The potential association between metabolic disorders and pulmonary tuberculosis: a Mendelian randomization study.

BACKGROUND: Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. METHOD: Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene-exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. RESULTS: According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484-5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140-14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269-5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028-0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040-1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035-1.841, P = 0.028) were directly correlated with the occurrence of PTB. CONCLUSIONS: This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.

Stabilizing High-Voltage Performance of Nickel-Rich Cathodes via Facile Solvothermally Synthesized Niobium-Doped Strontium Titanate.

Ni-rich layered ternary cathodes are promising candidates thanks to their low toxic Co-content and high energy density (∼800 Wh/kg). However, a critical challenge in developing Ni-rich cathodes is to improve cyclic stability, especially under high voltage (>4.3 V), which directly affects the performance and lifespan of the battery. In this study, niobium-doped strontium titanate (Nb-STO) is successfully synthesized via a facile solvothermal method and used as a surface modification layer onto the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode. The results exhibited that the Nb-STO modification significantly improved the cycling stability of the cathode material even under high-voltage (4.5 V) operational conditions. In particular, the best sample in our work could provide a high discharge capacity of ∼190 mAh/g after 100 cycles under 1 C with capacity retention over 84% in the voltage range of 3.0-4.5 V, superior to the pristine NCM811 (∼61%) and pure STO modified STO-811-600 (∼76%) samples under the same conditions. The improved electrochemical performance and stability of NCM811 under high voltage should be attributed to not only preventing the dissolution of the transition metals, further reducing the electrolyte's degradation by the end of charge, but also alleviating the internal resistance growth from uncontrollable cathode-electrolyte interface (CEI) evolution. These findings suggest that the as-synthesized STO with an optimized Nb-doping ratio could be a promising candidate for stabilizing Ni-rich cathode materials to facilitate the widespread commercialization of Ni-rich cathodes in modern LIBs.

m6A-methylated Lonp1 drives mitochondrial proteostasis stress to induce testicular pyroptosis upon environmental cadmium exposure.

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.

Adaptive under-sampling strategy for fast imaging in compressive sensing-based atomic force microscopy.

Compressive sensing (CS) can reconstruct the rest information almost without distortion by advanced computational algorithm, which significantly simplifies the process of atomic force microscope (AFM) scanning with high imaging quality. In common CS-AFM, the partial measurements randomly come from the whole region to be measured, which easily leads to detail loss and poor image quality in regions of interest (ROIs). Consequently, important microscopic phenomena are missed probably. In this paper, we developed an adaptive under-sampling strategy for CS-AFM to optimize the process of sampling. Under a certain under-sampling ratio, the weight coefficient of ROIs and regions of base (ROBs) were set to control the distribution of under-sampling points and corresponding measurement matrix. A series of simulations were completed to demonstrate the relationship between the weight coefficient of ROIs and image quality. After that, we verified the effectiveness of the method on our homemade AFM. Through a lot of simulations and experiments, we demonstrated how the proposed method optimized the sampling process of CS-AFM, which speeded up the process of AFM imaging with high quality.

Stabilization of Pd0 by Cu Alloying: Theory-Guided Design of Pd3Cu Electrocatalyst for Anodic Methanol Carbonylation.

Electrocatalytic carbonylation of CO and CH3OH to dimethyl carbonate (DMC) on metallic palladium (Pd) electrode offers a promising strategy for C1 valorization at the anode. However, its broader application is limited by the high working potential and the low DMC selectivity accompanied with severe methanol self-oxidation. Herein, our theoretical analysis of the intermediate adsorption interactions on both Pd0 and Pd4+ surfaces revealed that inevitable reconstruction of Pd surface under strongly oxidative potential diminishes its CO adsorption capacity, thus damaging the DMC formation. Further theoretical modeling indicates that doping Pd with Cu not only stabilizes low-valence Pd in oxidative environments but also lowers the overall energy barrier for DMC formation. Guided by this insight, we developed a facile two-step thermal shock method to prepare PdCu alloy electrocatalysts for DMC. Remarkably, the predicted Pd3Cu demonstrated the highest DMC selectivity among existing Pd-based electrocatalysts, reaching a peaked DMC selectivity of 93 % at 1.0 V versus Ag/AgCl electrode. (Quasi) in situ spectra investigations further confirmed the predicted dual role of Cu dopant in promoting Pd-catalyzed DMC formation.

