Improvement and exacerbation of multiple disparities in sexually transmitted infections among children and adolescents aged 6-22 years: An analysis of national surveillance data from 2013 to 2021.

To investigate the progress of disparities in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), gonorrhea, and syphilis among children and adolescents aged 6-22 years in China during 2013-2021. A total of 614 325 cases data were extracted from the Chinese Information System for Infectious Diseases Control and Prevention during 2013-2021. Puberty health education data were drew from the Student Health Surveillance in 2021. Disparity patterns and average annual percentage changes (AAPCs) in sexually transmitted infections (STIs) incidence or new cases in China were examined using descriptive statistics and joinpoint regression. The incidence across 345 cities was stratified by gross domestic product (GDP). Between 2013 and 2021, there were 614 325 reported cases of HIV/AIDS, gonorrhea, and syphilis among children and adolescents aged 6-22, with an annual average incidence of 24.0967 per 100 000. The expansion of HIV/AIDS has halted, yet the surge in gonorrhea and syphilis remains notably pronounced. The ratio of male to female AIDS incidence increased from 2.75 (2.60, 2.90) to 7.13 (6.68, 7.62), but that of syphilis changed from 0.33 (0.32, 0.34) to 0.56 (0.55, 0.57). Students and out-of-school individuals aged 13-15 experienced a notably high increase in STI cases, surpassing other age groups, with an average annual percentage increase of 29.2% and 26.3%, respectively. Nonstudents consistently had a higher incidence rate than students, with an IRR reaching 31.80 (31.24, 32.37) in 2021. A noticeable clustering pattern of new cases emerged in the southeastern region of the Heihe-Tengchong line, extending inland from the coastal areas. Districts and counties with lower rates of puberty sexual health education tended to have higher average STI incidence rates. At the prefecture and city levels, there was a noticeable upward trend on average STI incidence rates in cities with per capita GDPs. Strategies to address those disparities include promoting equitable health education, and widespread sexual health education, particularly in areas with limited access to education and experiencing rapid economic development. The effectiveness of sexual health education intervention needs to be further evaluated in well-designed studies.

Neurotoxic effects of triclosan in adolescent mice: Pyruvate kinase M2 dimer regulated Signal transducer and activator of transcription 3 phosphorylation mediated microglia activation and neuroinflammation.

Triclosan (TCS), a commonly used antibacterial agent, is associated with various harmful effects on mammalian neurodevelopment, particularly when exposed prenatally. This study investigated the impact of long-term exposure to TCS on the prefrontal cortex development in adolescent mice. We evaluated the motor ability, motor coordination, and anxiety behavior of mice using open field tests (OFT) and elevated cross maze tests (EPM). An increase in movement distance, number of passes through the central area, and open arm retention time was observed in mice treated with TCS. Hematoxylin eosin staining and Nissl staining also showed significant adverse reactions in the brain tissue of TCS-exposed group. TCS induced microglia activation and increased inflammatory factors expression in the prefrontal cortex. TCS also increased the expression of pyruvate kinase M2 (PKM2), thereby elevating the levels of PKM2 dimer, which entered the nucleus. Treatment with TEPP46 (PKM2 dimer nuclear translocation inhibitor) blocked the expression of inflammatory factors induced by TCS. TCS induced the phosphorylation of nuclear signal transducer and activator of transcription 3 (STAT3) in vivo and in vitro, upregulating the levels of inflammatory cytokines. The results also demonstrated the binding of PKM2 to STAT3, which promoted STAT3 phosphorylation at the Tyr705 site, thereby regulating the expression of inflammatory factors. These findings highlight the role of PKM2-regulated STAT3 phosphorylation in TCS-induced behavioral disorders in adolescents and propose a reliable treatment target for TCS.

The association of breastfeeding duration on metabolic syndrome among children and adolescents, stratified by birth weight for gestational age.

