Amino acid metabolism-related genes as potential biomarkers and the role of MATN3 in stomach adenocarcinoma: A bioinformatics, mendelian randomization and experimental validation study.

BACKGROUND: Stomach adenocarcinoma (STAD) is a major contributor to cancer-related mortality worldwide. Alterations in amino acid metabolism, which is integral to protein synthesis, have been observed across various tumor types. However, the prognostic significance of amino acid metabolism-related genes in STAD remains underexplored. METHODS: Transcriptomic gene expression and clinical data for STAD patients were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Amino acid metabolism-related gene sets were sourced from the Gene Set Enrichment Analysis (GSEA) database. A prognostic model was built using LASSO Cox regression based on the TCGA cohort and validated with GEO datasets (GSE84433, GSE84437, GSE84426). Kaplan-Meier analysis compared overall survival (OS) between high- and low-risk groups, and ROC curves assessed model accuracy. A nomogram predicted 1-, 3-, and 5-year survival. Copy number variations (CNVs) in model genes were visualized using data from the Xena platform, and mutation profiles were analyzed with "maftools" to create a waterfall plot. KEGG and GO enrichment analyses were performed to explore biological mechanisms. Immune infiltration and related functions were evaluated via ssGSEA, and Spearman correlation analyzed associations between risk scores and immune components. The TIDE database predicted immunotherapy efficacy, while FDA-approved drug sensitivity was assessed through CellMiner database. The role of MATN3 in STAD was further examined in vitro and in vivo, including amino acid-targeted metabolomic sequencing to assess its impact on metabolism. Finally, Mendelian randomization (MR) analysis evaluated the causal relationship between the model genes and gastric cancer. RESULTS: In this study, we developed a prognostic risk model for STAD based on three amino acid metabolism-related genes (SERPINE1, NRP1, MATN3) using LASSO regression analysis. CNV amplification was common in SERPINE1 and NRP1, while CNV deletion frequently occurred in MATN3. STAD patients were classified into high- and low-risk groups based on the median risk score, with the high-risk group showing worse prognosis. A nomogram incorporating the risk score and clinical factors was created to estimate 1-, 3-, and 5-year survival rates. Distinct mutation profiles were observed between risk groups, with KEGG pathway analysis showing immune-related pathways enriched in the high-risk group. High-risk scores were significantly associated with the C6 (TGF-ß dominant) subtype, while low-risk scores correlated with the C4 (lymphocyte-depleted) subtype. Higher risk scores also indicated increased immune infiltration, enhanced immune functions, lower tumor purity, and poorer immunotherapy response. Model genes were linked to anticancer drug sensitivity. Manipulating MATN3 expression showed that it promoted STAD cell proliferation and migration in vitro and tumor growth in vivo. Metabolomic sequencing revealed that MATN3 knockdown elevated levels of 30 amino acid metabolites, including alpha-aminobutyric acid, glycine, and aspartic acid, while reducing (S)-ß-Aminoisobutyric acid and argininosuccinic acid. MR analysis found a significant causal effect of NRP1 on gastric cancer, but no causal relationship for MATN3 or SERPINE1. CONCLUSION: In conclusion, the amino acid metabolism-related prognostic model shows promise as a valuable biomarker for predicting the clinical prognosis, selecting immunotherapy and drug treatment for STAD patients. Furthermore, our study has shed light on the potential value of the MATN3 as a promising strategy for combating the progression of STAD.

Exploring the Roles of the Swi2/Snf2 Gene Family in Maize Abiotic Stress Responses.