Dietary sodium acetate and sodium butyrate improve high-carbohydrate diet utilization by regulating gut microbiota, liver lipid metabolism, oxidative stress, and inflammation in largemouth bass (Micropterus salmoides).

BACKGROUND: Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate (HC) diet disrupt the homeostasis of the gut-liver axis in largemouth bass, resulting in decreased intestinal acetate and butyrate level. METHOD: Herein, we had concepted a set of feeding experiment to assess the effects of dietary sodium acetate (SA) and sodium butyrate (SB) on liver health and the intestinal microbiota in largemouth bass fed an HC diet. The experimental design comprised 5 isonitrogenous and isolipidic diets, including LC (9% starch), HC (18% starch), HCSA (18% starch; 2 g/kg SA), HCSB (18% starch; 2 g/kg SB), and HCSASB (18% starch; 1 g/kg SA + 1 g/kg SB). Juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were fed on these diets for 56 d. RESULTS: We found that dietary SA and SB reduced hepatic triglyceride accumulation by activating autophagy (ATG101, LC3B and TFEB), promoting lipolysis (CPT1α, HSL and AMPKα), and inhibiting adipogenesis (FAS, ACCA, SCD1 and PPARγ). In addition, SA and SB decreased oxidative stress in the liver (CAT, GPX1α and SOD1) by activating the Keap1-Nrf2 pathway. Meanwhile, SA and SB alleviated HC-induced inflammation by downregulating the expression of pro-inflammatory factors (IL-1ß, COX2 and Hepcidin1) through the NF-κB pathway. Importantly, SA and SB increased the abundance of bacteria that produced acetic acid and butyrate (Clostridium_sensu_stricto_1). Combined with the KEGG analysis, the results showed that SA and SB enriched carbohydrate metabolism and amino acid metabolism pathways, thereby improving the utilization of carbohydrates. Pearson correlation analysis indicated that growth performance was closely related to hepatic lipid deposition, autophagy, antioxidant capacity, inflammation, and intestinal microbial composition. CONCLUSIONS: In conclusion, dietary SA and SB can reduce hepatic lipid deposition; and alleviate oxidative stress and inflammation in largemouth bass fed on HC diet. These beneficial effects may be due to the altered composition of the gut microbiota caused by SA and SB. The improvement effects of SB were stronger than those associated with SA.

Precirrhotic Primary Biliary Cholangitis with Portal Hypertension: Bile Duct Injury Correlate.

Background/Aims: : The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: : This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: : Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions: : Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Association of prepregnancy body mass index and gestational weight gain trajectory with adverse pregnancy outcomes-a prospective cohort study in Shanghai.