BACKGROUND AND OBJECTIVES: This study aimed to examine the associations between breastfeeding duration and metabolic syndrome (MetS) in adolescents and to further investigate the role of birth weight for gestational age (GA) on these associations. METHODS: A total of 10 275 participants aged 7 to 18 years were included applying multistage cluster random sampling from a Chinese national survey. Birth weight was classified into small for GA (SGA), appropriate for GA (AGA) and large for GA (LGA). Information was collected through a self-administered questionnaire, physical examination and blood biochemical examination. Multivariable linear regression, logistic regression models, restricted cubic spline models were applied to assess the relationships of breastfeeding duration and MetS with different birth weight for GA. RESULTS: The prevalence of non-breastfeeding, 0-5, 6-12 and >12 months groups were 16.2%, 23.1%, 42.5% and 18.2%, and the prevalence of SGA and LGA was 11.9% and 12.7%, respectively. Prolonged breastfeeding duration was associated with higher odds of MetS (ß: 0.08, 95% CI: 0.03, 0.13), WC (ß: 3.49, 95% CI: 2.82, 4.16) and SBP (ß: 2.34, 95% CI: 1.80, 2.89). SGA and prolonged breastfeeding synergistically increased MetS risks, but LGA appeared to offset the adverse effects of prolonged breastfeeding. CONCLUSION: Prolonged breastfeeding may increase children's MetS risks. SGA synergies with prolonged breastfeeding increased MetS burden in children and adolescents, while LGA mitigated the risks. This reminds us that intensive attention should be paid to both early birth weight and subsequent living environment for children and adolescents' lifelong health.

Elucidation of key fatty aroma compound contributing to the hepatopancreas of Eriocheir sinensis using sensomics approach by GC-IMS and GC-MS-O.

Aroma is one of the most noticeable characteristics when consuming Chinese mitten crab (Eriocheir sinensis) and is crucial for consumer satisfaction and the development of industry. In this study, we utilized fingerprints and the sensomics approach to analyze volatiles in the hepatopancreas of E. sinensis from Chongming and Taixing. GC-IMS indicated that the odor profile was dominated by pungent (-), buttery (+), and fruity (+) from Chongming and was more prone to alcoholic (-), solvent (-), and aldehydic (+) in Taixing. Moreover, PLS-DA modeling identified 2-acetylthiazole and toluene as the primary differential compounds. Subsequently, fifteen active-aroma compounds with FD values of >4 was recombined in an odorless matrix to simulate the odor profile of the hepatopancreas. Notably, removing methional may significantly decrease the intensity of the fatty and toasted odors. The findings reveal the odor profile of hepatopancreas and establish a theoretical foundation for subsequent studies on flavor.

The Fault Diagnosis of Rolling Bearings Is Conducted by Employing a Dual-Branch Convolutional Capsule Neural Network.

Currently, many fault diagnosis methods for rolling bearings based on deep learning are facing two main challenges. Firstly, the deep learning model exhibits poor diagnostic performance and limited generalization ability in the presence of noise signals and varying loads. Secondly, there is incomplete utilization of fault information and inadequate extraction of fault features, leading to the low diagnostic accuracy of the model. To address these problems, this paper proposes an improved dual-branch convolutional capsule neural network for rolling bearing fault diagnosis. This method converts the collected bearing vibration signals into grayscale images to construct a grayscale image dataset. By fully considering the types of bearing faults and damage diameters, the data are labeled using a dual-label format. A multi-scale convolution module is introduced to extract features from the data and maximize feature information extraction. Additionally, a coordinate attention mechanism is incorporated into this module to better extract useful channel features and enhance feature extraction capability. Based on adaptive fusion between fault type (damage diameter) features and labels, a dual-branch convolutional capsule neural network model for rolling bearing fault diagnosis is established. The model was experimentally validated using both Case Western Reserve University's bearing dataset and self-made datasets. The experimental results demonstrate that the fault type branch of the model achieves an accuracy rate of 99.88%, while the damage diameter branch attains an accuracy rate of 99.72%. Both branches exhibit excellent classification performance and display robustness against noise interference and variable working conditions. In comparison with other algorithm models cited in the reference literature, the diagnostic capability of the model proposed in this study surpasses them. Furthermore, the generalization ability of the model is validated using a self-constructed laboratory dataset, yielding an average accuracy rate of 94.25% for both branches.

H-151 attenuates lipopolysaccharide-induced acute kidney injury by inhibiting the STING-TBK1 pathway.

