Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke.

JOURNAL/nrgr/04.03/01300535-202502000-00027/figure1/v/2024-05-28T214302Z/r/image-tiff Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury. Low-density lipoprotein receptor, a classic cholesterol regulatory receptor, has been found to inhibit NLR family pyrin domain containing protein 3 (NLRP3) inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer's disease. However, little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke. To address this issue in the present study, we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models. First, we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis. We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation. Second, we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus. Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype. Finally, we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin, an NLRP3 agonist, restored the neurotoxic astrocyte phenotype. These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

The genome sequencing and comparative genomics analysis of Rhizoctonia solani reveals a novel effector family owning a uinque domain in Basidiomycetes.

Rhizoctonia solani is a soil-borne pathogen with 14 anastomosis groups (AGs), and different subgroups are genetically diverse. However, the genetic factors contributing to the pathogenicity of the fungus have not been well characterized. In this study, the genome of R. solani AG1-ZJ was sequenced. As the result, a 41.57 Mb draft genome containing 12,197 putative coding genes was obtained. Comparative genomic analysis of 11 different AGs revealed conservation and unique characteristics between the AGs. Furthermore, a novel effector family containing a 67 amino acid conserved domain unique in basidiomycetous fungi was characterized. Two effectors containing the conserved domain in AG4-JY were identified, and named as RsUEB1 and RsUEB2. Furthermore, the spray-induced gene silencing strategy was used to generate a dsRNA capable of silencing the conserved domain sequence of RsUEB1 and RsUEB2. This dsRNA can significantly reduce the expression of RsUEB1 and RsUEB2 and the pathogenicity of AG4-JY on foxtail millet, maize, rice and wheat. In conclusion, this study provides significant insights into the pathogenicity mechanisms of R. solani. The identification of the conserved domain and the successful use of dsRNA silencing of the gene containing the conserved domain will offer a new strategy for controlling sheath blight in cereal crops.

Quarter-wave Pancharatnam-Berry phase gradient liquid crystal-enabled dual-polarization optical edge detection.

Here, we present a novel, to the best of our knowledge, optical edge detection scheme that can be operated in both linear and circular polarization modes, leveraging an optical spatial differentiator constructed by quarter-wave Pancharatnam-Berry (P-B) phase gradient element. After explaining the theoretical mechanism, we utilize a quarter-wave P-B phase liquid crystal polarization grating to validate the dual-polarization optical edge detection capability. We demonstrate that the orientation of linear polarization and the spin of circular polarization dictate the transition between edge and bright-field images. Besides, the linear and circular polarization modes exhibit broadband and monochromatic responsive properties, respectively. This mechanism, dependent on wavelength and polarization, holds promise for applications in color image processing, chiral sensing imaging, and polarization-entangled quantum imaging.

Insulin enhances acid-sensing ion channel currents in rat primary sensory neurons.

Insulin has been shown to modulate neuronal processes through insulin receptors. The ion channels located on neurons may be important targets for insulin/insulin receptor signaling. Both insulin receptors and acid-sensing ion channels (ASICs) are expressed in dorsal root ganglia (DRG) neurons. However, it is still unclear whether there is an interaction between them. Therefore, the purpose of this investigation was to determine the effects of insulin on the functional activity of ASICs. A 5 min application of insulin rapidly enhanced acid-evoked ASIC currents in rat DRG neurons in a concentration-dependent manner. Insulin shifted the concentration-response plot for ASIC currents upward, with an increase of 46.2 ± 7.6% in the maximal current response. The insulin-induced increase in ASIC currents was eliminated by the insulin receptor antagonist GSK1838705, the tyrosine kinase inhibitor lavendustin A, and the phosphatidylinositol-3 kinase antagonist wortmannin. Moreover, insulin increased the number of acid-triggered action potentials by activating insulin receptors. Finally, local administration of insulin exacerbated the spontaneous nociceptive behaviors induced by intraplantar acid injection and the mechanical hyperalgesia induced by intramuscular acid injections through peripheral insulin receptors. These results suggested that insulin/insulin receptor signaling enhanced the functional activity of ASICs via tyrosine kinase and phosphatidylinositol-3 kinase pathways. Our findings revealed that ASICs were targets in primary sensory neurons for insulin receptor signaling, which may underlie insulin modulation of pain.

