Insights into the microscopic heterogeneity of whey proteins between yak colostrum and mature milk based on 4D lable-free quantitative phosphoproteomics.

This study aimed to reveal the change patterns of the phosphorylation modification status of yak whey phosphoproteins during lactation and their physiological effects. Herein, we comprehensively characterized whey phosphoproteome in yak colostrum and mature milk using an ultra-high throughput phosphoproteomics approach incorporating trapped ion mobility technology. A total of 344 phosphorylation sites from 206 phosphoproteins were identified, with individual site modification predominating. Notably, 117 significantly different phosphorylation sites were distributed on 89 whey phosphoproteins. Gene ontology analysis indicated that these significantly different whey phosphoproteins (SDWPPs) were mainly annotated to carbohydrate metabolic process, membrane, extracellular region and calcium ion binding. Metabolic pathway enrichment analysis demonstrated that SDWPPs were critically involved in protein processing in endoplasmic reticulum, NOD-like receptor signaling pathway and N-glycan biosynthesis. Our results elucidate the phosphorylation profiles of yak whey phosphoproteins at different lactations and their adaptive regulatory role in meeting the nutritional requirements of yak calves during development.

Exploring the gut microbiota's effect on temporomandibular joint disorder: a two-sample Mendelian randomization analysis.

Background: Temporomandibular joint disorders (TMD) are highly prevalent among people. Numerous investigations have revealed the impact of gut microbiota in many diseases. However, the causal relationship between Temporomandibular joint disorders and gut microbiota remains unclear. Methods: Genome-Wide Association Studies (GWAS) refer to the identification of sequence variations, namely single nucleotide polymorphisms (SNPs), existing across the entire human genome. GWAS data were collected on gut microbiota and TMD. Then, instrumental variables were screened through F-values and removal of linkage disequilibrium. These SNPs underwent mendelian analysis using five mathematical models. Sensitivity analysis was conducted to further verify the stability of the results. Pathogenic factors of TMD mediate the causal relationship between gut microbiota and TMD were explored through a two-step Mendelian randomization analysis. Finally, reverse mendelian analysis was conducted to account for potential reverse effects. Results: The analysis of the data in this article suggests that some gut microbiota, including Coprobacter, Ruminococcus torques group, Catenibacterium, Lachnospiraceae, Turicibacter, Victivallis, MollicutesRF9, Methanobacteriales, Methanobacteriaceae, FamilyXI, Methanobacteria were identified as risk factors, while Peptococcaceae provides protection for TMD. Conclusion: The research reveals the relation of gut microbiota in TMD. These findings provide insights into the underlying mechanisms and suggest potential therapeutic strategy.

A Type of Ferrocene-Based Derivative FE-1 COF Material for Glycopeptide and Phosphopeptide Selective Enrichment.

In this work, a new type of FE-1 COF material is prepared by a reversible imine condensation reaction with diaminoferrocene and diaminodiformaldehyde as materials. The material is connected by imine bonds to form a COF skeleton, and the presence of plenty of nitrogen-containing groups gives the material good hydrophilicity; the presence of metal Fe ions provides the material application potential in the enrichment of phosphopeptides. According to the different binding abilities of N-glycopeptide and phosphopeptide on FE-1 COF, it can simultaneously enrich N-glycopeptide and phosphopeptide through different elution conditions to realize its controllable and selective enrichment. Using the above characteristics, 18 phosphopeptides were detected from α-casein hydrolysate, 8 phosphopeptides were detected from ß-casein hydrolysate and 21 glycopeptides were detected from IgG hydrolysate. Finally, the gradual elution strategy was used; 16 phosphopeptides and 19 glycopeptides were detected from the α-casein hydrolysate and IgG hydrolysate. The corresponding glycopeptides and phosphopeptides were identified from the human serum. It proves that the FE-1 COF material has a good enrichment effect on phosphopeptides and glycopeptides.