The maize Snf2 gene family plays a crucial role in chromatin remodeling and response to environmental stresses. In this study, we identified and analyzed 35 members of the maize Snf2 gene family (ZmCHR1 to ZmCHR35) using the Ensembl Plants database. Each protein contained conserved SNF2-N and Helicase-C domains. Phylogenetic analysis revealed six groups among the Snf2 proteins, with an uneven distribution across subfamilies. Physicochemical analysis indicated that the Snf2 proteins are hydrophilic, with varied amino acid lengths, isoelectric points, and molecular weights, and are predominantly localized in the nucleus. Chromosomal mapping showed that these genes are distributed across all ten maize chromosomes. Gene structure analysis revealed diverse exon-intron arrangements, while motif analysis identified 20 conserved motifs. Collinearity analysis highlighted gene duplication events, suggesting purifying selection. Cis-regulatory element analysis suggested involvement in abiotic and biotic stress responses. Expression analysis indicated tissue-specific expression patterns and differential expression under various stress conditions. Specifically, qRT-PCR validation under drought stress showed that certain Snf2 genes were upregulated at 12 h and downregulated at 24 h, revealing potential roles in drought tolerance. These findings provide a foundation for further exploration of the functional roles of the maize Snf2 gene family in development and stress responses.

SMTRI: A deep learning-based web service for predicting small molecules that target miRNA-mRNA interactions.

Mature microRNAs (miRNAs) are short, single-stranded RNAs that bind to target mRNAs and induce translational repression and gene silencing. Many miRNAs discovered in animals have been implicated in diseases and have recently been pursued as therapeutic targets. However, conventional pharmacological screening for candidate small-molecule drugs can be time-consuming and labor-intensive. Therefore, developing a computational program to assist mature miRNA-targeted drug discovery in silico is desirable. Our previous work (https://doi.org/10.1002/advs.201903451) revealed that the unique functional loops formed during Argonaute-mediated miRNA-mRNA interactions have stable structural characteristics and may serve as potential targets for small-molecule drug discovery. Developing drugs specifically targeting disease-related mature miRNAs and their target mRNAs would avoid affecting unrelated ones. Here, we present SMTRI, a convolutional neural network-based approach for efficiently predicting small molecules that target RNA secondary structural motifs formed by interactions between miRNAs and their target mRNAs. Measured on three additional testing sets, SMTRI outperformed state-of-the-art algorithms by 12.9%-30.3% in AUC and 2.0%-18.4% in accuracy. Moreover, four case studies on the published experimentally validated RNA-targeted small molecules also revealed the reliability of SMTRI.

Comparison of Hidden Blood Loss between Laparoendoscopic Single-Site Myomectomy and Conventional Laparoscopic Myomectomy.

OBJECTIVE: Laparoendoscopic single-site myomectomy (LESS-M) is widely applied for the treatment of uterine leiomyoma. The purposes of this study were to investigate differences in hidden blood loss between LESS-M and conventional laparoscopic myomectomy (CLM) during treatment of uterine leiomyoma and to identify the associated risk factors. DESIGN: This is a retrospective study. PARTICIPANTS: The participants of this study were patients who underwent laparoscopic myomectomy (114 and 156 for LESS-M and CLM, respectively) between July 1, 2019, and October 10, 2020, at the Second Affiliated Hospital of Wenzhou Medical University. SETTING: The study was conducted at the Second Affiliated Hospital of Wenzhou Medical University. METHODS: We enrolled a total of 114 and 156 patients who were treated with LESS-M and CLM, respectively, between July 1, 2019, and October 10, 2020. We collected clinical data, then applied the Nadler and Gross formula and multiple linear regression analysis to calculate the HBL and identify the associated risk factors, respectively. RESULTS: Patients in the LESS-M group had a VBL of 115.4 ± 180.6 mL and an HBL of 364.3 ± 252.6 mL, accounting for 74.4 ± 22.4% of true TBL. On the other hand, patients in the CLM group had VBL of 187.9 ± 198.5 mL, and HBL of 306.8 ± 304.7 mL, accounting for 58.9 ± 30.2% of true TBL. HBL was significantly higher in the LESS-M than the CLM group (p = 0.000). LIMITATIONS: This study was the small sample size used. CONCLUSIONS: HBL accounted for a significant percentage of TBL in laparoscopic myomectomy, especially in patients treated with LESS-M. Paying attention to perioperative blood changes coupled with fully understanding HBL might promote postoperative recovery of patients.

Oocytes maintain low ROS levels to support the dormancy of primordial follicles.

