Wheel-Running Exercise Alleviates Anxiety-Like Behavior via Down-Regulating S-Nitrosylation of Gephyrin in the Basolateral Amygdala of Male Rats.

Physical exercise has beneficial effect on anxiety disorders, but the underlying molecular mechanism remains largely unknown. Here, it is demonstrated that physical exercise can downregulate the S-nitrosylation of gephyrin (SNO-gephyrin) in the basolateral amygdala (BLA) to exert anxiolytic effects. It is found that the level of SNO-gephyrin is significantly increased in the BLA of high-anxiety rats and a downregulation of SNO-gephyrin at cysteines 212 and 284 produced anxiolytic effect. Mechanistically, inhibition of SNO-gephyrin by either Cys212 or Cys284 mutations increased the surface expression of GABAAR γ2 and the subsequent GABAergic neurotransmission, exerting anxiolytic effect in male rats. On the other side, overexpression of neuronal nitric oxide synthase in the BLA abolished the anxiolytic-like effects of physical exercise. This study reveals a key role of downregulating SNO-gephyrin in the anxiolytic effects of physical exercise, providing a new explanation for protein post-translational modifications in the brain after exercise.

The Association between Discrepancies in Parental Emotional Expressivity, Adolescent Loneliness and Depression: A Multi-Informant Study Using Response Surface Analysis.

Incongruent perceptions of parental emotional expressivity between parents and adolescents may signify relational challenges, potentially impacting adolescents' socioemotional adjustment. Direct evidence is still lacking and father-adolescent discrepancies are overlooked. This study employed a multi-informant design to investigate whether both mother-adolescent and father-adolescent discrepancies in perceptions of parental expressivity are related to adolescents' mental well-being, specifically focusing on loneliness and depression. Analyzing data from 681 families (mean age of adolescents = 15.5 years old, 51.2% girls, 40% only-children) in China revealed that adolescents tended to perceive paternal and maternal emotional expressivity more negatively than their parents, particularly fathers. Polynomial regression and response surface analysis showed significant links between parent-adolescent congruence and incongruence and adolescent loneliness. (In)Congruence between adolescents and mothers or fathers predicted later adolescent depression, mediated by adolescent loneliness and varied by the dimension of emotional expressivity. These findings provide insights into the roles of mothers' and fathers' emotional expressivity in shaping children's mental well-being during adolescence.

Global expansion of tropical cyclone precipitation footprint.

Precipitation from tropical cyclones (TCs) can cause massive damage from inland floods and is becoming more intense under a warming climate. However, knowledge gaps still exist in changes of spatial patterns in heavy TC precipitation. Here we define a metric, DIST30, as the mean radial distance from centers of clustered heavy rainfall cells (> 30 mm/3 h) to TC center, representing the footprint of heavy TC precipitation. There is significant global increase in DIST30 at a rate of 0.34 km/year. Increases of DIST30 cover 59.87% of total TC impact areas, with growth especially strong in the Western North Pacific, Northern Atlantic, and Southern Pacific. The XGBoost machine learning model showed that monthly DIST30 variability is majorly controlled by TC maximum wind speed, location, sea surface temperature, vertical wind shear, and total water column vapor. TC poleward migration in the Northern Hemisphere contributes substantially to the DIST30 upward trend globally.

Ecosystem engineers can regulate resource allocation strategies in associated plant species.

