Prediction model for low bone mass mineral density in type 2 diabetes: an observational cross-sectional study.

PURPOSE: Considering the prevalence of type 2 diabetes (T2D), osteoporosis should be considered a serious complication. However, an effective tool for the assessment of low bone mass mineral density (BMD) in T2D patients is not currently available. Therefore, the aim of our study was to establish a simple-to-use risk assessment tool by exploring risk factors for low BMD in T2D patients. METHODS: This study included 436 patients with a low BMD and 381 patients with a normal BMD. Multiple logistic regression analysis was performed to evaluate risk factors for low BMD in T2D patients. A nomogram was then developed from these results. A receiver operating characteristic (ROC) curve, calibration plot, and goodness-of-fit test were used to validate the nomogram. The clinical utility of the nomogram was also assessed. RESULTS: Multivariate logistic regression indicated that age, sex, education, body mass index (BMI), fasting C-peptide, high-density cholesterol (HDL), alkaline phosphatase (ALP), estimated glomerular filtration rate (eGFR), and type I collagen carboxy terminal peptide (S-CTX) were independent predictors for low BMD in T2D patients. The nomogram was developed from these variables using both the unadjusted area under the curve (AUC) and the bootstrap-corrected AUC (0.828). Calibration plots and the goodness-of-fit test demonstrated that the nomogram was well calibrated. CONCLUSIONS: The nomogram-illustrated model can be used by clinicians to easily predict the risk of low BMD in T2D patients. Our study also revealed that common factors are independent predictors of low BMD risk. Our results provide a new strategy for the prediction, investigation, and facilitation of low BMD in T2D patients.

Risk Prediction Model for Radiation-Induced Dermatitis in Patients with Cervical Carcinoma undergoing Chemoradiotherapy.

PURPOSE: Radiation-induced dermatitis (RD) is a common side effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs). METHODS: Using electronic medical records, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group. A predictive model was constructed to predict the development of RD in patients who underwent concurrent radiotherapy and chemotherapy for cervical cancer. Finally, the model's efficacy was validated using a receiver operating characteristic (ROC) curve. RESULTS: The incidence of radiation dermatitis was 89.5% (560/626) in the entire cohort, 88.6% (388/438) in the training group, and 91.5% (172/188) in the experimental group. The nomogram was established based on the following factors: age, the days between the beginning and conclusion of radiotherapy, the serum albumin (ALB) after chemoradiotherapy, the use of single or multiple drugs for concurrent chemotherapy, and the total dose of afterloading radiotherapy. Internal and external verification indicated that the model had good discriminatory ability. Overall, the model achieved an AUC of .66. CONCLUSIONS: The risk of RD in patients with cervical carcinoma undergoing chemoradiotherapy is high. A risk prediction model can be developed for RD in cervical carcinoma patients undergoing chemoradiotherapy, based on over 5 years of EMR data from a tertiary cancer hospital.

Extendin-4 blockade of T1R2/T1R3 activation improves Pseudomonas aeruginosa-related pneumonia in an animal model of chemically induced diabetes.

OBJECTIVE: Poorly controlled diabetes frequently exacerbates lung infection, thereby complicating treatment strategies. Recent studies have shown that exendin-4 exhibits not only hypoglycemic but also anti-inflammatory properties. This study aimed to explore the role of exendin-4 in lung infection with diabetes, as well as its association with NOD1/NF-κB and the T1R2/T1R3 sweet taste receptor. METHODS: 16HBE human bronchial epithelial cells cultured with 20 mM glucose were stimulated with lipopolysaccharide (LPS) isolated from Pseudomonas aeruginosa (PA). Furthermore, Sprague‒Dawley rats were fed a high-fat diet, followed by intraperitoneal injection of streptozotocin and intratracheal instillation of PA. The levels of TNF-α, IL-1ß and IL-6 were evaluated using ELISAs and RT‒qPCR. The expression of T1R2, T1R3, NOD1 and NF-κB p65 was assayed using western blotting and immunofluorescence staining. Pathological changes in the lungs of the rats were observed using hematoxylin and eosin (H&E) staining. RESULTS: At the same dose of LPS, the 20 mM glucose group produced more proinflammatory cytokines (TNF-α, IL-1ß and IL-6) and had higher levels of T1R2, T1R3, NOD1 and NF-κB p65 than the normal control group (with 5.6 mM glucose). However, preintervention with exendin-4 significantly reduced the levels of the aforementioned proinflammatory cytokines and signaling molecules. Similarly, diabetic rats infected with PA exhibited increased levels of proinflammatory cytokines in their lungs and increased expression of T1R2, T1R3, NOD1 and NF-κB p65, and these effects were reversed by exendin-4. CONCLUSIONS: Diabetic hyperglycemia can exacerbate inflammation during lung infection, promote the increase in NOD1/NF-κB, and promote T1R2/T1R3. Exendin-4 can ameliorate PA-related pneumonia with diabetes and overexpression of NOD1/NF-κB. Additionally, exendin-4 suppresses T1R2/T1R3, potentially through its hypoglycemic effect or through a direct mechanism. The correlation between heightened expression of T1R2/T1R3 and an intensified inflammatory response in lung infection with diabetes requires further investigation.

