Decomposition Analysis of Depressive Symptom Differences Among Older Adults With Hypertension Between Urban and Rural Areas: Cross-Sectional Study.

Background: Hypertension is the most prevalent chronic disease among China's older population, which comprises a growing proportion of the overall demographic. Older individuals with chronic diseases have a higher risk of developing depressive symptoms than their healthy counterparts, as evidenced in China's older population, where patients with hypertension exhibit varying rates of depression depending on residing in urban or rural areas. Objective: This study aimed to investigate factors influencing and contributing to the disparities in depressive symptoms among older urban and rural patients with hypertension in China. Methods: We used a cross-sectional study design and derived data from the 8th Chinese Longitudinal Health Longevity Survey of 2018. The Fairlie model was applied to analyze the factors contributing to disparities in depressive symptoms between urban and rural older populations with hypertension. Results: The sample size for this study was 5210, and 12.8% (n=669) of participants exhibited depressive symptoms. The proportions of depressive symptoms in rural and urban areas were 14.1% (n=468) and 10.7% (n=201), respectively. In rural areas, years of education (1-6 years: odds ratio [OR] 0.68, 95% CI 1.10-1.21; ≥7 years: OR 0.47, 95% CI 0.24-0.94), alcohol consumption (yes: OR 0.52, 95% CI 0.29-0.93), exercise (yes: OR 0.78, 95% CI 0.56-1.08), and sleep duration (6.0-7.9 hours: OR 0.29, 95% CI 0.17-0.52; 8.0-9.9 hours: OR 0.24, 95% CI 0.13-0.43; ≥10.0 hours: OR 0.22, 95% CI 0.11-0.41) were protective factors against depressive symptoms in older adults with hypertension, while gender (female: OR 1.94, 95% CI 1.33-2.81), self-reported income status (poor: OR 3.07, 95% CI 2.16-4.37), and activities of daily living (ADL) dysfunction (mild: OR 1.69, 95% CI 1.11-2.58; severe: OR 3.03, 95% CI 1.46-6.32) were risk factors. In urban areas, age (90-99 years: OR 0.37, 95% CI 0.16-0.81; ≥100 years: OR 0.19, 95% CI 0.06-0.66), exercise (yes: OR 0.33, 95% CI 0.22-0.51), and sleep duration (6.0-7.9 hours: OR 0.27, 95% CI 0.10-0.71; 8.0-9.9 hours: OR 0.16, 95% CI 0.06-0.44; ≥10.0 hours: OR 0.18, 95% CI 0.06-0.57) were protective factors, while years of education (1-6 years: OR 1.91, 95% CI 1.05-3.49), self-reported income status (poor: OR 2.94, 95% CI 1.43-6.08), and ADL dysfunction (mild: OR 2.38, 95% CI 1.39-4.06; severe: OR 3.26, 95% CI 1.21-8.76) were risk factors. The Fairlie model revealed that 91.61% of differences in depressive symptoms could be explained by covariates, including years of education (contribution 63.1%), self-reported income status (contribution 13.2%), exercise (contribution 45.7%), sleep duration (contribution 20.8%), ADL dysfunction (contribution -9.6%), and comorbidities (contribution -22.9%). Conclusions: Older patients with hypertension in rural areas had more depressive symptoms than their counterparts residing in urban areas, which could be explained by years of education, self-reported income status, exercise, sleep duration, ADL dysfunction, and comorbidities. Factors influencing depressive symptoms had similarities regarding exercise, sleep duration, self-reported income status, and ADL dysfunction as well as differences regarding age, gender, years of education, and alcohol consumption.

Unveiling the landscape of pathomics in personalized immunotherapy for lung cancer: a bibliometric analysis.