RhoA/ROCK-TAZ Axis regulates bone formation within calvarial trans-sutural distraction osteogenesis.

BACKGROUND: Craniofacial skeletal deformities can be addressed by applying tensile force to sutures to prompt sutural bone formation. The intricate process of mechanical modulation in craniofacial sutures involves complex biomechanical signal transduction. The small GTPase Ras homolog gene family member A (RhoA) functions as a key mechanotransduction protein, orchestrating the dynamic assembly of the cytoskeleton by activating the Rho-associated coiled-coil containing protein kinase (ROCK). Transcriptional coactivator with PDZ-binding motif (TAZ) serves as a crucial mediator in the regulation of genes and the orchestration of biological functions within the mechanotransduction signaling pathway. However, the role of RhoA/ROCK-TAZ in trans-sutural distraction osteogenesis has not been reported. METHODS: We utilized pre-osteoblast-specific RhoA deletion mice to establish an in vivo calvarial trans-sutural distraction model and an in vitro mechanical stretch model for pre-osteoblasts isolated from neonatal mice. Micro-CT and histological staining were utilized to detect the formation of new bone in the sagittal suture of the skull as well as the activation of RhoA, Osterix and TAZ. The activation of ROCK-limk-cofilin and the nuclear translocation of TAZ in pre-osteoblasts under mechanical tension were detected through Western blot, qRT-PCR, and immunofluorescence. RESULTS: The osteogenic differentiation of pre-osteoblasts was facilitated by mechanical tension through the activation of RhoA and Rho-associated kinase (ROCK), while ablation of RhoA impaired osteogenesis by inhibiting pre-osteoblast differentiation after suture expansion. Furthermore, inhibiting RhoA expression could block tensile-stimulated nuclear translocation of TAZ by preventing F-actin assembly through ROCK-LIM-domain kinase (LIMK)-cofilin pathway. In addition, the TAZ agonist TM-25659 could attenuate impaired osteogenesis caused by ablation of RhoA in pre-osteoblasts by increasing TAZ nuclear accumulation. CONCLUSIONS: This study demonstrates that mechanical stretching promotes the osteogenic differentiation of pre-osteoblasts in trans-sutural distraction osteogenesis, and this process is mediated by the RhoA/ROCK-TAZ signaling axis. Overall, our results may provide an insight for potential treatment strategies for craniosynostosis patients through trans-sutural distraction osteogenesis.

Accurate Quantification of Ten Methylated Purine Nucleosides by Highly Sensitive and Stable Isotope-Diluted UHPLC-MS/MS.

The dynamic landscape of cellular nucleotides/nucleosides associated with RNA metabolism, particularly in diseases like cancer, has spurred intensive interest. Here, we report a robust stable isotope-diluted UHPLC-ESI-MS/MS method for accurate quantification of 12 purine ribonucleosides, including 10 methylated purine nucleosides. By the use of thermally decomposable ammonium bicarbonate (NH4HCO3) as a mobile phase additive for UHPLC-MS/MS detection, the ESI-MS/MS signal responses of these target compounds were enhanced by 1.7-24.5 folds. Noteworthily, three methylated guanosine isomers (m1G, m2G, and m7G) and two methylated adenosine isomers (m1A and m6A) that are indistinguishable directly by mass spectrometry were well resolved with optimal UHPLC separation. Combined with methanol extraction and solid-phase extraction (SPE) pretreatment, the method quantified intracellular concentrations of three modified nucleosides (Gm, m1G, and m2G), which would otherwise be undetectable because of significant suppression of their signals by the interfering cellular matrix. Nine purine nucleosides were simultaneously quantified in 293T cells, and their concentrations ranged by 4 orders of magnitude. Overall, the method presents high recovery rates over 90% for endogenous modified purine nucleosides in cultured cells, along with good precision, linearity, and LOD ranging from 0.30 fmol to 0.37 pmol per 5 × 105 cells. The developed UHPLC-MS/MS method holds potential for screening purine nucleosides as diagnostic and prognostic biomarkers and for quantifying purine epigenetic nucleosides post-cell metabolome analysis, thereby providing a valuable analytical tool for intracellular nucleoside quantification in future clinical research.