Primordial follicles (PFs) function as the long-term reserve for female reproduction, remaining dormant in the ovaries and becoming progressively depleted with age. Oxidative stress plays an important role in promoting female reproductive senescence during aging, but the underlying mechanisms remain unclear. Here, we find that low levels of reactive oxygen species (ROS) are essential for sustaining PF dormancy. Compared to growing follicles, oocytes within PFs were shown to be more susceptible to ROS, which accumulates and damages PFs to promote reproductive senescence. Mechanistically, oocytes within PFs were shown to express high levels of the intracellular antioxidant enzyme superoxide dismutase 1 (SOD1), counteracting ROS accumulation. Decreased SOD1 expression, as a result of aging or through the experimental deletion of the Sod1 gene in oocytes, resulted in increased oxidative stress and triggered ferroptosis within PFs. In conclusion, this study identified antioxidant defense mechanisms protecting PFs in mouse ovaries and characterized cell death mechanisms of oxidative stress-induced PF death.

Chinese Medicines and Natural Medicine as Immunotherapeutic Agents for Gastric Cancer: Recent Advances.

BACKGROUD: According to the 2020 statistics from the World Health Organization's International Agency for Research on Cancer (IARC), it is projected that there will be over 1 million new cases of gastric cancer (GC) patients worldwide in 2020, resulting in approximately 770 000 deaths. Gastric cancer ranks fifth in terms of incidence rate and forth in death rate among malignant tumors. Despite advancements in early diagnostic techniques, the incidence of GC has exhibited a marginal decline; nevertheless, the mortality rate remains elevated for advanced inoperable patients with no currently available efficacious treatment options. RECENT FINDING: Chinese medicine (CM) has emerged as an efficacious treatment for GC, gradually gaining acceptance and widespread usage in China. It exhibits distinctive advantages in the prevention and treatment of metastasis. CM and natural medicine possess the ability to elicit antitumor effects by augmenting immune cell population, enhancing immune cell activity, and improving the tumor immune microenvironment. CMs and natural remedies encompass a diverse range of types, characterized by multiple targets, pathways, and extensive pharmacological effects. Consequently, they have become a prominent research area among oncologists worldwide. Numerous studies have demonstrated that CM and natural medicine can directly or indirectly enhance innate immune system components (including macrophages, natural killer cells, and myeloid suppressor cells), adaptive immune system elements (such as T lymphocytes and regulatory T cells), relevant cytokines (e.g., IL-2, IL-4, IL-10, TNF-α), and PD-1/PD-L1 axis regulation, thereby bolstering the cytotoxicity of immune cells against tumor cells. CONCLUSIONS: This ultimately leads to an improved tumor immune microenvironment facilitating superior antitumor efficacy. This paper critically examines the role of CM and natural medicine in regulating immunotherapy for GC, aiming to establish a new theoretical framework for the clinical treatment and prevention of gastric cancer within the realm of CM.

RLSynC: Offline-Online Reinforcement Learning for Synthon Completion.

Retrosynthesis is the process of determining the set of reactant molecules that can react to form a desired product. Semitemplate-based retrosynthesis methods, which imitate the reverse logic of synthesis reactions, first predict the reaction centers in the products and then complete the resulting synthons back into reactants. We develop a new offline-online reinforcement learning method RLSynC for synthon completion in semitemplate-based methods. RLSynC assigns one agent to each synthon, all of which complete the synthons by conducting actions step by step in a synchronized fashion. RLSynC learns the policy from both offline training episodes and online interactions, which allows RLSynC to explore new reaction spaces. RLSynC uses a standalone forward synthesis model to evaluate the likelihood of the predicted reactants in synthesizing a product and thus guides the action search. Our results demonstrate that RLSynC can outperform state-of-the-art synthon completion methods with improvements as high as 14.9%, highlighting its potential in synthesis planning.

Defective autophagy of pericytes enhances radiation-induced senescence promoting radiation brain injury.