Background: Pathomics has emerged as a promising biomarker that could facilitate personalized immunotherapy in lung cancer. It is essential to elucidate the global research trends and emerging prospects in this domain. Methods: The annual distribution, journals, authors, countries, institutions, and keywords of articles published between 2018 and 2023 were visualized and analyzed using CiteSpace and other bibliometric tools. Results: A total of 109 relevant articles or reviews were included, demonstrating an overall upward trend; The terms "deep learning", "tumor microenvironment", "biomarkers", "image analysis", "immunotherapy", and "survival prediction", etc. are hot keywords in this field. Conclusion: In future research endeavors, advanced methodologies involving artificial intelligence and pathomics will be deployed for the digital analysis of tumor tissues and the tumor microenvironment in lung cancer patients, leveraging histopathological tissue sections. Through the integration of comprehensive multi-omics data, this strategy aims to enhance the depth of assessment, characterization, and understanding of the tumor microenvironment, thereby elucidating a broader spectrum of tumor features. Consequently, the development of a multimodal fusion model will ensue, enabling precise evaluation of personalized immunotherapy efficacy and prognosis for lung cancer patients, potentially establishing a pivotal frontier in this domain of investigation.

Clinical application and evaluation of metagenomic next-generation sequencing in pathogen detection for suspected central nervous system infections.

Central nervous system Infections (CNSIs) is a disease characterized by complex pathogens, rapid disease progression, high mortality rate and high disability rate. Here, we evaluated the clinical value of metagenomic next generation sequencing (mNGS) in the diagnosis of central nervous system infections and explored the factors affecting the results of mNGS. We conducted a retrospective study to compare mNGS with conventional methods including culture, smear and etc. 111 suspected CNS infectious patients were enrolled in this study, and clinical data were recorded. Chi-square test were used to evaluate independent binomial variables, taking p < 0.05 as statistically significant threshold. Of the 111 enrolled cases, 57.7% (64/111) were diagnosed with central nervous system infections. From these cases, mNGS identified 39.6% (44/111) true-positive cases, 7.2% (8/111) false-positive case, 35.1% (39/111) true-negative cases, and 18.0% (20/111) false-negative cases. The sensitivity and specificity of mNGS were 68.7% (44/64) and 82.9% (39/47), respectively. Compared with culture, mNGS provided a higher pathogen detection rate in CNSIs patients (68.7% (44/64) vs. 26.5% (17/64), p < 0.0001). Compared to conventional methods, positive percent agreement and negative percent agreement was 84.60% (44/52) and 66.1% (39/59) separately. At a species-specific read number (SSRN) ≥ 2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] 0.758, 95% confidence interval [CI] 0.663-0.854). In bacterial CNSIs patients with significant CSF abnormalities (CSF WBC > 300*106/L), the positive rate of CSF mNGS is higher. To sum up, conventional microbiologic testing is insufficient to detect all neuroinvasive pathogens, and mNGS exhibited satisfactory diagnostic performance in CNSIs and with an overall detection rate higher than culture (p < 0.0001).

Association between Abortion and All-Cause and Cause-Specific Premature Mortality: A Prospective Cohort Study from the UK Biobank.

Background: Concerns have been raised about the increasing prevalence of both spontaneous and induced abortions worldwide, yet their effect on premature mortality remains poorly understood. We aimed to examine the associations between abortion and all-cause and cause-specific premature mortality, and the potential effect modification by maternal characteristics. Methods: Women aged 39 to 71 years at baseline (2006 to 2010) with prior pregnancies were derived from the UK Biobank and categorized as no abortion history, spontaneous abortion alone, induced abortion alone, and both spontaneous and induced abortions. All-cause and cause-specific mortality were ascertained through linkage to death certificate data, with premature death defined as occurring before the age of 70. Results: Of the 225,049 ever gravid women, 43,418 (19.3%) reported spontaneous abortion alone, 27,135 (12.1%) reported induced abortion alone, and 10,448 (4.6%) reported both spontaneous and induced abortions. During a median of 14.4 years of follow-up, 5,353 deaths were recorded, including 3,314 cancer-related and 1,444 cardiovascular deaths. Compared with no abortion history, spontaneous abortion alone was associated with an increased risk of all-cause premature mortality (adjusted hazard ratio [aHR] 1.10, 95% confidence interval [CI] 1.02 to 1.17), and induced abortion alone was associated with increased risks of all-cause (aHR 1.12, 95% CI 1.04 to 1.22) and cardiovascular mortality (aHR 1.27, 95% CI 1.09 to 1.48). The aHRs for all-cause and cardiovascular mortality were higher for recurrent abortions, whether spontaneous or induced (P trend < 0.05). The increased risk of all-cause mortality associated with induced abortion was higher in women with hypertensive disorders of pregnancy than in those without (40% vs. 9%, P interaction = 0.045). Conclusions: Either spontaneous or induced abortion alone was associated with an increased risk of premature mortality, with induced abortion alone particularly linked to cardiovascular death. Future studies are encouraged to explore the underlying mechanisms.