[Retracted] MicroRNA­30e inhibits adhesion, migration, invasion and cell cycle progression of prostate cancer cells via inhibition of the activation of the MAPK signaling pathway by downregulating CHRM3.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the Transwell invasion assay data shown in Fig. 7B on p. 451 were strikingly similar to data that had appeared in Fig. 3D in a previously published paper written by different authors at a different research institute, which had been received at the journal Cancer Letters at around the same time, and which has subsequently been retracted [Gu J, Wang Y, Wang X, Zhou D, Shao C, Zhou M and He Z: Downregulation of lncRNA GAS5 confers tamoxifen resistance by activating miR­222 in breast cancer. Cancer Lett 434: 1­10, 2018]. In addition, there were potentially anomalous features associated with the western blot and cell cycle data in this paper.  In view of the fact that certain of the data in the above article were also submitted to a different journal within the space of a few days, the Editor of International Journal of Oncology has decided that this paper should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 54: 443­454, 2019; DOI: 10.3892/ijo.2018.4647].

Prevalence of anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation in people with autoimmune skin diseases.

BACKGROUND: Autoimmune skin diseases (ASDs) such as psoriasis and vitiligo, in addition to causing visible skin symptoms, are closely associated with psychological health issues. However, a comprehensive understanding of the prevalence of these psychological comorbidities in affected individuals is lacking. This study aims to identify the prevalence of anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation in people with ASDs. METHOD: PubMed, MEDLINE, Web of Science, and Cochrane Library searches were conducted from 1993 to May 2024. Observational studies reporting prevalence data for anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation among people with ASDs were included in the analysis. The Newcastle-Ottawa scale was used to evaluate the quality of studies. RESULTS: The study included 114 studies from 37 countries including 823,975 participants. The estimated pooled prevalence of anxiety in patients with ASDs was 33.3% (95% CI: 27.3-29.3%). The estimated pooled prevalence of depression was 33.7% (95% CI: 29.2-38.1%). The estimated pooled prevalence of sleeping problems was 45.0% (95% CI:31.6-58.4%). The estimated pooled prevalence of cognitive impairment and suicidal ideation was 30.8% (95% CI:15.0-46.7%) and 21.6% (95% CI:13.4-29.8%), respectively. The most common mental disorder in patients with systemic lupus erythematosus and psoriasis was sleeping problems at 55.9% (95% CI: 35.6-76.1%, I2 = 97%) and 39.0% (95% CI: 21.1-56.9%, I2 = 99%). CONCLUSION: Among patients with ASDs, anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation were common. The most prevalent mental disorder among patients with systemic lupus erythematosus and psoriasis was sleeping problems. Those with ASDs may experience considerable psychological burdens, and integrated mental health support is necessary for their treatment.

Novel Strategy for Screening Target Proteins by the Common Drugs─Sofosbuvir-Specific Profiling of HCV Patient Serum.

