Enzymatic synthesis of pyridine heterocyclic compounds and their thermal stability.

An efficient method was discovered for catalyzing the esterification under air using Novozym 435 to obtain pyridine esters. The following conditions were found to be optimal: 60 mg of Novozyme 435, 5.0 mL of n-hexane, a molar ratio of 2:1 for nicotinic acids (0.4 mmol) to alcohols (0.2 mmol), 0.25 g of molecular sieve 3A, a revolution speed of 150 rpm, a reaction temperature of 50 °C, and reaction time of 48 h. Under nine cycles of Novozym 435, the 80 % yield was consistently obtained. Optimum conditions were used to synthesize 23 pyridine esters, including five novel compounds. Among them, gas chromatography-mass spectrometry-olfactometry (GC-MS-O) showed phenethyl nicotinate (3g), (E)-hex-4-en-1-yl nicotinate (3m), and octyl nicotinate (3n) possessed strong aromas. Thermogravimetric analysis (TG) revealed that the compounds 3g, 3m and 3n exhibited stability at the specified temperature. This finding provides theoretical support for adding pyridine esters fragrance to high-temperature processed food.

Lactobacillus salivarius ameliorates Mycoplasma gallisepticum-induced inflammation via the JAK/STAT signaling pathway involving respiratory microbiota and metabolites.

Mycoplasma gallisepticum (MG) can cause chronic respiratory disease (CRD) in chickens, which has a significant negative economic impact on the global poultry sector. Respiratory flora is the guardian of respiratory health, and its disorder is closely related to respiratory immunity and respiratory diseases. As a common probiotic in the chicken respiratory tract, Lactobacillus salivarius (L. salivarius) has potential antioxidant, growth performance enhancing, and anti-immunosuppressive properties. However, the specific mechanism through which L. salivarius protects against MG infection has not yet been thoroughly examined. This study intends to investigate whether L. salivarius could reduce MG-induced tracheal inflammation by modulating the respiratory microbiota and metabolites. The results indicated that L. salivarius reduced MG colonization significantly and alleviated the anomalous morphological changes by using the MG-infection model. L. salivarius also reduced the level of Th1 cell cytokines, increased the level of Th2 cell cytokines, and ameliorated immune imbalance during MG infection. In addition, L. salivarius improved the mucosal barrier, heightened immune function, and suppressed the Janus kinase/Signal transducer, and activator of transcription (JAK/STAT) signaling pathway. Notably, MG infection changed the composition of the respiratory microbiota and metabolites, and L. salivarius therapy partially reversed the aberrant respiratory microbiota and metabolite composition. Our results highlighted that these findings demonstrated that L. salivarius played a role in MG-mediated inflammatory damage and demonstrated that L. salivarius, by altering the respiratory microbiota and metabolites, could successfully prevent MG-induced inflammatory injury in chicken trachea.

Traditional Chinese herbal medicine retention enema combined with perineal massage (THREM): a promising therapeutic strategy for refractory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating condition characterized by lower urinary tract symptoms and persistent pelvic pain or discomfort lasting for more than three months. Currently available oral drug therapies exhibit limited efficacy in the treatment of CP/CPPS. Therefore, personalized and combination therapies are recommended by Chinese CP/CPPS guidelines, which primarily include traditional Chinese medicine, radiofrequency therapy, urethral lavage, transrectal prostate massage, extracorporeal shock wave therapy. However, a significant number of patients do not respond well to all types of these therapeutic methods. Among those who have sequentially or simultaneously undergone at least three different treatment modalities, in addition to oral medications, for more than 1 year, they are defined as patients with refractory CP/CPPS. This retrospective study aims to evaluate the clinical effect of traditional Chinese herbal medicine retention enema combined with perineal massage (THREM) in managing refractory CP/CPPS. Methods: A total of 20 patients with refractory CP/CPPS, who did not show significant improvement despite receiving multiple conventional treatments, including oral medications, were included in this study. Following THREM therapy, the International Prostate Symptom Score (IPSS), visual analogue scale (VAS), and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) quality of life (QoL) score were used to assess treatment efficacy. Results: Six months after THREM therapy, a significant decrease in IPSS, VAS, and QoL scores was observed (P<0.01). Importantly, 85% of the patients experienced a reduction in symptoms of ≥60%, with an average degree of alleviation reaching 70.25%±24.20%. Conclusions: THREM treatment demonstrated excellent efficacy in managing refractory CP/CPPS at least for 6 months. It has promising clinical application prospects. Further research is warranted to validate these results and explore the underlying mechanisms of THREM therapy.

