The Identification of a Novel Nucleomodulin MbovP467 of Mycoplasmopsis bovis and Its Potential Contribution in Pathogenesis.

Mycoplasmopsis bovis is a causative agent of crucial diseases in both dairy and beef cattle leading to substantial economic losses. However, limited control measures for M. bovis-related diseases exist due to a lack of understanding about the virulence factors of this pathogen, a common challenge in mycoplasma research. Consequently, this study aimed to characterize a novel nucleomodulin as a virulence-related factor of M. bovis. Employing bioinformatic tools, we initially predicted MbovP467 to be a secreted protein with a nuclear localization signal based on SignalP scores and the cNLS (Nuclear Localization Signal) Mapper, respectively. Subsequently, the MbovP467 gene was synthesized and cloned into a pEGFP plasmid with EGFP labeling to obtain a recombinant plasmid (rpEGFP-MbovP467) and then was also cloned in pET-30a with a consideration for an Escherichia coli codon bias and expressed and purified for the production of polyclonal antibodies against the recombinant MbovP467 protein. Confocal microscopy and a Western blotting assay confirmed the nuclear location of MbovP467 in bovine macrophages (BoMacs). RNA-seq data revealed 220 up-regulated and 20 down-regulated genes in the rpEGFP-MbovP467-treated BoMac group compared to the control group (pEGFP). A GO- and KEGG-enrichment analysis identified associations with inflammatory responses, G protein-coupled receptor signaling pathways, nuclear receptor activity, sequence-specific DNA binding, the regulation of cell proliferation, IL-8, apoptotic processes, cell growth and death, the TNF signaling pathway, the NF-κB signaling pathway, pathways in cancer, and protein families of signaling and cellular processes among the differentially expressed up-regulated mRNAs. Further experiments, investigating cell viability and the inflammatory response, demonstrated that MbovP467 reduces BoMac cell viability and induces the mRNA expression of IL-1ß, IL-6, IL-8, TNF-α, and apoptosis in BoMac cells. Further, MbovP467 increased the promoter activity of TNF-α. In conclusion, this study identified a new nucleomodulin, MbovP467, for M. bovis, which might have an important role in M. bovis pathogenesis.

Investigation of the safety and protective efficacy of an attenuated and marker M. bovis-BoHV-1 combined vaccine in bovines.

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker M. bovis-BoHV-1 combined vaccine based on the M. bovis HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4+, CD8+, and CD19+ cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the M. bovis HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an M. bovis-BoHV-1 combined vaccine for application in the cattle industry.

Association between dietary folate intake and severe abdominal aorta calcification in adults: A cross-sectional analysis of the national health and nutrition examination survey.

BACKGROUND: Prior studies have established a connection between folate intake and cardiovascular disease (CVD). Abdominal aortic calcification (AAC) has been introduced as a good predictor of CVD events, but no previous study has investigated the relationship between dietary folate intake and severe AAC. Therefore, the study aims to explore the association between dietary folate intake and severe AAC in the United States (US) middle-aged and elderly population. METHODS: This study employed cross-sectional data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to examine the relationship between dietary folate intake and severe AAC. Two 24-h dietary recall interviews were conducted to assess dietary folate intake and its sources, while a DXA scan was used to determine the AAC score. To analyze the association between dietary folate intake and severe AAC, a multivariable logistic regression model was applied, and a subgroup analysis was performed. RESULTS: Our analysis utilized data from 2640 participants aged 40 years and above, including 288 individuals diagnosed with severe AAC. After adjusting for confounding factors, we observed an inverted L-shaped association between folate intake and severe AAC. Upon further adjustment for specific confounding factors and covariates, the multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the second, third, and fourth quartiles of folate intake, using the first quartile as the reference, were as follows: 1.24 (0.86-1.79), 0.86 (0.58-1.27), and 0.63 (0.41-0.97), respectively. Subgroup analysis results were consistent with the logistic regression models, indicating concordant findings. Moreover, no significant interaction was observed in the subgroup analyses. CONCLUSIONS: The study findings suggest an inverted L-shaped association between dietary folate intake and severe AAC. However, additional prospective investigations are necessary to explore the impact of dietary folate intake on severe AAC in patients.

