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Abstract Aims Improvement in left ventricular ejection fraction (impEF) often presents in contemporary acute myocardial infarction (AMI) patients. New‐onset atrial fibrillation (NOAF) during AMI is an important predictor of subsequential heart failure (HF), while its impact on the trajectory of post‐MI left ventricular ejection fraction (LVEF) and prognostic implication in patients with and without impEF remains undetermined. We aimed to investigate the prognostic impacts of NOAF in AMI patients with and without impEF. Methods and results Consecutive AMI patients without a prior history of AF between February 2014 and March 2018 with baseline LVEF ≤ 40% and had ≥1 LVEF measurement after baseline were included. ImpEF was defined as a baseline LVEF ≤ 40% and a re‐evaluation showed both LVEF > 40% and an absolute increase of LVEF ≥ 10%. Persistently reduced EF (prEF) was defined as the second measurement of LVEF either ≤40% or an absolute increase of LVEF

Abstract Background Lung cancer is characterized by high morbidity and mortality due to the lack of practical early diagnostic and prognostic tools. The present study uses machine learning algorithms to construct a clinical predictive model for non-small cell lung cancer (NSCLC) patients. Methods Laboratory indices of the NSCLC patients at their initial visit were collected for quality control and exploratory analysis. By comparing the levels of the above indices between the survival and death groups, the statistically significant indices were selected for subsequent machine learning modeling. Ten machine learning algorithms were then employed to develop the predictive models with survival and recurrence as outcomes, respectively. Moreover, regression models were constructed using the random survival forest algorithm by incorporating the survival time dimension. Finally, critical variables in the optimal model were screened based on the interpretable algorithms to build a decision tree to facilitate clinical application. Results 682 patients were enrolled according to the inclusion and exclusion criteria. The preliminary comparison results revealed that except for fast blood glucose, CD3 +T cell proportion, NK cell proportion, and CA72-4, there were significant statistical differences in other tumor markers, inflammation, metabolism, and immune-related indices between the survival and death groups (p

In order to meet the high strength and high formability requirements of the tinplate market, the nitrogen strengthening method was used for the chemical composition of the tinplate, and the action mechanism of nitrogen on the full-process tinplate substrate was explored. The present study designed tinplate with different nitrogen contents (named as 20 N steel and 150 N steel), and conducted phase transformation research and recrystallization temperature tests. SEM, XRD, EBSD, TEM, chemical dissolution analysis and tensile tests were carried out, and the influence of annealing process on the microstructure, mechanical properties and precipitation of annealed sheet was also explained. With the increase of nitrogen content, the phase transformation temperature decreases, the hardness increases and the recrystallization temperature increases. The microstructures of 20 N steel and 150 N steel annealed at different annealing temperatures are composed of ferrite and cementite distributed in chains. At the same annealing temperature, the recrystallization degree of 20 N steel is higher, the {111} texture accounts for a larger proportion, and the grain size is larger. With the increase of annealing temperature, the yield strength and tensile strength show a downward trend, while the elongation shows an upward trend. Compared with 20 N steel, the yield strength and tensile strength of the 150 N annealed sheet are significantly improved, and the elongation is slightly reduced. The calculation results show that the mechanism of nitrogen improving the strength of tinplate is mainly solid solution strengthening, and the improvement effect of fine grain strengthening and precipitation strengthening is weak.

Abstract MAT2B works together with MAT2A to synthesize S-Adenosyl methionine (SAM) as the primary methyl donor. MAT2B, despite lacking catalytic activity, exerts regulatory control over the enzymatic activity of MAT2A. In addition to the enzymatic activity regulation, we find that, in an NADP+-dependent manner, MAT2B binds and stabilizes MAT2A. Disruption of the cellular NADP+ remodels the protein level of MAT2A. The pentose phosphatase pathway regulates the level of MAT2A protein through the interaction of NADP+ with MAT2B. Additionally, MAT2B-MAT2A interaction regulates the mRNA m6A modification and stability. In liver tumors, the Mat2a mRNA level is elevated but the protein level is decreased by the restricted NADP+. Blocking the interaction between MAT2B and MAT2A by the keto diet can suppress liver tumor growth. These findings reveal that MAT2B is essential for regulating the protein levels of MAT2A and connecting SAM synthesis to mRNA m6A.

Background/Objective: Children with ADHD demand for effective intervention with minimum side effect to improve executive function (EF) and health well-being. Method: This study used a three-arm partially-blinded randomized controlled trial to test the effects of two different kinds of 8-week game-based training programs (game-based HIIT program, GameHIIT; and game-based structured aerobic exercise program, GameSAE) on EF and other health indicators of children with ADHD, which was compared with a non-treatment control group. Results: A total of 49 children with ADHD completed the program. Analyses of EF tests and parental survey indicated that (i) there is no significant intragroup difference among all measures between pre-/post-intervention tests for two game-based intervention groups. The only significant intergroup difference was observed in self-monitor score of parent-reported child's EF between GameSAE group and the control (large effect). Similarly, cerebral hemodynamic responses also found no significant group effect for all EF tests. However, the time effects were observed in several channels in the GameHIIT group in two EF tests (Color Words Stroop Test and Tower of London Test). No significant change of participants' overall ADHD symptoms was found in the pre-/post-tests for three groups. Nonetheless, further analyses revealed that both of two game-based training programs exhibited the significant positive effects on child's PA levels and the large effects on levels of physical fitness, when they were compared to the control. Conclusion: By this study, a significant enhancement in physical fitness and PA levels were found in both game-based PA interventions when they were compared with control group. However, the effectiveness of game-based PA interventions on improving EF or reducing ADHD symptoms remains unclear. This implies that a larger intervention dosage or a tailored intervention design may be warranted to improve the EF of children with ADHD.

Abstract Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we described the changes in various immune cells during bone metastasis and discussed their related mechanisms. Osteoblasts, adipocytes, and other non‐immune cells closely related to bone metastasis were also included. This review also summarized the existing treatment methods and potential therapeutic targets, and provided insights for future studies of cancer bone metastasis.

Abstract The identification effector targets and characterization of their functions are crucial for understanding pathogen infection mechanisms and components of plant immunity. Here, we identify the effector UgsL, a ustilaginoidin synthetase with a key role in regulating virulence of the rice false smut fungus Ustilaginoidea virens. Heterologous expression of UgsL in rice (Oryza sativa) enhances plant susceptibility to multiple pathogens, and host-induced gene silencing of UgsL enhances plant resistance to U. virens, indicating that UgsL inhibits rice immunity. UgsL interacts with STRUBBELIG RECEPTOR KINASE 3 (OsSRF3). Genome editing and overexpression of OsSRF3 demonstrate that OsSRF3 plays a pivotal role in the resistance of rice to multiple pathogens. Remarkably, overexpressing OsSRF3 enhances resistance without adversely affecting plant growth or yield. We show that BRASSINOSTEROID RECEPTOR-ASSOCIATED KINASE 1 (OsBAK1) interacts with and phosphorylates OsSRF3 to activate pathogen-triggered immunity, inducing the mitogen-activated protein kinase cascade, a reactive oxygen species burst, callose deposition, and expression of defense-related genes. UgsL interferes with the phosphorylation of OsSRF3 by OsBAK1. Furthermore, UgsL mediates OsSRF3 degradation by facilitating its association with the ubiquitin-26S proteasome. Our results reveal that OsSRF3 positively regulates immunity in rice and that UgsL mediates its degradation, thereby inhibiting the activation of OsBAK1–OsSRF3-mediated immune pathways.

In this work, we aim to investigate the origin of the magnetic carriers in the lunar crust and the intensity of the ancient dynamo field. The magnetization and depth range of magnetic carriers are studied under a weak and a strong magnetic anomaly in Mare Tranquillitatis and in Oceanus Procellarum, respectively, where the surface ages are 3.6 and 3.3 billion years. A sophisticated three-dimensional amplitude inversion software program from a geophysical survey is used to reconstruct the distributions of magnetization in the lunar crust. Because no globally measured surface magnetic field exists for the Moon, a crustal magnetic anomaly model with a grid resolution of 0.2° is used. The depth range of the magnetic source is fixed by the boundary identified by a relative criterion, which is 20% of the recovered maximum magnetization. The central burial depths of the magnetic carriers are approximately 15 km and 25 km under Reiner Gamma and Mare Tranquillitatis, respectively. The volumes of the two magnetic sources are at scales of 104 and 105 km3, respectively. The aforementioned differences may imply a hotter crust under Reiner Gamma than Mare Tranquillitatis by 3.3 billion years. The results support the view that the magma intrusions magnetized by an ancient magnetic field could be the origin of magnetic anomalies under Reiner Gamma and Mare Tranquillitatis. Compared with previous works, the maximum magnetization of 3 A/m under Reiner Gamma supports the intensity of the field being several microteslas.