Aromative Dephosphinidenation of a Bisphosphirane-Fused Anthracene toward E-H (E = H, Si, N and P) Bond Activation.

A bisphosphirane-fused anthracene (5) was prepared by treatment of a sterically encumbered amino phosphorus dichloride (3) with MgA•3THF (A = anthracene). X-ray diffraction analysis revealed a pentacyclic framework consisting of 5 with two phosphirane rings fused to the anthracene in a trans-fashion. Compound 5 has been shown to be an efficient phosphinidene synthon, readily liberating two transient phosphinidene units for subsequent downstream bond activation via the reductive elimination of anthracene under mild conditions. The formal oxidative addition of H2 and E-H (E = Si, N, P) bonds by the liberated phosphinidene provided diphosphine and substituted phosphines. Furthermore, phosphinidene transfer to alkenes and alkynes smoothly yielded the corresponding phosphiranes and phosphirenes. The mechanism of the H2 activation by 5 was investigated by density functional theory (DFT) calculations.

Alterations of the bile microbiome is associated with progression-free survival in pancreatic ductal adenocarcinoma patients.

BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDAC) display an altered oral, gastrointestinal, and intra-pancreatic microbiome compared to healthy individuals. However, knowledge regarding the bile microbiome and its potential impact on progression-free survival in PDACs remains limited. METHODS: Patients with PDAC (n = 45), including 20 matched pairs before and after surgery, and benign controls (n = 16) were included prospectively. The characteristics of the microbiomes of the total 81 bile were revealed by 16  S-rRNA gene sequencing. PDAC patients were divided into distinct groups based on tumor marker levels, disease staging, before and after surgery, as well as progression free survival (PFS) for further analysis. Disease diagnostic model was formulated utilizing the random forest algorithm. RESULTS: PDAC patients harbor a unique and diverse bile microbiome (PCoA, weighted Unifrac, p = 0.038), and the increasing microbial diversity is correlated with dysbiosis according to key microbes and microbial functions. Aliihoeflea emerged as the genus displaying the most significant alteration among two groups (p < 0.01). Significant differences were found in beta diversity of the bile microbiome between long-term PFS and short-term PFS groups (PCoA, weighted Unifrac, p = 0.005). Bacillota and Actinomycetota were identified as altered phylum between two groups associated with progression-free survival in all PDAC patients. Additionally, we identified three biomarkers as the most suitable set for the random forest model, which indicated a significantly elevated likelihood of disease occurrence in the PDAC group (p < 0.0001). The area under the receiver operating characteristic (ROC) curve reached 80.8% with a 95% confidence interval ranging from 55.0 to 100%. Due to the scarcity of bile samples, we were unable to conduct further external verification. CONCLUSION: PDAC is characterized by an altered microbiome of bile ducts. Biliary dysbiosis is linked with progression-free survival in all PDACs. This study revealed the alteration of the bile microbiome in PDACs and successfully developed a diagnostic model for PDAC.

Successfully saving a child with destuctive iliac artery damage by hybrid surgery.

Non-iatrogenic trauma of the iliac artery is rarely reported but is always life-threatening. In this report, we describe the case of a child with complete transection and partial disappearance of the iliac artery caused by bicycle handlebar impalement. He experienced catastrophic hemorrhage, malignant arrhythmia, and difficulty in exploring transected vessel stumps. Aggressive infusion, blood transfusion in time, and pediatric vascular characteristics help delay the deterioration during anesthesia induction. Eventually he was successfully rescued by performing interventional balloon occlusion and open revascularization after more than 7 h post-trauma. A series of interventions and precautionary methods may benefit such severely injured patients; thus, these methods should be highlighted.

The role of AMPKα subunit in Alzheimer's disease: In-depth analysis and future prospects.