An optimized culturomics strategy for isolation of human milk microbiota.

Viable microorganisms and a diverse microbial ecosystem found in human milk play a crucial role in promoting healthy immune system and shaping the microbial community in the infant's gut. Culturomics is a method to obtain a comprehensive repertoire of human milk microbiota. However, culturomics is an onerous procedure, and needs expertise, making it difficult to be widely implemented. Currently, there is no efficient and feasible culturomics method specifically designed for human milk microbiota yet. Therefore, the aim of this study was to develop a more efficient and feasible culturomics method specifically designed for human milk microbiota. We obtained fresh samples of human milk from healthy Chinese mothers and conducted a 27-day enrichment process using blood culture bottles. Bacterial isolates were harvested at different time intervals and cultured on four different types of media. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, we identified a total of 6601 colonies and successfully obtained 865 strains, representing 4 phyla, 21 genera, and 54 species. By combining CBA and MRS media, we were able to cultivate over 94.4% of bacterial species with high diversity, including species-specific microorganisms. Prolonged pre-incubation in blood culture bottles significantly increased the number of bacterial species by about 33% and improved the isolation efficiency of beneficial bacteria with low abundance in human milk. After optimization, we reduced the pre-incubation time in blood culture bottles and selected optimal picking time-points (0, 3, and 6 days) at 37°C. By testing 6601 colonies using MALDI-TOF MS, we estimated that this new protocol could obtain more than 90% of bacterial species, reducing the workload by 57.0%. In conclusion, our new culturomics strategy, which involves the combination of CBA and MRS media, extended pre-incubation enrichment, and optimized picking time-points, is a feasible method for studying the human milk microbiota. This protocol significantly improves the efficiency of culturomics and allows for the establishment of a comprehensive repertoire of bacterial species and strains in human milk.

Securin acetylation prevents precocious separase activation and premature sister chromatid separation.

Lysine acetylation of non-histone proteins plays crucial roles in many cellular processes. In this study, we examine the role of lysine acetylation during sister chromatid separation in mitosis. We investigate the acetylation of securin at K21 by cell-cycle-dependent acetylome analysis and uncover its role in separase-triggered chromosome segregation during mitosis. Prior to the onset of anaphase, the acetylated securin via TIP60 prevents its degradation by the APC/CCDC20-mediated ubiquitin-proteasome system. This, in turn, restrains precocious activation of separase and premature separation of sister chromatids. Additionally, the acetylation-dependent stability of securin is also enhanced by its dephosphorylation. As anaphase approaches, HDAC1-mediated deacetylation of securin promotes its degradation, allowing released separase to cleave centromeric cohesin. Blocking securin deacetylation leads to longer anaphase duration and errors in chromosome segregation. Thus, this study illustrates the emerging role of securin acetylation dynamics in mitotic progression and genetic stability.

Initial nutrient condition determines the recovery speed of quiescent cells in fission yeast.

Most of microbe cells spend the majority of their times in quiescence due to unfavorable environmental conditions. The study of this dominant state is crucial for understanding the basic cell physiology. Retained recovery ability is a critical property of quiescent cells, which consists of two features: how long the cells can survive (the survivability) and how fast they can recover (the recovery activity). While the survivability has been extensively studied under the background of chronological aging, how the recovery activity depends on the quiescent time and what factors influence its dynamics have not been addressed quantitatively. In this work, we systematically quantified both the survivability and the recovery activity of long-lived quiescent fission yeast cells at the single cell level under various nutrient conditions. It provides the most profound evolutionary dynamics of quiescent cell regeneration ability described to date. We found that the single cell recovery time linearly increased with the starvation time before the survivability significantly declined. This linearity was robust under various nutrient conditions and the recovery speed was predetermined by the initial nutrient condition. Transcriptome profiling further revealed that quiescence states under different nutrient conditions evolve in a common trajectory but with different speed. Our results demonstrated that cellular quiescence has a continuous spectrum of depths and its physiology is greatly influenced by environmental conditions.