Abstract Background Endometriosis is well known as a chronic inflammatory disease. The development of endometriosis is heavily influenced by the estrogen receptor β (ERβ), while NOD-like receptors (NLRs) family CARD domain-containing 5 (NLRC5) exhibits anti-inflammatory properties during endometriosis. However, whether NLRC5-mediated anti-inflammation is involved in the ERβ-mediated endometriosis is still uncertain. This study aimed to assess that relation. Methods Nine cases of eutopic endometrial tissue and ten cases of ectopic endometrial tissue were collected from patients with endometriosis, and endometrial samples from ten healthy fertile women were analyzed, and the expression levels of ERβ were quantified using immunohistochemistry (IHC). Subsequently, we constructed mouse model of endometriosis by intraperitoneal injection. We detected the expression of ERβ, NLRC5, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-10 and measured the volume of ectopic lesions in mice with endometriosis. In vitro, human endometrial stromal cells (hESCs) were transfected respectively with ERβ-overexpressing and NLRC5-overexpressing plasmids. We then assessed the expression of ERβ and NLRC5 using quantitative real-time PCR (qRT-PCR) and western blot analysis. Furthermore, we measured the concentrations of TNF-α, IL-6, and IL-10 in the cell culture supernatant through enzyme-linked immunosorbent assay (ELISA). Additionally, we evaluated the migration and invasion ability of hESCs using transwell and wound healing assays. Results Inhibition of NLRC5 expression promotes the development of ectopic lesions in mice with endometriosis, upregulates the expression of pro-inflammatory factors TNF-α and IL-6, and downregulates the expression of anti-inflammatory factor IL-10. The high expression of NLRC5 in endometriosis depended on the ERβ overexpression. And ERβ promoted the migration of hESCs partially depend on inflammatory microenvironment. Lastly, NLRC5 overexpression inhibited ERβ-mediated development and inflammatory response of endometriosis. Conclusions Our results suggest that the innate immune molecule NLRC5-mediated anti-inflammation participates in ERβ-mediated endometriosis development, and partly clarifies the pathological mechanism of endometriosis, expanding our knowledge of the specific molecules related to the inflammatory response involved in endometriosis and potentially providing a new therapeutic target for endometriosis.

Abstract Since 2016, China has progressively relaxed family planning policies to stimulate birth rates. This paper examines the behavioral health repercussions of China’s 2016 universal two-child policy (UTCP) by analyzing sleep pattern data from China Family Panel Studies. Napping is a composite indicator that denotes health outcomes, job quality, and personal well-being. It reveals work conditions and environments to some extent. UTCP may lead to heightened social expectations regarding pregnancy likelihood, and changes in social expectations within the workplace may make work environments less equitable and more stressful for females. Leveraging a difference-in-difference model, this paper explores how napping behaviors among the working-age cohort have responded to the policy shifts. Our analysis reveals a gender discrepancy in response to the policy, specifically, females exhibit a discernible reduction in the likelihood of napping, as well as in the duration of both daytime naps and daily sleep. Conversely, such effects are not significant among males. These results suggest policy consequences extend beyond individuals directly impacted by childbirth or contemplating parenthood. Hence, while promoting fertility is still the government’s goal, policymakers are encouraged to consider the broader challenges the female population faces from social and workplace environment factors.

Abstract Background Mothers play a crucial role in influencing their daughters’ HPV vaccination decisions. Addressing barriers to receiving HPV vaccination among mothers of girls may achieve two goals in one strike: increasing vaccination coverage among both mothers and their daughters. This study aims to examine the HPV vaccination uptake and its determinants among mothers of girls in China at both the individual and interpersonal levels. Methods From July to October 2023, a cross-sectional online study was conducted to investigate HPV vaccine refusal for daughters aged 9–17 years among 11,678 mothers in Shenzhen, China. A randomized selection method was employed, targeting 11 primary schools and 13 secondary schools in Shenzhen. The research team invited mothers of girls to participate in an anonymous online survey. Multilevel logistic regression models (level 1: schools; level 2: individual participants) were employed to analyze the data. Results Among 11,678 mothers, 41.1% self-reported receiving at least one dose of HPV vaccination. Through multilevel logistic regression analysis, eight items measuring illness representations of HPV, which refers to how people think about HPV, were associated with higher HPV vaccination uptake (AOR: 1.02–1.14). These items included identity (identifying symptoms of HPV), timeline (whether HPV is acute/chronic), negative consequences, personal and treatment control (whether HPV is under volitional control), concern, negative emotions, and coherence (overall understanding of HPV). In addition, participants refusing HPV vaccines for the index daughters (AOR: 0.82, 95%CI: 0.76, 0.89) had lower vaccine uptake. Perceived more difficulties in accessing the 9-valent vaccines (AOR: 1.06, 95%CI: 1.04, 1.08) and more satisfaction with vaccine-related promotional materials (AOR: 1.50, 95%CI: 1.46, 1.54) at the individual level were associated with higher vaccine uptake. At the interpersonal factors, higher frequency of exposure to testimonials given by others about HPV vaccination on social media (AOR: 1.19, 95%CI: 1.14, 1.25) and thoughtful consideration of the veracity of the information (AOR: 1.11, 95%CI: 1.07, 1.16) were correlated with higher HPV vaccination uptake. Conclusions These findings offer essential implications for modifying HPV disease perceptions, addressing difficulties in accessing the 9-valent HPV vaccines, and enhancing health communication needs to improve HPV vaccine uptake among mothers of girls.

Abstract Depressive symptoms occur commonly in Alzheimer’s disease (AD). Although abnormalities in the amygdala-frontal circuit have been linked to emotional dysregulation and cognitive impairment, the neurological basis underlying these associations in AD patients with depressive symptoms (ADD) is unclear. We aimed to investigate the relationship between the amygdala-frontal circuit and depressive symptoms and cognitive function in ADD. We recruited 60 ADD, 60 AD patients without depressive symptoms (ADND), and 60 healthy controls (HC). Functional connectivity (FC) maps of the bilateral amygdala were compared. Fractional anisotropy (FA) of the amygdala-frontal circuit connected by the uncinate fasciculus (UF) was calculated using automated fiber quantification (AFQ). In addition, mediation analysis was performed to explore the effects of the amygdala-frontal circuit on the relationship between depressive symptoms and cognitive function. We found decreased bilateral amygdala FC with the inferior frontal gyrus (IFG) in the ADD group compared to the ADND and HC groups. Moreover, FA in the left frontal UF (nodes 64–97) was significantly lower in the ADD group than ADND group. Notably, amygdala-based FC with IFG and the left frontal UF FA mediated the relationship between depressive symptoms and cognitive function in ADD, with mediating effects ranging between 15 and 18%. Our study is the first to demonstrate the mediating effect of functional and microstructural abnormalities in the amygdala-frontal circuit in ADD. The findings suggest that the amygdala-frontal circuit may underlie emotional dysregulation in ADD, providing potential targets for treatment strategies.

Abstract This study delves into the correlation between childhood trauma and non-suicidal self-injury (NSSI) behaviors among high school students. Additionally, it examines the mediating role of stress perception and the moderating role of the teacher-student relationship in this association. A questionnaire survey was administered to 1,329 high school students in Yunnan Province to assess childhood trauma, NSSI behaviors, and stress perception. Firstly, the survey revealed a 12% prevalence of NSSI, with girls exhibiting a higher occurrence compared to boys (OR = 0.413, 95% CI: 0.280–0.609). Secondly, childhood trauma emerged as a significant predictor of NSSI behavior, irrespective of gender or whether the individual was an only child (r = 0.17, P

Abstract Background Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay. Methods Utilizing patient data from the First Medical Center of the People’s Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets. Results The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay. Conclusions The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.

Background and aimThis study aimed to develop a predictive model for early neurological deterioration (END) in branch atheromatous disease (BAD) affecting the lenticulostriate artery (LSA) territory using machine learning. Additionally, it aimed to explore the underlying mechanisms of END occurrence in this context.MethodsWe conducted a retrospective analysis of consecutive ischemic stroke patients with BAD in the LSA territory admitted to Dongyang People’s Hospital from January 1, 2018, to September 30, 2023. Significant predictors were identified using LASSO regression, and nine machine learning algorithms were employed to construct models. The logistic regression model demonstrated superior performance and was selected for further analysis.ResultsA total of 380 patients were included, with 268 in the training set and 112 in the validation set. Logistic regression identified stroke history, systolic pressure, conglomerated beads sign, middle cerebral artery (MCA) shape, and parent artery stenosis as significant predictors of END. The developed nomogram exhibited good discriminative ability and calibration. Additionally, the decision curve analysis indicated the practical clinical utility of the nomogram.ConclusionThe novel nomogram incorporating systolic pressure, stroke history, conglomerated beads sign, parent artery stenosis, and MCA shape provides a practical tool for assessing the risk of early neurological deterioration in BAD affecting the LSA territory. This model enhances clinical decision-making and personalized treatment strategies.

