for the activation and efficacy of T cells, and may play a role in regulating the immune environment. This study aimed to investigate the potential role of glutamine in the activation and proliferation of induced regulatory T cells (iTregs). METHODS: CD4+CD45RA+T cells were sorted from peripheral blood mononuclear cells and cultured to analyze iTreg differentiation. Glutamine was then added to the culture system to evaluate the effects of glutamine on iTregs by determining oxidative phosphorylation (OXPHOS), apoptosis, and cytokine secretion. Additionally, a humanized murine graft-versus-host disease (GVHD) model was constructed to confirm the efficacy of glutamine-treated iTregs in vivo. RESULTS: After being cultured in vitro, glutamine significantly enhanced the levels of Foxp3, CTLA-4, CD39, CD69, IL-10, TGF-ß, and Ki67 (CTLA-4, IL-10, TGF-ß are immunosuppressive markers of iTregs) compared with that of the control iTregs (P < 0.05). Furthermore, the growth curve showed that the proliferative ability of glutamine-treated iTregs was better than that of the control iTregs (P < 0.01). Compared with the control iTregs, glutamine supplementation significantly increased oxygen consumption rates and ATP production (P < 0.05), significantly downregulated Annexin V and Caspase 3, and upregulated BCL2 (P < 0.05). However, GPNA significantly reversed the effects of glutamine (P < 0.05). Finally, a xeno-GVHD mouse model was successfully established to confirm that glutamine-treated iTregs increased the mice survival rate, delayed weight loss, and alleviated colon injury. CONCLUSION: Glutamine supplementation can improve the activity and immunosuppressive action of iTregs, and the possible mechanisms by which this occurs are related to cell proliferation, apoptosis, and OXPHOS.
Lithium iodide is commonly used in the production of batteries and drugs. Currently, the neutralization method is the primary means of producing lithium iodide. This method involves using hydriodic acid as a raw material, adding lithium carbonate or lithium hydroxide, and obtaining lithium iodide through evaporation and concentration. However, hydriodic acid is chemically unstable. Its preparation can lead to explosive accidents and encountering high temperatures generates toxic iodine vapors. These limitations restrict its industrial production. The study evaluates the impact of membrane stack configuration, operating voltage, and initial concentrations and volume ratios of reactants on the production process. Electrodialysis metathesis, characterized by a simpler process flow, lower energy consumption, and environmental benefits, emerges as an effective technique for electrically driven membrane separation in lithium salt production and purification. Under the specific conditions of a C-C-A-C-A-C membrane stack configuration, operating voltage at 25 V, initial potassium iodide concentration at 0.4 mol/L, initial lithium sulfate concentration at 0.2 mol/L, and a 1:1 volume ratio of product liquid to raw material liquid, the method achieves a lithium iodide purity of 98.9% with a production cost of approximately 0.502 $/kg LiI.