The role of sleep quality and anxiety symptoms in the association between childhood trauma and self-harm attempt: A chain-mediated analysis in the UK Biobank.

BACKGROUND: Childhood trauma is a risk factor for self-harm/suicidal behavior, but research on the potential association linking sleep quality and anxiety symptoms to childhood trauma and self-harm attempt is limited. The aim of this study was to describe the mediating role of sleep quality and anxiety symptoms between childhood trauma and self-harm attempt, and to provide a scientific basis for the prevention of self-harm behaviors. METHODS: This study ultimately included 11,063 study participants who participated in the baseline survey of this large prospective cohort study of the UK Biobank. We used structural equation modeling (SEM) to analyze the chain mediating role of sleep quality and anxiety symptoms in childhood trauma and self-harm attempt while controlling for covariates. RESULTS: A total of 19.58 % of study participants self-reported self-harm attempt. Sleep quality was negatively correlated with childhood trauma, anxiety symptoms, and self-harm attempt (p < 0.01). Childhood trauma, anxiety symptoms, and self-harm attempt were positively correlated (p < 0.01). In addition, after adjusting for confounders, anxiety symptoms were able to partially mediate the association between childhood trauma and self-harm attempt (effect value: 0.042, p < 0.01), and sleep quality and anxiety symptoms can chain mediate the association between childhood trauma and self-harm attempt (effect value:0.002, p < 0.01), with a total mediating effect of 65.67 % of the total effect. Subgroup analyses further showed that the mediating effects of sleep quality and anxiety symptoms on childhood trauma and self-harm attempt differed across age, gender, ethnicity, and smoking and drinking subgroups. CONCLUSIONS: This study found a complex relationship between childhood trauma, sleep quality, anxiety symptoms, and self-harm attempt, with sleep quality and anxiety symptoms mediating the relationship between childhood trauma and self-harm attempt. Multiple avenues of intervention, such as the provision of professional psychological interventions and timely monitoring, should be used to improve the sleep quality and mental health of individuals with traumatic childhood experiences and to prevent the occurrence of emotionally harmful behaviors such as self-harm/suicide.

The association between team behaviors and competitive anxiety among team-handball players: the mediating role of achievement goals.

Team sports athletes may encounter significant stress, leading to competitive anxiety. The anxiety levels can be influenced by team behaviors and achievement goals. This study aims to investigate the relationship between team behaviors (i.e., perceptions of controlling coaching behavior and team cohesion) and competitive anxiety, and to examine the mediation effects of achievement goals (i.e., task-oriented and ego-oriented) on the relationship. A total of 298 team-handball players were involved in the study, ages ranging from 16 to 24 years old (M = 18.44, SD = 3.09). A cross-sectional research design was adopted, and structural equation modeling was utilized to analyze path coefficients and mediating effects. Findings indicated that perceptions of controlling coaching behaviors had significant positive predictions for state and somatic anxiety (ß = 0.22, 0.29) and negative predictions for self-confidence (ß = -0.19). Team cohesion had significant negative predictions for state anxiety (ß = -0.31) and positive predictions for self-confidence (ß = 0.58). In addition, ego-oriented goals play a positive mediating role in the relationship between team behaviors and competitive anxiety (ß = 0.03-0.35), while task-oriented goals play a negative mediating role in the relationship between team behaviors and competitive anxiety (ß = -0.18 - -0.03). In conclusion, team behaviors have a significant relationship with competitive anxiety, with achievement goals playing a mediating role among them. Therefore, to alleviate team sports athletes' competitive anxiety, it is recommended to reduce coach control behaviors, enhance team cohesion, and employ psychological training methods (e.g., mindfulness or meditation) to strengthen athletes' task-oriented goals.