ABSTRACT S-palmitoylation is an important reversible protein post-translational modification in organisms. However, its role in fungi is uncertain. Here, we found the treatment of the rice false fungus Ustilaginoidea virens with S-palmitoylation inhibitor 2 BP resulted in a significant decrease in fungal virulence. Comprehensive identification of S-palmitoylation sites and proteins in U. virens revealed a total of 4,089 S-palmitoylation sites identified among 2,192 proteins and that S-palmitoylated proteins were involved in diverse biological processes. Among the five palmitoyltransferases, UvPfa3 and UvPfa4 were found to regulate the pathogenicity of U. virens. We then performed quantitative proteomic analysis of ∆UvPfa3 and ∆UvPfa4 mutants. Interestingly, S-palmitoylated proteins were significantly enriched in the mitogen-activated protein kinase and autophagy pathways, and MAP kinase UvSlt2 was confirmed to be an S-palmitoylated protein which was palmitoylated by UvPfa4. Mutations of S-palmitoylation sites in UvSlt2 resulted in significantly reduced fungal virulence and decreased kinase enzymatic activity and phosphorylation levels. Simulations of molecular dynamics demonstrated mutation of S-palmitoylation sites in UvSlt2 causing decreased hydrophobic solvent-accessible surface area, thereby weakening the bonding force with its substrate UvRlm1. Taken together, S-palmitoylation promotes U. virens virulence through palmitoylation of MAP kinase UvSlt2 by palmitoyltransferase UvPfa4. This enhances the enzymatic phosphorylation activity of the kinase, thereby increasing hydrophobic solvent-accessible surface area and binding activity between the UvSlt2 enzyme and its substrate UvRlm1. Our studies provide a framework for dissecting the biological functions of S-palmitoylation and reveal an important role for S-palmitoylation in regulating the virulence of the pathogen.IMPORTANCES-palmitoylation is an important post-translational lipid modification of proteins. However, its role in fungi is uncertain. In this study, we found that S-palmitoylation promotes virulence of rice false smut fungus U. virens through palmitoylation of MAP kinase UvSlt2 by palmitoyltransferase UvPfa4. This enhances the enzymatic phosphorylation activity of the kinase, thereby increasing hydrophobic solvent-accessible surface area and binding activity between the UvSlt2 enzyme and its substrate UvRlm1. Our studies provide a framework for dissecting the biological functions of S-palmitoylation and reveal an important role for S-palmitoylation in regulating the virulence of the pathogen. This is the first functional study to reveal the role of S-palmitoylation in fungal virulence.

With the growing demand for applications in disease diagnostics, bioanalysis, and health monitoring, developing efficient biosensing systems for fast detections and trace analysis of biomarkers is of great significance. In this work, an embedded optofluidic biosensing platform is proposed, which consists of asymmetrical core-offset optical fiber (ACOOF) structure, microfluidic chip and photoelectric detection system. In particular, by introducing the concept of optical fiber bridge, an ACOOF structure is designed to improve the optical coupling efficiency and reduce the limit of detection (LOD) of the developed sensor. On this basis, the human epidermal growth factor (EGF) was detected by constructing optofluidic chip and enzyme-linked immunosorbent assay (ELISA) kit. The LOD was 0.587 pg/mL. Leveraging the developed biosensing platform integrated with our chip, we achieved trace analysis with high specificity, as demonstrated by the measurement of interleukin 1α (IL-1α) with a low LOD of 43.3 fg/mL. Monitoring these two biomarkers is important for early cancer diagnosis. Beyond this, this novel platform has the potential for a range of applications, including disease diagnosis and management, bioanalysis, and health and environmental monitoring, with a focus on alternative biomarker targets.

ABSTRACTThis study investigated the influences of mother-daughter communication and social media on mothers’ HPV vaccine refusal for their daughters aged 9–17. A cross-sectional online survey among 11,728 mothers of girls aged 9–17 in Shenzhen, China was implemented between July and October 2023. Multi-level logistic regression models were fitted. Among 11,728 participants, 43.2% refused to have their daughters receive an HPV vaccination. In multivariate analysis, more openness in the mother-daughter communication (AOR: 0.99, 95%CI: 0.98, 0.99), perceived more positive outcomes of mother-daughter communication (AOR: 0.77, 95%CI: 0.75, 0.79), higher frequency of exposure to testimonials about daughters’ HPV vaccination (AOR: 0.81, 95%CI: 0.78, 0.85) and information encouraging parents to vaccinate their daughters against HPV on social media (AOR: 0.76, 95%CI: 0.73, 0.79), and thoughtful consideration of the veracity of the information specific to HPV vaccines (AOR: 0.80, 95%CI: 0.77, 0.83) were associated with lower vaccine refusal. Mothers who were not the main decision-makers of daughters’ HPV vaccination (AOR: 1.28 to 1.46), negative outcome expectancies of mother-daughter communication (AOR: 1.06, 95%CI: 1.04, 1.08), and mothers’ HPV vaccine refusal (AOR: 2.81, 95%CI: 2.58, 3.06) were associated with higher vaccine refusal for their daughters. The level of mothers’ HPV vaccine refusal for their daughters was high in China. Openness and outcome expectancies of mother-daughter communication and information exposure on social media were considered key determinants of HPV vaccine refusal for daughters. Future HPV vaccination programs should consider these interpersonal factors.

Introduction: Parkinson’s disease (PD) and Alzheimer’s disease (AD) are common neurodegenerative diseases with multifaceted etiology. Nutritional and metabolic abnormalities are frequently implicated in PD and AD. In this observational study, we analyzed a series of nutritional markers, and aimed to understand their association with AD and PD risk. Methods: A total of 424 PD patients, 314 AD patients, and 388 healthy controls were included. Nutritional markers including Hemoglobin A1c, vitamin B12, folate, apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), low-density lipoprotein (LDL), high-density lipoprotein, triglyceride, total cholesterol (TC), uric acid and homocysteine (HCY) were measured. Significance for odds ratios examining was P

Purpose Systemic immune-inflammation index (SII) was an indicator which could reflect immune response and systemic inflammation. We aim to explore the relationship between SII and diabetic nephropathy (DN). Methods SII was calculated as neutrophil count × platelet count/lymphocyte count. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnosis power of SII. Univariate and multivariate logistic analysis were conducted to assess SII as the risk factor for DN. A restricted cubic spline model was carried out to show the nonlinear association between SII and DN. Results Two hundred participants were enrolled, with an average age of 56.6 ± 13.4 years; 54% participants were categorized as DN. Spearman association analysis showed SII was positive associated with increased urinary albumin to creatinine ratio and serum creatinine, while negative associated with eGFR and serum albumin. The ROC curve revealed that the maximum area under the curve (AUC) was 0.761 (95% CI, 0.694-0.828, P

BackgroundPeritoneal dialysis-related peritonitis (PDRP) is one of the most common complications of peritoneal dialysis (PD). Understanding the risk factors and etiological characteristics is indispensable for infection prevention and improving the outcome and life quality.MethodsA total of 70 PD patients were separated into the PDRP group (n=25) and the control group (n=45). Variables, including gender, age, body mass index, primary diseases, and history of basic diseases, in the two groups were analyzed to assess the risk factors of PDRP. Metagenomic next-generation sequencing (mNGS) and microbial culture were compared in detecting pathogenic microorganisms. Gut microbiota analysis was performed in 35 PDRP patients based on mNGS data.ResultsDialysis time and times of dialysate change were the risk factors of PDRP, and times of dialysate change was the independent risk factor of PDRP (p = 0.046). mNGS produced higher sensitivity (65.79%) than microbial culture (36.84%) in identifying pathogenic microorganisms. Staphylococcus aureus and Klebsiella pneumoniae (four cases) were the most frequent pathogens causing PDRP, followed by Staphylococcus capitis (three cases). β diversity of the gut microbiota was significantly different between patients with fewer times of dialysate change (≤4) and more (>5), as well as between patients with gram-positive (G+) bacterial and gram-negative (G−) bacterial infection.ConclusionThe dialysis time and times of dialysate changes not only are risk factors for peritonitis in PD patients but also stimulate significant changes in the gut microbiome structure in PDRP patients. These findings may provide a novel viewpoint for the management of patients with PDRP.