U-Shaped Association between Serum Chloride Levels and In-Hospital Mortality in Patients with Congestive Heart Failure in Intensive Care Units.

Serum chloride level has clinical significance in the prognosis of heart failure. Little is known regarding the association between serum chloride levels and in-hospital mortality in patients with heart failure.This retrospective study used clinical data obtained from the Medical Information Mart for Intensive Care Database. The study cohort comprised patients who were categorized on the basis of their serum chloride levels, and the primary endpoint was in-hospital mortality. To assess the impact of serum chloride levels at the time of intensive care unit admission on in-hospital mortality, we used various statistical approaches, including multivariable logistic regression models, a generalized additive model, and a two-piecewise linear regression model. In addition, subgroup analysis was conducted to examine the robustness of the main findings.This study comprised 15,983 participants. When compared with the reference group (Q5), the groups with the highest (Q7) and lowest (Q1) blood chloride levels exhibited increased in-hospital mortality, with fully adjusted odds ratios (ORs) of 1.36 [95% confidence interval (CI): 1.08-1.71] and 1.25 (95% CI: 1-1.56), respectively. A U-shaped relationship was observed between blood chloride levels and in-hospital mortality, with the lowest risk observed at a threshold of 105.017 mmol/L. The effect sizes and corresponding CIs below and above the threshold were 0.969 (95% CI: 0.957-0.982) and 1.039 (95% CI: 1.002-1.076), respectively. Stratified analyses demonstrated the robustness of this correlation.The relationship between serum chloride levels and in-hospital mortality in patients with heart failure was U-shaped, with an inflection point of 105.017 mmol/L.

Engineered hsa-miR-455-3p-Abundant Extracellular Vesicles Derived from 3D-Cultured Adipose Mesenchymal Stem Cells for Tissue-Engineering Hyaline Cartilage Regeneration.

Efforts are made to enhance the inherent potential of extracellular vesicles (EVs) by utilizing 3D culture platforms and engineered strategies for functional cargo-loading. Three distinct types of adipose mesenchymal stem cells-derived EVs (ADSCs-EVs) are successfully isolated utilizing 3D culture platforms consisting of porous gelatin methacryloyl (PG), PG combined with sericin methacryloyl (PG/SerMA), or PG combined with chondroitin sulfate methacryloyl (PG/ChSMA). These correspond to PG-EVs, PG/SerMA-EVs, and PG/ChSMA-EVs, respectively. Unique microRNA (miRNA) profiles are observed in each type of ADSCs-EVs. Notably, PG-EVs encapsulate higher levels of hsa-miR-455-3p and deliver more hsa-miR-455-3p to chondrocytes, which results in the activation of the hsa-miR-455-3p/PAK2/Smad2/3 axis and the subsequent hyaline cartilage regeneration. Furthermore, the functionality of PG-EVs is optimized through engineered strategies, including agomir/lentivirus transfection, electroporation, and Exo-Fect transfection. These strategies, referred to as Agomir-EVs, Lentivirus-EVs, Electroporation-EVs, and Exo-Fect-EVs, respectively, are ranked based on their efficacy in encapsulating hsa-miR-455-3p, delivering hsa-miR-455-3p to chondrocytes, and promoting cartilage formation via the hsa-miR-455-3p/PAK2/Smad2/3 axis. Notably, Exo-Fect-EVs exhibit the highest efficiency. Collectively, the 3D culture conditions and engineered strategies have an impact on the miRNA profiles and cartilage regeneration capabilities of ADSCs-EVs. The findings provide valuable insights into the mechanisms underlying the promotion of cartilage regeneration by ADSCs-EVs.

ELOVL6 promotes the progression of head and neck squamous cell carcinoma via activating WNT/ß-catenin pathway.