Sepsis is a severe systemic infectious disease that often leads to multi-organ dysfunction. One of the common and serious complications of sepsis is renal injury. In this study, we aimed to investigate the potential mechanistic role of a novel compound called H-151 in septic kidney injury. We also examined its impact on renal function and mouse survival rates. Initially, we confirmed abnormal activation of the STING-TBK1 signaling pathway in the kidneys of septic mice. Subsequently, we treated the mice with H-151 and observed significant improvement in sepsis-induced renal dysfunction. This was evidenced by reductions in blood creatinine and urea nitrogen levels, as well as a marked decrease in inflammatory cytokine levels. Furthermore, H-151 substantially improved the seven-day survival rate of septic mice, indicating its therapeutic potential. Importantly, H-151 also exhibited an inhibitory effect on renal apoptosis levels, further highlighting its mechanism of protecting against septic kidney injury. These study findings not only offer new insights into the treatment of septic renal injury but also provide crucial clues for further investigations into the regulatory mechanisms of the STING-TBK1 signaling pathway and potential drug targets.

Genome wide-scale CRISPR-Cas9 knockout screens identify a fitness score for optimized risk stratification in colorectal cancer.

BACKGROUND: The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions. METHODS: we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes. A regression model was built using colorectal cancer-specific fitness genes, which was validated in other three independent cohorts. 30 published gene expression signatures were also retrieved. FINDINGS: We defined a total of 1828 genes that were colorectal cancer-specific fitness genes and identified a 22 colorectal cancer-specific fitness gene (CFG22) score. A high CFG22 score represented unfavorable recurrence and mortality rates, which was validated in three independent cohorts. Combined with age, and TNM stage, the CFG22 model can provide guidance for the prognosis of colorectal cancer patients. Analysis of genomic abnormalities and infiltrating immune cells in the CFG22 risk stratification revealed molecular pathological difference between the subgroups. Besides, drug analysis found that CFG22 high patients were more sensitive to clofibrate. INTERPRETATION: The CFG22 model provided a powerful auxiliary prediction tool for identifying colorectal cancer patients with high recurrence risk and poor prognosis, optimizing precise treatment and improving clinical efficacy.

Association among abnormal glycolipids, reproductive hormones, and cognitive dysfunction in female patients with bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) show abnormalities in glucolipid metabolism and reproductive hormone levels, which are of concern in women with BD. This study was dedicated to investigating the glucolipid and reproductive hormone levels of female patients, and to preliminarily investigating their relationships with cognition. METHODS: A total of 58 unmedicated female BD patients, 61 stable-medicated female BD patients, and 63 healthy controls (HC) were recruited in this study. Serum glycolipid indexes and reproductive hormones were measured. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test). RESULTS: Patients with BD showed significant cognitive impairment (p < 0.05), which was not affected by medication. Triglycerides (TG), luteinizing hormone (LH), and high-density lipoprotein cholesterol (HDL-c) were altered in stable-medicated BD patients. In addition, regression analysis showed that progesterone (PRGE) and prolactin (PRL) were negatively associated with cognitive performance in stable-medicated BD patients. CONCLUSIONS: Female BD patients may have cognitive deficits and abnormal levels of glycolipids and reproductive hormones. And abnormal levels of glycolipids and reproductive hormones may be associated with cognitive dysfunction in female BD patients.

Persistence and Variation of the Indirect Effects of COVID-19 Restrictions on the Spectrum of Notifiable Infectious Diseases in China: Analysis of National Surveillance Among Children and Adolescents From 2018 to 2021.