OBJECTIVES: The objective was to investigate the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) trajectories with adverse pregnancy outcomes (APOs). DESIGN: This was a prospective cohort study. SETTING: This study was conducted in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai, China. PRIMARY AND SECONDARY OUTCOME MEASURES: A cohort study involving a total of 2174 pregnant women was conducted. Each participant was followed to record weekly weight gain and pregnancy outcomes. The Institute of Medicine classification was used to categorise prepregnancy BMI, and four GWG trajectories were identified using a latent class growth model. RESULTS: The adjusted ORs for the risks of large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) were significantly greater for women with prepregnancy overweight/obesity (OR=1.77, 2.13, 1.95 and 4.24; 95% CI 1.3 to 2.42, 1.32 to 3.46, 1.43 to 2.66 and 2.01 to 8.93, respectively) and lower for those who were underweight than for those with normal weight (excluding HDP) (OR=0.35, 0.27 and 0.59; 95% CI 0.22 to 0.53, 0.11 to 0.66 and 0.36 to 0.89, respectively). The risk of small for gestational age (SGA) and low birth weight (LBW) was significantly increased in the underweight group (OR=3.11, 2.20; 95% CI 1.63 to 5.92, 1.10 to 4.41; respectively) compared with the normal-weight group; however, the risk did not decrease in the overweight/obese group (p=0.942, 0.697, respectively). GWG was divided into four trajectories, accounting for 16.6%, 41.4%, 31.7% and 10.3% of the participants, respectively. After adjustment for confounding factors, the risk of LGA was 1.54 times greater for women in the slow GWG trajectory group than for those in the extremely slow GWG trajectory group (95% CI 1.07 to 2.21); the risk of SGA and LBW was 0.37 times and 0.46 times lower for women in the moderate GWG trajectory group and 0.14 times and 0.15 times lower for women in the rapid GWG trajectory group, respectively; the risk of macrosomia and LGA was 2.65 times and 2.70 times greater for women in the moderate GWG trajectory group and 3.53 times and 4.36 times greater for women in the rapid GWG trajectory group, respectively; and the women in the other three trajectory groups had a lower risk of GDM than did those in the extremely slow GWG trajectory group, but there was not much variation in the ORs. Notably, different GWG trajectories did not affect the risk of HDP. CONCLUSIONS: As independent risk factors, excessively high and low prepregnancy BMI and GWG can increase the risk of APOs.

Prevalence of antibiotics, antibiotic resistance genes, and their associations in municipal wastewater treatment plants along the Yangtze River basin, China.

The overuse and misuse of antibiotics have resulted in the pollution of antibiotics and antibiotic resistance genes (ARGs) in municipal wastewater treatment plants (WWTPs), posing threats to ecological security and human health. Thus, a comprehensive investigation was conducted to assess the occurrence, removal efficiency, and ecological risk of antibiotics, along with the diversity, abundance, and co-occurrence of ARGs, and their correlations in 13 WWTPs along the Yangtze River Basin. Among 35 target antibiotics, 23 antibiotics within 6 categories were detected in all the samples. Amoxicillin (AMO), ofloxacin (OFL), and pefloxacin (PEF) were predominant in influents, while AMO exhibited dominance with the highest concentration of 1409 ng/L in effluents. Although antibiotic removal performance varied among different WWTPs, a significant decrease in each antibiotic category and overall antibiotics was observed in effluents compared with that in influents (p < 0.05). Remarkably, ecological risk assessment revealed high risks associated with AMO and ciprofloxacin (CIP) and medium risks linked to several antibiotics, notably including OFL, roxithromycin (ROX), clarithromycin (CLA), and tetracycline (TC). Furthermore, 96 ARG subtypes within 12 resistance types were detected in this study, and the total absolute abundance and diversity of ARGs were significantly decreased from influents to effluents (p < 0.05). Enrichment of 38 ARGs (e.g., blaNDM, ermA, vatA, mexA, and dfrA25) in effluents indicated potential health risks. Various mobile genetic elements (MGEs), exhibited significant correlations with a majority of ARGs in both influents and effluents, such as intⅠ1, tnpA1, tnpA5, and tp614, underscoring the important role of MGEs in contributing to the ARG dissemination. Many antibiotics displayed lower correlations with corresponding ARGs, but exhibited higher correlations with other ARGs, suggesting complex selective pressures influencing ARG propagation. Overall, the incomplete elimination of antibiotics and ARGs in WWTPs is likely to pose adverse impacts on aquatic ecosystems in the Yangtze River Basin.

Adaptive Synaptic Scaling in Spiking Networks for Continual Learning and Enhanced Robustness.