It is the scientific basis of precision medicine to study all of the targets of drugs based on the interaction between drugs and proteins. It is worth paying attention to unknown proteins that interact with drugs to find new targets for the design of new drugs. Herein, we developed a protein profiling strategy based on drug-protein interactions and drug-modified magnetic nanoparticles and took hepatitis C virus (HCV) and its corresponding drug sofosbuvir (SOF) as an example. A SOF-modified magnetic separation medium (Fe3O4@POSS@SOF) was prepared, and a gradient elution strategy was employed and optimized to profile specific proteins interacted with SOF. A series of proteomic analyses were performed to profile proteins based on SOF-protein interactions (SPIs) in the serum of HCV patients to evaluate the specificity of the profiling strategy. As a result, five proteins were profiled with strong SPIs and exhibited high relevance with liver tissue, which were potentially new drug targets. Among them, HSP60 was used to confirm the highly specific interactions between the SOF and its binding proteins by Western blotting analysis. Besides, 124 and 29 differential proteins were profiled by SOF material from three HCV patient serum and pooled 20 HCV patient serum, respectively, by comparing with healthy human serum. In comparison with those profiled by the polyhedral oligomeric silsesquioxane (POSS) material, differential proteins profiled by the SOF material were highly associated with liver diseases through GO analysis and pathway analysis. Furthermore, four common differential proteins profiled by SOF material but not by POSS material were found to be identical and expressed consistently in both pooled serum samples and independent serum samples, which might potentially be biomarkers of HCV infection. Taken together, our study proposes a highly specific protein profiling strategy to display distinctive proteomic profiles, providing a novel idea for drug design and development.

Bioreduction of Se(IV) by Lactiplantibacillus plantarum NML21 and synthesis of selenium nanospheres Se(0).

Selenium nanospheres (SeNPs) show less toxicity and greater bioavailability than selenite salts. This research demonstrated the substantial tolerance and efficient conversion of Se(IV) into SeNPs by Lactiplantibacillus plantarum NML21. The bioreduction process of Se(IV) and the properties of SeNPs, including their morphology, particle size, and stability, were investigated with techniques including SEM, EDX, TEM, XPS, FT-IR, dynamic light scattering, XRD, and Raman spectroscopy. Under high selenium stress, certain cells displayed significant deformation and rupture, and released SeNPs as the main product of the bioreduction of Se(IV). These SeNPs were red, amorphous, zero-valent, and spherical, with an average diameter of 160 nm. Spectroscopic analysis highlighted that the functional groups of CO and CO are key to the bioreduction of Se(IV). The study suggested preliminary mechanisms for the bioreduction of Se(IV) and the formation and release of SeNPs by lactic acid bacteria. NML21 may therefore be a promising candidate for SeNPs synthesis.

[Preparation technology comparison and performance evaluation of different protein A affinity chromatographic materials].

Protein A affinity chromatographic materials are widely used in clinical medicine and biomedicine because of their specific interactions with immunoglobulin G (IgG). Both the characteristics of the matrix, such as its structure and morphology, and the surface modification method contribute to the affinity properties of the packing materials. The specific, orderly, and oriented immobilization of protein A can reduce its steric hindrance with the matrix and preserve its bioactive sites. In this study, four types of affinity chromatographic materials were obtained using agarose and polyglycidyl methacrylate (PGMA) spheres as substrates, and multifunctional epoxy and maleimide groups were used to fix protein A. The effects of the ethylenediamine concentration, reaction pH, buffer concentration, and other conditions on the coupling efficiency of protein A and adsorption performance of IgG were evaluated. Multifunctional epoxy materials were prepared by converting part of the epoxy groups of the agarose and PGMA matrices into amino groups using 0.2 and 1.6 mol/L ethylenediamine, respectively. Protein A was coupled to the multifunctional epoxy materials using 5 mmol/L borate buffer (pH 8) as the reaction solution. When protein A was immobilized on the substrates by maleimide groups, the agarose and PGMA substrates were activated with 25% (v/v) ethylenediamine for 16 h to convert all epoxy groups into amino groups. The maleimide materials were then converted into amino-modified materials by adding 3 mg/mL 3-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) dissolved in dimethyl sulfoxide (DMSO) and then suspended in 5 mmol/L borate buffer (pH 8). The maleimide groups reacted specifically with the C-terminal of the sulfhydryl group of recombinant protein A to achieve highly selective fixation on both the agarose and PGMA substrates. The adsorption performance of the affinity materials for IgG was improved by optimizing the bonding conditions of protein A, such as the matrix type, matrix particle size, and protein A content, and the adsorption properties of each affinity material for IgG were determined. The column pressure of the protein A affinity materials prepared using agarose or PGMA as the matrix via the maleimide method was subsequently evaluated at different flow rates. The affinity materials prepared with PGMA as the matrix exhibited superior mechanical strength compared with the materials prepared with agarose. Moreover, an excellent linear relationship between the flow rate and column pressure of 80 mL/min was observed for this affinity material. Subsequently, the effect of the particle size of the PGMA matrix on the binding capacity of IgG was investigated. Under the same protein A content, the dynamic binding capacity of the affinity materials on the PGMA matrix was higher when the particle size was 44-88 µm than when other particle sizes were used. The properties of the affinity materials prepared using the multifunctional epoxy and maleimide-modified materials were compared by synthesizing affinity materials with different protein A coupling amounts of 1, 2, 4, 6, 8, and 10 mg/mL. The dynamic and static binding capacities of each material for bovine IgG were then determined. The prepared affinity material was packed into a chromatographic column to purify IgG from bovine colostrum. Although all materials showed specific adsorption selectivity for IgG, the affinity material prepared by immobilizing protein A on the PGMA matrix with maleimide showed significantly better performance and achieved a higher dynamic binding capacity at a lower protein grafting amount. When the protein grafting amount was 15.71 mg/mL, the dynamic binding capacity of bovine IgG was 32.23 mg/mL, and the dynamic binding capacity of human IgG reached 54.41 mg/mL. After 160 cycles of alkali treatment, the dynamic binding capacity of the material reached 94.6% of the initial value, indicating its good stability. The developed method is appropriate for the production of protein A affinity chromatographic materials and shows great potential in the fields of protein immobilization and immunoadsorption material synthesis.