BackgroundAcute graft-versus-host disease (aGVHD) is a common complication after allogeneic hematopoietic cell transplantation (allo-HSCT), with high morbidity and mortality. Although glucocorticoids are the standard treatment, only half of patients achieve complete remission. Thus, there is an urgent need to screen biomarkers for the diagnosis of aGVHD to assist in the identification of individuals at risk of aGVHD. This study was to construct prediction models for the occurrence and severity of aGVHD using two machine learning algorithms based on serum biochemical data.MethodsClinical data of 120 patients with hematological diseases who received allo-HSCT were retrospectively analyzed. Seventy-six patients developed aGVHD, including 56 grade I/II and 20 grade III/IV. First, 15 serum biochemical indicators were considered as potential risk factors, and the differences in the levels of indicators between non-aGVHD and aGVHD were observed, followed by evaluation of the diagnostic property. Subsequently, to develop the prediction models for the occurrence and severity of aGVHD, LASSO and random forest (RF) analyses were performed with experimental indicators. Finally, Venn diagram analysis was utilized to obtain shared biomarkers in the two algorithms to construct the nomogram. The model performance was measured by calibration curves. Internal and external validations were performed based on risk score models and ROC curve analyses.ResultsTotal 12 of 15 indicators exhibited significant differences between the aGVHD and non-aGVHD groups, with AUC values > 0.75. In machine learning analysis, eight features (LAG-3, TLR-2, PD-L1, IP-10, elafin, REG-3α, ST2, TIM3) and seven variables (LAG-3, TLR-2, PD-1, Flt_3, IL-9, elafin, TIM3) were selected to distinguish aGVHD vs. non-aGVHD as well as grade I/II vs. III/IV, respectively. Further, the corresponding nomogram models were established and calibration curves showed that prediction was in good agreement with the actual probability. Biomarker-based risk score model was constructed, which obtained AUC value >0.89 in internal and external datasets.ConclusionClinical variables screened through learning algorithm can predict the risk and severity of aGVHD. Our findings may help clinicians develop more personalized and reasonable management strategies.

ABSTRACT Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), is one of the most malignant tumors of the digestive system. Emerging evidence suggests the involvement of the microbiome and metabolic substances in the development of PDAC, yet the results remain contradictory. This study aims to identify the alterations and relationships in intratumoral microbiome and metabolites in PDAC. We collected matched tumor and normal adjacent tissue (NAT) samples from 105 PDAC patients and performed a 6-year follow-up. 2bRAD-M sequencing, untargeted liquid chromatography-tandem mass spectrometry, and untargeted gas chromatography-mass spectrometry were performed. Compared with NATs, microbial α-diversity decreased in PDAC tumors. The relative abundance of Staphylococcus aureus, Cutibacterium acnes, and Cutibacterium granulosum was higher in PDAC tumor after adjusting for confounding factors body mass index and M stage, and the presence of Ralstonia pickettii_B was found associated with a worse overall survival. Metabolomic analysis revealed distinctive differences in composition between PDAC and NAT, with 553 discriminative metabolites identified. Differential metabolites were revealed to originate from the microbiota and showed significant interactions with shifted bacterial species through KO (KEGG Orthology) genes. These findings suggest that the PDAC microenvironment harbors unique microbial-derived enzymatic reactions, potentially influencing the occurrence and development of PDAC by modulating the levels of glycerol-3-phosphate, succinate, carbonate, and beta-alanine.IMPORTANCEWe conducted a large sample-size pancreatic adenocarcinoma microbiome study using a novel microbiome sequencing method and two metabolomic assays. Two significant outcomes of our analysis are: (i) commensal opportunistic pathogens Staphylococcus aureus, Cutibacterium acnes, and Cutibacterium granulosum were enriched in pancreatic ductal adenocarcinoma (PDAC) tumors compared with normal adjacent tissues, and (ii) worse overall survival was found related to the presence of Ralstonia pickettii_B. Microbial species affect the tumorigenesis, metastasis, and prognosis of PDAC via unique microbe-enzyme-metabolite interaction. Thus, our study highlights the need for further investigation of the potential associations between pancreatic microbiota-derived omics signatures, which may drive the clinical transformation of microbiome-derived strategies toward therapy-targeted bacteria.

Introduction Late-life depression (LLD) is a global public health issue, often accompanied by cognitive impairments that can exacerbate the severity of depression and impair social functioning. Despite being a well-established treatment for LLD, the suitability of problem-solving therapy (PST) for individuals with LLD and varying degrees of cognitive impairments warrants further investigation. This paper presents the protocol for a systematic review and meta-analysis of randomised controlled trials (RCTs) aimed at evaluating the effectiveness and acceptability of PST for this specific demographic.Methods/analysis Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we will conduct a systematic review to synthesise existing research on PST for individuals in this demographic. We will comprehensively search multiple databases and sources, including PubMed, EMBASE, the Cochrane Database and APA PsycNET from inception to October 2023, without language, publication year or type restrictions. Relevant studies will be manually screened from the references. Only RCTs involving PST for LLD will be included. The primary efficacy outcome will be the standardised mean difference in total scores on continuous depression severity scales across different comparison arms. Data extraction will be conducted independently by two reviewers (CH and J-JW), and methodological rigour will be assessed using the Cochrane Risk of Bias assessment tool. Subgroup and sensitivity analyses will be performed to investigate the impact of concomitant cognitive impairments and to evaluate the robustness of the findings.Ethics and dissemination The meta-analysis project is expected to be ethically unproblematic and does not require approval from a research ethics committee. The results of this study will be shared through articles in scholarly peer-reviewed journals and presentations in various formats, both print and digital.PROSPERO registration number CRD42023473782

Squamous cell carcinoma of the head and neck (HNSCC) is a difficult-to-treat cancer and treatment is challenging due to recurrence or metastasis. Therefore, there is an urgent need to explore more effective targeted therapies to improve the clinical outcomes and survival of HNSCC patients. The nanomedicine is emerging as a promising strategy to achieve maximal anti-tumor effect in cancer therapy. In this review, we summarize some important signaling pathways and present the current and potential roles of various nanomaterial drug-delivery formulations in HNSCC treatment, aiming to understand the pathogenesis of HNSCC and further improve the therapeutic efficacy of nanomaterial HNSCC. This article seeks to highlight the exciting potential of novel nanomaterials for targeted cancer therapy in HNSCC and thus provide motivation for further research in this field.

Background Histone deacetylase (HDAC), a kind of protease that regulates gene expression by modifying protein acetylation levels, is usually aberrantly activated in tumors. The approved pan-HDAC inhibitors (HDACi) have exhibited clinical benefits for hematopoietic malignancies. Recently, HDACis have emerged as enhancers of antitumor immunity. However, the effect of HDACs on the tumor immune microenvironment of lung adenocarcinoma (LUAD) and the underlying mechanism is largely unknown.Methods C57BL/6J and BALB/c nude mice with subcutaneous tumors were used for in vivo therapeutic effects and mechanistic investigations. Flow cytometry was used to measure the toxicity and exhaustion of human CD8+T cells after co-culturing with tumor cells and to determine the immunophenotype of tumor-infiltrating CD8+T cells. A series of experimental techniques, including RNA sequencing, quantitative PCR, western blot, ELISA, mass spectrometry, co-immunoprecipitation, chromatin immunoprecipitation and immunohistochemistry, were used to explore the underlying molecular mechanism.Results The pan-HDACi vorinostat (SAHA) promoted CD8+T cell infiltration and effector function in LUAD through suppressing FGL1, a newly identified major ligand of LAG-3. Mechanistically, SAHA inhibited the activity of HDAC1, an essential deacetylase of JAK1. This increased the acetylation level of JAK1 at lysine 1109, thus promoting its proteasomal degradation and subsequently reducing STAT3-driven FGL1 transcription. The combination regimen of SAHA and anti-LAG-3 therapy was further explored in an immunocompetent LUAD mouse model. Compared with those receiving control or single agent treatments, mice receiving combination therapy exhibited a lower tumor burden and superior CD8+T-cell-killing activity.Conclusions Our results revealed a novel mechanism by which the HDACi SAHA potentiates CD8+T-cell-mediated antitumor activity through the HDAC1/JAK1/FGL1 axis, providing a rationale for the combined use of HDACis and immunotherapy.