Differences in the expression of long noncoding RNAs in peripheral blood mononuclear cells indicate potential biomarkers for rheumatoid arthritis.

OBJECTIVE: Long noncoding RNAs (lncRNAs) play an increasingly important role in various autoimmune diseases. We aimed to characterize the expression profiles of lncRNAs in peripheral blood mononuclear cells (PBMCs) from RA patients and to assess the potential of these lncRNAs as RA biomarkers. METHODS: Whole-transcriptome sequencing was used to establish a lncRNA expression profile. A total of 155 RA patients, 145 healthy controls, 59 systemic lupus erythematosus (SLE) patients and 59 primary Sjögren's syndrome (pSS) patients were recruited for this study. Four candidate lncRNAs (linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7) were validated via qRT-PCR in independent samples, and their expression, association with RA clinical features and value as RA biomarkers were evaluated. RESULTS: Linc00152 and lnc-ADM-1 exhibited upregulated expression (p = 0.001, p = 0.014, respectively), while ITSN1-2 and lnc-FTH1-7 exhibited downregulated expression (both p < 0.001, respectively) in RA patients compared to controls. Lnc-ADM-1 and lnc-FTH1-7 expression correlated positively with the C4 level (p = 0.016 and p = 0.012, respectively). ITSN1-2 levels were negatively associated with CRP levels (p = 0.024). Linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7 showed potential as RA biomarkers, with the four-lncRNA panel distinguishing RA patients from controls, SLE patients, or pSS patients (AUC = 0.886, 0.746, and 0.749, respectively). CONCLUSION: The altered expression of linc00152, lnc-ADM-1, ITSN1-2 and lnc-FTH1-7 in RA patients suggested that these genes may serve as potential biomarkers for RA and could be involved in its pathogenesis.

Spinal cord stimulation for postural abnormalities in Parkinson's disease: 1-year prospective pilot study.

BACKGROUND: Postural abnormalities (PA) are common in the advanced stages of Parkinson's disease (PD), but effective therapies are lacking. A few studies suggested that spinal cord stimulation (SCS) could be a potential therapy whereas its effect is still uncertain. We aimed to investigate whether SCS had potential for benefiting PD patients with PA. METHODS: T8-12 SCS was operated on six PD patients with PA and all patients were followed for one year. Evaluations were made before and after SCS. Moreover, three patients were tested separately with SCS on-state and off-state to confirm the efficacy of SCS. RESULTS: Improvements in lateral trunk flexion degree, anterior thoracolumbar flexion degree and motor function were found after SCS. The improvements diminished while SCS was turned off. CONCLUSIONS: Lower thoracic SCS may be effective for improving PA in PD patients, but further studies are needed to confirm this conclusion. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024326, Registered on 6th July 2019; https://www.chictr.org.cn/showproj.aspx?proj=40835 .

Inflammatory bowel disease and allergic diseases: A Mendelian randomization study.