Balancing the biomass requirements of different functions for the purpose of population reproduction and persistence can be challenging for alpine plants due to extreme environmental stresses from both above- and below-ground sources. The presence of ecosystem engineers in alpine ecosystems effectively alleviates microenvironmental stresses, hence promoting the survival and growth of other less stress-tolerant species. However, the influence of ecosystem engineers on plant resource allocation strategies remains highly unexplored. In this study, we compared resource allocation strategies, including biomass accumulation, reproductive effort (RE), root fraction (RF), as well as relationships between different functions, among four alpine plant species belonging to Gentianaceae across bare ground, tussock grass-, cushion-, and shrub-engineered microhabitats. Shrub-engineered microhabitats exerted the strongest effects on regulating plant resource allocation patterns, followed by tussock grass- and cushion-engineered microhabitats. Additionally, apart from microhabitats, population background and plant life history also significantly influenced resource allocation strategies. Generally, plants established within engineered microhabitats exhibited higher biomass accumulation, as well as increased flower, leaf and stem production. Furthermore, individuals within engineered microhabitats commonly displayed lower RF, indicating a greater allocation of resources to above-ground functions while reducing allocation to root development. RE of annual plants was significantly higher than that of perennial plants. However, individuals of annual plants within engineered microhabitats showed lower RE compared to their counterparts in bare ground habitats; whereas perennial species demonstrated similar RE between microhabitat types. Moreover, RE was generally independent of plant size in bare-ground habitats but exhibited size-dependency in certain populations for some species within specific engineered microhabitat types. However, size-dependency did exist for absolute reproductive and root biomass allocation in most of the cases examined here. No trade-offs were observed between flower mass and flower number, nor between leaf mass and leaf number. The capacity of ecosystem engineers to regulate resource allocation strategies in associated plants was confirmed. However, the resource allocation patterns resulted synergistically from the ecosystem engineering effects, population environmental backgrounds, and plant life history strategies. In general, such regulations can improve individual survival and reproductive potential, potentially promoting population persistence in challenging alpine environments.

Association between serum chloride and in-hospital mortality in congestive heart failure with diabetes: Data from the MIMIC-IV database.

Background: Congestive heart failure (CHF) demonstrates a heightened prevalence in individuals with diabetes mellitus within Intensive Care Units. The occurrence of abnormal chloride levels is frequently observed in critically ill patients, yet its clinical significance remains subject to debate. This study endeavors to explore the relationship between serum chloride levels and in-hospital mortality among patients affected by both congestive heart failure and diabetes. Methods: A retrospective cohort study was conducted, utilizing data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, focusing on adult patients in the United States. The impact of serum chloride levels upon ICU admission on in-hospital mortality was analyzed using multivariable logistic regression models, generalized additive models and subgroup analysis. Results: The study encompassed 7,063 patients with coexisting diabetes and congestive heart failure. The fully adjusted model revealed an inverse association between serum chloride levels and in-hospital mortality. As a tertile variable (Q3 vs Q1), the odds ratio (OR) was 0.73 with a 95% confidence interval (CI) of 0.54-0.98 (p = 0.039). As a continuous variable, per 1 mmol/L increment, the OR (95% CI) was 0.97 (0.96-0.99, p = 0.01). The relationship between serum chloride and in-hospital mortality demonstrated linearity (non-linear p = 0.958). Stratified analyses further validated the robustness of this correlation. Conclusions: Serum chloride levels exhibited a negative association with in-hospital mortality in patients with both congestive heart failure and diabetes. Nevertheless, prospective, randomized, controlled studies are warranted to corroborate and validate the findings presented in this investigation.

Sex-specific facilitation and reproduction of the gynodioecious cushion plant Arenaria polytrichoides on the Himalaya-Hengduan mountains, SW China.

When benefiting other beneficiaries, cushion plants may reciprocally receive feedback effects. The feedback effects on different sex morphs, however, remains unclear. In this study, taking the gynodioecious Arenaria polytrichiodes as a model species, we aimed to assess the sex-specific facilitation intensity of cushion plant by measuring the beneficiary cover ratio, and to assess the potential costs in cushion reproductive functions by measuring the flower and fruit cover ratios. The total beneficiary cover ratio was similar between females and hermaphrodites. Females produced much less flowers but more fruits than hermaphrodites. These results suggested that females and hermaphrodites possess similar facilitation intensity, and female cushion A. polytrichoides may allocate more resources saved from pollen production to seed production, while hermaphrodites possibly allocate more resources to pollen production hence reducing seed production. The surface areas covered by beneficiaries produced less flowers and fruits than areas without beneficiaries. In addition, strong negative correlations between beneficiary cover and flower cover were detected for both females and hermaphrodites, but the correlation strength were similar for these two sex morphs. However, the correlation between beneficiary cover and fruit cover was only significantly negative for females, suggesting that beneficiary plants negatively affect fruit reproduction of females while have neutral effects on hermaphrodites. All the results suggest that to facilitate other beneficiaries can induce reproductive costs on cushion A. polytrichoides, with females possibly suffering greater cost than hermaphrodites. Such differentiation in reproductive costs between sex morphs, in long-term perspective, may imply sex imbalance in population dynamics.