Sparse reconstruction of sound field using pattern-coupled Bayesian compressive sensing.

Conventional near-field acoustic holography based on compressive sensing either does not fully exploit the underlying block-sparse structures of the signal or suffers from a mismatch between the actual and predefined block structure due to the lack of prior information about block partitions, resulting in poor accuracy in sound field reconstruction. In this paper, a pattern-coupled Bayesian compressive sensing method is proposed for sparse reconstruction of sound fields. The proposed method establishes a hierarchical Gaussian-Gamma probability model with a pattern-coupled prior based on the equivalent source method, transforming the sound field reconstruction problem into recovering the sparse coefficient vector of the equivalent source strengths within the compressive sensing framework. A set of hyperparameters is introduced to control the sparsity of each element in the sparse coefficient vector of the equivalent source strengths, where the sparsity of each element is determined by both its own hyperparameters and those of its immediate neighbors. This approach enables the promotion of block sparse solutions and achieves better performance in solving for the sparse coefficient vector of the equivalent source strengths without prior information of block partitions. The effectiveness and superiority of the proposed method in reconstructing sound fields are verified by simulations and experiments.

A Random Forest Algorithm for Assessing Risk Factors Associated With Chronic Kidney Disease: Observational Study.

BACKGROUND: The prevalence and mortality rate of chronic kidney disease (CKD) are increasing year by year, and it has become a global public health issue. The economic burden caused by CKD is increasing at a rate of 1% per year. CKD is highly prevalent and its treatment cost is high but unfortunately remains unknown. Therefore, early detection and intervention are vital means to mitigate the treatment burden on patients and decrease disease progression. OBJECTIVE: In this study, we investigated the advantages of using the random forest (RF) algorithm for assessing risk factors associated with CKD. METHODS: We included 40,686 people with complete screening records who underwent screening between January 1, 2015, and December 22, 2020, in Jing'an District, Shanghai, China. We grouped the participants into those with and those without CKD by staging based on the glomerular filtration rate staging and grouping based on albuminuria. Using a logistic regression model, we determined the relationship between CKD and risk factors. The RF machine learning algorithm was used to score the predictive variables and rank them based on their importance to construct a prediction model. RESULTS: The logistic regression model revealed that gender, older age, obesity, abnormal index estimated glomerular filtration rate, retirement status, and participation in urban employee medical insurance were significantly associated with the risk of CKD. On RF algorithm-based screening, the top 4 factors influencing CKD were age, albuminuria, working status, and urinary albumin-creatinine ratio. The RF model predicted an area under the receiver operating characteristic curve of 93.15%. CONCLUSIONS: Our findings reveal that the RF algorithm has significant predictive value for assessing risk factors associated with CKD and allows the screening of individuals with risk factors. This has crucial implications for early intervention and prevention of CKD.

Diclofenac sodium effectively inhibits the biofilm formation of Staphylococcus epidermidis.

Staphylococcus epidermidis is an opportunistic pathogen commonly implicated in medical device-related infections. Its propensity to form biofilms not only leads to chronic infections but also exacerbates the issue of antibiotic resistance, necessitating high-dose antimicrobial treatments. In this study, we explored the use of diclofenac sodium, a non-steroidal anti-inflammatory drug, as an anti-biofilm agent against S. epidermidis. In this study, crystal violet staining and confocal laser scanning microscope analysis showed that diclofenac sodium, at subinhibitory concentration (0.4 mM), significantly inhibited biofilm formation in both methicillin-susceptible and methicillin-resistant S. epidermidis isolates. MTT assays demonstrated that 0.4 mM diclofenac sodium reduced the metabolic activity of biofilms by 25.21-49.01% compared to untreated controls. Additionally, the treatment of diclofenac sodium resulted in a significant decrease (56.01-65.67%) in initial bacterial adhesion, a crucial early phase of biofilm development. Notably, diclofenac sodium decreased the production of polysaccharide intercellular adhesin (PIA), a key component of the S. epidermidis biofilm matrix, in a dose-dependent manner. Real-time quantitative PCR analysis revealed that diclofenac sodium treatment downregulated biofilm-associated genes icaA, fnbA, and sigB and upregulated negative regulatory genes icaR and luxS, providing potential mechanistic insights. These findings indicate that diclofenac sodium inhibits S. epidermidis biofilm formation by affecting initial bacterial adhesion and the PIA synthesis. This underscores the potential of diclofenac sodium as a supplementary antimicrobial agent in combating staphylococcal biofilm-associated infections.