BACKGROUND: Inflammatory bowel disease (IBD) and allergic diseases possess similar genetic backgrounds and pathogenesis. Observational studies have shown a correlation, but the exact direction of cause and effect remains unclear. The aim of this Mendelian randomization (MR) study is to assess bidirectional causality between inflammatory bowel disease and allergic diseases. METHOD: We comprehensively analyzed the causal relationship between inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC) and allergic disease (asthma, Hay fever, and eczema) as a whole, allergic conjunctivitis (AC), atopic dermatitis (AD), allergic asthma (AAS), and allergic rhinitis (AR) by performing a bidirectional Mendelian randomization study using summary-level data from genome-wide association studies. The analysis results mainly came from the random-effects model of inverse variance weighted (IVW-RE). In addition, multivariate Mendelian randomization (MVMR) analysis was conducted to adjust the effect of body mass index (BMI) on the instrumental variables. RESULTS: The IVW-RE method revealed that IBD genetically increased the risk of allergic disease as a whole (OR = 1.03, 95% CI = 1.01-1.04, fdr.p = .015), AC (OR = 1.04, 95% CI = 1.01-1.06, fdr.p = .011), and AD (OR = 1.06, 95% CI = 1.02-1.09, fdr.p = .004). Subgroup analysis further confirmed that CD increased the risk of allergic disease as a whole (OR = 1.02, 95% CI = 1.00-1.03, fdr.p = .031), AC (OR = 1.03, 95% CI = 1.01-1.05, fdr.p = .012), AD (OR = 1.06, 95% CI = 1.02-1.09, fdr.p = 2E-05), AAS (OR = 1.05, 95% CI = 1.02-1.08, fdr.p = .002) and AR (OR = 1.03, 95% CI = 1.00-1.07, fdr.p = .025), UC increased the risk of AAS (OR = 1.02, 95% CI = 0.98-1.07, fdr.p = .038). MVMR results showed that after taking BMI as secondary exposure, the causal effects of IBD on AC, IBD on AD, CD on allergic disease as a whole, CD on AC, CD on AD, CD on AAS, and CD on AR were still statistically significant. No significant association was observed in the reverse MR analysis. CONCLUSION: This Mendelian randomized study demonstrated that IBD is a risk factor for allergic diseases, which is largely attributed to its subtype CD increasing the risk of AC, AD, ASS, and AR. Further investigations are needed to explore the causal relationship between allergic diseases and IBD.

Patterns and socioeconomic differences in secondhand exposure to cigarettes, e-cigarettes, and heated tobacco products at home in Hong Kong adolescents.

INTRODUCTION: Smoke or aerosols from cigarettes, e-cigarettes (ECs), or heated tobacco products (HTPs) are harmful. Yet, there is little knowledge about the specific patterns of secondhand tobacco exposure by source within household settings and the socioeconomic status (SES) differences in adolescents. METHODS: We used territory-representative student data from a cross-sectional school-based survey in 2020-2021 to calculate the weighted prevalence of secondhand exposure to cigarettes, e-cigarettes, and HTPs in the past seven days. Parental education and perceived family affluence were used as indicators of socioeconomic status. Generalized linear mixed models were used to analyze associations. RESULTS: Among 22039 participants, 29.8% reported any secondhand tobacco exposure (SH-Any) at home, primarily from cigarettes (27.4%), followed by e-cigarettes (4.0%) and HTPs (0.9%). Tertiary parental education level was associated with lower SH-Any exposure (Adjusted odds ratio, AOR=0.49; 95% CI: 0.45-0.53, p<0.001), fewer exposure days (ß= -0.685, p<0.001), lower exposure to cigarettes (SH-CC) (AOR=0.49; 95% CI: 0.45-0.54, p<0.001) and to e-cigarettes or HTPs (SH-EC/HTP) (AOR=0.57; 95% CI: 0.45-0.71, p<0.001). 'Poor' family affluence was associated with higher exposures [AOR(SH-Any) =1.14; 95% CI: 1.06-1.22, p=0.001; ß(days)=0.160, p<0.001; AOR(SH-CC) =1.15; 95% CI: 1.07-1.24, p<0.001], except for SH-EC/HTP exposure, which was higher in students in an affluent family (AOR =1.66; 95% CI: 1.25-2.21, p<0.001). Significant SES differences in SH-EC/HTP exposure were found only in groups with low parental education level. Dose-response relationships were found between lower SH-Any and SH-CC and higher SES categories (p for trend<0.001). CONCLUSIONS: Adolescents experienced a high prevalence of tobacco smoke exposure at home, primarily from cigarettes. Higher SES was associated with lower tobacco exposure, except for SH-EC/HTP, which was higher among adolescents from affluent families. Additionally, high parental education level was protective against exposure to SH-EC/HTP. Comprehensive control measures to reduce the use of these tobacco products are needed to protect adolescents of diverse socioeconomic backgrounds.

Potential Applications of Blautia wexlerae in the Regulation of Host Metabolism.