This study was to explore the role of ELOVL6 in the development of head and neck squamous cell carcinoma (HNSCC). Considering its previously identified oncogenic role in hepatocellular carcinoma. ELOVL6 gene expression, clinicopathological analysis, enrichment analysis, and immune infiltration analysis were based on the data from Gene Expression Omnibus and The Cancer Genome Atlas, with additional bioinformatics analyses performed. Human HNSCC tissue microarray and cell lines were used. The expression of ELOVL6 in HNSCC was detected by quantitative polymerase chain reaction, immunohistochemistry assay, and western blot analysis. The proliferation ability of HNSCC cells, invasion, and apoptosis were evaluated using cell counting kit-8 method, Transwell assay, and flow cytometry, respectively. Based on the data derived from the cancer databases and our HNSCC cell and tissue studies, we found that ELOVL6 was overexpressed in HNSCC. Moreover, ELOVL6 expression level had a positive correlation with clinicopathology of HNSCC. Gene set enrichment analysis showed that ELOVL6 affected the occurrence of HNSCC through WNT signaling pathway. Functional experiments demonstrated that ELOVL6 knockdown inhibited the proliferation and invasion of HNSCC cells while promoting apoptosis. Additionally, compound 3f, an agonist of WNT/ß-catenin signaling pathway, enhances the effect of ELOVL6 on the progression of HNSCC cells. ELOVL6 is upregulated in HNSCC and promotes the development of HNSCC cells by inducing WNT/ß-catenin signaling pathway. ELOVL6 stands a potential target for the treatment of HNSCC and a prognosis indicator of human HNSCC.

U-shaped association between serum calcium and in-hospital mortality in patients with congestive heart failure.

AIMS: Serum calcium level is widely used for evaluating disease severity, but its impact on clinical outcomes in patients with congestive heart failure (CHF) remains poorly understood. The aim of this study is to investigate the relationship between serum calcium levels and in-hospital mortality in CHF patients. METHODS AND RESULTS: We conducted a retrospective analysis utilizing clinical data from the Medical Information Mart for Intensive Care database, encompassing a cohort of 15 983 CHF patients. This cohort was stratified based on their serum calcium levels, with the primary objective being the determination of in-hospital mortality. To assess the impact of admission serum calcium levels on in-hospital mortality, we employed various statistical methodologies, including multivariable logistic regression models, a generalized additive model, a two-piecewise linear regression model, and subgroup analysis. Comparative analysis of the reference group (Q3) revealed increased in-hospital mortality in the first quintile (Q1, the group with the lowest blood calcium level) and the fifth quintile (Q5, the group with the highest blood calcium level), with fully adjusted odds ratios of 1.38 [95% confidence interval (CI): 1.13-1.68, P = 0.002] and 1.23 (95% CI: 1.01-1.5, P = 0.038), respectively. A U-shaped relationship was observed between serum calcium levels and in-hospital mortality, with the lowest risk occurring at a threshold of 8.35 mg/dL. The effect sizes and corresponding CIs below and above this threshold were 0.782 (95% CI: 0.667-0.915, P = 0.0023) and 1.147 (95% CI: 1.034-1.273, P = 0.0094), respectively. Stratified analyses confirmed the robustness of this correlation. CONCLUSIONS: Our study identifies a U-shaped association between serum calcium levels and in-hospital mortality in CHF patients, with a notable inflection point at 8.35 mg/dL. Further investigation through prospective, randomized, and controlled studies is warranted to validate the findings presented in this study.

SNAT2-mediated regulation of estrogen and progesterone in the proliferation of goat mammary epithelial cells.

The development of the goat mammary gland is mainly under the control of ovarian hormones particularly estrogen and progesterone (P4). Amino acids play an essential role in mammary gland development and milk production, and sodium-coupled neutral amino acid transporter 2 (SNAT2) was reported to be expressed in the mammary gland of rats and bovine mammary epithelial cells, which may affect the synthesis of milk proteins or mammary cell proliferation by mediating prolactin, 17ß-estradiol (E2) or methionine function. However, whether SNAT2 mediates the regulatory effects of E2 and P4 on the development of the ruminant mammary gland is still unclear. In this study, we show that E2 and P4 could increase the proliferation of goat mammary epithelial cells (GMECs) and regulate SNAT2 mRNA and protein expression in a dose-dependent manner. Further investigation revealed that SNAT2 is abundantly expressed in the mammary gland during late pregnancy and early lactation, while knockdown and overexpression of SNAT2 in GMECs could inhibit or enhance E2- and P4-induced cell proliferation as well as mammalian target of rapamycin (mTOR) signaling. We also found that the accelerated proliferation induced by SNAT2 overexpression in GMECs was suppressed by the mTOR signaling pathway inhibitor rapamycin. This indicates that the regulation of GMECs proliferation mediated by SNAT2 in response to E2 and P4 is dependent on the mTOR signaling pathway. Finally, we found that the total content of the amino acids in GMECs changed after knocking-down and overexpressing SNAT2. In summary, the results demonstrate that the regulatory effects of E2 and P4 on GMECs proliferation may be mediated by the SNAT2-transported amino acid pathway. These results may offer a novel nutritional target for improving the development of the ruminant mammary gland and milk production.