BACKGROUND: Beyond the direct effect of COVID-19 infection on young people, the wider impact of the pandemic on other infectious diseases remains unknown. OBJECTIVE: This study aims to assess changes in the incidence and mortality of 42 notifiable infectious diseases during the pandemic among children and adolescents in China, compared with prepandemic levels. METHODS: The Notifiable Infectious Disease Surveillance System of China was used to detect new cases and fatalities among individuals aged 5-22 years across 42 notifiable infectious diseases spanning from 2018 to 2021. These infectious diseases were categorized into 5 groups: respiratory, gastrointestinal and enterovirus, sexually transmitted and blood-borne, zoonotic, and vector-borne diseases. Each year (2018-2021) was segmented into 4 phases: phase 1 (January 1-22), phase 2 (January 23-April 7), phase 3 (April 8-August 31), and phase 4 (September 1-December 31) according to the varying intensities of pandemic restrictive measures in 2020. Generalized linear models were applied to assess the change in the incidence and mortality within each disease category, using 2018 and 2019 as the reference. RESULTS: A total of 4,898,260 incident cases and 3701 deaths were included. The overall incidence of notifiable infectious diseases decreased sharply during the first year of the COVID-19 pandemic (2020) compared with prepandemic levels (2018 and 2019), and then rebounded in 2021, particularly in South China. Across the past 4 years, the number of deaths steadily decreased. The incidence of diseases rebounded differentially by the pandemic phase. For instance, although seasonal influenza dominated respiratory diseases in 2019, it showed a substantial decline during the pandemic (percent change in phase 2 2020: 0.21, 95% CI 0.09-0.50), which persisted until 2021 (percent change in phase 4 2021: 1.02, 95% CI 0.74-1.41). The incidence of gastrointestinal and enterovirus diseases decreased by 33.6% during 2020 but rebounded by 56.9% in 2021, mainly driven by hand, foot, and mouth disease (percent change in phase 3 2021: 1.28, 95% CI 1.17-1.41) and infectious diarrhea (percent change in phase 3 2020: 1.22, 95% CI 1.17-1.28). Sexually transmitted and blood-borne diseases were restrained during the first year of 2021 but rebounded quickly in 2021, mainly driven by syphilis (percent change in phase 3 2020: 1.31, 95% CI 1.23-1.40) and gonorrhea (percent change in phase 3 2020: 1.10, 95% CI 1.05-1.16). Zoonotic diseases were not dampened by the pandemic but continued to increase across the study period, mainly due to brucellosis (percent change in phase 2 2020: 0.94, 95% CI 0.75-1.16). Vector-borne diseases showed a continuous decline during 2020, dominated by hemorrhagic fever (percent change in phase 2 2020: 0.68, 95% CI 0.53-0.87), but rebounded in 2021. CONCLUSIONS: The COVID-19 pandemic was associated with a marked decline in notifiable infectious diseases in Chinese children and adolescents. These effects were not sustained, with evidence of a rebound to prepandemic levels by late 2021. To effectively address the postpandemic resurgence of infectious diseases in children and adolescents, it will be essential to maintain disease surveillance and strengthen the implementation of various initiatives. These include extending immunization programs, prioritizing the management of sexually transmitted infections, continuing feasible nonpharmaceutical intervention projects, and effectively managing imported infections.

Differentiated impacts of short-term exposure to fine particulate constituents on infectious diseases in 507 cities of Chinese children and adolescents: A nationwide time-stratified case-crossover study from 2008 to 2021.

This study assesses the association of short-term exposure to PM2.5 (particles ≤2.5 µm) on infectious diseases among Chinese children and adolescents. Analyzing data from 507 cities (2008-2021) on 42 diseases, it focuses on PM2.5 components (black carbon (BC), ammonium (NH4+), inorganic nitrate (NO3-), organic matter (OM), and sulfate (SO42-)). PM2.5 constituents significantly associated with incidence. Sulfate showed the most substantial effect, increasing all-cause infectious disease risk by 2.72 % per interquartile range (IQR) increase. It was followed by BC (2.04 % increase), OM (1.70 %), NO3- (1.67 %), and NH4+ (0.79 %). Specifically, sulfate and BC had pronounced impacts on respiratory diseases, with sulfate linked to a 10.73 % increase in seasonal influenza risk and NO3- to a 16.39 % rise in tuberculosis. Exposure to PM2.5 also marginally increased risks for gastrointestinal, enterovirus, and vectorborne diseases like dengue (7.46 % increase with SO42-). Sexually transmitted and bloodborne diseases saw an approximate 6.26 % increase in incidence, with specific constituents linked to diseases like hepatitis C and syphilis. The study concludes that managing PM2.5 levels could substantially reduce infectious disease incidence, particularly in China's middle-northern regions. It highlights the necessity of stringent air quality standards and targeted disease prevention, aligning PM2.5 management with international guidelines for public health protection.

Long-term variations of urban-Rural disparities in infectious disease burden of over 8.44 million children, adolescents, and youth in China from 2013 to 2021: An observational study.