The features of male breast cancer in China: A real-world study.

BACKGROUND: Male breast cancer (MBC) is a rare disease. Although several large-scale studies have investigated MBC patients in other countries, the features of MBC patients in China have not been fully explored. This study aims to explore the features of Chinese MBC patients comprehensively. METHODS: We retrospectively collected data of MBC patients from 36 centers in China. Overall survival (OS) was evaluated by the Kaplan-Meier method, log-rank test, and Cox regression analyses. Multivariate Cox analyses were used to identify independent prognostic factors of the patients. RESULTS: In total, 1119 patients were included. The mean age at diagnosis was 60.9 years, and a significant extension over time was observed (P < 0.001). The majority of the patients (89.1 %) received mastectomy. Sentinel lymph node biopsy was performed in 7.8 % of the patients diagnosed in 2009 or earlier, and this percentage increased significantly to 38.8 % in 2020 or later (P < 0.001). The five-year OS rate for the population was 85.5 % [95 % confidence interval (CI), 82.8 %-88.4 %]. Multivariate Cox analysis identified taxane-based [T-based, hazard ratio (HR) = 0.32, 95 % CI, 0.13 to 0.78, P = 0.012] and anthracycline plus taxane-based (A + T-based, HR = 0.47, 95 % CI, 0.23 to 0.96, P = 0.037) regimens as independent protective factors for OS. However, the anthracycline-based regimen showed no significance in outcome (P = 0.175). CONCLUSION: As the most extensive MBC study in China, we described the characteristics, treatment and prognosis of Chinese MBC population comprehensively. T-based and A + T-based regimens were protective factors for OS in these patients. More research is required for this population.

A non-invasive artificial intelligence model for identifying axillary pathological complete response to neoadjuvant chemotherapy in breast cancer: a secondary analysis to multicenter clinical trial.

BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.

Effect of dietary supplementation with sanguinarine on meat quality and lipid metabolism of broilers.

Dietary Macleaya cordata extract (MCE) can improve the meat quality of poultry. However, the specific mechanism by which MCE regulates the meat quality has not been clarified yet. Sanguinarine (SAN) is one of the important natural active components in MCE. Our study aims to explore the regulatory mechanism of dietary SAN supplementation on meat quality through transcriptomic and gut microbiome analysis, thereby providing a basis for regularing meat quality with MCE. 240 1-day-old broilers were divided into 4 groups according to different doses of SAN (0, 0.225, 0.75, and 2.25 mg/kg). The results indicated that SAN significantly improve the physicochemical quality indicators of breast and thigh muscle in broilers, improved the serum biochemical indexes. Through transcriptome sequencing analysis of the liver and ileum tissues of broilers, we found that the differentially expressed genes induced by SAN were mainly enriched in lipid metabolism, which were related to the peroxisome proliferator-activated receptor (PPAR) pathway. It reconfirmed that SAN can regulate lipid metabolism in the body by promoting the expression of genes related to cholesterol metabolism, fatty acid transport and oxidation by RT-PCR, this ultimately affects the physicochemical quality of muscle. Additionally, through 16S rRNA sequencing analysis, we found that dietary addition of SAN increased the relative abundance of Bacteroides, Lactobacillus and unclassified_f_Lachnospiraceae, while decreased the relative abundance of Alistipes in ceca. To further investigate the impact of gut microbiota on lipid metabolism, we conducted a correlation analysis of PPAR pathway factor expression in cecum tissue and microflora structure. The results showed that Bacteroides exhibited a positive correlation with the expression of most genes in the PPAR signaling pathway. Unclassified_f__Lachnospiraceae is positively correlated with PPARγ, Cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and Acyl-CoA synthetase long-chain family member 5 (ACSL5). In conclusion, dietary addition of SAN can promote the genes expression of the PPAR pathway, target the regulation of intestinal microflora structure and abundance and regulate lipid metabolism, thereby improving meat quality of broilers.

Evaluating the prognostic value of systemic immune-inflammatory index in patients with acute decompensated heart failure.