HFSCCD: A Hybrid Neural Network for Fetal Standard Cardiac Cycle Detection in Ultrasound Videos.

In the fetal cardiac ultrasound examination, standard cardiac cycle (SCC) recognition is the essential foundation for diagnosing congenital heart disease. Previous studies have mostly focused on the detection of adult CCs, which may not be applicable to the fetus. In clinical practice, localization of SCCs needs to recognize end-systole (ES) and end-diastole (ED) frames accurately, ensuring that every frame in the cycle is a standard view. Most existing methods are not based on the detection of key anatomical structures, which may not recognize irrelevant views and background frames, results containing non-standard frames, or even it does not work in clinical practice. We propose an end-to-end hybrid neural network based on an object detector to detect SCCs from fetal ultrasound videos efficiently, which consists of 3 modules, namely Anatomical Structure Detection (ASD), Cardiac Cycle Localization (CCL), and Standard Plane Recognition (SPR). Specifically, ASD uses an object detector to identify 9 key anatomical structures, 3 cardiac motion phases, and the corresponding confidence scores from fetal ultrasound videos. On this basis, we propose a joint probability method in the CCL to learn the cardiac motion cycle based on the 3 cardiac motion phases. In SPR, to reduce the impact of structure detection errors on the accuracy of the standard plane recognition, we use XGBoost algorithm to learn the relation knowledge of the detected anatomical structures. We evaluate our method on the test fetal ultrasound video datasets and clinical examination cases and achieve remarkable results. This study may pave the way for clinical practices.

Detection methods and dynamic characteristics of specific antibodies in patients with COVID-19: A review of the early literature.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic. Early and accurate diagnosis and quarantine remain the most effective mitigation strategy. Although reverse transcriptase polymerase chain reaction (RT-qPCR) is the gold standard for COVID-19 diagnosis, recent studies suggest that nucleic acids were undetectable in a significant number of cases with clinical features of COVID-19.Serological assays for SARS-CoV-2 play a role in diagnosis of COVID-19, in understanding viral epidemiology and screening convalescent sera for therapeutic and prophylactic purposes, to better understand the immune response to the virus, and to assess the degree and duration of the response of specific antibodies. In this article, we retrieved PubMed, Embase, China National Knowledge Infrastructure (CNKI) and WEB OF SCI databases for articles and reviews published before December 1, 2022. Using "IgM, IgG,IgA, neutralizing antibody, specific antibody,COVID-19, dynamic characteristics" as keywords, and comprehensively reviewed on their basis.According to the authors' criteria, only articles deemed relevant were included, covering original articles, case series, experimental studies, reviews, and case reports. Articles on performance evaluation, opinion pieces, and technical issues were excluded. From the onset of COVID-19 symptoms, the median time of seroconversion was 11 days for immunoglobulin A (IgA), the median time of peak antibody titer was 23 (16-30 days) for IgA.Immunoglobulin M (IgM) is detected prior to immunoglobulin G (IgG), peaking 2-5 weeks post symptom onset and detectable for a minimum of 8 weeks in the immunocompetent.Neutralizing antibodies were earliest detectable within 6-7 days following disease onset, with levels increasing until days 14-22 before levelling and then decreasing, but titres were lower in clinically mild disease. Different clinical types of patients showed different antibody responses to SARS-CoV-2, with severe COVID-19 patients > non-severe COVID-19 patients > asymptomatic infected persons, but no difference in the early stage of the disease. Usually, IgM and IgA antibodies are detectable earlier than IgG antibodies.IgA antibodys plays an important role in local mucosal immunity.Detection of IgM antibodies tends to indicate recent exposure to SARS-CoV-2, whereas the detection of COVID-19 IgG antibodies indicates virus exposure some time ago. The detection of potent neutralizing antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines.With the emergence of immune escape variants of SARS-CoV-2, humoral immunity is being challenged, and a detailed understanding of Specific antibodies is critical to guide vaccine design strategies and antibody-mediated therapies.