BACKGROUND: An accelerated epidemiological transition, spurred by economic development and urbanization, has led to a rapid transformation of the disease spectrum. However, this transition has resulted in a divergent change in the burden of infectious diseases between urban and rural areas. The objective of our study was to evaluate the long-term urban-rural disparities in infectious diseases among children, adolescents, and youths in China, while also examining the specific diseases driving these disparities. METHODS AND FINDINGS: This observational study examined data on 43 notifiable infectious diseases from 8,442,956 cases from individuals aged 4 to 24 years, with 4,487,043 cases in urban areas and 3,955,913 in rural areas. The data from 2013 to 2021 were obtained from China's Notifiable Infectious Disease Surveillance System. The 43 infectious diseases were categorized into 7 categories: vaccine-preventable, bacterial, gastrointestinal and enterovirus, sexually transmitted and bloodborne, vectorborne, zoonotic, and quarantinable diseases. The calculation of infectious disease incidence was stratified by urban and rural areas. We used the index of incidence rate ratio (IRR), calculated by dividing the urban incidence rate by the rural incidence rate for each disease category, to assess the urban-rural disparity. During the nine-year study period, most notifiable infectious diseases in both urban and rural areas exhibited either a decreased or stable pattern. However, a significant and progressively widening urban-rural disparity in notifiable infectious diseases was observed. Children, adolescents, and youths in urban areas experienced a higher average yearly incidence compared to their rural counterparts, with rates of 439 per 100,000 compared to 211 per 100,000, respectively (IRR: 2.078, 95% CI [2.075, 2.081]; p < 0.001). From 2013 to 2021, this disparity was primarily driven by higher incidences of pertussis (IRR: 1.782, 95% CI [1.705, 1.862]; p < 0.001) and seasonal influenza (IRR: 3.213, 95% CI [3.205, 3.220]; p < 0.001) among vaccine-preventable diseases, tuberculosis (IRR: 1.011, 95% CI [1.006, 1.015]; p < 0.001), and scarlet fever (IRR: 2.942, 95% CI [2.918, 2.966]; p < 0.001) among bacterial diseases, infectious diarrhea (IRR: 1.932, 95% CI [1.924, 1.939]; p < 0.001), and hand, foot, and mouth disease (IRR: 2.501, 95% CI [2.491, 2.510]; p < 0.001) among gastrointestinal and enterovirus diseases, dengue (IRR: 11.952, 95% CI [11.313, 12.628]; p < 0.001) among vectorborne diseases, and 4 sexually transmitted and bloodborne diseases (syphilis: IRR 1.743, 95% CI [1.731, 1.755], p < 0.001; gonorrhea: IRR 2.658, 95% CI [2.635, 2.682], p < 0.001; HIV/AIDS: IRR 2.269, 95% CI [2.239, 2.299], p < 0.001; hepatitis C: IRR 1.540, 95% CI [1.506, 1.575], p < 0.001), but was partially offset by lower incidences of most zoonotic and quarantinable diseases in urban areas (for example, brucellosis among zoonotic: IRR 0.516, 95% CI [0.498, 0.534], p < 0.001; hemorrhagic fever among quarantinable: IRR 0.930, 95% CI [0.881, 0.981], p = 0.008). Additionally, the overall urban-rural disparity was particularly pronounced in the middle (IRR: 1.704, 95% CI [1.699, 1.708]; p < 0.001) and northeastern regions (IRR: 1.713, 95% CI [1.700, 1.726]; p < 0.001) of China. A primary limitation of our study is that the incidence was calculated based on annual average population data without accounting for population mobility. CONCLUSIONS: A significant urban-rural disparity in notifiable infectious diseases among children, adolescents, and youths was evident from our study. The burden in urban areas exceeded that in rural areas by more than 2-fold, and this gap appears to be widening, particularly influenced by tuberculosis, scarlet fever, infectious diarrhea, and typhus. These findings underscore the urgent need for interventions to mitigate infectious diseases and address the growing urban-rural disparity.

Association of the external environmental exposome and obesity: A comprehensive nationwide study in 2019 among Chinese children and adolescents.