Ultra-flat bands at large twist angles in group-V twisted bilayer materials.

Flat bands in 2D twisted materials are key to the realization of correlation-related exotic phenomena. However, a flat band often was achieved in the large system with a very small twist angle, which enormously increases the computational and experimental complexity. In this work, we proposed group-V twisted bilayer materials, including P, As, and Sb in the ß phase with large twist angles. The band structure of twisted bilayer materials up to 2524 atoms has been investigated by a deep learning method DeepH, which significantly reduces the computational time. Our results show that the bandgap and the flat bandwidth of twisted bilayer ß-P, ß-As, and ß-Sb reduce gradually with the decreasing of twist angle, and the ultra-flat band with bandwidth approaching 0 eV is achieved. Interestingly, we found that a twist angle of 9.43° is sufficient to achieve the band flatness for ß-As comparable to that of twist bilayer graphene at the magic angle of 1.08°. Moreover, we also find that the bandgap reduces with decreasing interlayer distance while the flat band is still preserved, which suggests interlayer distance as an effective routine to tune the bandgap of flat band systems. Our research provides a feasible platform for exploring physical phenomena related to flat bands in twisted layered 2D materials.

The metabolic activation of pentachlorophenol to chloranil as a potent inhibitor of human and rat placental 3ß-hydroxysteroid dehydrogenases.

Pentachlorophenol (PCP) is a widely used pesticide. However, whether PCP and its metabolite chloranil have endocrine-disrupting effects by inhibiting placental 3ß-hydroxysteroid dehydrogenase 1 (3ß-HSD1) remains unclear. The study used in vitro assays with human and rat placental microsomes to measure 3ß-HSD activity as well as human JAr cells to evaluate progesterone production. The results showed that PCP exhibited moderate inhibition of human 3ß-HSD1, with an IC50 value of 29.83 µM and displayed mixed inhibition in terms of mode of action. Conversely, chloranil proved to be a potent inhibitor, demonstrating an IC50 value of 147 nM, and displaying a mixed mode of action. PCP significantly decreased progesterone production by JAr cells at 50 µM, while chloranil markedly reduced progesterone production at ≥1 µM. Interestingly, PCP and chloranil moderately inhibited rat placental homolog 3ß-HSD4, with IC50 values of 27.94 and 23.42 µM, respectively. Dithiothreitol (DTT) alone significantly increased human 3ß-HSD1 activity. Chloranil not PCP mediated inhibition of human 3ß-HSD1 activity was completely reversed by DTT and that of rat 3ß-HSD4 was partially reversed by DTT. Docking analysis revealed that both PCP and chloranil can bind to the catalytic domain of 3ß-HSDs. The difference in the amino acid residue Cys83 in human 3ß-HSD1 may explain why chloranil is a potent inhibitor through its interaction with the cysteine residue of human 3ß-HSD1. In conclusion, PCP is metabolically activated to chloranil as a potent inhibitor of human 3ß-HSD1.