AIMS: The value of the systemic immune-inflammatory index (SII) in assessing adverse outcomes in various cardiovascular diseases has been extensively discussed. This study aims to evaluate the predictive value and risk stratification ability of SII for 30 day mortality in patients with acute decompensated heart failure (ADHF). METHODS: This analysis included 1452 patients hospitalized for ADHF, all the participants being part of the China Jiangxi-acute decompensated heart failure1 project. The risk stratification capability of the SII in patients with ADHF, as well as its correlation with the 30 day mortality risk among ADHF patients, was evaluated utilizing Kaplan-Meier survival analysis and multivariable Cox regression models. A restricted cubic spline was employed to model the dose-response relationship between the two, and the receiver operating characteristic curve was utilized to assess the predictive ability of SII for 30 day mortality. RESULTS: The Kaplan-Meier analysis revealed that the risk of mortality in the high SII group (SII ≥ 980 × 109/L) was significantly greater than that in the low SII group (SII < 980 × 109/L, log-rank P < 0.001). After adjusting for various confounding factors, a higher SII was associated with an increased risk of 30 day mortality in ADHF patients [hazard ratio (HR) = 2.03, 95% confidence interval (CI): 1.34-3.08]. Further restricted cubic spline analysis revealed a non-linear dose-response relationship between the two (P for non-linear = 0.006). Receiver operating characteristic analysis demonstrated that SII had a high accuracy in predicting 30 day mortality events in ADHF patients (AUC = 0.7479), and the optimal predictive threshold was calculated to be 980 × 109/L, a sensitivity of 0.7547 and a specificity of 0.7234. CONCLUSIONS: This study found a significant positive association between SII and 30 day all-cause mortality in ADHF patients. We determined the SII cut-off point for predicting 30 day all-cause mortality in patients with ADHF to be 980 × 109/L.

Research on prediction and evaluation algorithm of sports athletes performance based on neural network.

BACKGROUND: The Ultimate Fighting Championship (UFC) stands as a prominent global platform for professional mixed martial arts, captivating audiences worldwide. With its continuous growth and globalization efforts, UFC events have garnered significant attention and achieved commendable results. However, as the scale of development expands, the operational demands on UFC events intensify. At its core, UFC thrives on the exceptional performances of its athletes, which serve as the primary allure for audiences. OBJECTIVE: This study aims to enhance the allure of UFC matches and cultivate exceptional athletes by predicting athlete performance on the field. To achieve this, a recurrent neural network prediction model based on Bidirectional Long Short-Term Memory (BiLSTM) is proposed. The model seeks to leverage athlete portraits and characteristics for performance prediction. METHODS: The proposed methodology involves constructing athlete portraits and analyzing athlete characteristics to develop the prediction model. The BiLSTM-based recurrent neural network is utilized for its ability to capture temporal dependencies in sequential data. The model's performance is assessed through experimental analysis. RESULTS: Experimental results demonstrate that the athlete performance prediction model achieved an overall accuracy of 0.7524. Comparative analysis reveals that the proposed BiLSTM model outperforms traditional methods such as Linear Regression and Multilayer Perceptron (MLP), showcasing superior prediction accuracy. CONCLUSION: This study introduces a novel approach to predicting athlete performance in UFC matches using a BiLSTM-based recurrent neural network. By leveraging athlete portraits and characteristics, the proposed model offers improved accuracy compared to classical methods. Enhancing the predictive capabilities in UFC not only enriches the viewing experience but also contributes to the development of exceptional athletes in the sport.

Bifonazole caffeate: The first molecular salt of bifonazole with enhanced biopharmaceutical property based on experiments and quantum chemistry research.

In order to make novel breakthroughs in molecular salt studies of BCS class-IV antifungal medication bifonazole (BIF), a salification-driven strategy towards ameliorating attributes and aiding augment efficiency is raised. This strategy fully harnesses structural characters together attributes and benefits of caffeic acid (CAF) to concurrently enhance dissolvability and permeability of BIF by introducing the two ingredients into the identical molecular salt lattice through the salification reaction, which, coupled with the aroused potential activity of CAF significantly amplifies the antifungal efficacy of BIF. Guided by this route, the first BIF-organic molecular salt, BIF-CAF, is directionally designed and synthesized with satisfactorily structural characterizations and integrated theoretical and experimental explorations on the pharmaceutical properties. Single-crystal X-ray diffraction resolving confirms that there is a lipid-water amphiphilic sandwich structure constructed by robust charge-assistant hydrogen bonds in the salt crystal, endowing the molecular salt with the potential to enhance both dissolvability and permeability relative to the parent drug, which is validated by experimental evaluations. Remarkably, the comprehensive DFT-based theoretical investigations covering frontier molecular orbital, molecular electrostatic potential, Hirshfeld surface analysis, reduced density gradient, topology, sphericity and planarity analysis strongly support these observations, thereby allowing some positive relationships between macroscopic properties and microstructures of the molecular salt can be made. Intriguingly, the optimal properties, together with the stimulated activity of CAF markedly augment in vitro antifungal ability of the molecular salt, with magnifying inhibition zones and reducing minimum inhibitory concentrations. These findings fill in the gaps on researches of BIF-organic molecular salt, and adequately exemplify the feasibility and validity by integrating theoretical and experimental approaches to resolve BIF's problems via the salification-driven tactic.