Synaptic plasticity plays a critical role in the expression power of brain neural networks. Among diverse plasticity rules, synaptic scaling presents indispensable effects on homeostasis maintenance and synaptic strength regulation. In the current modeling of brain-inspired spiking neural networks (SNN), backpropagation through time is widely adopted because it can achieve high performance using a small number of time steps. Nevertheless, the synaptic scaling mechanism has not yet been well touched. In this work, we propose an experience-dependent adaptive synaptic scaling mechanism (AS-SNN) for spiking neural networks. The learning process has two stages: First, in the forward path, adaptive short-term potentiation or depression is triggered for each synapse according to afferent stimuli intensity accumulated by presynaptic historical neural activities. Second, in the backward path, long-term consolidation is executed through gradient signals regulated by the corresponding scaling factor. This mechanism shapes the pattern selectivity of synapses and the information transfer they mediate. We theoretically prove that the proposed adaptive synaptic scaling function follows a contraction map and finally converges to an expected fixed point, in accordance with state-of-the-art results in three tasks on perturbation resistance, continual learning, and graph learning. Specifically, for the perturbation resistance and continual learning tasks, our approach improves the accuracy on the N-MNIST benchmark over the baseline by 44% and 25%, respectively. An expected firing rate callback and sparse coding can be observed in graph learning. Extensive experiments on ablation study and cost evaluation evidence the effectiveness and efficiency of our nonparametric adaptive scaling method, which demonstrates the great potential of SNN in continual learning and robust learning.

Causal relationship between psychiatric disorders and sensorineural hearing loss: A bidirectional two-sample mendelian randomization analysis.

OBJECTIVE: This study employed bidirectional two-sample Mendelian randomization (MR) to investigate the causal links between psychiatric disorders and sensorineural hearing loss (SNHL). METHODS: Instrumental variables were chosen from genome-wide association studies of schizophrenia (SCH, N = 127,906), bipolar disorder (BD, N = 51,710), major depressive disorder (MDD, N = 500,199), and SNHL (N = 212,544). In the univariable MR analysis, the inverse-variance weighted method (IVW) was conducted as the primary analysis, complemented by various sensitivity analyses to ensure result robustness. RESULTS: SCH exhibited a decreased the risk of SNHL (OR = 0.949, P = 0.005), whereas BD showed an increased incidence of SNHL (OR = 1.145, P = 0.005). No causal association was found for MDD on SNHL (OR = 1.088, P = 0.246). Multivariable MR validated these results. In the reverse direction, genetically predicted SNHL was linked to a decreased risk of SCH with suggestive significance (OR = 0.912, P = 0.023). No reverse causal relationships were observed for SNHL influencing BD or MDD. These findings remained consistent across various MR methods and sensitivity analyses. CONCLUSION: This study demonstrated that the causal relationships between diverse psychiatric disorders with SNHL were heterogeneous. Specifically, SCH was inversely associated with SNHL susceptibility, and similarly, a reduced risk of SNHL was observed in schizophrenia patients. In contrast, BD exhibited an increased incidence of SNHL, although SNHL did not influence the prevalence of BD. No causal association between MDD and SNHL was found.

Change analysis for intermediate disease markers in nutritional epidemiology: a causal inference perspective.

BACKGROUND: Several approaches are commonly used to estimate the effect of diet on changes of various intermediate disease markers in prospective studies, including "change-score analysis", "concurrent change-change analysis" and "lagged change-change analysis". Although empirical evidence suggests that concurrent change-change analysis is most robust, consistent, and biologically plausible, in-depth dissection and comparison of these approaches from a causal inference perspective is lacking. We intend to explicitly elucidate and compare the underlying causal model, causal estimand and interpretation of these approaches, intuitively illustrate it with directed acyclic graph (DAG), and further clarify strengths and limitations of the recommended concurrent change-change analysis through simulations. METHODS: Causal model and DAG are deployed to clarify the causal estimand and interpretation of each approach theoretically. Monte Carlo simulation is used to explore the performance of distinct approaches under different extents of time-invariant heterogeneity and the performance of concurrent change-change analysis when its causal identification assumptions are violated. RESULTS: Concurrent change-change analysis targets the contemporaneous effect of exposure on outcome (measured at the same survey wave), which is more relevant and plausible in studying the associations of diet and intermediate biomarkers in prospective studies, while change-score analysis and lagged change-change analysis target the effect of exposure on outcome after one-period timespan (typically several years). Concurrent change-change analysis always yields unbiased estimates even with severe unobserved time-invariant confounding, while the other two approaches are always biased even without time-invariant heterogeneity. However, concurrent change-change analysis produces almost linearly increasing estimation bias with violation of its causal identification assumptions becoming more serious. CONCLUSIONS: Concurrent change-change analysis might be the most superior method in studying the diet and intermediate biomarkers in prospective studies, which targets the most plausible estimand and circumvents the bias from unobserved individual heterogeneity. Importantly, careful examination of the vital identification assumptions behind it should be underscored before applying this promising method.