OBJECTIVE: Children and adolescents are particularly vulnerable to the effects of various environmental factors, which could disrupt growth processes and potentially lead to obesity. Currently, comprehensive and systematic assessments of these environmental exposures during developmental periods are lacking. Therefore, this study aims to evaluate the association between external environmental exposures and the incidence of obesity in children and adolescents. METHODS: Data was collected from the 2019 Chinese National Survey on Students' Constitution and Health, including 214,659 Han children aged 7 to 19. Body Mass Index (BMI) and BMI-for-age z-score (zBMI) were the metrics used to assess overweight and obesity prevalence. The study assessed 18 environmental factors, including air pollutants, natural space, land cover, meteorological conditions, built environment, road conditions, and artificial light at night. Exposome-wide association study (ExWAS) to analyze individual exposures' associations with health outcomes, and Weighted Quantile Sum (WQS) to assess cumulative exposure effects. RESULTS: Among the children and adolescents, there were 24.2 % participants classified as overweight or obesity. Notably, 17 out of 18 environmental factors exhibited significant associations with zBMI and overweight/obesity. Seven air pollutants, road conditions, and built density were positively correlated with higher zBMI and obesity risk, while NDVI, forests, and meteorological factors showed negative correlations. Co-exposure analysis highlighted that SO2, ALAN, PM10, and trunk road density significantly increased zBMI, whereas rainfall, grassland, and forest exposure reduced it. Theoretically reduction in the number and prevalence of cases was calculated, indicating potential reductions in prevalence of up to 4.51 % for positive exposures and 5.09 % for negative exposures. Notably, substantial reductions were observed in regions with high pollution levels. CONCLUSION: This large-scale investigation, encompassing various environmental exposures in schools, highlights the significant impact of air pollution, road characteristics, rainfall, and forest coverage on childhood obesity.

Association of childhood trauma, social support, cognition, and suicidality in females with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a severe mental disorder with heavy disease burden. Females with BD are special populations who suffer a lot from childhood trauma, social support, cognitive deficits, and suicidality. In this study, the relationship among childhood trauma, social support, and clinical symptoms of BD was investigated and the risk factors for suicidality were explored in female patients with BD. METHODS: This study included 57 drug-naive female BD patients, 64 female BD patients with long-term medication, and 50 age-matched female healthy controls. Childhood trauma, social support, clinical symptoms, cognition, and suicidality (suicide ideation, suicide plan, suicide attempt, suicide frequency) were measured with scales. RESULTS: Compared with healthy controls, females with BD showed higher levels of childhood trauma and suicidality, and lower levels of social support and cognitive deficits. In the drug-naïve BD group, social support mediated the relationship between childhood trauma and insomnia symptoms (indirect effect: ab = 0.025). In the BD with long-term medication group, mania symptom was associated with suicide plan (OR = 1.127, p = 0.030), childhood trauma was associated with suicide attempt (OR = 1.088, p = 0.018), and years of education (OR = 0.773, p = 0.028), childhood trauma (OR = 1.059, p = 0.009), and delayed memory (OR= 1.091, p= 0.016) was associated with suicide frequency (OR = 1.091, p = 0.016). CONCLUSIONS: This study provides initial evidence that social support partially explains the relationship between childhood trauma and clinical symptoms in females with BD. Additionally, mania symptoms, childhood trauma, and delayed memory were risk factors for suicidality. Interventions providing social support and improving cognitive function may be beneficial for females with BD who are exposed to childhood trauma and with high suicide risk.

A high-throughput DNA analysis method based on isothermal amplification on a suspension microarray for detecting mpox virus and viruses with comparable symptoms.