Association between dietary calcium intake and severe abdominal aorta calcification among American adults: a cross-sectional analysis of the National Health and Nutrition Examination Survey.

BACKGROUND: Evidence regarding the relationship between dietary calcium intake and severe abdominal aortic calcification (AAC) is limited. Therefore, this study aimed to investigate the association between dietary calcium intake and severe AAC in American adults based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS: The present cross-sectional study utilized data from the NHANES 2013-2014, a population-based dataset. Dietary calcium intake was assessed using two 24-h dietary recall interviews. Quantification of the AAC scores was accomplished utilizing the Kauppila score system, whereby severe AAC was defined as having an AAC score greater than 6. We used multivariable logistic regression models, a restricted cubic spline analysis, and a two-piecewise linear regression model to show the effect of calcium intake on severe AAC. RESULTS: Out of the 2640 individuals examined, 10.9% had severe AAC. Following the adjustment for confounding variables, an independent association was discovered between an augmented intake of dietary calcium and the incidence of severe AAC. When comparing individuals in the second quartile (Q2) of dietary calcium intake with those in the lowest quartile (Q1), a decrease in the occurrence of severe AAC was observed (odds ratio: 0.66; 95% confidence interval: 0.44-0.99). Furthermore, the relationship between dietary calcium intake and severe AAC demonstrated an L-shaped pattern, with an inflection point observed at 907.259 mg/day. Subgroup analyses revealed no significant interaction effects. CONCLUSION: The study revealed that the relationship between dietary calcium intake and severe AAC in American adults is L-shaped, with an inflection point of 907.259 mg/day. Further research is required to confirm this association.

Epigenetic mechanisms in depression: Implications for pathogenesis and treatment.

The risk of depression is influenced by both genetic and environmental factors. It has been suggested that epigenetic mechanisms may mediate the risk of depression following exposure to adverse life events. Epigenetics encompasses stable alterations in gene expression that are controlled through transcriptional, post-transcriptional, translational, or post-translational processes, including DNA modifications, chromatin remodeling, histone modifications, RNA modifications, and non-coding RNA (ncRNA) regulation, without any changes in the DNA sequence. In this review, we explore recent research advancements in the realm of epigenetics concerning depression. Furthermore, we evaluate the potential of epigenetic changes as diagnostic and therapeutic biomarkers for depression.

Dual roles of CCDC102A in governing centrosome duplication and cohesion.

In animal cells, the dysregulation of centrosome duplication and cohesion maintenance leads to abnormal spindle assembly and chromosomal instability, contributing to developmental disorders and tumorigenesis. However, the molecular mechanisms involved in maintaining accurate centrosome number control and tethering are not fully understood. Here, we identified coiled-coil domain-containing 102A (CCDC102A) as a centrosomal protein exhibiting a barrel-like structure in the proximal regions of parent centrioles, where it prevents centrosome overduplication by restricting interactions between Cep192 and Cep152 on centrosomes, thereby ensuring bipolar spindle formation. Additionally, CCDC102A regulates the centrosome linker by recruiting and binding C-Nap1; it is removed from the centrosome after Nek2A-mediated phosphorylation at the onset of mitosis. Overall, our results indicate that CCDC102A participates in controlling centrosome number and maintaining centrosome cohesion, suggesting that a well-tuned system regulates centrosome structure and function throughout the cell cycle.