Mechanical Stretch-Induced ATP Release from Osteocytes Promotes Osteogenesis of Bone Marrow Mesenchymal Stem Cells.

BACKGROUND: Mandibular distraction osteogenesis (MDO) is a highly effective method for bone regeneration, commonly employed in treating craniofacial defects and deformities. Osteocytes sense mechanical forces in the pericellular space, relay external stimuli to biochemical changes, and send signals to other effector cells, including bone marrow mesenchymal stem cells (BM-MSCs), to regulate bone resorption and formation. Piezo1 potentially affects the secretion signal molecules of bone cells under mechanical stretch. The primary aim of this study was to enhance our comprehension of the molecular biology underlying this therapeutic approach and to identify specific signaling molecules that facilitate bone formation in response to stretch forces. METHODS: Mechanical stretching was applied to negative controls and Piezo1 knockdown osteocyte-like MLO-Y4 cells. Alkaline phosphatase and Alizarin Red S staining were used to survey the osteogenic potential of BM-MSCs. The production and secretion content of adenosine triphosphate (ATP) was measured using ATP content determination analysis. Pathway-related and osteo-specific genes and proteins were evaluated using real-time polymerase chain reaction (RT-PCR), Western blots, and immunofluorescence. Mitochondrial organization was examined with a transmission electron microscope. RESULTS: The conditioned medium of stretch-exposed MLO-Y4s significantly upregulated osteogenesis-related indicators of BM-MSCs (p < 0.001). The upregulation of BM-MSC osteogenesis was associated with ATP release from osteocytes. Mechanically induced calcium transfer and transcriptional coactivator with PDZ-binding motif (TAZ) nuclear translocation mediated by Piezo1 could promote mitochondrial fission and ATP release. Osteocytes detected stretch forces through Piezo1, triggering calcium influx, TAZ nuclear translocation, and ATP production. CONCLUSIONS: The stretch stimulation of Piezo1 induces calcium influx, which in turn promotes calcium-related TAZ nuclear translocation, changes in mitochondrial dynamics, and the release of ATP in osteocytes. This signaling cascade leads to an up-regulation in the osteogenic capacity of BM-MSCs. Mitochondrial energy metabolism of mechanosensitive protein Piezo1-dependent and ATP release may provide a new effective intervention method for mechanically related bone remodeling.

S100A4 modulates cell proliferation, apoptosis and fibrosis in the hyperplastic prostate.

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men worldwide that may result in lower urinary tract symptoms (LUTS). At present, the specific pathophysiological mechanism for BPH/LUTS LUTS remains unclear. S100 calcium binding protein A4 (S100A4), a member of the calcium binding protein family, regulates a variety of biological processes including cell proliferation, apoptosis and fibrosis. The aim of the current study was to explore and clarify the possible role of S100A4 in BPH/LUTS. The human prostate stromal cell line (WPMY-1), rat prostate epithelial cells, human prostate tissues and two BPH rat models were employed in this study. The expression and localization of S100A4 were detected by quantitative real time PCR (qRT-PCR), immunofluorescence microscopy, Western blotting and immunohistochemistry analysis. Also, S100A4 knockdown or overexpression cell models were constructed and a BPH rat model was induced with testosterone propionate (T) or phenylephrine (PE). The BPH animals were treated with Niclosamide, a S100A4 transcription inhibitor. Results demonstrated that S100A4 was mainly localized in human prostatic stroma and rat prostatic epithelium, and showed a higher expression in BPH. Knockdown of S100A4 induced cell apoptosis, cell proliferation arrest and a reduction of tissue fibrosis markers. Overexpression of S100A4 reversed the aforementioned changes. We also demonstrated that S100A4 regulated proliferation and apoptosis mainly through the ERK pathway and modulated fibrosis via Wnt/ß-catenin signaling. In conclusion, our novel data demonstrate that S100A4 could play a crucial role in BPH development and may be explored as a new therapeutic target of BPH.