BACKGROUND: Mpox is a zoonotic disease caused by mpox virus (MPXV) infection. Since May 2022, there has been a marked increase in human mpox cases in different regions. Rash, fever, and sore throat are typical signs of mpox. However, other viruses, such as the B virus (BV), herpes simplex virus types 1 (HSV-1), herpes simplex virus types 2 (HSV-2), and varicella zoster virus (VZV), can also infect people and cause comparable symptoms. Therefore, clinical symptoms and signs alone make distinguishing MPXV from these viruses difficult. RESULTS: In this study, we combined suspension microarray technology with recombinase-aided amplification technology (RAA) to establish a high-throughput, sensitive, and quantitative method for detecting MPXV and other viruses that can cause similar symptoms. The experimental results confirmed that the technique has outstanding sensitivity, with a minimum detection limit (LOD) of 0.1 fM and a linear range of 0.3 fM to 20 pM, spanning five orders of magnitude. The approach also exhibits exquisite selectivity, as the amplified signal can only be detected when the target virus nucleic acid is present. Additionally, serum recoveries ranging from 80.52% to 119.09% suggest that the detection outcomes are generally considered reliable. Moreover, the time required for detection using this high-throughput method is very short. After DNA extraction, the detection signal amplified by isothermal amplification on the bead array can be obtained in just 1 h. SIGNIFICANCE AND NOVELTY: Our research introduces a new technique that utilizes suspension microarray technology and isothermal amplification to create a high-throughput nucleic acid assay. This innovative method offers multiple benefits compared to current techniques, such as being cost-effective, time-efficient, highly sensitive, and having high throughput capabilities. Furthermore, the assay is applicable not only for detecting MPXV and viruses with similar symptoms, but also for clinical diagnostics, food safety, and environmental monitoring, rendering it an effective tool for screening harmful microorganisms.

ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human ß-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells.

Triclosan induces liver injury in long-life exposed mice via activation of TLR4/NF-κB/NLRP3 pathway.

Triclosan (TCS) is a widely used synthetic, with broad-spectrum antibacterial properties found in both pharmaceuticals and personal care products. More specifically, it is hepatotoxic in rodents and exhibits differential effects in mice and humans. However, the mechanisms underlying TCS-induced liver toxicity have not been elucidated. This study examined the role of the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB)/ nod-like receptor protein 3 (NLRP3) pathway in TCS-exposed liver toxicity by established a long-life TCS-exposed mice liver injury model. The 24 C57BL/6 pregnant mice exposed to TCS (0, 50 and 100 mg/kg) every day during the gestation and nursing period. After weaning, the male mice were left to continue administrate with TCS until 8 weeks of age. Then, mice in each group were sacrificed for investigation. Long-life exposure to TCS resulted in a reduction of body weight in growth mice. TCS exposure caused the increase of serum ALT, AST and ALP. The situation of inflammatory cell infiltration, macrophage recruitment and collagen fiber deposition in TCS-exposed mice liver tissues were performed by histological analysis including hematoxylin-eosin, Masson, Sirius red, and immunohistochemistry staining. Protein expression levels in TLR4/NF-κB/NLRP3 pathway was measured through Western blot, and the NLRP3 inflammasome activation was measured using real-time quantitative PCR (RT-qPCR). The results showed that exposure to TCS elevated TLR4, myeloid differentiation factor 88 (Myd88), TNF receptor associated factor 6 (TRAF6), enhanced NF-κB activation, and affected NLRP3 inflammasome activation in mice liver. Collectively, these findings indicate that long-life exposure to TCS-induced mice by upregulating the TLR4-Myd88-TRAF6 pathway, activating the NF-κB signaling cascade, initiating the NLRP3 inflammasome pathway, and ultimately leading to liver injury, including inflammation, hepatocyte pyroptosis and hepatofibrosis. Henceforth, the TLR4/NF-κB/NLRP3 pathway may now provide a theoretical basis and valuable therapeutic targets for overcoming TCS-induced liver toxicity.

Doping proanthocyanidins into gel/zirconium hybrid hydrogel to reshape the microenvironment of diabetic wounds for healing acceleration.

Infection and chronic inflammation caused by oxidative stress are major challenges in chronic wound healing. Preparing a simple, efficient hydrogel with reactive oxygen-scavenging properties for chronic wound repair is a promising strategy. Herein, we report an injectable, self-repairing hydrogel with antioxidant and antibacterial properties that can be used to regenerate diabetic wounds. Hydrogels are prepared by coordination crosslinking of gelatin (Gel), a natural biopolymer derived from collagen, with Zr4+. Because of the dynamic properties of metal ion coordination bonds and the bactericidal effect of Zr4+, the obtained coordination hydrogels exhibit self-healing, injectable, and antibacterial properties. The plant polyphenol "proanthocyanidins," which has reactive oxygen-scavenging and anti-inflammatory effects, was simultaneously loaded into the coordination hydrogel during cross-linking. We obtained a versatile hydrogel that is easy to prepare, resistant to mechanical irritation, and antioxidant, and antibacterial in vitro. We further demonstrated that the injectable self-healing hydrogels could effectively repair diabetic skin wounds and accelerate collagen deposition and wound healing. This study shows that the multifunctional antioxidant hydrogel has great potential in developing multifunctional biomaterials for chronic wound healing.