The current status of apathy in patients with dementia and its factors: A systematic review.

OBJECTIVE: To systematically evaluate the current status of apathy in dementia patients and its associated factors. METHODS: We searched Chinese and English databases to collect studies on the associated factors of apathy in patients with dementia from inception to March 14, 2023. Two researchers independently screened the literature, evaluated the quality, and extracted the data RESULTS: A total of 20 studies were included, and the incidence of apathy in patients with dementia ranged from 21 % to 90 %. According to the model of apathy proposed by Massimo in 2018, the associated factors were divided into individual factors for dementia patients, caregiver factors, and environmental factors. The individual factors of apathy in patients with dementia mainly include demographic characteristics, the severity of cognitive impairment, a combination of other behavioral and psychological symptoms of dementia, acute medical problems or adverse drug reactions, unmet needs, and malnutrition. Caregiver factors mainly include emotional expressions of hostility or criticism towards dementia patients and caregivers' expectations for a better life in the future. Environmental factors mainly include too high or too low stimulation and a lack of daytime activities CONCLUSIONS: Existing studies have shown that the incidence of apathy in dementia patients is high and is affected by multi-dimensional factors. There are more studies on individual factors in dementia patients and fewer studies on caregivers and environmental factors. In the future, a large number of high-quality studies are needed to demonstrate the mechanism of apathy in dementia patients and to find more related factors.

Multiagent Continual Coordination via Progressive Task Contextualization.

Cooperative multiagent reinforcement learning (MARL) has attracted significant attention and has the potential for many real-world applications. Previous arts mainly focus on facilitating the coordination ability from different aspects (e.g., nonstationarity and credit assignment) in single-task or multitask scenarios, ignoring the stream of tasks that appear in a continual manner. This ignorance makes the continual coordination an unexplored territory, neither in problem formulation nor efficient algorithms designed. Toward tackling the mentioned issue, this article proposes an approach, multiagent continual coordination via progressive task contextualization (MACPro). The key point lies in obtaining a factorized policy, using shared feature extraction layers but separated independent task heads, each specializing in a specific class of tasks. The task heads can be progressively expanded based on the learned task contextualization. Moreover, to cater to the popular centralized training with decentralized execution (CTDE) paradigm in MARL, each agent learns to predict and adopt the most relevant policy head based on local information in a decentralized manner. We show in multiple multiagent benchmarks that existing continual learning methods fail, while MACPro is able to achieve close-to-optimal performance. More results also disclose the effectiveness of MACPro from multiple aspects, such as high generalization ability.

Bi-Parameter MRI Could Quantitatively Assess the Zonal Heterogeneity of Prostate Cancer.

INTRODUCTION: Prostate cancer (PCa) located in the peripheral zone (PZ) and transitional zone (TZ) showed a different clinical and pathological characteristic. This passage aims to preliminarily evaluate the relationship between the zonal heterogeneity of PCa quantitatively assessed by bpMRI and pathological risk stratification of the primary lesion. METHODS: This prospective study was conducted from January 2019 to February 2023. A total of 113 PCa patients whose bpMRI data indicated that the lesions located in only 1 single zone of the prostate were selected. A transrectal ultrasound and MRI-targeted biopsy were performed to verify the bpMRI results, and then radical prostatectomy (RP) was performed in 3 weeks after the biopsy. The high-risk (HR) group was defined as ISUP grades ≥ 3. Binary regression was performed to evaluate if the zonal heterogeneity could be an independent predictor of the HR group. The receiver operator characteristic (ROC) curve was performed to analyze the added value of zonal location in predicting the HR group. RESULTS: PSA, T staging, and ISUP grades, incidence of positive surgical margins were significantly lower in the TZ PCa, and the ADCmin, and ADCmean values in the TZ PCa were significantly higher (all P < .01). The zonal heterogeneity could independently predict the HR group patients (OR: 5.170 [1.663-16.067], P = .005) and improve the predicting efficiency of HR patients (AUC 0.824, 95% CI, 0.741-0.889). CONCLUSIONS: BpMRI could quantitively assess the zonal heterogeneity of PCa precisely and increase the predicting efficacy of HR patients, which can provide better help for clinical individualized treatment.