BACKGROUND: Radiation-induced brain injury (RBI) represents a major challenge for cancer patients undergoing cranial radiotherapy. However, the molecular mechanisms and therapeutic strategies of RBI remain inconclusive. With the continuous exploration of the mechanisms of RBI, an increasing number of studies have implicated cerebrovascular dysfunction as a key factor in RBI-related cognitive impairment. As pericytes are a component of the neurovascular unit, there is still a lack of understanding in current research about the specific role and function of pericytes in RBI. METHODS: We constructed a mouse model of RBI-associated cognitive dysfunction in vivo and an in vitro radiation-induced pericyte model to explore the effects of senescent pericytes on the blood-brain barrier and normal CNS cells, even glioma cells. To further clarify the effects of pericyte autophagy on senescence, molecular mechanisms were explored at the animal and cellular levels. Finally, we validated the clearance of pericyte senescence by using senolytic drug and all-trans retinoic acid to investigate the role of radiation-induced pericyte senescence. RESULTS: Our findings indicated that radiation-induced pericyte senescence plays a key role in blood-brain barrier dysfunction, leading to RBI and subsequent cognitive decline. Strikingly, pericyte senescence also contributes to the growth and invasion of glioma cells. We further demonstrate that defective autophagy in pericytes is a vital regulatory mechanism for pericyte senescence. Moreover, autophagy activated by rapamycin can reverse pericyte senescence. Notably, the elimination of senescent cells by senolytic drugs significantly mitigated radiation-induced cognitive dysfunction. DISSCUSSION: Our results demonstrated that pericyte senescence may be a promising therapeutic target for RBI and glioma progression.

An Immune-Enhancing Injectable Hydrogel Loaded with Esketamine and DDP Promotes Painless Immunochemotherapy to Inhibit Breast Cancer Growth.

Chemotherapy is the cornerstone of triple-negative breast cancer. The poor effectiveness and severe neuropathic pain caused by it have a significant impact on the immune system. Studies confirmed that immune cells in the tumor microenvironment (TME), have critical roles in tumor immune regulation and prognosis. In this study, it is revealed that the painless administration of Esketamine, combined with Cisplatin (DDP), can exert an anti-tumor effect, which is further boosted by the hydrogel delivery system. It is also discovered that Esketamine combined with DDP co-loaded in Poloxamer Hydrogel (PDEH) induces local immunity by increasing mature Dendritic Cells (mDCs) and activated T cells in PDEH group while the regulatory T cells (Tregs) known as CD4+CD25+FoxP3+decreased significantly. Finally, , CD8+ and CD4+ T cells in the spleen exhibited a significant increase, suggesting a lasting immune impact of PDEH. This study proposes that Esketamine can serve as a painless immune modulator, enhancing an anti-tumor effect while co-loaded in poloxamer hydrogel with DDP. Along with improving immune cells in the microenvironment, it can potentially alleviate anxiety and depression. With its outstanding bio-safety profile, it offers promising new possibilities for painless clinical therapy.

Effects of Latilactobacillus sakei LZ217 on Gastric Mucosal Colonization, Metabolic Interference, and Urease Expression in Helicobacter pylori Infection.

Emerging evidence suggests differential antagonism of lactic acid-producing bacteria (LAB) to Helicobacter pylori, posing challenges to human health and food safety due to unclear mechanisms. This study assessed 21 LAB strains from various sources on H. pylori growth, urease activity, and coaggregation. Composite scoring revealed that Latilactobacillus sakei LZ217, derived from fresh milk, demonstrates strong inhibitory effects on both H. pylori growth and urease activity. L. sakei LZ217 significantly reduced H. pylori adherence of gastric cells in vitro, with inhibition ratios of 47.62%. Furthermore, in vivo results showed that L. sakei LZ217 alleviated H. pylori-induced gastric mucosa damage and inflammation in mice. Metabolomic exploration revealed metabolic perturbations in H. pylori induced by L. sakei LZ217, including reduced amino acid levels (e.g., isoleucine, leucine, glutamate, aspartate, and phenylalanine) and impaired carbohydrate and nucleotide synthesis, contributing to the suppression of ureA (28.30%), ureE (84.88%), and ureF (59.59%) expressions in H. pylori. This study underscores the efficacy of LAB against H. pylori and highlights metabolic pathways as promising targets for future interventions against H. pylori growth and colonization.

miRNA Sequencing Analysis in Maize Roots Treated with Neutral and Alkaline Salts.