Wogonin preconditioning of MSCs improved their therapeutic efficiency for colitis through promoting glycolysis.

Inflammatory bowel diseases (IBDs) are prevalent and debilitating diseases with limited clinical treatment strategies. Mesenchymal stem cell (MSCs) are pluripotent stem cells with self-renewal capability and multiple immunomodulatory effects, which make them a promising therapeutic approach for IBDs. Thus, optimization of MSCs regimes is crucial for their further clinical application. Wogonin, a flavonoid-like compound with extensive immunomodulatory and adjuvant effects, has been investigated as a potential pretreatment for MSCs in IBD treatment. In this study, we employed the DSS-induced acute colitis mouse model to compare the therapeutic effectiveness of MSCs in pretreated with or without wogonin and further explore the underlying mechanism. Compared to untreated MSCs, MSCwogonin (pretreated with wogonin) showed greater effectiveness in the treatment of colitis. Further experiments revealed that wogonin treatment activated the AKT signaling pathway, resulting in higher cellular glycolysis. Inhibition of AKT phosphorylation by perifosine not only decreased glycolysis but impaired the therapeutic efficiency of MSCwogonin. Consistent with these results, qPCR data indicated that wogonin treatment induced the expression of immunomodulatory molecules IL-10, IDO, and AGR1, which were reduced by perifosine. Together, our data demonstrated that wogonin preconditioning strategy further augmented the therapeutic efficacy of MSCs via promoting glycolysis, which should be a promising strategy for optimizing MSCs therapy in IBDs.

Lineage Replacement and Genetic Changes of Four HR-HPV Types during the Period of Vaccine Coverage: A Six-Year Retrospective Study in Eastern China.

OBJECTIVE: This study aimed to provide clinical evidence for lineage replacement and genetic changes of High-Risk Human Papillomavirus (HR-HPV) during the period of vaccine coverage and characterize those changes in eastern China. METHODS: This study consisted of two stages. A total of 90,583 patients visiting the Obstetrics and Gynecology Hospital of Fudan University from March 2018 to March 2022 were included in the HPV typing analysis. Another 1076 patients who tested positive for HPV31, 33, 52, or 58 from November 2020 to August 2023 were further included for HPV sequencing. Vaccination records, especially vaccine types and the third dose administration time, medical history, and cervical cytology samples were collected. Viral DNA sequencing was then conducted, followed by phylogenetic analysis and sequence alignment. RESULTS: The overall proportion of HPV31 and 58 infections increased by 1.23% and 0.51%, respectively, while infection by HPV33 and 52 decreased by 0.42% and 1.43%, respectively, within the four-year vaccination coverage period. The proportion of HPV31 C lineage infections showed a 22.17% increase in the vaccinated group, while that of the HPV58 A2 sublineage showed a 12.96% increase. T267A and T274N in the F-G loop of HPV31 L1 protein, L150F in the D-E loop, and T375N in the H-I loop of HPV58 L1 protein were identified as high-frequency escape-related mutations. CONCLUSIONS: Differences in epidemic lineage changes and dominant mutation accumulation may result in a proportional difference in trends of HPV infection. New epidemic lineages and high-frequency escape-related mutations should be noted during the vaccine coverage period, and regional epidemic variants should be considered during the development of next-generation vaccines.

From Research to Roach Traps: Practical Considerations for a Home-Based Asthma Program.

