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Background Inflammatory bowel disease (IBD) is a chronic and relapsing gastrointestinal disorder whose global disease burden continues to rise, making it a significant public health issue. In recent years, rapid socioeconomic development in East Asia has led to notable changes in lifestyle and dietary patterns, accompanied by dynamic shifts in the epidemiological characteristics of IBD. However, there remains a lack of systematic comparison and analysis of the long-term disease burden and evolutionary trends of IBD across five East Asian countries and regions: China, Japan, South Korea, North Korea, and Mongolia. Based on data from The Global Burden of Disease Study 2021 (GBD 2021), this study aims to comprehensively describe the trends in incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of IBD in The region from 1990 to 2021, thereby providing a basis for differentiated prevention and control strategies. Methods Descriptive analysis, Joinpoint regression, and age–period–cohort (APC) modeling were employed to examine epidemiological patterns and trends. Results Significant variations in IBD burden were observed across the region. China and South Korea experienced the most rapid increases in incidence and prevalence, exhibiting a profile of “high morbidity and low disability.” Japan demonstrated a stabilizing disease burden alongside a continuing decline in standardized mortality rates, reflecting its advanced healthcare system. North Korea and Mongolia currently have a relatively low overall burden; however, a notable rise in incidence among young Mongolians suggests an emerging risk of early-onset IBD. APC analysis further indicated complex influences from environmental factors, healthcare resource allocation, and lifestyle changes such as Westernized diets. The study proposes tailored prevention strategies: high-SDI countries should optimize geriatric care systems, medium-SDI countries should enhance preventive interventions for adolescents, and low-SDI countries should prioritize the establishment of primary screening networks. Conclusion These findings provide a scientific basis for differentiated IBD prevention and control in East Asia and contribute to a deeper understanding of the epidemiological transition of chronic diseases.

Lactate, a metabolite which is elevated in various developmental and pathological processes, exerts its signal through alanyl tRNA synthetases (AARS)-catalyzed protein lactylation. Herein, we report that elevated lactate and gain-of-function mitochondrial AARS ( AARS2 ) mutations-induced hyper-lactylation promotes premature ovarian insufficiency (POI). Serum lactate is elevated in POI patients. POI-driving AARS2 mutations gain lactyltransferase activity. AARS2 lactylates and inactivates carnitine palmitoyl transferase 2 (CPT2), resulting in FFA accumulation that activates peroxisome proliferator-activated receptor γ (PPARγ), and potentiates follicle-stimulating hormone (FSH) to initiate follicle development. These, in synergy with the anabolites accumulation effects of AARS2, promoted lactylation-induced PDHA1 inactivation promote granular cell (GC) proliferation and primordial follicle development. GC-specific AARS2 overexpression does not affect primordial follicle number but speed up follicle depletion. AARS2 ablation or lactylation-inhibiting β-alanine treatments can prevent folliculogenesis and POI traits in mouse. These findings reveal that lactate signal drives follicle development, and inhibiting lactate signal could treat/prevent POI.

Snf5 (sucrose nonfermenting) is a core component of the SWI/SNF complexes and regulates diverse cellular processes in model eukaryotes. In plant pathogenic fungi, its biological function and underlying mechanisms remain unexplored. In this study, we investigated the biological roles of MoSnf5 in plant infection and fungal development in the rice blast pathogen Magnaporthe oryzae. The gene deletion mutants of MoSNF5 exhibited slower vegetative hyphal growth, severe defects in conidiogenesis, and impaired virulence and galactose utilization capacities. Domain dissection assays showed that the Snf5 domain and the N- and C-termini of MoSnf5 were all required for its full functions. Co-immunoprecipitation and yeast two-hybrid assays showed that MoSnf5 physically interacts with four proteins, including a transcription initiation factor MoTaf14. Interestingly, the ∆MoTaf14 mutants showed similar phenotypes as the ∆Mosnf5 mutants on fungal virulence and development. Moreover, assays on GFP-MoAtg8 expression and localization showed that both the ∆Mosnf5 and ∆MoTaf14 mutants were defective in autophagy. Taken together, MoSnf5 regulates fungal virulence, growth, and conidiation, possibly through regulating galactose utilization and autophagy in M. oryzae.