Metal Nanoparticles Assisted Ultrafast Laser Plasmonic Microwelding of Oxide-Semiconductor Interconnects.

Integration of wafer-scale oxide and semiconductor materials meets the difficulties of residual stress and materials incompatibility. In this work, Ag NPs thin film is contributed as an energy confinement layer between oxide (Sapphire) and semiconductor (Si) wafers to localize the materials interaction during ultrafast laser irradiation. Due to the plasmonic effects generated within constructed dielectric-metal-dielectric structures (i.e., Sapphire-Ag-Si), thermal diffusion and chemical reaction between Ag and its neighboring materials facilitate the microwelding of Sapphire and Si wafers. Ag NPs can be totally sintered within the junction area to bridge oxide and semiconductor, while Al─O─Ag bond and Ag─Si bond are formed at Ag-Sapphire and Ag─Si interfaces, respectively. As-received heterogeneous joint exhibits a high shear strength up to 5.4 MPa, with the fracture occurring inside Si wafer. Meanwhile, insertion of metal nanolayer can greatly relieve the residual stress-induced microcracking inside the brittle materials. Such wafer-scale Sapphire and Si interconnects thus show robust strength and excellent impermeability even after thermal shocking (-40 °C to 120 °C) for 200 cycles. This metal NPs layer-assisted plasmonic microwelding technology can extend to broad materials integration, which is promising for high-performance microdevices development in MEMS, MOEMS, or microfluidics.

Beyond the Stereotype of Tolerance: Diversified Milieu and Contextual Difference.

We explore whether there are value preferences of creative workers in addition to tolerance and how these value preferences vary among different occupation categories and countries. We use a dataset of 1968 and 1076 observations in China and the U.S., respectively, from the World Values Survey dataset (2017-2020, wave 7) (WVS 7), with a Structure Equation Modelling (SEM) and Multinomial Logit Model (MLM) at the micro level. The findings reveal that (1) the Chinese sample is more likely to have a balanced preference of tolerance towards migrants, religions, and homosexuality, while the American sample's preference of tolerance is much more likely to be interpreted as accepting homosexuality only; (2) the American sample also shows preferences towards responsibility, technology, work style, and political actions, while a preference for happiness and political actions is identified in the Chinese sample; and (3) with a higher level of creativity, the difference regarding understanding of tolerance is more likely to be highlighted between China and the U.S. This study provides a quite unconventional perspective for understanding the composition of preferences and, to a certain extent, reconciles the inconsistency between the theoretical advocacy of building up a selected milieu and the reality of creative workers' blended value mix.

Advancing Spiking Neural Networks Toward Deep Residual Learning.