Prognostic significance of systemic immune inflammatory index in NSCLC: a meta-analysis.

Aim: The aim of this meta-analysis was to investigate the relationship between the baseline systemic immune inflammatory index (SII) and prognosis in patients with NSCLC. Materials & methods: The relation between pretreatment SII and overall survival, disease-free survival, cancer-specific survival, progression-free survival and recurrence-free survival in NSCLC patients was analyzed combined with hazard ratio and 95% CI. Results: The results showed that high SII was significantly correlated with overall survival and progression-free survival of NSCLC patients, but not with disease-free survival, cancer-specific survival and recurrence-free survival. Conclusion: The study suggests that a higher SII has association with worse prognosis in NSCLC patients. PROSPERO registration number: CRD42022336270.

The Establishment of a Novel γ-Interferon In Vitro Release Assay for the Differentiation of Mycobacterial Bovis-Infected and BCG-Vaccinated Cattle.

BCG vaccination is increasingly reconsidered in the effective prevention of bovine tuberculosis (bTB). However, the primary challenge in BCG vaccination for cattle is the lack of a technique for differentiating between infected and vaccinated animals (DIVA). This study aimed to establish a novel DIVA diagnostic test based on an interferon-gamma in vitro release assay (IGRA). The plasmid encoding three differential antigens (Rv3872, CFP-10, and ESAT-6) absent in BCG genes but present in virulent M. bovis was previously constructed. Thus, a recombinant protein called RCE (Rv3872, CFP-10, and ESAT-6) was expressed, and an RCE-based DIVA IGRA (RCE-IGRA) was established. The RCE concentration was optimized at 4 µg/mL by evaluating 97 cattle (74 of which were bTB-positive, and 23 were negative) using a commercial IGRA bTB diagnostic kit. Further, 84 cattle were tested in parallel with the RCE-IGRA and commercial PPD-based IGRA (PPD-IGRA), and the results showed a high correlation with a kappa value of 0.83. The study included BCG-vaccinated calves (n = 6), bTB-positive cattle (n = 6), and bTB-negative non-vaccinated calves (n = 6). After 3 months post-vaccination, PPD-IGRA generated positive results in both vaccinated and infected calves. However, RCE-IGRA developed positive results in infected calves but negative results in vaccinated calves. In conclusion, this DIVA method has broad prospects in differentiating BCG vaccination from natural infection to prevent bTB.

A quick and innovative pipeline for producing chondrocyte-homing peptide-modified extracellular vesicles by three-dimensional dynamic culture of hADSCs spheroids to modulate the fate of remaining ear chondrocytes in the M1 macrophage-infiltrated microenvironment.

BACKGROUND: Extracellular vesicles (EVs) derived from human adipose-derived mesenchymal stem cells (hADSCs) have shown great therapeutic potential in plastic and reconstructive surgery. However, the limited production and functional molecule loading of EVs hinder their clinical translation. Traditional two-dimensional culture of hADSCs results in stemness loss and cellular senescence, which is unfavorable for the production and functional molecule loading of EVs. Recent advances in regenerative medicine advocate for the use of three-dimensional culture of hADSCs to produce EVs, as it more accurately simulates their physiological state. Moreover, the successful application of EVs in tissue engineering relies on the targeted delivery of EVs to cells within biomaterial scaffolds. METHODS AND RESULTS: The hADSCs spheroids and hADSCs gelatin methacrylate (GelMA) microspheres are utilized to produce three-dimensional cultured EVs, corresponding to hADSCs spheroids-EVs and hADSCs microspheres-EVs respectively. hADSCs spheroids-EVs demonstrate excellent production and functional molecule loading compared with hADSCs microspheres-EVs. The upregulation of eight miRNAs (i.e. hsa-miR-486-5p, hsa-miR-423-5p, hsa-miR-92a-3p, hsa-miR-122-5p, hsa-miR-223-3p, hsa-miR-320a, hsa-miR-126-3p, and hsa-miR-25-3p) and the downregulation of hsa-miR-146b-5p within hADSCs spheroids-EVs show the potential of improving the fate of remaining ear chondrocytes and promoting cartilage formation probably through integrated regulatory mechanisms. Additionally, a quick and innovative pipeline is developed for isolating chondrocyte homing peptide-modified EVs (CHP-EVs) from three-dimensional dynamic cultures of hADSCs spheroids. CHP-EVs are produced by genetically fusing a CHP at the N-terminus of the exosomal surface protein LAMP2B. The CHP + LAMP2B-transfected hADSCs spheroids were cultured with wave motion to promote the secretion of CHP-EVs. A harvesting method is used to enable the time-dependent collection of CHP-EVs. The pipeline is easy to set up and quick to use for the isolation of CHP-EVs. Compared with nontagged EVs, CHP-EVs penetrate the biomaterial scaffolds and specifically deliver the therapeutic miRNAs to the remaining ear chondrocytes. Functionally, CHP-EVs show a major effect on promoting cell proliferation, reducing cell apoptosis and enhancing cartilage formation in remaining ear chondrocytes in the M1 macrophage-infiltrated microenvironment. CONCLUSIONS: In summary, an innovative pipeline is developed to obtain CHP-EVs from three-dimensional dynamic culture of hADSCs spheroids. This pipeline can be customized to increase EVs production and functional molecule loading, which meets the requirements for regulating remaining ear chondrocyte fate in the M1 macrophage-infiltrated microenvironment.