Summary: Background: Little is known about the complex associations of socioeconomic status (SES) and healthy lifestyle with cognitive dysfunction. Methods: Using data from the Health and Retirement Study (HRS) [2008–2020] and the English Longitudinal Study of Ageing (ELSA) [2004–2018], SES was constructed by latent class analysis using education level, total household income and wealth. Overall healthy lifestyle was derived using information on never smoking, low to moderate alcohol consumption (drinks/day: (0, 1] for women and (0, 2] for men), top tertile of physical activity, and active social contact. Findings: A total of 12,437 and 6565 participants from the HRS and ELSA were included (40.8% and 46.0% men and mean age 69.3 years and 65.1 years, respectively). Compared with participants of high SES, those of low SES had higher risk of incident dementia (hazard ratio 3.17, 95% confidence interval 2.72–3.69 in the HRS; 1.43, 1.09–1.86 in the ELSA), and the proportions mediated by overall lifestyle were 10.4% (7.3%–14.6%) and 2.7% (0.5%–14.0%), respectively. Compared with participants of high SES and favorable lifestyle, those with low SES and unfavorable lifestyle had a higher risk of incident dementia (4.27, 3.40–5.38 in the HRS; 2.02, 1.25–3.27 in the ELSA) and accelerated rate of global cognitive decline (β = −0.058 SD/year; 95% CI: −0.073, −0.043 in the HRS; β = −0.049 SD/year; 95% CI: −0.063, −0.035 in the ELSA). Interpretation: Unhealthy lifestyle only mediated a small proportion of the socioeconomic inequality in dementia risk in both US and UK older adults. Funding: This work was supported by grants from the National Natural Science Foundation of China (82088102 and 82370819), the National Key R&D Program of China (2023YFC2506700), the Shanghai Municipal Government (22Y31900300), the Shanghai Clinical Research Center for Metabolic Diseases (19MC1910100), the Innovative Research Team of High-Level Local Universities in Shanghai, the Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission (202340084), and Ruijin Hospital Youth Incubation Project (KY20240805). Y.X. is supported by the National Top Young Talents program.

Abstract Targeted and immunotherapy combined with interventional therapy can improve the prognosis of advanced cancer patients, and it has become a hot spot to find the new therapeutic schemes, but most of which are not satisfactory. Single-cell RNA sequencing was performed in PDX mouse models with or without TCC therapy. 2-’O-Methylation modification and multiplex immunofluorescence staining were used to explore the function and mechanism of SAMD4B in the immune context of HCC. Here, we propose for the first time a synergistic immunochemotherapy that exerts a potent antitumour effect for patients with advanced hepatocellular carcinoma (HCC) in clinical practice based on three common antitumour drugs and found that HCC patients with new synergistic immunochemotherapy had better three-year overall survival (p = 0.004) and significantly higher survival ratio (increased by 2.3 times) than the control group. We further reveal the immunoregulatory mechanism of synergistic immunochemotherapy through 2’-O-Methylation modification mediated by SAMD4B, a tumour suppressor gene. Mechanistically, SAMD4B, increased by the reduced mutations of upstream genes NOTCH1 and NOTCH2, affected the instability of APOA2 mRNA by 2-’O-Methylation modification of the C-terminus. The decreased APOA2 further attenuated programmed death ligand 1 (PD-L1) level with a direct interaction pattern. The high-SAMD4B tumour tissues contained fewer native CD29+CD8+ T cells, which improved immune microenvironment to achieve the effect of antitumour effect. Overall, we developed a potent synergistic immunochemotherapy strategy that exerts an efficient anti-HCC effect inducing SAMD4B-APOA2-PD-L1 axis to inhibit tumour immune evasion.

Mpox is a zoonotic infectious disease caused by the mpox virus (MPXV). Historically, the majority of mpox cases have been documented in Central Africa. However, since May 2022, there has been a notable rise in reported cases from regions beyond Africa. Currently, over 110 countries spanning Europe, North America, South America, Asia, and other territories have reported mpox infections. This report details a case involving a patient who identifies as a man who has sex with men (MSM) and is concurrently infected with MPXV, human immunodeficiency virus type 1 (HIV-1), Pneumocystis jiroveci, as well as extensively drug-resistant tuberculosis (XDR-TB). This patient had also received a vaccination for smallpox in the past. Additionally, we provide photographic documentation charting the progression of dermatological manifestations associated with mpox. This case highlights the significance of sexual intercourse as a crucial mode of transmission for mpox. The rapid and widespread dissemination of the MPXV across various regions, especially among MSM communities, underscores the importance of enhancing preventive education efforts targeted at high-risk populations.

Abstract Background Global life expectancy is rising, with the 60 + age group projected to hit 2 billion by 2050. Aging impacts the immune system. A notable marker of immune system aging is the presence of Aging-Related Immune Cell Phenotypes (ARIPs). Despite their importance, links between immune cell phenotypes including ARIPs and mortality are underexplored. We prospectively investigated 16 different immune cell phenotypes using flow cytometry and IL-6 in relation to survival outcome among dementia-free Framingham Heart Study (FHS) offspring cohort participants who attended the seventh exam (1998–2001). Results Among 996 participants (mean age 62 years, range 40 to 88 years, 52% female), the 19-year survival rate was 65%. Adjusting for age, sex, and cytomegalovirus (CMV) serostatus, higher CD4/CD8 and Tc17/CD8 + Treg ratios were significantly associated with lower all-cause mortality (HR: 0.86 [0.76–0.96], 0.84 [0.74–0.94], respectively), while higher CD8 regulatory cell levels (CD8 + CD25 + FoxP3 +) were associated with increased all-cause mortality risk (HR = 1.17, [1.03–1.32]). Elevated IL-6 levels correlated with higher all-cause, cardiovascular, and non-cardiovascular mortality (HR = 1.43 [1.26–1.62], 1.70 [1.31–2.21], and 1.36 [1.18–1.57], respectively). However, after adjusting for cardiovascular risk factors and prevalent cancer alongside age, sex, and CMV, immune cell phenotypes were no longer associated with mortality in our cohort. Nonetheless, IL-6 remained significantly associated with all-cause and cardiovascular mortality (HRs: 1.3 [1.13–1.49], 1.5 [1.12–1.99], respectively). Conclusions In 19-year follow-up, higher Tc17/CD8 + Treg and CD4/CD8 ratios were associated with lower all-cause mortality, while the CD8 + CD25 + FoxP3 + (CD8 + Treg) phenotype showed increased risk. Elevated IL-6 levels consistently correlated with amplified mortality risks. These findings highlight the links between immune phenotypes and mortality, suggesting implications for future research and clinical considerations.

Acinetobacter baumannii is a pathogenic bacterium widespread in human environments, especially in intensive care units, and is associated with high morbidity and infection rates. Multiple drug resistance in A. baumannii frequently leads to the death of patients, making the development of multi-effect antibacterial agents against this bacterium a research hotspot. We have previously found that the X33 antimicrobial oligopeptide can effectively inhibit the growth of Penicillium digitatum and Candida albicans. Herein, we evaluated the antibacterial activity of X33 antimicrobial oligopeptide against A. baumannii by determining the minimum inhibitory concentration, inhibition zone, and growth curve. The increase in extracellular alkaline phosphatase and the leakage of intracellular compounds confirmed the effect of X33 antimicrobial oligopeptide on the cell wall and membrane. Changes in reactive oxygen species, malondialdehyde, ATP, reducing sugar, soluble protein, and pyruvate content demonstrated that the incubation with X33 antimicrobial oligopeptide affected energy metabolism and oxidative stress. Consistent with the physiological characteristics, transcriptomics analysis indicated that incubation with X33 antimicrobial oligopeptide significantly induced changes in the expression of 2339 genes, including 1262 upregulated and 1077 downregulated genes, which participate in oxidative phosphorylation, ribosome, quorum sensing, fatty acid degradation, glycolysis/gluconeogenesis, and citrate cycle pathways. These results provide a fundamental basis for investigating the mechanism of X33 antimicrobial oligopeptide as a potential drug against A. baumannii.