Soil salinization/alkalization is a complex environmental factor that includes not only neutral salt NaCl but also other components like Na2CO3. miRNAs, as small molecules that regulate gene expression post-transcriptionally, are involved in plant responses to abiotic stress. In this study, maize seedling roots were treated for 5 h with 100 mM NaCl, 50 mM Na2CO3, and H2O, respectively. Sequencing analysis of differentially expressed miRNAs under these conditions revealed that the Na2CO3 treatment group had the most differentially expressed miRNAs. Cluster analysis indicated their main involvement in the regulation of ion transport, binding, metabolism, and phenylpropanoid and flavonoid biosynthesis pathways. The unique differentially expressed miRNAs in the NaCl treatment group were related to the sulfur metabolism pathway. This indicates a significant difference in the response patterns of maize to different treatment groups. This study provides theoretical evidence and genetic resources for further analysis of the molecular mechanisms behind maize's salt-alkali tolerance.

Shear-Sensitive circRNA-LONP2 Promotes Endothelial Inflammation and Atherosclerosis by Targeting NRF2/HO1 Signaling.

Hemodynamic shear stress is a frictional force that acts on vascular endothelial cells and is essential for endothelial homeostasis. Physiological laminar shear stress (LSS) suppresses endothelial inflammation and protects arteries from atherosclerosis. Herein, we screened differentially expressed circular RNAs (circRNAs) that were significantly altered in LSS-stimulated endothelial cells and found that circRNA-LONP2 was involved in modulating the flow-dependent inflammatory response. Furthermore, endothelial circRNA-LONP2 overexpression promoted endothelial inflammation and atherosclerosis in vitro and in vivo. Mechanistically, circRNA-LONP2 competitively sponged miR-200a-3p and subsequently promoted Kelch-like ECH-associated protein 1, Yes-associated protein 1, and enhancer of zeste homolog 2 expression, thereby inactivating nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling, promoting oxidative stress and endothelial inflammation, and accelerating atherosclerosis. LSS-induced down-regulation of circRNA-LONP2 suppresses endothelial inflammation, at least in part, by activating the miR-200a-3p-mediated nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. CircRNA-LONP2 may serve as a new therapeutic target for atherosclerosis.

Exopolysaccharide from Lacticaseibacillus paracasei alleviates gastritis in Helicobacter pylori-infected mice by regulating gastric microbiota.

Introduction: Many probiotics have the ability to produce extracellular polysaccharides (EPS). EPS derived from these probiotics has been confirmed to regulate the host intestinal microecological balance and alleviate the symptoms of diseases caused by gastrointestinal microecological imbalance. Results: Lactic acid bacteria (LAB) strain with good exopolysaccharide (EPS) producing ability, namely, Lacticaseibacillus paracasei ZFM54 (L. paracasei ZFM54) was screened. The fermentation conditions of L. paracasei ZFM54 for EPS production were optimized. The EPS54 was characterized by chemical component and monosaccharide composition determination, UV, FT-IR and NMR spectra analysis. Cango red, SEM, AFM and XRD analysis were conducted to characterize the structure of EPS54. The EPS54 effectively reduced the colonization of Helicobacter pylori to AGS cells and recovered the cell morphology. EPS54 could also effectively alleviate the gastritis in the H. pylori-infected mice by down-regulating the mRNA expression levels of pro-inflammatory cytokines IL-6, IL-8, IL-1ß and TNF-α and up-regulating the mRNA expression of inflammatory cytokine IL-10 in gastric cells. EPS54 was also found to be able to positively regulate the structure of gastric microbiota. Conclusion: The EPS 54 from L. paracasei ZFM54 can alleviate gastritis in H. pylori-infected mice by modulating the gastric microbiota.

Effect of comfortable nursing on postoperative nausea and vomiting in patients with idiopathic scoliosis after posterior orthopedic surgery.