CONTEXT: Home-based asthma interventions have a significant evidence base as an effective means to address moderate and severe breathing concerns triggered by home conditions. However, the literature lacks logistical and staffing considerations necessary to successfully implement such a program at a governmental level. This practice report and process evaluation outlines practical details and lessons learned during a healthy homes pilot, and how they were addressed in the design of a permanent program. OBJECTIVE: To inform the creation of a permanent home-based asthma intervention at the Alexandria Health Department (AHD) (City of Alexandria, Virginia) and understand the tools and resources necessary for success. INTERVENTION: Participating households received a health and environmental assessment, followed by cleaning supplies, relevant education, and referrals to partners for services. AHD staff tracked challenges and insights at each step of the intervention. At the end of the pilot, staff worked with the community to identify solutions and design a permanent program. CONCLUSIONS: Although the pilot model was constructed based on existing case studies, technical assistance from national experts, and guidance documents, the team still experienced challenges around recruitment, staff support, home visit implementation, and impact evaluation. While pilots and existing literature can be instructive for identifying issues, work with residents and partners to develop a uniquely tailored community program was essential for practical success. IMPLICATIONS ON POLICY AND PRACTICE: Health departments developing new initiatives should consider both the staff and participant experience throughout the creation of administrative and programmatic processes. Testing out draft versions of these processes and materials using internal and external focus groups can identify potential bottlenecks and solutions upfront.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

WTAP-mediated m6A modification of KLF6 aggravates hypoxia/reoxygenation-induced human cardiomyocyte injury.

BACKGROUND: Myocardial infarction (MI) is a severe condition that typically results from the ischemia and necrosis of heart muscle. Kruppel-like factor 6 (KLF6) can aggravate myocardial ischemia/reperfusion injury. This work aims to reveal its role and mechanism in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. METHODS: Human cardiomyocyte (AC16) was exposed to hypoxic treatment to mimic MI-like cell injury. mRNA expression levels of KLF6 and WT1 associated protein (WTAP) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was detected by western blotting assay. Cell viability was assessed by CCK-8 assay. Cell apoptosis and cell cycle were investigated by flow cytometry. Enzyme-linked immunosorbent assays were conducted to detect IL-1ß, TNF-α and IL-6 levels. Fe 2+ colorimetric assay kit was used to detect Fe 2+ level. MDA Content Assay Kit was used to detect MDA level. Cellular ROS Assay kit was applied to assess ROS level. The association of KLF6 and WTAP was identified by RNA immunoprecipitation assay and dual-luciferase reporter assay. RESULTS: KLF6 and WTAP expression at mRNA and protein levels were significantly upregulated in serum samples of MI patients and H/R-induced AC16 cells when compared with control groups. KLF6 silencing attenuated H/R-induced AC16 cell apoptosis, inflammatory response, oxidative stress and ferroptosis. Additionally, WTAP stabilized KLF6 mRNA by regulating its m6A modification. Further, WTAP knockdown rescued H/R-induced AC16 cell apoptosis, inflammatory response, oxidative stress and ferroptosis by decreasing KLF6 expression. CONCLUSION: WTAP-mediated m6A modification of KLF6 aggravated hypoxia/reoxygenation-induced apoptosis, inflammatory response, oxidative stress and ferroptosis of human cardiomyocytes, providing a therapeutic strategy for MI.

Manipulating the processing window of directed self-assembly in contact hole shrinking with binary block copolymer/homopolymer blending.

Directed self-assembly (DSA) lithography has demonstrated significant potential in fabricating integrated circuits. However, DSA encounters limited processing windows due to the requirement for precise matching between the period of block copolymers (BCPs) and graphoepitaxy templates. We propose a binary BCP/homopolymer blending strategy to manipulate the self-assembly behavior and the processing window of graphoepitaxy DSA in contact hole shrinking. By carefully tailoring the blending rates of poly(methyl methacrylate) (PMMA) with different molecular weights in cylindrical polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA), we manipulate the period and morphology of BCP/homopolymer self-assembly. Specifically, we employ BCP/homopolymer blending to fine-tune the critical dimension (CD) of contact holes with PS-affined topographical templates. Subsequent pattern transferring is achieved by selectively etching defect-free shrinkable cylinders as hard masks. Furthermore, self-consistent field theory (SCFT) simulation was employed to explore the self-assembly of BCP/homopolymer blending in confined cylindrical space and the results were in good consistency with the experimental results.