Abstract Background Alcohol screening and brief intervention (SBI) is an evidence-based intervention recommended by the World Health Organization. This study applied the Consolidated Framework for Implementation Research (CFIR) to understand facilitators and barriers of SBI implementation in primary care settings in Hong Kong, China. Methods This was a sequential mixed-method study. In-depth interviews of 21 physicians and 20 nurses working in the primary care settings from the public and private sectors were first conducted to identify CFIR constructs that were relevant to SBI implementation in the Chinese context and potential factors not covered by the CFIR. A questionnaire was then developed based on the qualitative findings to investigate factors associated with SBI implementation among 282 physicians and 295 nurses. Results The in-depth interviews identified 22 CFIR constructs that were facilitators or barriers of SBI implementation in Hong Kong. In addition, the stigmatization of alcohol dependence was a barrier and the belief that it was important for people to control the amount of alcohol intake in any situation was mentioned as a facilitator to implement SBI. In the survey, 22% of the participants implemented SBI in the past year. Factors associated with the SBI implementation echoed most of the qualitative findings. Among physicians and nurses in both sectors, they were more likely to implement SBI when perceiving stronger evidence supporting SBI, better knowledge and self-efficacy to implement SBI, more available resources, and clearer planning for SBI implementation in the clinics but less likely to do so when perceiving SBI implementation to be complicated and of higher cost, and drinking approved by the Chinese culture. Participants were more likely to implement SBI when perceiving SBI fit better with the existing practice and better leadership engagement in the public sector, but not in the private sector. Perceiving a stronger need and greater importance to implement SBI were associated with higher likelihood of SBI implementation among physicians, but not among nurses. Perceiving better organizational culture supporting SBI was positively associated with SBI implementation among nurses, but not among physicians. Conclusions There was a significant gap between SBI evidence and its implementation. Some strategies to improve SBI implementation may be different between physicians and nurses and between those in the public and private sectors. The CFIR is a useful framework for understanding facilitators and barriers of SBI implementation in primary care settings.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high probability of recurrence and distant metastasis. Liver metastasis is the predominant metastatic mode developed in most pancreatic cancer cases, which seriously affects the overall survival rate of patients. Abnormally activated endoplasmic reticulum stress and lipid metabolism reprogramming are closely related to tumor growth and metastasis. This study aims to construct a prognostic model based on endoplasmic reticulum stress and lipid metabolism for pancreatic cancer, and further explore its correlation with tumor immunity and the possibility of immunotherapy. Methods Transcriptomic and clinical data are acquired from TCGA, ICGC, and GEO databases. Potential prognostic genes were screened by consistent clustering and WGCNA methods, and the whole cohort was randomly divided into training and testing groups. The prognostic model was constructed by machine learning method in the training cohort and verified in the test, TCGA and ICGC cohorts. The clinical application of this model and its relationship with tumor immunity were analyzed, and the relationship between endoplasmic reticulum stress and intercellular communication was further explored. Results A total of 92 characteristic genes related to endoplasmic reticulum stress, lipid metabolism and liver metastasis were identified in pancreatic cancer. We established and validated a prognostic model for pancreatic cancer with 7 signatures, including ADH1C, APOE, RAP1GAP, NPC1L1, P4HB, SOD2, and TNFSF10. This model is considered to be an independent prognosticator and is a more accurate predictor of overall survival than age, gender, and stage. TIDE score was increased in high-risk group, while the infiltration levels of CD8+ T cells and M1 macrophages were decreased. The number and intensity of intercellular communication were increased in the high ER stress group. Conclusions We constructed and validated a novel prognostic model for pancreatic cancer, which can also be used as an instrumental variable to predict the prognosis and immune microenvironment. In addition, this study revealed the effect of ER stress on cell–cell communication in the tumor microenvironment.

Abstract Background Urinary incontinence is highly prevalent in women while pelvic floor muscle training is recommended as the first-line therapy. However, the exact treatment regimen is poorly understood. Also, patients with pelvic floor muscle damage may have decreased muscle proprioception and cannot contract their muscles properly. Other conservative treatments including electromagnetic stimulation are suggested by several guidelines. Thus, the present study aims to compare the effectiveness of electromagnetic stimulation combined with pelvic floor muscle training as a conjunct treatment for urinary incontinence and different treatment frequencies will be investigated. Methods/design This is a randomized, controlled clinical trial. We will include 165 patients with urinary incontinence from the outpatient center. Participants who meet the inclusion criteria will be randomly allocated to three groups: the pelvic floor muscle training group (active control group), the low-frequency electromagnetic stimulation group (group 1), and the high-frequency electromagnetic stimulation group (group 2). Both group 1 and group 2 will receive ten sessions of electromagnetic stimulation. Group 1 will be treated twice per week for 5 weeks while group 2 will receive 10 days of continuous treatment. The primary outcome is the change in International Consultation on Incontinence Questionnaire–Short Form cores after the ten sessions of the treatment, while the secondary outcomes include a 3-day bladder diary, pelvic floor muscle function, pelvic organ prolapse quantification, and quality of life assessed by SF-12. All the measurements will be assessed at baseline, after the intervention, and after 3 months of follow-up. Discussion The present trial is designed to investigate the effects of a conjunct physiotherapy program for urinary incontinence in women. We hypothesize that this strategy is more effective than pelvic floor muscle training alone, and high-frequency electromagnetic stimulation will be superior to the low-frequency magnetic stimulation group.

Abstract Gastric cancer (GC) is a common malignant tumor worldwide, especially in East Asia, with high incidence and mortality rate. Epigenetic modifications have been reported to participate in the progression of gastric cancer, among which m6A is the most abundant and important chemical modification in RNAs. Fat mass and obesity-associated protein (FTO) is the first identified RNA demethylase but little is known about its role in gastric cancer. In our study, data from TCGA and clinical samples showed that FTO was highly expressed in gastric cancer tissues. Kaplan–Meier plotter suggested that patients with the high level of FTO had a poor prognosis. In vitro and in vivo experiments confirmed the role of FTO in promoting gastric cancer cell proliferation. Mechanistically, we found that FTO bound to circFAM192A at the specific site and removed the m6A modification in circFAM192A, protecting it from degradation. CircFAM192A subsequently interacted with the leucine transporter solute carrier family 7 member 5 (SLC7A5) and enhancing its stability. As a result, an increased amount of SLC7A5 was on the membrane, which facilitated leucine uptake and activated the mTOR signaling pathway. Therefore, our study demonstrated that FTO promoted gastric cancer proliferation through the circFAM192A/SLC7A5 axis in the m6A-dependent manner. Our study shed new light on the role of FTO in gastric cancer progression.

BackgroundAdolescence is a period characterized by rapid biological and psychological change, and adolescents have a heightened risk of depression. Parental rearing is an important influencing factor for depression in adolescence. However, the mechanism of influence needs further exploration.MethodsA total of 1839 adolescents were recruited from a junior and a senior high school in Zhongshan City, Guangdong Province, China. They were requested to completed the Parental Bonding Instrument (PBI), Self-Compassion Scale (SCS), and Depression Anxiety and Stress Scale-21(DASS-21).ResultsAdolescents recalled their mothers as being more caring and controlling than their fathers. Parental care (maternal care, paternal care) and parental encouragement of autonomy (maternal encouragement of autonomy, paternal encouragement of autonomy) were both negative predictors of depression, while parental control (maternal control, paternal control) was positive predictor of depression. Self-compassion mediated all relationships between parental rearing styles (parental care, parental encouragement of autonomy, and parental control) and depression but played different mediating roles (complete or incomplete mediating role) in different relationships.ConclusionSelf-compassion plays a mediator role in all relationships between perceived parental rearing styles (parental care, parental encouragement of autonomy, and parental control) and depression. Adolescents who grown up with less parental care, less parental encouragement of autonomy, and high parental control deserve special attention. Educators and clinicians could help those adolescents reduce the occurrence of depression by increasing their level of self-compassion.

BackgroundMale factory workers in China are vulnerable to HIV transmission. Commercial and nonmarital noncommercial contacts are the driving forces of heterosexual HIV transmission among male factory workers in China. There is a lack of effective HIV interventions for male factory workers in China. ObjectiveThe primary objective of this randomized controlled trial was to compare the efficacy of an enhanced versus the standard version of a WeChat mini program in reducing sexual intercourse with nonregular female sex partners and female sex workers among male factory workers in Shenzhen, China. MethodsA nonblinded 2-arm parallel randomized controlled trial was conducted between December 2021 and April 2023. Participants were adult male factory workers in Shenzhen who had access to a smartphone and WeChat. Those who had oral or anal sex with a man or self-reported as HIV positive were excluded. A total of 247 participants were randomly assigned to the intervention group (n=125, 50.6%) or the control group (n=122, 49.4%); 221 (89.5%) and 220 (89.1%) completed follow-up surveys at T1 (6 months after completion of the interventions) and T2 (6 months after T1). Participants in the control group had access to the standard WeChat mini program that provided basic HIV-related knowledge and information about local free HIV testing services. Participants in the intervention group had access to the enhanced WeChat mini program. The enhanced mini program covered all the information in the standard mini program. In addition, the enhanced mini program assessed users’ behaviors and invited users to watch different web-based videos on reducing nonmarital sexual contacts and promoting HIV testing based on their behavioral characteristics at months 0 and 1. The videos were developed based on in-depth interviews with male factory workers. Intention-to-treat analysis was used for outcome analyses. Multiple imputation was used to replace missing outcome values at T1 and T2. ResultsAt T1, fewer participants in the intervention group reported sexual intercourse with a nonregular female sex partner in the past 6 months compared with the control group (1/125, 0.8% vs 8/122, 6.6%; relative risk=0.12, 95% CI 0.02-0.96; P=.02). However, there were no between-group differences in sexual intercourse with a nonregular female sex partner at T2 (10/125, 8% vs 14/122, 11.5%; P=.36) or sexual intercourse with a female sex worker at T1 (2/125, 1.6% vs 2/122, 1.6%; P=.98) or T2 (8/125, 6.4% vs 8/122, 6.6%; P=.96). ConclusionsThe enhanced WeChat mini program was more effective than the standard WeChat mini program in reducing sexual intercourse with nonregular female sex partners among male factory workers in the short term but not in the longer term. Improvements should be made to the WeChat mini program before implementation. Trial RegistrationClinicalTrials.gov NCT05811611; https://clinicaltrials.gov/study/NCT05811611