The AMP-activated protein kinase α (AMPKα) subunit is the catalytic subunit in the AMPK complex, playing a crucial role in AMPK activation. It has two isoforms: AMPKα1 and AMPKα2. Emerging evidence suggests that the AMPKα subunit exhibits subtype-specific effects in Alzheimer's disease (AD). This review discusses the role of the AMPKα subunit in the pathogenesis of AD, including its impact on ß-amyloid (Aß) pathology, Tau pathology, metabolic disorders, inflammation, mitochondrial dysfunction, inflammasome and pyroptosis. Additionally, it reviews the distinct roles of its isoforms, AMPKα1 and AMPKα2, in AD, which may provide more precise targets for future drug development in AD.

Universal Copolymerization of Crosslinked Polyether Electrolytes for All-Solid-State Lithium-Metal Batteries.

Solid polymer electrolytes (SPEs) are pivotal in advancing the practical implementation of all-solid-state batteries. Poly(1,3-dioxane) (PDOL)-based electrolytes have attracted significant attention due to the pseudo-high conductivity achieved through sophisticated in situ polymerization methods; however, such PDOL-based electrolytes present challenges of crystallization over time and monomers residual during processing. In this study, integrating LiTFSI and LiDFOB as a universal copolymerization strategy for developing high-performance PDOL electrolytes with a wide range of epoxy crosslinkers is proposed. It is discovered that this approach leverages the protective effects of TFSI anions on the boron active center and catalyzes polymer chain growth via crosslinking. The homogenously crosslinked (benzene-centered) PDOL electrolyte exhibits remarkable thermo-mechanical stability (up to 100 °C), high ion migration number (tLi+ = 0.42), a wide electrochemical window (≈5.0 V vs Li+/Li), and high ionic conductivity (4.5×10-4 S cm-1). Notably, the crosslinked PDOL electrolyte is in the all-solid-state with minimal monomer/oligomer residual, exhibiting no crystallization during relaxation, delivering a robust performance in all-solid-state lithium metal batteries.

Association between Whole-Grain Intake and Obesity Defined by Different Anthropometric Indicators and Dose-Response Relationship Analysis among U.S. Adults: A Population-Based Study.

Existing research shows an inconsistent correlation between whole-grain intake and obesity risk, with limited study on the dose-response relationship. Here, we aimed to examine this association and dose-response relationship among U.S. adults who participated in a NHANES (2003-2018). The intake of whole grain was collected and calculated from two rounds of 24 h dietary recall. Obesity was categorized based on body mass index (BMI) and waist circumference (WC). Weighted multivariable logistic regression models were used to calculate the odds of obesity according to whole-grain intake, and the dose-response relationship was modeled by restricted cubic spline regression. Among the 27,862 participants, 38.3% had general obesity, while 58.3% had abdominal obesity. After multivariate adjustment of potential confounders, the participants in the highest quintile of whole-grain intake had a lower prevalence of general obesity (OR 0.79; 95% CI 0.72-0.88) and abdominal obesity (OR 0.80; 95% CI 0.73-0.89) compared with those in the lowest category. Spline regression showed an inversely linear dose-response association between whole-grain intake and the prevalence of general obesity and abdominal obesity. In conclusion, a higher whole-grain intake was associated with lower odds of obesity, both general and abdominal. Our findings highlight the importance of increasing the whole-grain intake to prevent and manage obesity.

Effect of Vaginal Microecological Disorders on the Increased Risk of Abnormal Cervical Cytology Among Women With Human Immunodeficiency Virus in China.

BACKGROUND: Abnormal cervical cytology is commonly observed in women with human immunodeficiency virus (WWH). METHODS: A cross-sectional study was conducted with 130 WWH and 147 age-matched healthy controls, who underwent gynecological examinations at Beijing Ditan Hospital. The presence of abnormal cervical cytology in WWH was predicted after performing a logistic regression analysis. RESULTS: Multivariate logistic regression revealed 3 independent factors, among which CD4 cell count ≥350 cells/µL was the protective factor, while human papillomavirus infection and abnormal vaginal pH were the risk factors. CONCLUSIONS: Vaginal microecological disorders can increase the risk of abnormal cervical cytology in WWH.

The bioinfomatics analysis of the M1 macrophage-related gene CXCL9 signature in cervical cancer.