Prevalence of Adeno-Associated Virus-9-Neutralizing Antibody in Chinese Patients with Duchenne Muscular Dystrophy.

The delivery of a mini-dystrophin gene to skeletal muscles using recombinant adeno-associated virus serotype (AAV) holds great potential as a gene therapy for Duchenne muscular dystrophy (DMD). However, the presence of anti-AAV-neutralizing antibodies (NAbs) may impede the effectiveness of gene transduction. This study aimed to evaluate the prevalence of anti-AAV9 NAbs in Chinese patients with DMD, and to characterize the target population for an AAV gene therapy. A total of one hundred male patients with DMD were included in this study, and demographic and clinical data were collected. A blood specimen was obtained from each participant for the purpose of evaluating the existence of anti-AAV9 NAbs through a cell-based functional assay conducted at a central laboratory. A NAb titer exceeding 1:4 was considered positive. The positivity rates of anti-AAV9 NAb were compared among different subgroups. The median age of this DMD cohort was 8 years old, ranging from 3 to 15 years of age. Forty-two percent of patients tested positive for anti-AAV9 NAb. Notably, all samples from patients under 4 years of age tested negative, and the positivity rates of anti-AAV9 NAb differed significantly across the three age subgroups (<4 years old, ≥4 years old and <12 years old, and ≥12 years old, χ2 = 7.221, p = 0.023). Further investigation into the living environment revealed a higher positivity rate of anti-AAV9 NAb in rural patients compared with urban patients (χ2 = 3.923, p = 0.048). Moreover, the prevalence in patients from different cities/provinces varied greatly (χ2 = 16.550, p = 0.003). There was no statistically significant difference in the positivity rate of NAb among subgroups of patients with different motor functions (ambulatory or nonambulatory) and different treatment strategies (taking or not taking glucocorticoid). In Chinese DMD patients, the prevalence of anti-AAV9 NAb was found to reach 42%. Moreover, the antibody-positive rate in children <4 years of age was low and revealed notable regional discrepancies.

ZNFX1 promotes AMPK-mediated autophagy against Mycobacterium tuberculosis by stabilizing Prkaa2 mRNA.

Tuberculosis has the highest mortality rate worldwide for a chronic infectious disease caused by a single pathogen. RNA-binding proteins (RBPs) are involved in autophagy - a key defense mechanism against Mycobacterium tuberculosis (M. tuberculosis) infection - by modulating RNA stability and forming intricate regulatory networks. However, the functions of host RBPs during M. tuberculosis infection remain relatively unexplored. Zinc finger NFX1-type containing 1 (ZNFX1), a conserved RBP critically involved in immune deficiency diseases and mycobacterial infections, is significantly upregulated in M. tuberculosis-infected macrophages. Here, we aimed to explore the immunoregulatory functions of ZNFX1 during M. tuberculosis infection. We observed that Znfx1 knockout markedly compromised the multifaceted immune responses mediated by macrophages. This compromise resulted in reduced phagocytosis, suppressed macrophage activation, increased M. tuberculosis burden, progressive lung tissue injury, and chronic inflammation in M. tuberculosis-infected mice. Mechanistic investigations revealed that the absence of ZNFX1 inhibited autophagy, consequently mediating immune suppression. ZNFX1 critically maintained AMPK-regulated autophagic flux by stabilizing protein kinase AMP-activated catalytic subunit alpha 2 mRNA, which encodes a key catalytic α subunit of AMPK, through its zinc finger region. This process contributed to M. tuberculosis growth suppression. These findings reveal a function of ZNFX1 in establishing anti-M. tuberculosis immune responses, enhancing our understanding of the roles of RBPs in tuberculosis immunity and providing a promising approach to bolster antituberculosis immunotherapy.