BackgroundThe Herpesviridae family contains several human-related viruses, which are able to establish colonizing and latency in the human body, posing a significant threat to the prognosis of patients. Pulmonary infections represent one of the predominant infectious diseases globally, characterized by diverse and multifaceted clinical manifestations that have consistently attracted clinician’s concern. However, the relationship of herpesviruses on the prognosis of pulmonary infections and the respiratory microbiota remains poorly understood.MethodsHere, we retrospectively analyzed respiratory samples from 100 patients with pulmonary infection detected by metagenomic next-generation sequencing (mNGS).ResultsEmploying mNGS, five herpesvirus species were detected: Human alphaherpesvirus 1 (HSV-1), Human gammaherpesvirus 4 (EBV), Human betaherpesvirus 5 (CMV), Human betaherpesvirus 7 (HHV-7), and Human betaherpesvirus 6B (HHV-6B). Regression analysis showed that the age and positivity of herpesviruses in patients were independently correlated with ICU admission rates. In addition, positivity of herpesvirus was related with increased ICU days and total hospital stay. The herpesvirus-positive group demonstrated markedly higher incidences of co-infections and fungi-positive, predominantly involving Pneumocystis jirovecii and Aspergillus fumigatus. Analysis of respiratory microbiota revealed a substantially altered community composition within the herpesvirus-positive group, and herpesviruses were significantly positively correlated with the diverse respiratory opportunistic pathogens.ConclusionOverall results substantiate that the active herpesviruses in patients with pulmonary infections were significantly associated with high ICU admission rate. Moreover, the herpesviruses promotes the dysbiosis of the respiratory microbiota and an increased proportion of co-infections. These insights could contribute to unraveling the underlying mechanisms connecting active herpesviruses to the progression of severe illnesses.

Abstract Mammalian cochlear hair cells (HCs) are essential for hearing, and damage to HCs results in severe hearing impairment. Damaged HCs can be regenerated by neighboring supporting cells (SCs), thus the functional regeneration of HCs is the main goal for the restoration of auditory function in vivo. Here, cochlear SC trans‐differentiation into outer and inner HC by the induced expression of the key transcription factors Atoh1 and its co‐regulators Gfi1, Pou4f3, and Six1 (GPAS), which are necessary for SCs that are destined for HC development and maturation via the AAV‐ie targeting the inner ear stem cells are successfully achieved. Single‐cell nuclear sequencing and lineaging tracing results showed that the majority of new Atoh1‐derived HCs are in a state of initiating differentiation, while GP (Gfi1, Pou4f3) and GPS (Gfi1, Pou4f3, and Six1) enhanced the Atoh1‐induced new HCs into inner and outer HCs. Moreover, the patch‐clamp analysis indicated that newborn inner HCs induced by GPAS forced expression have similar electrophysiological characteristics to those of native inner HCs. Also, GPAS can induce HC regeneration in the HC‐damaged mice model. In summary, the study demonstrates that AAV‐mediated co‐regulation of multiple genes, such as GPAS, is an effective means to achieve functional HC regeneration in the mouse cochlea.

Background: China started to implement the HPV vaccination program for females in 2016. This study investigated associations between mothers’ decisional conflicts, satisfaction with governmental health promotion materials, and their daughters’ HPV vaccination uptake. Methods: A cross-sectional online survey was conducted between July and October 2023 among mothers of girls aged 9–17 years in Shenzhen, China. Participants were mothers having a daughter aged 9–17 years at the survey date and a smartphone with internet access. About 3 % of all primary and secondary schools in Shenzhen were randomly selected by the research team (11 primary schools and 13 secondary schools). Teachers at the selected schools invited mothers of female students aged 9–17 years to complete an anonymous online questionnaire. Multivariate logistic regression was fitted. Results: Among 11,728 mothers who completed the survey, 18.9% of their index daughters received at least one dose of HPV vaccination. In multivariate analysis, less decisional conflict about the choice of HPV vaccines for their daughters (AOR: 1.07, 95%CI: 1.05, 1.10), more satisfaction with the government’s health promotional materials related to HPV vaccines (AOR: 1.15, 95%CI: 1.12, 1.19), receiving more cue to action from significant others (AOR: 1.23, 95%CI: 1.19, 1.27), and perceived higher self-efficacy related to HPV vaccines (AOR: 1.79, 95%CI: 1.67, 1.92) were associated with a higher uptake of HPV vaccines. Perceived susceptibility to HPV (AOR: 0.79, 95%CI: 0.74, 0.85), perceived barriers to having the index daughter receive HPV vaccines (AOR: 0.82, 95%CI: 0.80, 0.84), and mothers who were hesitant to receive HPV vaccination (AOR: 0.75, 95%CI: 0.68, 0.84) were associated with a lower uptake. Conclusion: HPV vaccination uptake was low among girls in China. Future health promotion should address mothers’ decisional conflicts about the choice of HPV vaccines for their daughters and improve the health promotional materials. School-based HPV vaccination programs might be useful.

BackgroundThis study aims to screen inflammation-related genes closely associated with the prognosis of hepatocellular carcinoma (HCC) to accurately forecast the prognosis of HCC patients.MethodsGene expression matrices and clinical information for liver cancer samples were obtained from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). An intersection of differentially expressed genes of HCC and normal and GeneCards yielded inflammation-related genes associated with HCC. Cox regression and the minor absolute shrinkage and selection operator (LASSO) regression analysis to filter genes associated with HCC prognosis. The prognostic value of the model was confirmed by drawing Kaplan–Meier and ROC curves. Select differentially expressed genes between the high-risk and low-risk groups and perform GO and KEGG pathways analyses. CIBERSORT analysis was conducted to assess associations of risk models with immune cells and verified using real-time qPCR.ResultsA total of six hub genes (C3, CTNNB1, CYBC1, DNASE1L3, IRAK1, and SERPINE1) were selected using multivariate Cox regression to construct a prognostic model. The validation evaluation of the prognostic model showed that it has an excellent ability to predict prognosis. A line plot was drawn to indicate the HCC patients’ survival, and the calibration curve revealed satisfactory predictability. Among the six hub genes, C3 and DNASE1L3 are relatively low expressed in HCCLM3 and 97H liver cancer cell lines, while CTNNB1, CYBC1, IRAK1, and SERPINE1 are relatively overexpressed in liver cancer cell lines.ConclusionOne new inflammatory factor-associated prognostic model was constructed in this study. The risk score can be an independent predictor for judging the prognosis of HCC patients’ survival.

Buckling restrained brace is an important structure for improving the seismic resistance of structures. Conducting research on new types of buckling restrained brace can improve the seismic performance and reliability of buckling resistant support. Four different types of buckling restrained braces specimens were designed and manufactured: cross-shaped square steel pipe members, cross-shaped round steel pipe members, cross-shaped carbon fiber members, and in-line carbon fiber members. By conducting quasi-static tests, the force displacement hysteresis curves, skeleton curves, stiffness degradation, equivalent viscous damping coefficient, and energy dissipation ratio of four different types of buckling restrained brace were analyzed. The research results showed that all four buckling restrained brace specimens have good hysteresis performance. The load-bearing capacity and energy consumption performance of the three specimens of square steel pipe, round steel pipe and carbon fiber with the same core unit are the same, but the inline type is worse than the cross type. The core unit specimen with a width of 80 mm is about 60% higher in bearing capacity and energy consumption than a specimen with a width of 50 mm. The core unit of some specimens undergoes multi-wave buckling. For carbon fiber specimens, the CFRP is prone to breakage due to the lateral thrust of the restraining unit. Therefore, steel hoop or stirrup should be added to the end to improve the restraint effect when designing and manufacturing.