ParaCPI: A Parallel Graph Convolutional Network for Compound-Protein Interaction Prediction.

Identifying compound-protein interactions (CPIs) is critical in drug discovery, as accurate prediction of CPIs can remarkably reduce the time and cost of new drug development. The rapid growth of existing biological knowledge has opened up possibilities for leveraging known biological knowledge to predict unknown CPIs. However, existing CPI prediction models still fall short of meeting the needs of practical drug discovery applications. A novel parallel graph convolutional network model for CPI prediction (ParaCPI) is proposed in this study. This model constructs feature representation of compounds using a unique approach to predict unknown CPIs from known CPI data more effectively. Experiments are conducted on five public datasets, and the results are compared with current state-of-the-art (SOTA) models under three different experimental settings to evaluate the model's performance. In the three cold-start settings, ParaCPI achieves an average performance gain of 26.75%, 23.84%, and 14.68% in terms of area under the curve compared with the other SOTA models. In addition, the results of the experiments in the case study show ParaCPI's superior ability to predict unknown CPIs based on known data, with higher accuracy and stronger generalization compared with the SOTA models. Researchers can leverage ParaCPI to accelerate the drug discovery process.

A Novel Multiepitope Fusion Antigen as a Vaccine Candidate for the Prevention of Enterotoxigenic E. coli-Induced Calf Diarrhea.

Calf diarrhea caused by enterotoxigenic E. coli (ETEC) poses an enormous economic challenge in the cattle industry. Fimbriae and enterotoxin are crucial virulence factors and vaccine targets of ETEC. Since these proteins have complicated components with large molecular masses, the development of vaccines by directly expressing these potential targets is cumbersome Therefore, this study aimed to develop a multiepitope fusion antigen designated as MEFA by integrating major epitopes of FanC and Fim41a subunits and a toxoid epitope of STa into the F17G framework. The 3D modeling predicted that the MEFA protein displayed the epitopes from these four antigens on its surface, demonstrating the desired structural characteristics. Then, the MEFA protein was subsequently expressed and purified for mouse immunization. Following that, our homemade ELISA showed that the mouse antiserum had a consistent increase in polyclonal antibody levels with the highest titer of 1:217 to MEFA. Furthermore, the western blot assay demonstrated that this anti-MEFA serum could react with all four antigens. Further, this antiserum exhibited inhibition on ETEC adhesion to HCT-8 cells with inhibitory rates of 92.8%, 84.3%, and 87.9% against F17+, F5+, and F41+ ETEC strains, respectively. Additionally, the stimulatory effect of STa toxin on HCT-8 cells was decreased by approximately 75.3% by anti-MEFA serum. This study demonstrates that the MEFA protein would be an antigen candidate for novel subunit vaccines for preventing ETEC-induced diarrhea in cattle.

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.

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.

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.

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.

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.