BACKGROUND: The expression and function of coexpression genes of M1 macrophage in cervical cancer have not been identified. And the CXCL9-expressing tumour-associated macrophage has been poorly reported in cervical cancer. METHODS: To clarify the regulatory gene network of M1 macrophage in cervical cancer, we downloaded gene expression profiles of cervical cancer patients in TCGA database to identify M1 macrophage coexpression genes. Then we constructed the protein-protein interaction networks by STRING database and performed functional enrichment analysis to investigate the biological effects of the coexpression genes. Next, we used multiple bioinformatics databases and experiments to overall investigate coexpression gene CXCL9, including western blot assay and immunohistochemistry assay, GeneMANIA, Kaplan-Meier Plotter, Xenashiny, TISCH2, ACLBI, HPA, TISIDB, GSCA and cBioPortal databases. RESULTS: There were 77 positive coexpression genes and 5 negative coexpression genes in M1 macrophage. The coexpression genes in M1 macrophage participated in the production and function of chemokines and chemokine receptors. Especially, CXCL9 was positively correlated with M1 macrophage infiltration levels in cervical cancer. CXCL9 expression would significantly decrease and high CXCL9 levels were linked to good prognosis in the cervical cancer tumour patients, it manifestly expressed in blood immune cells, and was positively related to immune checkpoints. CXCL9 amplification was the most common type of mutation. The CXCL9 gene interaction network could regulate immune-related signalling pathways, and CXCL9 amplification was the most common mutation type in cervical cancer. Meanwhile, CXCL9 may had clinical significance for the drug response in cervical cancer, possibly mediating resistance to chemotherapy and targeted drug therapy. CONCLUSION: Our findings may provide new insight into the M1 macrophage coexpression gene network and molecular mechanisms in cervical cancer, and indicated that M1 macrophage association gene CXCL9 may serve as a good prognostic gene and a potential therapeutic target for cervical cancer therapies.

Cervical cancer is a common gynaecological malignancy, investigating the precise gene expression regulation of M1 macrophage is crucial for understanding the changes in the immune microenvironment of cervical cancer. In our study, a total of 82 coexpression genes with M1 macrophages were identified, and these genes were involved in the production and biological processes of chemokines and chemokine receptors. Especially, the chemokine CXCL9 was positively correlated with M1 macrophage infiltration levels in cervical cancer. CXCL9 as a protective factor, it manifestly expressed in blood immune cells, and was positively related to immune checkpoints. CXCL9 amplification was the most common type of mutation. And CXCL9 expression could have an effect on the sensitivity of some chemicals or targeted drugs against cervical cancer. These findings may provide new insight into the M1 macrophage coexpression gene network and molecular mechanisms, and shed light on the role of CXCL9 in cervical cancer.

Application of Delayed Repeated Enema With Sedation in Pediatric Intussusception: A Single Center Retrospective Study.

OBJECTIVE: This study aimed to evaluate the clinical application of delayed repeated air enema (DRE) with sedation in pediatric intussusception. METHOD: We retrospectively assessed cases of idiopathic intussusception treated with air enema reduction at the emergency department of Beijing Children's Hospital affiliated to Capital Medical University from January 2016 to August 2019. The included cases were assigned to the success or failure groups based on the outcomes of DRE with sedation. General patient information, clinical manifestations, test results, and surgical conditions were collected for comparative analysis. RESULTS: A total of 3052 cases were initially diagnosed with intussusception and underwent air enema reduction. Ultimately, 211 cases were included, with 162 in the success group and 49 in the failure group. The success rate of DRE with sedation was 76.8% (162/211), with an overall reduction success rate of 97.8% (2984/3052). Univariate logistic regression analysis showed that patients in the failure group had a significantly higher proportion of patients with age ≤1 year, bloody stools, and left-sided intussusception before DRE compared to the success group (OR = 2.3, 95%CI: 1.1∼4.6, P = 0.023; OR = 3.4, 95%CI: 1.6∼7.2, P = 0.002 and OR = 12.6, 95%CI: 4.6∼34.6, P < 0.001). Multiple logistic regression analysis based on these three factors revealed that the risk of DRE failure was 10.1 times higher in cases with the left-sided intussusception before DRE. CONCLUSIONS: DRE with sedation can improve the overall enema reduction success rate for intussusception and has good feasibility and safety profiles. Left-sided intussusception before DRE is an independent risk factor for enema failure.