A novel lysosome-related prognostic signature associated with prognosis and immune infiltration landscape in oral squamous cell carcinoma.

Background: Predicting the outcome of oral squamous cell carcinoma (OSCC) is challenging due to its diverse nature and intricate causes. This research explores how lysosome-associated genes (LRGs) might forecast overall survival (OS) and correlate with immune infiltration in OSCC patients. Methods: We analyzed OSCC patients' LRGs' mRNA expression data and clinical details from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through univariate Cox regression, we pinpointed LRGs with prognostic potential. A signature comprising 12 LRGs linked to prognosis was developed via the Least Absolute Shrinkage and Selection Operator (LASSO) in a training dataset. Patients were classified as higher or lower risk based on their risk scores, and the prognostic independence of the risk score was assessed using multivariate analysis. The model's robustness and precision were confirmed through bioinformatics in the GEO test set. Differential gene expression analysis between risk groups highlighted functional disparities, while various immune evaluation methods elucidated immune differences. Results: The prognostic framework utilized 12 LRGs (SLC46A3, MANBA, NEU1, SDCBP, BRI3, TMEM175, CD164, GPC1, SFTPB, TPP1, Biglycan (BGN) and TMEM192), showing that higher risk was associated with poorer OS. This set of genes independently predicted OS in OSCC, linking LRGs to cellular adhesion and extracellular matrix involvement. Initial assessments using ssGSEA and CIBERSORT suggested that the adverse outcomes in the higher-risk cohort may be tied to immune system deregulation. Conclusion: Twelve-LRGs signature has been identified for OSCC prognosis prediction, offering novel directions for lysosome-targeted therapies against OSCC.

Screening of Lactiplantibacillus plantarum NML21 and Its Maintenance on Postharvest Quality of Agaricus bisporus through Anti-Browning and Mitigation of Oxidative Damage.

Browning and other undesirable effects on Agaricus bisporus (A. bisporus) during storage seriously affect its commercial value. In this study, a strain, Lactiplantibacillus plantarum NML21, that resists browning and delays the deterioration of A. bisporus was screened among 72 strains of lactic acid bacteria (LAB), and its preservative effect was analyzed. The results demonstrated that gallic acid, catechin, and protocatechuic acid promoted the growth of NML21, and the strain conversion rates of gallic acid and protocatechuic acid reached 97.16% and 95.85%, respectively. During a 15 d storage of the samples, the NML21 treatment displayed a reduction in the browning index (58.4), weight loss (2.64%), respiration rate (325.45 mg kg-1 h-1), and firmness (0.65 N). The treatment further inhibited Pseudomonas spp. growth and polyphenol oxidase activity, improved the antioxidant capacity, reduced the accumulation of reactive oxygen species, and reduced the malonaldehyde content and cell membrane conductivity. Taken together, the optimized concentrations of NML21 may extend the shelf life of A. bisporus for 3-6 d and could be a useful technique for preserving fresh produce.

Pseudo-targeted lipidomics insights into lipid discrepancies between yak colostrum and mature milk based on UHPLC-Qtrap-MS.