Objective: To evaluate the effect of comfort nursing on postoperative nausea and vomiting in patients with idiopathic scoliosis undergoing posterior correction surgery. Methods: 92 patients with idiopathic scoliosis were taken as the subjects and segmented into a control group and an experimental group (n = 46/each group). The former received routine care, while the latter one performed comfortable care. The observation period is 48 h after surgery. Record and compare the incidence, grade, frequency, and pain level of nausea and vomiting in both groups, as well as postoperative physical signs and symptoms, drug use, and postoperative recovery. Investigating the patient's satisfaction with nursing care. The research data is analyzed using SPSS26.0 software. P < 0.05 means statistical significance. Results: Within 48 h after surgery, the number of nausea and vomiting in the control is 24 and the experimental group is 8, with an incidence rate of 52% and 16%. The latter is significantly lower than that in the control. The average number of nausea and vomiting episodes in the control is 2.5, significantly higher than the 0.45 episodes in the experimental set. There is a significant difference in the frequency of nausea and vomiting/temperature and urine volume/scores of nausea, vomiting, dizziness, headache, decreased appetite, and discomfort between the two groups (P < 0.05). Conclusion: Comfortable care has a relieving effect on postoperative nausea and vomiting in patients with idiopathic scoliosis after posterior correction surgery. It can low down the incidence and frequency of nausea and vomiting, and reduce the score of related symptoms. Comfortable care can also help patients recover after surgery, increase dietary intake, and improve nutritional status. Comfortable care has a significant effect on postoperative nausea and vomiting in cases with idiopathic scoliosis undergoing posterior correction surgery, which can improve their postoperative recovery and quality of life.

BCL6B-dependent suppression of ETV2 hampers endothelial cell differentiation.

BACKGROUND: B-cell CLL/lymphoma 6 member B (BCL6B) operates as a sequence-specific transcriptional repressor within the nucleus, playing crucial roles in various biological functions, including tumor suppression, immune response, stem cell self-renew, and vascular angiogenesis. However, whether BCL6B is involved in endothelial cell (EC) development has remained largely unknown. ETS variant transcription factor 2 (ETV2) is well known to facilitate EC differentiation. This study aims to determine the important role of BCL6B in EC differentiation and its potential mechanisms. METHODS: Doxycycline-inducible human induced pluripotent stem cell (hiPSC) lines with BCL6B overexpression or BCL6B knockdown were established and subjected to differentiate into ECs and vessel organoids (VOs). RNA sequencing analysis was performed to identify potential signal pathways regulated by BCL6B during EC differentiation from hiPSCs. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of pluripotency and vascular-specific marker genes expression. EC differentiation efficiency was determined by Flow cytometry analysis. The performance of EC was evaluated by in vitro Tube formation assay. The protein expression and the vessel-like structures were assessed using immunofluorescence analysis or western blot. Luciferase reporter gene assay and chromatin immunoprecipitation (ChIP)-PCR analysis were used to determine the regulatory relationship between BCL6B and ETV2. RESULTS: Functional ECs and VOs were successfully generated from hiPSCs. Notably, overexpression of BCL6B suppressed while knockdown of BCL6B improved EC differentiation from hiPSCs. Additionally, the overexpression of BCL6B attenuated the capacity of derived hiPSC-ECs to form a tubular structure. Furthermore, compared to the control VOs, BCL6B overexpression repressed the growth of VOs, whereas BCL6B knockdown had little effect on the size of VOs. RNA sequencing analysis confirmed that our differentiation protocol induced landscape changes for cell/tissue/system developmental process, particularly vascular development and tube morphogenesis, which were significantly modulated by BCL6B. Subsequent experiments confirmed the inhibitory effect of BCL6B is facilitated by the binding of BCL6B to the promoter region of ETV2, led to the suppression of ETV2's transcriptional activity. Importantly, the inhibitory effect of BCL6B overexpression on EC differentiation from hiPSCs could be rescued by ETV2 overexpression. CONCLUSIONS: BCL6B inhibits EC differentiation and hinders VO development by repressing the transcriptional activity of ETV2.