Blautia wexlerae (B. wexlerae) is a strong candidate with the potential to become a next-generation probiotics (NGPs) and has recently been shown for the first time to exhibit potential in modulating host metabolic levels and alleviating metabolic diseases. However, the factors affecting the change in abundance of B. wexlerae and the pattern of its abundance change in the associated indications remain to be further investigated. Here, we summarize information from published studies related to B. wexlerae; analyze the effects of food source factors such as prebiotics, probiotics, low protein foods, polyphenols, vitamins, and other factors on the abundance of B. wexlerae; and explore the patterns of changes in the abundance of B. wexlerae in metabolic diseases, neurological diseases, and other diseases. At the same time, the development potential of B. wexlerae was evaluated in the direction of functional foods and special medical foods.

Mechanical Strain Induces and Increases Vesicular Release Monitored by Microfabricated Stretchable Electrodes.

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single-cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events, however, the effects of mechanical force on vesicular release has been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4-ethylenedioxythiophene) conductive ink, which achieved real-time quantitation of strain-induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channel in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines release by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide a revealing insight on the regulatory effects of mechanical stimuli on vesicular exocytosis.

Prevalence and Burden of Multiple Sclerosis in China, 1990-2019: Findings From the Global Burden of Disease Study 2019.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is the leading cause of neurologic disability in young adults, but the burden caused by MS in China is lacking. We aimed to comprehensively describe the prevalence and health loss due to MS by demographic and geographical variables from 1990 to 2019 across China. METHODS: Data were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). We used GBD methodology to systematically analyze the prevalence, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) due to MS by age, sex, and location from 1990 to 2019 in mainland China and its provinces. We also compared the MS burden in China with the world and other Group of 20 (G20) countries. RESULTS: In 2019, 42,571 (95% uncertainty interval [UI] 33,001-53,329) individuals in China had MS, which doubled from 1990. The age-standardized prevalence rate of MS was 2.32 per 100,000 (95% UI 1.78-2.91), which increased by 23.31% (95% UI 20.50-25.89) from 1990, with most of the growth occurring after 2010. There was a positive latitudinal gradient with the increasing prevalence from south to north across China. The total DALYs caused by MS were 71,439 (95% UI 58,360-92,254) in 2019, ranking China third among G20 countries. Most of the MS burden in China derived from premature mortality, with the higher fraction of YLLs than that at the global level and most other G20 countries. From 1990 to 2019, the age-standardized DALY and YLL rate had nonsignificant changes; however, the age-standardized YLD rate substantially increased by 23.33% (95% UI 20.50-25.89). The geographic distribution of MS burden varied at the provincial level in China, with a slight downward trend in the age-standardized DALY rates along with increasing Socio-Demographic Index over the study period. DISCUSSION: Although China has a low risk of MS, the substantial and increasing prevalent cases should not be underestimated. The high burden due to premature death and geographic disparity of MS burden reveals insufficient management of MS in China, highlighting the needs for increased awareness and effective intervention.

Occurrence and combined exposure of phthalate esters in urban soil, surface dust, atmospheric dustfall, and commercial food in the semi-arid industrial city of Lanzhou, Northwest China.