Yak milk is essential to maintain the normal physiological functions of herders in Tibetan areas of China. However, the lipid components of yak colostrum (YC) and mature milk (YM) have not been systematically studied. We employed a quantitative lipidomics to comprehensively describe the alterations in the milk lipid profile of lactating yaks. Herein, totally 851 lipids from 28 lipid subclasses in YC and YM were identified and screened for 43 significantly different lipids (SDLs; variable importance in projection > 1, fold change < 0.5 or > 2 with P < 0.05), with cholesterol ester (CE, 16:0) and triacylglycerol (TAG, 54:6 (20:5), 50:1 (16:0), 56:6 (20:5)) were the potential lipid biomarkers. Fourteen SDLs were modulated downwards, and 29 SDLs were modulated upwards in YM. Moreover, by analyzing lipid metabolic pathways in these SDLs, glycerophospholipid metabolism was the most critical. Our results furnish integral lipid details for evaluating yak milk's nutritional quality.

Non-pharmacological interventions for preventing suicide attempts: A systematic review and network meta-analysis.

Suicide attempts can cause serious physical harm or death. It would be crucial to gain a better understanding of the comparative efficacy of non-pharmacological interventions. We aimed to identify which non-pharmacological interventions are more effective in preventing suicide attempts. PubMed, Web of Science, and EMBASE databases were searched systematically from their inception until 3 April 2023. To be eligible for inclusion, randomized controlled trials (RCTs) had to meet the following criteria: Participants were individuals who had suicidal ideation or a history of severe self-harm or attempted suicide. A network meta-analysis was performed using a random effects model to estimate the treatment effect of various non-pharmacological interventions. (PROSPERO registration number: CRD42023411393). We obtained data from 54 studies involving 17,630 participants. Our primary analysis found that Cognitive therapy (CT) (OR=0.19, 95%CI =0.04-0.81), Dialectical Behavior Therapy (DBT) (OR=0.37, 95%CI =0.13-0.97), Cognitive-behavioral therapy (CBT) (OR=0.42, 95%CI =0.17-0.99), and Brief intervention and contact (BIC) (OR=0.65, 95%CI=0.44-0.94) were superior to TAU (within the longest available follow-up time) in preventing suicide attempts, while other intervention methods do not show significant advantages over TAU. Secondary analysis showed that the two intervention measures (CT and BIC) were effective when follow-up time did not exceed 6 months, but there was no effective intervention measure with longer follow-up times. CT, DBT, CBT, and BIC have a better effect in preventing suicide attempts than other non-pharmacological interventions. Additional research is necessary to validate which interventions, as well as which combinations of interventions, are the most effective.

Comprehensive Characterization of HATs and HDACs in Human Cancers Reveals Their Role in Immune Checkpoint Blockade.

Histone acetylation that controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs), as one of major epigenetic mechanisms controls transcription and its abnormal regulation was implicated in various aspects of cancer. However, the comprehensive understanding of HDACs and HATs in cancer is still lacking. Systematically analysis through 33 cancer types based on next-generation sequence data reveals heterogeneous expression pattern of HDACs and HATs across different cancer types. In particular, HDAC10 and HDAC6 show significant downregulation in most cancers. Principal components analysis (PCA) of pan-cancer reveals significant difference of HDACs and HATs between normal tissues and normal tissue adjacent to the tumor. The abnormal expression of HDACs and HATs was partially due to CNV and DNA methylation in multiple types of cancer. Prognostic significance (AUC reached 0.736) of HDACs and HATs demonstrates a five-gene signature including KAT2A, HAT1, KAT5, CREBBP and SIRT1 in KIRC. Analysis of NCI-60 drug database reveals the cytotoxic effect of several drugs are associated with dysregulated expression of HDACs and HATs. Analysis of immune infiltration and immunotherapy reveals that KAT2B and HDAC9 are associated with immune infiltration and immunotherapy. Our analysis provided comprehensive understanding of the regulation and implication of HDACs and HATs in pan-cancer. These findings provide novel evidence for biological investigating potential individual HDACs and HATs in the development and therapy of cancer in the future.