P2X7R Modulates NEK7-NLRP3 Interaction to Exacerbate Experimental Autoimmune Prostatitis via GSDMD-mediated Prostate Epithelial Cell Pyroptosis.

Chronic prostatitis is one of the most common urologic diseases that troubles young men, with unclear etiology and ineffective treatment approach. Pyroptosis is a novel model of cell death, and its roles in chronic prostatitis are unknown. In this study, P2X7R, NEK7, and GSDMD-NT expression levels were detected in prostate tissues from benign prostate hyperplasia (BPH) patients and experiment autoimmune prostatitis (EAP) mice. P2X7R agonist, antagonist, NLRP3 inhibitor, and disulfiram were used to explore the roles of the P2X7R-NEK7-NLRP3 axis in prostate epithelial cell pyroptosis and chronic prostatitis development. We found that P2X7R, NEK7, and GSDMD-NT were highly expressed in the prostate epithelial cells of BPH patients with prostatic inflammation and EAP mice. Activation of P2X7R exacerbated prostatic inflammation and increased NLRP3 inflammasome component expressions and T helper 17 (Th17) cell proportion. Moreover, P2X7R-mediated potassium efflux promoted NEK7-NLRP3 interaction, and NLRP3 assembly and activation, which caused GSDMD-NT-mediated prostate epithelial cell pyroptosis to exacerbate EAP development. Disulfiram could effectively improve EAP by inhibiting GSDMD-NT-mediated prostate epithelial cell pyroptosis. In conclusion, the P2X7R-NEK7-NLRP3 axis could promote GSDMD-NT-mediated prostate epithelial cell pyroptosis and chronic prostatitis development, and disulfiram may be an effective drug to treat chronic prostatitis.

Halicin: A New Horizon in Antibacterial Therapy against Veterinary Pathogens.

It is crucial to discover novel antimicrobial drugs to combat resistance. This study investigated the antibacterial properties of halicin (SU3327), an AI-identified anti-diabetic drug, against 13 kinds of common clinical pathogens of animal origin, including multidrug-resistant strains. Employing minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assessments, halicin demonstrated a broad-spectrum antibacterial effect. Time-killing assays revealed its concentration-dependent bactericidal activity against Escherichia coli ATCC 25922 (E. coli ATCC 25922), Staphylococcus aureus ATCC 29213 (S. aureus ATCC 29213), and Actinobacillus pleuropneumoniae S6 (APP S6) after 4 h of treatment at concentrations above the MIC. Halicin exhibited longer post-antibiotic effects (PAEs) and sub-MIC effects (PA-SMEs) for E. coli 25922, S. aureus 29213, and APP S6 compared to ceftiofur and ciprofloxacin, the commonly used veterinary antimicrobial agents, indicating sustained antibacterial action. Additionally, the results of consecutive passaging experiments over 40 d at sub-inhibitory concentrations showed that bacteria exhibited difficulty in developing resistance to halicin. Toxicology studies confirmed that halicin exhibited low acute toxicity, being non-mutagenic, non-reproductive-toxic, and non-genotoxic. Blood biochemical results suggested that halicin has no significant impact on hematological parameters, liver function, and kidney function. Furthermore, halicin effectively treated respiratory A. pleuropneumoniae infections in murine models. These results underscore the potential of halicin as a new antibacterial agent with applications against clinically relevant pathogens in veterinary medicine.

High-quality quasi-bound state in the continuum enabled single-nanoparticle virus detection.

Bound states in the continuum (BICs) have emerged as a powerful platform for boosting light-matter interactions because they provide an alternative way of realizing optical resonances with ultrahigh quality(Q-) factors, accompanied by extreme field confinement. In this work, we realized an optical biosensor by introducing a quasi-BIC (qBIC) supported by an elaborated all-dielectric dimer grating. Thanks to the excellent field confinement within the air gap of grating enabled by such a high-Q qBIC, the figure of merit (FOM) of a biosensor is up to 18,908.7 RIU-1. Furthermore, we demonstrated that such a high-Q grating can help push the limit of optical biosensing to the single-particle level. Our results may find exciting applications in extreme biochemical sensing like COVID-19 with ultralow concentration.