T cell infiltration mediates neurodegeneration and cognitive decline in Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with pathological features of ß-amyloid (Aß) and hyperphosphorylated tau protein accumulation in the brain, often accompanied by cognitive decline. So far, our understanding of the extent and role of adaptive immune responses in AD has been quite limited. T cells, as essential members of the adaptive immune system, exhibit quantitative and functional abnormalities in the brains of AD patients. Dysfunction of the blood-brain barrier (BBB) in AD is considered one of the factors leading to T cell infiltration. Moreover, the degree of neuronal loss in AD is correlated with the quantity of T cells. We first describe the differentiation and subset functions of peripheral T cells in AD patients and provide an overview of the key findings related to BBB dysfunction and how T cells infiltrate the brain parenchyma through the BBB. Furthermore, we emphasize the risk factors associated with AD, including Aß, Tau protein, microglial cells, apolipoprotein E (ApoE), and neuroinflammation. We discuss their regulation of T cell activation and proliferation, as well as the connection between T cells, neurodegeneration, and cognitive decline. Understanding the innate immune response is crucial for providing comprehensive personalized therapeutic strategies for AD.

Genomic surveillance and evolutionary dynamics of type 2 porcine reproductive and respiratory syndrome virus in China spanning the African swine fever outbreak.

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a serious threat to the pig industry in China. Our previous study demonstrated that PRRSV persists with local circulations and overseas imports in China and has formed a relatively stable epidemic pattern. However, the sudden African swine fever (ASF) outbreak in 2018 caused serious damage to China's pig industry structure, which resulted in about 40 per cent of pigs being slaughtered. The pig yields recovered by the end of 2019. Thus, whether the ASF outbreak reframed PRRSV evolution with changes in pig populations and further posed new threats to the pig industry becomes a matter of concern. For this purpose, we conducted genomic surveillance and recombination, NSP2 polymorphism, population dynamics, and geographical spread analysis of PRRSV-2, which is dominant in China. The results showed that the prevalence of ASF had no significant effects on genetic diversities like lineage composition, recombination patterns, and NSP2 insertion and deletion patterns but was likely to lead to changes in PRRSV-2 recombination frequency. As for circulation of the two major sub-lineages of Lineage 1, there was no apparent transmission of NADC30-like among provinces, while NADC34-like had obvious signs of inter-provincial transmission and foreign importation during the ASF epidemic. In addition, two suspected vaccine recombinant epidemic strains suggest a slight safety issue of vaccine use. Herein, the interference of ASF to the PRRSV-2 evolutionary pattern was evaluated and vaccine safety was analyzed, in order to monitor the potential threat of PRRSV-2 to China's pig industry in the post-epidemic era of ASF.

KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma.

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Correlation between symptoms and cognitive function changes in patients with primary insomnia and pathways in gut microbiota.

Background: Primary insomnia (PI) refers to syndromes of difficulty falling asleep, poor sleep quality, early awakening, and difficulty falling asleep after waking up. Although there have been numerous studies, the specific etiology and pathogenesis of PI are still misunderstanding. In recent years, the gut microbiota has been proved to be involved in the metabolism of many mental disorders. But the specific mechanisms of its involvement in PI have not been fully elucidated. This study aims to explore the relationship between the gut microbiota and the symptoms, cognitive function changes in PI. Methods: In this study, the gut microbiota of PI patients and healthy controls was profiled by performing stool 16s rRNA gene sequencing. The co-occurrence network was constructed by using Weight Gene Co-expression Network Analysis (WGCNA) algorithm. The correlation between gut microbiota associated pathways and traits in PI were predicted. Results: WGCNA results demonstrated several Operational Taxonomic Units (OTU) modules are correlated to symptoms. By using PICRUSt2 software, we predicted the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of microbiota in modules. For instance, sleep efficiency may be correlated with the presence of Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane and chlorobenzene degradation. Total sleep time may be correlated with the presence of Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation and Biosynthesis of unsaturated fatty acids. The severity of insomnia may be correlated with Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism and RNA polymerase. Change of name score in Montreal Cognitive Assessment (MoCA) may be correlated with Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation in Gut Microbiota (GM). Conclusion: This study revealed the potential relationships between gut microbiota and PI. By using pathway prediction and enrichment analysis, we concluded many metabolic pathways may associated with some important traits of insomnia patients, including sleep efficiency, severe insomnia, total sleep time and change of name score in MoCA. The metabolic pathways include Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane, chlorobenzene degradation, Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation.Our study demonstrated that PI patients demonstrate significant changes in gut microbiota, which will help delineate the relationship between gut microbiota and syndromes of PI.