A total of 138 samples including urban soil, surface dust, atmospheric dustfall, and commercial food were collected from the semi-arid industrial city of Lanzhou in Northwest China, and 22 phthalate esters (PAEs) were analyzed in these samples by gas chromatography-mass spectrometry for the pollution characteristics, potential sources, and combined exposure risks of PAEs. The results showed that the total concentration of 22 PAEs (Æ©22PAEs) presented surface dust (4.94 × 104 ng/g) â‰« dustfall (1.56 × 104 ng/g) â‰« food (2.14 × 103 ng/g) â‰« urban soil (533 ng/g). Di-n-butyl phthalate (DNBP), di-isobutyl phthalate, di(2-ethylhexyl) phthalate (DEHP), and di-isononyl phthalate/di-isodecyl phthalate were predominant in the environmental media and commercial food, being controlled by priority (52.1%-65.5%) and non-priority (62.1%) PAEs, respectively. Elevated Æ©22PAEs in the urban soil and surface dust was found in the west, middle, and east of Lanzhou. Principal component analysis indicated that PAEs the urban soil and surface dust were related with the emissions of products containing PAEs, atmosphere depositions, and traffic and industrial emissions. PAEs in the foods were associated with the growth and processing environment. The health risk assessment of United States Environmental Protection Agency based on the Chinese population exposure parameters indicated that the total exposure dose of 22 PAEs was from 0.111 to 0.226 mg/kg/day, which were above the reference dose (0.02 mg/kg/day) and tolerable daily intake (TDI, 0.05 mg/kg/day) for DEHP (0.0333-0.0631 mg/kg/day), and TDI (0.01 mg/kg/day) for DNBP (0.0213-0.0405 mg/kg/day), implying that the exposure of PAEs via multi-media should not be ignored; the total non-carcinogenic risk of six priority PAEs was below 1 for the three environmental media (1.21 × 10-5-2.90 × 10-3), while close to 1 for food (4.74 × 10-1-8.76 × 10-1), suggesting a potential non-carcinogenic risk of human exposure to PAEs in food; the total carcinogenic risk of BBP and DEHP was below 1 × 10-6 for the three environmental media (9.13 × 10-10-5.72 × 10-7), while above 1 × 10-4 for DEHP in food (1.02 × 10-4), suggesting a significantly carcinogenic risk of human exposure to DEHP in food. The current research results can provide certain supports for pollution and risk prevention of PAEs.

Adjoint Algorithm Design of Selective Mode Reflecting Metastructure for BAL Applications.

Broad-area lasers (BALs) have found applications in a variety of crucial fields on account of their high output power and high energy transfer efficiency. However, they suffer from poor spatial beam quality due to multi-mode behavior along the waveguide transverse direction. In this paper, we propose a novel metasurface waveguide structure acting as a transverse mode selective back-reflector for BALs. In order to effectively inverse design such a structure, a digital adjoint algorithm is introduced to adapt the considerably large design area and the high degree of freedom. As a proof of the concept, a device structure with a design area of 40 × 20 µm2 is investigated. The simulation results exhibit high fundamental mode reflection (above 90%), while higher-order transverse mode reflections are suppressed below 0.2%. This is, to our knowledge, the largest device structure designed based on the inverse method. We exploited such a device and the method and further investigated the device's robustness and feasibility of the inverse method. The results are elaborately discussed.

Urban-rural differences in the association between occupational physical activity and mortality in Chinese working population: evidence from a nationwide cohort study.

Background: Despite emerging studies suggesting that occupational physical activity (OPA) might be harmful to health, the available evidence is not definitive. Most of these research studies were conducted in high-income Western countries or in urbanized setting. In China, where over one-third of the population resides in rural area, the impact of OPA on health is not well understood. The goal of this study is to investigate how the association between OPA and mortality vary by urban-rural settings. Methods: Baseline data on OPA was gathered using the Global Physical Activity Questionnaire from 30,650 urban and 49,674 rural working adults as part of the 2013-2014 China Chronic Disease and Risk Factor Surveillance. Participants were followed for a median of 6.2 years, and death records were retrieved from the National Mortality Surveillance System until December 31, 2019. The multivariable Cox proportional hazard model was used to examine urban-rural differences in the association between OPA and all-cause and cardiovascular disease (CVD) mortality. Subgroup analyses were performed by sex, socioeconomic status, leisure time, transportation, and non-occupational physical activity. Findings: During the study period, 1342 deaths were recorded, of which 426 were caused by CVD. In rural area, working adults engaging in occupational moderate-to-vigorous physical activity (MVPA) for ≥40 h per week, compared to those without any, had an adjusted hazard ratio of 0.60 (95% CI: 0.49-0.73) for all-cause mortality and 0.55 (95% CI: 0.37-0.83) for CVD mortality. However, no significant association was found in urban area (0.84 [0.61-1.15] for all-cause mortality, Pinteraction = 0.036; and 0.94 [0.53-1.66] for CVD mortality, Pinteraction = 0.098). The negative associations of occupational MVPA with mortality were more pronounced in women, non-smokers, and those with less non-occupational physical activities. Hypertension, heart rate, and diabetes were important contributors to the relationship between occupational MVPA and mortality. Interpretation: The findings from the current study did not support the notion that high levels of OPA would induce harm. On the contrary, in rural setting, higher levels of OPA were associated with lower mortality risks. Furthermore, the observed urban-rural differences in the association between OPA and mortality underscored the need for context-specific public health guidelines on physical activities. Funding: R&D Program of Beijing Municipal Education Commission (KM202210025026),National Key Research and Development Program of China (2021YFC2500201), and Young Elite Scientist Sponsorship Program by BAST (BYESS2023385).