Platelet-derived microparticles adoptively transfer integrin ß3 to promote antitumor effect of tumor-infiltrating T cells.

Approximately two-thirds of hepatocellular carcinoma (HCC) is considered a "cold tumor" characterized by few tumor-infiltrating T cells and an abundance of immunosuppressive cells. Cilengitide, an integrin αvß3 inhibitor, has failed in clinical trials as a potential anticancer drug. This failure implies that integrin αvß3 may play an important role in immune cells. However, the expression and potential role of integrin αvß3 in T cells of HCC patients remain unknown. Here, we established two HCC models and found that cilengitide had a dual effect on the HCC microenvironment by exerting both antitumor effect and immunosuppressive effect on T cells. This may partly explain the failure of cilengitide in clinical trials. In clinical specimens, HCC-infiltrating T cells exhibited deficient expression and activation of integrin ß3, which was associated with poor T-cell infiltration into tumors. Additionally, integrin ß3 functioned as a positive immunomodulatory molecule to facilitate T-cell infiltration and T helper 1-type immune response in vitro. Furthermore, T cells and platelet-derived microparticles (PMPs) co-culture assay revealed that PMPs adoptively transferred integrin ß3 to T cells and positively regulated T cell immune response. This process was mediated by clathrin-dependent endocytosis and macropinocytosis. Our data demonstrate that integrin ß3 deficiency on HCC-infiltrating T cells may be involved in shaping the immunosuppressive tumor microenvironment. PMPs transfer integrin ß3 to T cells and positively regulate T cell immune response, which may provide a new insight into immune therapy of HCC.

Identification of a novel adenovirus in liver tissue sample of the Great Himalayan leaf-nosed bat (Hipposideros armiger).

Bats are important reservoirs for many zoonotic viruses. To explore and monitor potential novel viruses carried by bats, 21 liver samples of bats (Hipposideros armiger) were collected from Yunnan Province in southern China. Only one (4.8%) of all models was detected with adenovirus. The whole genome strain obtained by the viral metagenomics method combined with PCR was temporarily named YN01. The complete genome of YN01 was 37,676 bp, with a G + C content of 55.20% and 28 open reading frames. Phylogenetic analysis indicated that the strain YN01 can be classified as genus Mastadenovirus and was the most similar to the adenovirus isolated from Rhinolophus sinicus in China in 2016. The analysis is needed to verify the possibility of cross-species transmission. This virological investigation has increased our understanding of the ecology of bat-borne viruses in this area and provided a reference for possible future infectious diseases.

Association between dietary total choline and abdominal aorta calcification among older US adults: A cross-sectional study of the National Health and Nutrition Examination Survey.

BACKGROUND: Numerous studies indicate a potential bidirectional association between dietary choline intake and its derivative, betaine, and subclinical atherosclerosis. However, little research has been conducted on the relationship between dietary choline and severe abdominal aortic calcification (SAAC). METHODS: This cross-sectional study analyzed population-based data from the National Health and Nutrition Examination Survey (2013-2014). Choline intake and food sources were measured using two 24-h dietary-recall interviews. The abdominal aortic calcification score was measured using a dual-emission x-ray absorptiometry scan. To assess the relationship between choline intake and SAAC, the study utilized restricted cubic spline and a multivariable logistic regression model. RESULTS: Among the 2640 individuals included in the study, 10.9% had SAAC. After adjusting for all selected covariates, compared with the lowest quartile of dietary choline, the odds ratios of SAAC for the second-quartile, third-quartile, and fourth-quartile dietary choline intake were 0.63 (95% confidence interval [CI], 0.43-0.93), 0.63 (95% CI, 0.42-0.94), and 0.77 (95% CI, 0.5-1.16), respectively. The study found an L-shaped relationship between dietary choline and SAAC in the dose-response analysis. Subgroup analyses did not demonstrate any statistically significant interaction effects for any subgroup. CONCLUSION: The study found that a higher intake of dietary choline is associated with a lower prevalence of SAAC. The dose-response analysis revealed an L-shaped relationship between dietary choline and SAAC. However, further studies are warranted to investigate the direct role of choline in the development of SAAC.