Personalized and continuous care intervention affects rehabilitation, living quality, and negative emotions of patients with breast cancer.

BACKGROUND: Breast cancer is among the most common malignancies worldwide. With progress in treatment methods and levels, the overall survival period has been prolonged, and the demand for quality care has increased. AIM: To investigate the effect of individualized and continuous care intervention in patients with breast cancer. METHODS: Two hundred patients with breast cancer who received systemic therapy at The First Affiliated Hospital of Hebei North University (January 2021 to July 2023) were retrospectively selected as research participants. Among them, 134 received routine care intervention (routing group) and 66 received personalized and continuous care (intervention group). Self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Functional Assessment of Cancer Therapy-Breast (FACT-B) scores, including limb shoulder joint activity, complication rate, and care satisfaction, were compared between both groups after care. RESULTS: SAS and SDS scores were lower in the intervention group than in the routing group at one and three months after care. The total FACT-B scores and five dimensions in the intervention group were higher than those in the routing group at three months of care. The range of motion of shoulder anteflexion, posterior extension, abduction, internal rotation, and external rotation in the intervention group was higher than that in the routing group one month after care. The incidence of postoperative complications was 18.18% lower in the intervention group than in the routing group (34.33%; P <0.05). Satisfaction with care was 90.91% higher in the intervention group than in the routing group (78.36%; P <0.05). CONCLUSION: Personalized and continuous care can alleviate negative emotions in patients with breast cancer, quicken rehabilitation of limb function, decrease the incidence of complications, and improve living quality and care satisfaction.

Association between body mass index and semen quality: a systematic review and meta-analysis.

The continuous decline of human semen quality during the past decades has drawn much concern globally. Previous studies have suggested a link between abnormal BMI and semen quality decline, but the results remain inconsistent. This systematic review and meta-analysis aimed to evaluate the association between body mass index (BMI) and semen quality. We searched PubMed, Embase, and Web of Science for eligible studies from inception to April 17, 2022. We considered men with BMI < 25.0 kg/m2 as the reference and calculated the pooled weighted mean difference of men with overweight (BMI 25.0-29.9 kg/m2), obesity (BMI ≥ 30.0 kg/m2), class I obesity (BMI 30.0-34.9 kg/m2), and class II/III obesity (BMI ≥ 35.0 kg/m2). A total of 5070 articles were identified, of which 50 studies were included (71,337 subjects). Compared with men with BMI < 25.0 kg/m2, men with obesity had an average reduction of 0.24 ml in semen volume, 19.56 × 106 in total sperm number, 2.21% in total motility, 5.95% in progressive motility, and 1.08% in normal forms, respectively, while men with overweight had an average reduction of 0.08 ml in semen volume and 2.91% in progressive motility, respectively. The reduction of semen quality was more pronounced among men with obesity than that among men with overweight. Moreover, significant reductions in semen quality were identified in men with different classes of obesity, which were more pronounced in men with class II/III obesity than that in men with class I obesity. Across men from the general population, infertile or subfertile men, and suspiciously subfertile men, we identified significant semen quality reductions in men with obesity/overweight. In conclusion, obesity and overweight were significantly associated with semen quality reductions, suggesting that maintaining normal weight may help prevent semen quality decline.

Study on the Prediction of Liver Injury in Acute Pancreatitis Patients by Radiomic Model Based on Contrast-Enhanced Computed Tomography.

OBJECTIVES: to predict liver injury in acute pancreatitis (AP) patients by establishing a radiomics model based on contrast-enhanced computed tomography (CECT). METHODS: a total of 1223 radiomic features were extracted from late arterial-phase pancreatic CECT images of 209 AP patients (146 in the training cohort and 63 in the test cohort), and the optimal radiomic features retained after dimensionality reduction by least absolute shrinkage and selection operator (LASSO) were used to construct a radiomic model through logistic regression analysis. In addition, clinical features were collected to develop a clinical model, and a joint model was established by combining the best radiomic features and clinical features to evaluate the practicality and application value of the radiomic models, clinical model and combined model. RESULTS: four potential features were selected from the pancreatic parenchyma to construct the radiomic model, and the area under the receiver operating characteristic curve (AUC) of the radiomic model was significantly greater than that of the clinical model for both the training cohort (0.993 vs. 0.653, p = 0.000) and test cohort (0.910 vs. 0.574, p = 0.000). The joint model had a greater AUC than the radiomics model for both the training cohort (0.997 vs. 0.993, p = 0.357) and test cohort (0.925 vs. 0.910, p = 0.302). CONCLUSIONS: the radiomic model based on CECT has good performance in predicting liver injury in AP patients and can guide clinical decision-making and improve the prognosis of patients with AP.