Despite the rapid progress of neuromorphic computing, inadequate capacity and insufficient representation power of spiking neural networks (SNNs) severely restrict their application scope in practice. Residual learning and shortcuts have been evidenced as an important approach for training deep neural networks, but rarely did previous work assessed their applicability to the specifics of SNNs. In this article, we first identify that this negligence leads to impeded information flow and the accompanying degradation problem in a spiking version of vanilla ResNet. To address this issue, we propose a novel SNN-oriented residual architecture termed MS-ResNet, which establishes membrane-based shortcut pathways, and further proves that the gradient norm equality can be achieved in MS-ResNet by introducing block dynamical isometry theory, which ensures the network can be well-behaved in a depth-insensitive way. Thus, we are able to significantly extend the depth of directly trained SNNs, e.g., up to 482 layers on CIFAR-10 and 104 layers on ImageNet, without observing any slight degradation problem. To validate the effectiveness of MS-ResNet, experiments on both frame-based and neuromorphic datasets are conducted. MS-ResNet104 achieves a superior result of 76.02% accuracy on ImageNet, which is the highest to the best of our knowledge in the domain of directly trained SNNs. Great energy efficiency is also observed, with an average of only one spike per neuron needed to classify an input sample. We believe our powerful and scalable models will provide strong support for further exploration of SNNs.

Fighting with Aging: The Secret for Keeping Health and Longevity of Naked Mole Rats.

Health and longevity are the dreams of mankind and the main field of the medical community. The naked mole rat (NMR) is a unique murine animal with extremely long lives (exceeding 38 years), revealing little signs of aging such as reproductive decline, neural degenerative diseases, and cancer. They provide us with valuable perspectives on preventing age-related diseases. This review systematically summarized the characters of different systems of naked mole rats in aging resistance, and furtherly exploited the mechanisms for aging resistance form genome, telomeres, protein recycling, metabolism, and oxidative stress attitudes. As a species with a high similarity with human beings, it cannot be ruled out that after reasonable validity, safety and ethical evaluation, the dominant genes of naked mole rats will be developed in medical transformation, to realize the dream of human health and longevity.

Sex- and time-specific associations of obesity with glycaemic traits: A two-step multivariate Mendelian randomization study.

AIM: To assess the sex- and time-specific causal effects of obesity-related anthropometric traits on glycaemic traits. MATERIALS AND METHODS: We used univariate and multivariate Mendelian randomization to assess the causal associations of anthropometric traits (gestational variables, birth weight, childhood body mass index [BMI], BMI, waist-to-hip ratio [WHR], BMI-adjusted WHR [WHRadj BMI]) with fasting glucose and insulin in Europeans from the Early Growth Genetics Consortium (n ≤ 298 142), the UK Biobank, the Genetic Investigation of Anthropometric Traits Consortium (n ≤ 697 734; females: n ≤ 434 794; males: n ≤ 374 754) and the Meta-Analyses of Glucose and Insulin-related traits Consortium (n ≤ 151 188; females: n ≤ 73 089; males: n ≤ 67 506), adjusting for maternal genetic effects, smoking, alcohol consumption, and age at menarche. RESULTS: We observed a null association for gestational variables, a negative association for birth weight, and positive associations for childhood BMI and adult traits (BMI, WHR, and WHRadj BMI). In female participants, increased birth weight causally decreased fasting insulin (betaIVW , -0.07, 95% confidence interval [CI] -0.11 to -0.03; p = 1.92 × 10-3 ), but not glucose levels, which was annulled by adjusting for age at menarche. In male participants, increased birth weight causally decreased fasting glucose (betainverse-variance-weighted (IVW) , -0.07, 95% CI -0.11 to -0.03; p = 3.22 × 10-4 ), but not insulin levels. In time-specific analyses, independent effects of birth weight were absent in female participants, and were more pronounced in male participants. Independent effects of childhood BMI were attenuated in both sexes; independent effects of adult traits differed by sex. CONCLUSIONS: Our findings provide evidence for causal and independent effects of sex- and time-specific anthropometric traits on glycaemic variables, and highlight the importance of considering multiple obesity exposures at different time points in the life course.

Forsythia suspensa polyphenols regulate macrophage M1 polarization to alleviate intestinal inflammation in mice.