Trends in cardiovascular risk factor prevalence, treatment, and control among US adolescents aged 12 to 19 years, 2001 to March 2020.

BACKGROUND: Early-life cardiovascular risk factors (CVRFs) are known to be associated with target organ damage during adolescence and premature cardiovascular morbidity and mortality during adulthood. However, contemporary data describing whether the prevalence of CVRFs and treatment and control rates have changed are limited. This study aimed to examine the temporal trends in the prevalence, treatment, and control of CVRFs among US adolescents over the past 2 decades. METHODS: This is a serial cross-sectional study using data from nine National Health and Nutrition Examination Survey cycles (January 2001-March 2020). US adolescents (aged 12 to 19 years) with information regarding CVRFs (including hypertension, elevated blood pressure [BP], diabetes, prediabetes, hyperlipidemia, obesity, overweight, cigarette use, inactive physical activity, and poor diet quality) were included. Age-adjusted trends in CVRF prevalence, treatment, and control were examined. Joinpoint regression analysis was performed to estimate changes in the prevalence, treatment, and control over time. The variation by sociodemographic characteristics were also described. RESULTS: A total of 15,155 US adolescents aged 12 to 19 years (representing ≈ 32.4 million people) were included. From 2001 to March 2020, there was an increase in the prevalence of prediabetes (from 12.5% [95% confidence interval (CI), 10.2%-14.9%] to 37.6% [95% CI, 29.1%-46.2%]) and overweight/obesity (from 21.1% [95% CI, 19.3%-22.8%] to 24.8% [95% CI, 21.4%-28.2%]; from 16.0% [95% CI, 14.1%-17.9%] to 20.3% [95% CI, 17.9%-22.7%]; respectively), no improvement in the prevalence of elevated BP (from 10.4% [95% CI, 8.9%-11.8%] to 11.0% [95% CI, 8.7%-13.4%]), diabetes (from 0.7% [95% CI, 0.2%-1.2%] to 1.2% [95% CI, 0.3%-2.2%]), and poor diet quality (from 76.1% [95% CI, 74.0%-78.2%] to 71.7% [95% CI, 68.5%-74.9%]), and a decrease in the prevalence of hypertension (from 8.1% [95% CI, 6.9%-9.4%] to 5.5% [95% CI, 3.7%-7.3%]), hyperlipidemia (from 34.2% [95% CI, 30.9%-37.5%] to 22.8% [95% CI, 18.7%-26.8%]), cigarette use (from 18.0% [95% CI, 15.7%-20.3%] to 3.5% [95% CI, 2.0%-5.0%]), and inactive physical activity (from 83.0% [95% CI, 80.7%-85.3%] to 9.5% [95% CI, 4.2%-14.8%]). Sex and race/ethnicity affected the evolution of CVRF prevalence differently. Whilst treatment rates for hypertension and diabetes did not improve significantly (from 9.6% [95% CI, 3.5%-15.8%] to 6.0% [95% CI, 1.4%-10.6%]; from 51.0% [95% CI, 23.3%-78.7%] to 26.5% [95% CI, 0.0%-54.7%]; respectively), BP control was relatively stable (from 75.7% [95% CI, 56.8%-94.7%] to 73.5% [95% CI, 40.3%-100.0%]), while glycemic control improved to a certain extent, although it remained suboptimal (from 11.8% [95% CI, 0.0%-31.5%] to 62.7% [95% CI, 62.7%-62.7%]). CONCLUSIONS: From 2001 to March 2020, although prediabetes and overweight/obesity increased, hypertension, hyperlipidemia, cigarette use, and inactive physical activity decreased among US adolescents aged 12 to 19 years, whereas elevated BP, diabetes, and poor diet quality remained unchanged. There were disparities in CVRF prevalence and trends across sociodemographic subpopulations. While treatment and control rates for hypertension and diabetes plateaued, BP control were stable, and improved glycemic control was observed.