[Mechanism of protective effect of n-butanol extract of Pulsatilla Decoction on vaginal epithelial cells under Candida albicans stimulation through EGFR/MAPK pathway based on transcriptomics].

This study aimed to investigate the protective effect and its underlying mechanism of n-butanol extract of Pulsatilla Decoction(BEPD) containing medicinal serum on vaginal epithelial cells under Candida glabrata stimulation via the epidermal growth factor receptor/mitogen activated protein kinase( EGFR/MAPK) pathway based on transcriptomics. A vulvovaginal candidiasis(VVC) mouse model was established first and transcriptome sequencing was performed for the vaginal mucosa tissues to analyze the gene expression differences among the control, VVC model, and BEPD intervention groups. Simultaneously, BEPD-containing serum and fluconazole-containing serum were prepared. A431 cells were divided into the control, model, blank serum, fluconazole-containing serum, BEPD-containing serum, EGFR agonist and EGFR inhibitor groups. Additionally, in vitro experiments were conducted using BEPD-containing serum, fluconazole-containing serum, and an EGFR agonist and inhibitor to investigate the intervention mechanisms of BEPD on C. glabrata-induced vaginal epithelial cell damage. Cell counting kit-8(CCK-8) assay was utilized to determine the safe concentrations of C. glabrata, drug-containing serum, and compounds on A431 cells. Enzyme-linked immunosorbent assay(ELISA)was employed to measure the expression levels of interleukin(IL)-1ß, IL-6, granulocyte-macrophage colony-stimulating factor(GMCSF), granulocyte CSF(G-CSF), chemokine(C-X-C motif) ligand 20(CCL20), and lactate dehydrogenase(LDH). Gram staining was used to evaluate the adhesion of C. glabrata to vaginal epithelial cells. Flow cytometry was utilized to assess the effect of C.glabrata on A431 cell apoptosis. Based on the transcriptomics results, immunofluorescence was performed to measure the expressions of p-EGFR and p-ERK1/2 proteins, while Western blot validated the expressions of p-EGFR, p-ERK1/2, p-C-Fos, p-P38, Bax and Bcl-2 proteins. Sequencing results showed that compared with the VVC model, BEPD treatment up-regulated 1 075 genes and downregulated 927 genes, mainly enriched in immune-inflammatory pathways, including MAPK. Mechanistically, BEPD significantly reduced the expression of p-EGFR, p-ERK1/2, p-C-Fos and p-P38, as well as the secretion of IL-1ß, IL-6, GM-CSF, G-CSF and CCL20, LDH release induced by C. glabrata, and the adhesion of C. glabrata to A431 cells, suggesting that BEPD exerts a protective effect on vaginal epithelial cells damaged by C. glabrata infection by modulating the EGFR/MAPK axis. In addition, BEPD downregulated the pro-apoptotic protein Bax expression and up-regulated the anti-apoptotic protein Bcl-2 expression, leading to a reduction in C. glabrata-induced cell apoptosis. In conclusion, this study reveals that the intervention of BEPD in C. glabrata-induced VVC may be attributed to its regulation of the EGFR/MAPK pathway, which protects vaginal epithelial cells.

Design of multi-epitope vaccine against porcine rotavirus using computational biology and molecular dynamics simulation approaches.