Cell-wall-anchored proteins affect invasive host colonization and biofilm formation in Staphylococcus aureus.

As a major human and animal pathogen, Staphylococcus aureus can attach to medical implants (abiotic surface) or host tissues (biotic surface), and further establish robust biofilms which enhances resistance and persistence to host immune system and antibiotics. Cell-wall-anchored proteins (CWAPs) covalently link to peptidoglycan, and largely facilitate the colonization of S. aureus on various surfaces (including adhesion and biofilm formation) and invasion into host cells (including adhesion, immune evasion, iron acquisition and biofilm formation). During biofilm formation, CWAPs function in adhesion, aggregation, collagen-like fiber network formation, and consortia formation. In this review, we firstly focus on the structural features of CWAPs, including their intracellular function and interactions with host cells, as well as the functions and ligand binding of CWAPs in different stages of S. aureus biofilm formation. Then, the roles of CWAPs in different biofilm processes with regards in development of therapeutic approaches are clarified, followed by the association between CWAPs genes and clonal lineages. By touching upon these aspects, we hope to provide comprehensive knowledge and clearer understanding on the CWAPs of S. aureus and their roles in biofilm formation, which may further aid in prevention and treatment infection and vaccine development.

Invited review: Role of Bacillus licheniformis in the dairy industry- friends or foes?

Bacillus licheniformis is one of the major spore-forming bacteria with great genotypic diversity in raw milk, dairy ingredients, final dairy products, and is found throughout the dairy processing continuum. Though being widely used as a probiotic strain, this species also serves as a potential risk in the dairy industry based on its roles in foodborne illness and dairy spoilage. Biofilm formation of B. licheniformis in combined with the heat resistance of its spores, make it impossible to prevent the presence of B. licheniformis in final dairy products by traditional cleaning and disinfection procedures. Despite the extensive efforts on the identification of B. licheniformis from various dairy samples, no reviews have been reported on both hazard and benefits of this spore-former. This review discusses the prevalence of B. licheniformis from raw milk to commercial dairy products, biofilm formation and spoilage potential of B. licheniformis, and its potential prevention methods. In addition, the potential benefits of B. licheniformis in the dairy industry were also summarized.

Characterisation of a SapYZU11@ZnFe2O4 biosensor reveals its mechanism for the rapid and sensitive colourimetric detection of viable Staphylococcus aureus in food matrices.

Although bacteriophage-based biosensors hold promise for detecting Staphylococcus aureus in food products in a timely, simple, and sensitive manner, the associated targeting mechanism of the biosensors remains unclear. Herein, a colourimetric biosensor SapYZU11@ZnFe2O4, based on a broad-spectrum S. aureus lytic phage SapYZU11 and a ZnFe2O4 nanozyme, was constructed, and its capacity to detect viable S. aureus in food was evaluated. Characterisation of SapYZU11@ZnFe2O4 revealed its effective immobilisation, outstanding biological activity, and peroxidase-like capability. The peroxidase activity of SapYZU11@ZnFe2O4 significantly decreased after the addition of S. aureus, potentially due to blockage of the nanozyme active sites. Moreover, SapYZU11@ZnFe2O4 can detect S. aureus from various sources and S. aureus isolates that phage SapYZU11 could not lyse. This may be facilitated by the adsorption of the special receptor-binding proteins on the phage tail fibre and wall teichoic acid receptors of S. aureus. Besides, SapYZU11@ZnFe2O4 exhibited remarkable sensitivity and specificity when employing colourimetric techniques to rapidly determine viable S. aureus counts in food samples, with a detection limit of 0.87 × 102 CFU/mL. Thus, SapYZU11@ZnFe2O4 has broad application prospects for the detection of viable S. aureus cells on food substrates.