The impact of general anesthesia on the outcomes of preterm infants with gestational age less than 32 weeks delivered via cesarean section.

Background: Recent advancements in China's perinatal and neonatal intensive care have significantly reduced neonatal mortality, yet preterm births before 32 weeks remain the primary cause of neonatal fatalities and contribute to long-term disabilities. The prognosis of very preterm infants (VPIs) is significantly affected by factors including the intrauterine environment, delivery method and neonatal intensive care. Cesarean section which often used for preterm births has implications that are not fully understood, particularly concerning the type of anesthesia used. This study examines the impact of general anesthesia (GA) during cesarean delivery on VPI outcomes, aiming to identify strategies for mitigating GA-associated risks. Methods: This cohort study analyzed 1,029 VPIs born via cesarean section under 32 weeks' gestation at our single-center from 1 January 2018, to 31 December 2022. Detailed medical records, encompassing perioperative information, maternal data and neonatal outcomes were meticulously examined. The primary aim of this investigation was to compare maternal characteristics and neonatal outcomes between VPIs delivered under GA and neuraxial anesthesia (NA). A significance level of p < 0.05 was established. Results: Of the 1,029 VPIs analyzed, 87.95% (n = 905) were delivered via NA and 12.05% (n = 124) via GA. Mothers with hypertensive pregnancy diseases and emergency operations were more inclined to choose GA. VPIs delivered under GA showed a lower Apgar score at one and 5 minutes (p < 0.01), increased need for tracheal intubation resuscitation (32.2% vs. 12.2%, p < 0.01) and a greater incidence of severe neurological injury (SNI) (14.5% vs. 5%, p < 0.01). Multivariable analysis revealed GA was significantly associated with lower Apgar scores at one (OR 6.321, 95% CI 3.729-10.714; p < 0.01) and 5 minutes (OR 4.535, 95% CI 2.975-6.913; p < 0.01), higher risk of tracheal intubation resuscitation (OR = 3.133, 95% CI = 1.939-5.061; p < 0.01) and SNI (OR = 3.019, 95% CI = 1.615-5.643; p < 0.01). Furthermore, for VPIs delivered under GA, a prolonged interval from skin incision to fetus delivery was associated with a lower 5-min Apgar score (p < 0.01). Conclusion: This study revealed the significant impact of GA on adverse outcomes among VPIs. In cases when GA is required, proactive measures should be instituted for the care of VPIs such as expediting the interval from skin incision to fetal delivery.

DGK5 phosphorylation finetunes PA homeostasis in plant immunity.

Phosphatidic acid (PA) as a universal second messenger is transiently and rapidly produced upon immune activation in plants. A recent study by Kong et al. elucidated a mechanism for maintaining PA homeostasis via two uncoupled phosphorylation events of DIACYLGLYCEROL KINASE 5 (DGK5) at different phosphorylation sites by two distinct kinases.

Silicon Vacancies Diamond/Silk/PVA Hierarchical Physical Unclonable Functions for Multi-Level Encryption.

Physical unclonable functions (PUFs) have emerged as a promising encryption technology, utilizing intrinsic physical identifiers that offer enhanced security and tamper resistance. Multi-level PUFs boost system complexity, thereby improving system reliability and fault tolerance. However, crosstalk-free multi-level PUFs remain a persistent challenge. In this study, a hierarchical PUF system that harnesses the spontaneous phase separation of silk fibroin /PVA blend and the random distribution of silicon-vacancy diamonds within the blend is presented. The thermodynamic instability of phase separation and inherent unpredictability of diamond dispersion gives rise to intricate random patterns at two distinct scales, enabling time-efficient hierarchical authentication for cryptographic keys. These patterns are complementary yet independent, inherently resistant to replication and damage thus affording robust security and reliability to the proposed system. Furthermore, customized authentication algorithms are constructed: visual PUFs authentication utilizes neural network combined structural similarity index measure, while spectral PUFs authentication employs Hamming distance and cross-correlation bit operation. This hierarchical PUF system attains a high recognition rate without interscale crosstalk. Additionally, the coding capacity is exponentially enhanced using M-ary encoding to reinforce multi-level encryption. Hierarchical PUFs hold significant potential for immediate application, offering unprecedented data protection and cryptographic key authentication capabilities.