Porcine Rotavirus (PoRV) is a significant pathogen affecting swine-rearing regions globally, presenting a substantial threat to the economic development of the livestock sector. At present, no specific pharmaceuticals are available for this disease, and treatment options remain exceedingly limited. This study seeks to design a multi-epitope peptide vaccine for PoRV employing bioinformatics approaches to robustly activate T-cell and B-cell immune responses. Two antigenic proteins, VP7 and VP8*, were selected from PoRV, and potential immunogenic T-cell and B-cell epitopes were predicted using immunoinformatic tools. These epitopes were further screened according to non-toxicity, antigenicity, non-allergenicity, and immunogenicity criteria. The selected epitopes were linked with linkers to form a novel multi-epitope vaccine construct, with the PADRE sequence (AKFVAAWTLKAAA) and RS09 peptide attached at the N-terminus of the designed peptide chain to enhance the vaccine's antigenicity. Protein-protein docking of the vaccine constructs with toll-like receptors (TLR3 and TLR4) was conducted using computational methods, with the lowest energy docking results selected as the optimal predictive model. Subsequently, molecular dynamics (MD) simulation methods were employed to assess the stability of the protein vaccine constructs and TLR3 and TLR4 receptors. The results indicated that the vaccine-TLR3 and vaccine-TLR4 docking models remained stable throughout the simulation period. Additionally, the C-IMMSIM tool was utilized to determine the immunogenic triggering capability of the vaccine protein, demonstrating that the constructed vaccine protein could induce both cell-mediated and humoral immune responses, thereby playing a role in eliciting host immune responses. In conclusion, this study successfully constructed a multi-epitope vaccine against PoRV and validated the stability and efficacy of the vaccine through computational analysis. However, as the study is purely computational, experimental evaluation is required to validate the safety and immunogenicity of the newly constructed vaccine protein.

Improved Patient Adherence to Family-Based Helicobacter pylori Infection Control and Management Strategy in Central China and Its Influencing Factors.

BACKGROUND: Patient adherence status to the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management strategy remains unclear, so are its influencing factors. We aim to investigate family members' adherence and its influencing factors during the family-based H. pylori infection management practice for related disease prevention. MATERIALS AND METHODS: Based on our previously family-based H. pylori survey in 2021, 282 families including 772 individuals were followed up 2 years after the initial survey to compare if the investigation and education might improve family member's adherence. The participant's adherence to H. pylori infection awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were followed up, and their influencing factors were also analyzed. RESULTS: The overall participant's adherence to recommendations on H. pylori awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were 77% (187/243), 67.3% (138/205), 60.1% (211/351), 46.5% (107/230), 45.6% (159/349), and 39.1% (213/545), respectively; and all showed improvements compared with their prior survey stages. The top reasons for rejection to treatment, retest, and gastroscopy were forgetting or unaware of H. pylori infection (30.3%), busy (32.8%), and asymptomatic (67.9%), respectively. Independent risk factor for low adherence to treatment was occupation (e.g., staff: OR 4.49, 95% CI 1.34-15.10). Independent favorable factors for treatment adherence were individuals at the ages of 18-44 years (OR 0.19, 95% CI 0.04-0.89) and had a large family size (e.g., four family members: OR 0.15, 95% CI 0.06-0.41); for retest adherence, it was individuals at the ages of 60-69 years (OR 0.23, 95% CI 0.06-0.97); for gastroscopy adherence, it was individuals at the age of 60-69 years (OR 0.46, 95% CI 0.28-0.75), and with gastrointestinal symptoms (OR 0.57, 95% CI 0.36-0.90). CONCLUSIONS: Family-based H. pylori management increases individual adherence to treatment, retest, and awareness, and there are also improved adherence to gastroscopy, publicity, and personal hygiene recommendations; further efforts are required to enhance the individual adherence rate for related disease prevention.

Triflate anion chemistry for enhanced four-electron zinc-iodine aqueous batteries.

I+ hydrolysis, sluggish iodine redox kinetics and the instability of Zn anodes are the primary challenges for aqueous four-electron zinc-iodine batteries (4eZIBs). Herein, the OTf- anion chemistry in aqueous electrolyte is essential for developing advanced 4eZIBs. It is elucidated that OTf- anions establish weak hydrogen bonds (H bonds) with water to stabilize I+ species while optimizing a water-lean Zn2+ coordination structure to mitigate Zn dendrites and corrosion. Moreover, the interaction of the OTf- anions with the iodine species results in an increased equilibrium average intermolecular bond length of the iodine species, facilitating the 4e redox kinetics of iodine with improved reversibility.