Abstract Objectives To develop a multiparameter magnetic resonance imaging (MRI)-based radiomics approach that can accurately predict the tumor cell proliferation status of serous ovarian carcinoma (SOC). Materials and methods A total of 134 patients with SOC who met the inclusion and exclusion criteria were retrospectively screened from institution A, spanning from January 2016 to March 2022. Additionally, an external validation set comprising 42 SOC patients from institution B was also included. The region of interest was determined by drawing each ovarian mass boundaries manually slice-by-slice on T2-weighted imaging fat-suppressed fast spin-echo (T2FSE) and T1 with contrast enhancement (T1CE) images using ITK-SNAP software. The handcrafted radiomic features were extracted, and then were selected using variance threshold algorithm, SelectKBest algorithm, and least absolute shrinkage and selection operator. The optimal radiomic scores and the clinical/radiological independent predictors were integrated as a combined model. Results Compared with the area under the curve (AUC) values of each radiomic signature of T2FSE and T1CE, respectively, the AUC value of the radiomic signature (T1CE-T2FSE) was the highest in the training set (0.999 vs. 0.965 and 0.860). The homogeneous solid component of the ovarian mass was considered the only independent predictor of tumor cell proliferation status among the clinical/radiological variables. The AUC of the radiomic–radiological model was 0.999. Conclusions The radiomic–radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can accurately predict tumor cell proliferation status of SOC which has high repeatability and may enable more targeted and effective treatment strategies. Critical relevance statement The proposed radiomic–radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can predict tumor cell proliferation status of SOC which has high repeatability and may guide individualized treatment programs. Key points • The radiomic–radiological nomogram may guide individualized treatment programs of SOC. • This radiomic–radiological nomogram showed a favorable prediction ability. • Homogeneous slightly higher signal intensity on T2FSE is vital for Ki-67. Graphical Abstract

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid type, and MPC3-energy type, based on the enrichment scores of metabolic pathways extracted from the Reactome database. The MPC3 cluster exhibited characteristics of energy metabolism, with heightened glycolysis, cofactors, and nucleotide metabolism, showing a trend toward increased aggressiveness and poorer survival rates. On the other hand, MPC1 and MPC2 primarily involved lipid and amino acid metabolism, respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles and potential therapeutic agents were explored and compared among ESCC cell lines with different MPCs. MPC3 amplified energy metabolism markers, especially carnitines. In contrast, MPC1 and MPC2 predominantly had elevated levels of lipids (primarily triacylglycerol) and amino acids, respectively. Furthermore, MPC3 demonstrated a suboptimal clinical response to PD-L1 immunotherapy but showed increased sensitivity to the doramapimod chemotherapy regimen, as evident from drug sensitivity evaluations. These insights pave the way for a more personalized therapeutic approach, potentially enhancing treatment precision for ESCC patients.

Abstract Background Hepatocellular carcinoma (HCC) is characterized by aggressive progression and elevated mortality rates. This study aimed to investigate the regulatory effects of RBBP7 on HCC pathogenesis and the underlying mechanisms. Methods The expression and clinical feature of RBBP7 were evaluated using bioinformatics analysis and the assessment of clinical HCC samples. CCK8 and colony formation were employed to estimate cell proliferation function of RBBP7. Aerobic glycolysis levels of RBBP7 were evaluated by measuring ATP levels, lactic acid production, glucose uptake capacity, and the expression of relevant enzymes (PFKM, PKM2, and LDHA). The phosphorylation levels in PI3K/AKT signaling were measured by western blotting. The regulatory effect of transcription factors of specificity protein 1 (SP1) on RBBP7 mRNA expression was confirmed in dual-luciferase reporter assays and chromatin immunoprecipitation experiments. The proliferation- and glycolysis-associated proteins were assessed using immunofluorescence staining in vivo. Results We found that RBBP7 is expressed at high levels in HCC and predicts poor survival. Functional assays showed that RBBP7 promoted HCC proliferation and glycolysis. Mechanistically, it was demonstrated that RBBP7 activates the PI3K/AKT pathway, a crucial pathway in glycolysis, contributing to the progression of HCC. The outcomes of the dual-luciferase assay further confirmed that SP1 is capable of activating the promoter of RBBP7. Conclusions RBBP7, which is up-regulated by SP1, promotes HCC cell proliferation and glycolysis through the PI3K/AKT pathway. The findings of this study suggest that RBBP7 is a potential biomarker for HCC.

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous and lethal hepatobiliary tumor with few therapeutic strategies. The metabolic reprogramming of tumor cells plays an essential role in the development of tumors, while the metabolic molecular classification of iCCA is largely unknown. Here, we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients, hoping to provide a novel perspective to understand and treat iCCA. Methods We performed integrated multiomics analysis in 116 iCCA samples, including whole‐exome sequencing, bulk RNA‐sequencing and proteome analysis. Based on the non‐negative matrix factorization method and the protein abundance of metabolic genes in human genome‐scale metabolic models, the metabolic subtype of iCCA was determined. Survival and prognostic gene analyses were used to compare overall survival (OS) differences between metabolic subtypes. Cell proliferation analysis, 5‐ethynyl‐2'‐deoxyuridine (EdU) assay, colony formation assay, RNA‐sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinase α (DGKA) in iCCA cells. Results Three metabolic subtypes (S1‐S3) with subtype‐specific biomarkers of iCCA were identified. These metabolic subtypes presented with distinct prognoses, metabolic features, immune microenvironments, and genetic alterations. The S2 subtype with the worst survival showed the activation of some special metabolic processes, immune‐suppressed microenvironment and Kirsten rat sarcoma viral oncogene homolog (KRAS)/AT‐rich interactive domain 1A (ARID1A) mutations. Among the S2 subtype‐specific upregulated proteins, DGKA was further identified as a potential drug target for iCCA, which promoted cell proliferation by enhancing phosphatidic acid (PA) metabolism and activating mitogen‐activated protein kinase (MAPK) signaling. Conclusion Via multiomics analyses, we identified three metabolic subtypes of iCCA, revealing that the S2 subtype exhibited the poorest survival outcomes. We further identified DGKA as a potential target for the S2 subtype.

Deep learning methods, especially convolutional neural networks (CNNs) and vision transformers (ViTs), are frequently employed to perform semantic segmentation of high-resolution remotely sensed images. However, CNNs are constrained by their restricted receptive fields, while ViTs face challenges due to their quadratic complexity. Recently, the Mamba model, featuring linear complexity and a global receptive field, has gained extensive attention for vision tasks. In such tasks, images need to be serialized to form sequences compatible with the Mamba model. Numerous research efforts have explored scanning strategies to serialize images, aiming to enhance the Mamba model's understanding of images. However, the effectiveness of these scanning strategies remains uncertain. In this research, we conduct a comprehensive experimental investigation on the impact of mainstream scanning directions and their combinations on semantic segmentation of remotely sensed images. Through extensive experiments on the LoveDA, ISPRS Potsdam, ISPRS Vaihingen, and UAVid datasets, we demonstrate that no single scanning strategy outperforms others, regardless of their complexity or the number of scanning directions involved. A simple, single scanning direction is deemed sufficient for semantic segmentation of high-resolution remotely sensed images. Relevant directions for future research are also recommended.

Purposes Traffic flow prediction is crucial for the effective management and operation of urban transportation systems. The flows of different road sections or intersections in a traffic network change dynamically with time, meanwhile the flows of spatially neighboring road sections or intersections affect each other. In order to better learn the spatial and temporal correlation of the traffic flow of different road sections or intersections from the traffic flow sequences, and to improve the performance of short-term prediction of traffic flow, in this paper we propose a traffic flow prediction method based on Dynamic Graph Convolution Network with Multi-head Attention (DGCNMA). Methods The DGCNMA model first introduces graph convolution networks into the Transformer framework to learn the spatial embedding of traffic flow sequences and incorporate them into the traffic flow sequences, and then adopts the mechanism of Multi-head Attention to capture the temporal and spatial correlation of the traffic flow sequences from multiple perspectives at the same time; second, the Interactive Dynamic Graph Convolution Network is introduced to simultaneously learn the local and global spatial-temporal correlations of traffic flow sequences through the interactive learning of convolutional network and dynamic graph convolutional network, and the interactive fusion of parity subsequence features. Findings Experiments on highway traffic flow datasets (PEMS03, PEMS04, PEMS08) and subway crowd flow datasets (HZME inflow and HZME outflow) show that the proposed DGCNMA model has better traffic flow prediction performance than the baseline models.

Marine fishing is related to the balance of marine natural ecosystem and national food security. At present, marine fishing industry in China develops rapidly and its market prospect is broad, but there are still some problems to be solved. This paper analyzes the current situation of marine fishery and related laws in China, and puts forward development suggestions for a series of problems, such as the defects of the fishing license system, the weak operability of the quota fishing system, and the lack of scientificity of the "one-size-fits-all" off-season fishing moratorium. The following development suggestions are provided: (1) Improve the restrictive management measures of the fishing license system, strengthen supervision and raise the threshold for entry; (2) Increase the operational legal provisions of fishing quotas, and to establish a database of total available catches for marine fisheries and to establish a corresponding system of government financial subsidies; (3) Learn from Canada, the United States and other marine fishery developed countries’ advanced experience to improve the fishing moratorium in the summer.