Exercise training decreases lactylation and prevents myocardial ischemia-reperfusion injury by inhibiting YTHDF2.

Exercise improves cardiac function and metabolism. Although long-term exercise leads to circulating and micro-environmental metabolic changes, the effect of exercise on protein post-translational lactylation modifications as well as its functional relevance is unclear. Here, we report that lactate can regulate cardiomyocyte changes by improving protein lactylation levels and elevating intracellular N6-methyladenosine RNA-binding protein YTHDF2. The intrinsic disorder region of YTHDF2 but not the RNA m6A-binding activity is indispensable for its regulatory function in influencing cardiomyocyte cell size changes and oxygen glucose deprivation/re-oxygenation (OGD/R)-stimulated apoptosis via upregulating Ras GTPase-activating protein-binding protein 1 (G3BP1). Downregulation of YTHDF2 is required for exercise-induced physiological cardiac hypertrophy. Moreover, myocardial YTHDF2 inhibition alleviated ischemia/reperfusion-induced acute injury and pathological remodeling. Our results here link lactate and lactylation modifications with RNA m6A reader YTHDF2 and highlight the physiological importance of this innovative post-transcriptional intrinsic regulation mechanism of cardiomyocyte responses to exercise. Decreasing lactylation or inhibiting YTHDF2/G3BP1 might represent a promising therapeutic strategy for cardiac diseases.

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B-cell activating factor (BAFF), a critical regulator of B cells, is involved in various autoimmune diseases. Inflammatory bowel disease (IBD) is a group of chronic and recurrent intestinal inflammatory disorders with unclear etiology, and its global incidence has been increasing in recent years. Abnormal immune responses triggered by multiple factors are closely related to the pathogenesis of IBD. Previous studies have confirmed the association of B-cell abnormal activation and increased production of autoantibodies with the development of ulcerative colitis. However, the involvement of BAFF in the mechanisms of IBD remains unclear. This review summarizes the potential role of BAFF in the pathogenesis of IBD and provides an overview of targeted therapies on BAFF in IBD, aiming to contribute insights for targeted treatments of IBD.

Causal effects of PM2.5 exposure on neuropsychiatric disorders and the mediation via gut microbiota: A Mendelian randomization study.

BACKGROUND: Growing evidence has revealed the impacts of exposure to fine particulate matter (PM2.5) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies. METHODS: This study aimed to examine the causal effects of exposure to PM2.5 on 4 major neuropsychiatric disorders (number of cases = 18,381 for autism spectrum disorder [ASD], 38,691 for attention deficit hyperactivity disorder [ADHD], 67,390 for schizophrenia, and 21,982 cases for Alzheimer's disease [AD]), and the mediation pathway through gut microbiota. Two-sample Mendelian randomization (MR) analyses were performed, in which genetic instruments were identified from genome-wide association studies (GWASs). The included GWASs were available from (1) MRC Integrative Epidemiology Unit (MRC-IEU) for PM2.5, PMcoarse, PM10, and NOX; (2) the Psychiatric Genomics Consortium (PGC) for ASD, ADHD, and schizophrenia; (3) MRC-IEU for AD; and (4) MiBioGen for gut microbiota. Multivariable MR analyses were conducted to adjust for exposure to NOX, PMcoarse, and PM10. We also examined the mediation effects of gut microbiota in the associations between PM2.5 exposure levels and neuropsychiatric disorders, using two-step MR analyses. RESULTS: Each 1 standard deviation (1.06 ug/m3) increment in PM2.5 concentrations was associated with elevated risk of ASD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.00-2.02), ADHD (1.51, 1.15-1.98), schizophrenia (1.47, 1.15-1.87), and AD (1.57, 1.16-2.12). For all the 4 neurodevelopmental disorders, the results were robust under various sensitivity analyses, while the MR-Egger method yielded non-significant outcomes. The associations remained significant for all the 4 neuropsychiatric disorders after adjusting for PMcoarse, while non-significant after adjusting for NOX and PM10. The effects of PM2.5 exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%. CONCLUSIONS: This study suggested that exposure to PM2.5 would increase the risk of neuropsychiatric disorders, partially by influencing the profile of gut microbiota. Comprehensive regulations on air pollutants are needed to help prevent neuropsychiatric disorders.