The mutation of Japanese encephalitis virus envelope protein residue 389 attenuates viral neuroinvasiveness.

The envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness.

Exploring the potential of isorhapontigenin: attenuating Staphylococcus aureus virulence through MgrA-mediated regulation.

The emerging prevalence of drug-resistant Staphylococcus aureus isolates underscores the urgent need for alternative therapeutic strategies due to the declining effectiveness of traditional antibiotics in clinical settings. MgrA, a key virulence regulator in S. aureus, orchestrates the expression of numerous virulence factors. Here, we report the discovery of isorhapontigenin, a methoxylated analog of resveratrol, as a potential anti-virulence agent against S. aureus. Isorhapontigenin effectively inhibits the hemolytic activity of S. aureus in a non-bactericidal manner. Additionally, it significantly reduces the cytotoxicity of S. aureus and impairs its ability to survive in macrophages. Mechanistically, isorhapontigenin modulates the expression of virulence factors, dose-dependently downregulating hla and upregulating the MgrA-regulated gene spa. Electrophoretic mobility shift assays demonstrated that isorhapontigenin inhibits the binding of MgrA to the hla promoter in a dose-dependent manner. Thermal shift assays confirmed the direct interaction between isorhapontigenin and the MgrA protein. The in vivo experiments demonstrated that isorhapontigenin significantly reduced the area of skin abscesses and improved survival in a pneumonia model while decreasing bacterial burden and inflammation in the lungs. In conclusion, isorhapontigenin holds potential as a candidate drug for further development as an anti-virulence agent for treating S. aureus infections. IMPORTANCE: The emergence of antibiotic-resistant Staphylococcus aureus strains presents a formidable challenge to public health, necessitating novel approaches in combating these pathogens. Traditional antibiotics are becoming increasingly ineffective, leading to a pressing need for innovative therapeutic strategies. In this study, targeting virulence factors that play a crucial role in the pathogenesis of bacterial infections offers a promising alternative to circumvent resistance mechanisms. The discovery of isorhapontigenin as an inhibitor of S. aureus virulence represents a significant advance in anti-virulence therapy.

A risk prediction model for delayed bleeding after ESD for gastric precancerous lesions.

OBJECTIVE: To investigate the risk factors for delayed postoperative bleeding after endoscopic submucosal dissection (ESD) in patients with gastric precancerous lesions and to construct a risk prediction model. METHODS: This retrospective analysis included clinical data from patients with gastric precancerous lesions who underwent ESD at Wuhan University People's Hospital between November 2016 and June 2022. An XGBoost model was built to predict delayed bleeding after ESD using risk factors identified by univariable and multivariate logistic regression analysis. The model was evaluated using receiver operating characteristic curves (ROC), and SHapely Additive exPlanations (SHAP) analysis was used to interpret the model. RESULTS: Seven factors were statistically associated with delayed postoperative bleeding in gastric precancerous lesions after ESD: age, low-grade intraepithelial neoplasia, hypertension, lesion size ≥ 40 mm, operative time ≥ 120 min, female, and nonuse of hemoclips. A risk prediction model was established. In the training cohort, the model achieved an AUC of 0.97 (0.96-0.98), a sensitivity of 0.90, a specificity of 0.94, and an F1 score of 0.91. In the validation cohort, the AUC was 0.94(0.90-0.98), with a sensitivity of 0.85, a specificity of 0.89, and an F1 score of 0.85. In the test cohort, the AUC was 0.94 (0.89-0.99), the sensitivity was 0.80, the specificity was 0.92, and the F1 score was 0.84, indicating strong predictive capability. CONCLUSION: In this study, an XGBoost prediction model for assessing the risk of delayed postoperative bleeding after ESD in patients with gastric precancerous lesions was developed and validated. This model can be applied in clinical practice to effectively predict the risk of post-ESD bleeding for individual patients.