BACKGROUND: Inflammatory bowel disease (IBD) was a chronic intestinal disease related to autoimmunity, and its pathogenesis was complex. Forsythia suspensa (F. suspensa) had good anti-inflammatory and antioxidant effects. The active component polyphenols had significant effects in the treatment of intestinal inflammation. Researches had found that polarization, pyroptosis and apoptosis of macrophages can drive the occurrence and development of colitis. PURPOSE: In this study, we examined whether F. suspensa polyphenols (FPP) mitigated DSS-induced colitis, and explored its potential mechanisms. METHODS: The potential targets of F. suspensa in intestinal inflammation were predicted through network pharmacology. Using LPS and IFN-γ induced macrophage M1 polarization in J774A.1 cells. Macrophage polarization was detected through RT-qPCR, flow cytometry and ELISA. Ulcerative colitis (UC) in mice was induced by 2.5% DSS for 7 days, and then oral administrated different doses of FPP for another 7 days. Then we assessed the body weight, diarrhea, bleeding in stool, colon length, cytokines of serum and pathology of colon. The effects of FPP on the gut microbiota in mice also tested and evaluated. RESULTS: Our results showed that the main active ingredient of F. suspensa in protecting intestinal inflammation were polyphenols and F. suspensa was multi-targeted in the treatment of intestinal inflammation. FPP inhibited M1 polarization and polarizes towards M2 in J774A.1 cells. FPP inhibited pyroptosis and apoptosis to exert anti-inflammatory effects. FPP had a good protective effect on DSS induced UC in mice. In unison, FPP inhibited M1 polarization, apoptosis, and pyroptosis in UC mice. FPP regulated intestinal homeostasis in mice with UC by improving the gut microbiota and enhancing the intestinal metabolites short-chain fatty acid (SCFAs). CONCLUSIONS: These data indicated that FPP may alleviate UC by inhibiting M1 polarization in mice. Collectively, these findings suggest that the reduction of colitis by FPP may related to macrophage polarization, pyroptosis and apoptosis.

A novel online calculator based on clinical features and hematological parameters to predict total skin clearance in patients with moderate to severe psoriasis.

BACKGROUND: Treatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience partial improvement. OBJECTIVE: This study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response. METHODS: A total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively. RESULTS: The following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670-0.773) and validation cohort (AUC, 0.715; 95% CI 0.665-0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications. CONCLUSIONS: This study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility. Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256 .

Decreased risk of COVID-19 and long COVID in patients with psoriasis receiving IL-23 inhibitor: A cross-sectional cohort study from China.

Background: Although clinical trials and real-world data suggest that the risk of COVID-19 and its complications is not exacerbated in patients with psoriasis treated by biological agents, the evidence for this is still limited. Objectives: We aimed to assess the outcomes of COVID-19 among Chinese patients with psoriasis treated by IL-23 inhibitor, and to compare these variables in patients receiving other therapies. Methods: A cross-sectional cohort study was conducted to compare psoriasis treatment with IL-23 inhibitor to other treatment methods. All the patients received a questionnaire that contained questions about their psoriasis treatment, COVID-19 symptoms, and related risk factors. The prevalence of COVID-19 was calculated, and logistic regression analyses were performed to determine the association between treatment method and COVID-19 risk. The symptoms of COVID-19 and long COVID were described for each treatment group. Results: Between December 2022 and February 2023, 732 patients with psoriasis were included in the final analysis. 549 patients had a SARS-CoV-2 infection during the study period. Our results showed that individuals who worked outdoors had a decreased risk of COVID-19, as did those who had other allergic disease. With regard to the effect of the treatment regimens, IL-23 inhibitor treatment was associated with a decreased risk of COVID-19 compared to almost all the other treatments except acitretin. Fever was the most common symptom, but the maximum temperature and duration of fever were comparable among the treatment groups. Patients treated with IL-23 inhibitor were more likely to be asymptomatic after recovery compared to patients treated with methotrexate, narrow-bound ultra violet B, or TNF-α inhibitor. Conclusions: IL-23 inhibitor treatment may lower the risk of COVID-19 and long COVID. Thus, IL-23 inhibitor treatment might be beneficial and positively considered for patients with psoriasis who require systemic treatment during periods when there is a surge in COVID-19 cases.