This study aims to analyze the endoscopic and pathological characteristics of colorectal laterally spreading tumors (LSTs) to assist malignant risk stratification to inform selection of the appropriate treatment strategy. Patients with colorectal LST were selected as retrospective study objects. Characteristics, including endoscopic findings and the most common site of LSTs of different diameters and histological types, were analyzed. The risk factors for malignancy in colorectal LST were explored by multivariate logistic regression analysis. LSTs with diameters of ≥20 mm were found mainly in the rectum and mainly with granular-mixed (G-M) morphology (36% and 44.6%, respectively; < 0.05), while LSTs with diameters of <20 mm were found mainly in the ascending colon and mainly with granular-homogenous (G-H) morphology (40.9% and 46.2%, respectively; p < 0.05). Adenoma was the main histological type in patients with tumors of all diameters. However, the cancerization rate of LSTs was 31% in patients with tumor diameter ≥20 mm, while there was no invasive cancer in patients with tumor diameter < 20 mm. In the low-grade dysphasia (adenoma) group, most of the lesions were located in the ascending colon and most had the morphology LST-G-H (35.8% and 39.2%, respectively; p < 0.05). In the cancerization group, most of the lesions were located in the rectum, with the morphology LST-G-M (51.6% and 67.2%, respectively; p < 0.05), and the diameter was larger than that of the adenoma group (33.84 ± 17.99 mm vs 21.68 ± 8.99 mm). The rectum was the most common site for an LST with a diameter ≥20 mm and cancerization, of which the morphology was mainly LST-G-M (endoscopic submucosal dissection is the preferred treatment for this type of LST). LST malignancy was found to be correlated with lesion diameter, location, and morphological appearance.

The standardization of the online government service platform is of great significance to simplify the procedures and improve the efficiency of administrative licensing agencies. In this paper, the definition of online government service platform, from the law, policy background, the practice level, carry out the work of government services online analysis summarizes the necessity, the role of online government service platform and the existing problems, and analysis the reasons from the dimension of standardization, standardization can be targeted to summarize proposed online government service platform construction of three aspects of the role.

Hyperpolarization-activated currents (Ih) mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels modulate excitability of myelinated A- and Ah-type visceral ganglion neurons (VGN). Whether alterations in Ih underlie the previously reported reduction of excitability of myelinated Ah-type VGNs following ovariectomy (OVX) has remained unclear. Here we used the intact nodose ganglion preparation in conjunction with electrophysiological approaches to examine the role of Ih remodeling in altering Ah-type neuron excitability following ovariectomy in adult rats. Ah-type neurons were identified based on their afferent conduction velocity. Ah-type neurons in nodose ganglia from non-OVX rats exhibited a voltage 'sag' as well as 'rebound' action potentials immediately following hyperpolarizing current injections, which both were suppressed by the Ih blocker ZD7288. Repetitive spike activity induced afterhyperpolarizations lasting several hundreds of milliseconds (termed post-excitatory membrane hyperpolarizations, PEMHs), which were significantly reduced by ZD7288, suggesting that they resulted from transient deactivation of Ih during the preceding spike trains. Ovariectomy reduced whole-cell Ih density, caused a hyperpolarizing shift of the voltage-dependence of Ih activation, and slowed Ih activation. OVX-induced Ih remodeling was accompanied by a flattening of the stimulus frequency/response curve and loss of PEMHs. Also, HCN1 mRNA levels were reduced by ∼30% in nodose ganglia from OVX rats compared with their non-OVX counterparts. Acute exposure of nodose ganglia to 17beta-estradiol partly restored Ih density and accelerated Ih activation in Ah-type cells. In conclusion, Ih plays a significant role in modulating the excitability of myelinated Ah-type VGNs in adult female rats.

As a major contributor to neonatal death and neurological sequelae, hypoxic-ischemic encephalopathy (HIE) lacks a viable medication for treatment. Oxidative stress induced by hypoxic-ischemic brain damage (HIBD) predisposes neurons to ferroptosis due to the fact that neonates accumulate high levels of polyunsaturated fatty acids for their brain developmental needs but their antioxidant capacity is immature. Ferroptosis is a form of cell death caused by excessive accumulation of iron-dependent lipid peroxidation and is closely associated with mitochondria. Mitophagy is a type of mitochondrial quality control mechanism that degrades damaged mitochondria and maintains cellular homeostasis. In this study we employed mitophagy agonists and inhibitors to explore the mechanisms by which mitophagy exerted ferroptosis resistance in a neonatal rat HIE model. Seven-days-old neonatal rats were subjected to ligation of the right common carotid artery, followed by exposure to hypoxia for 2 h. The neonatal rats were treated with a mitophagy activator Tat-SPK2 peptide (0.5, 1 mg/kg, i.p.) 1 h before hypoxia, or in combination with mitochondrial division inhibitor-1 (Mdivi-1, 20 mg/kg, i.p.), and ferroptosis inhibitor Ferrostatin-1 (Fer-1) (2 mg/kg, i.p.) at the end of the hypoxia period. The regulation of ferroptosis by mitophagy was also investigated in primary cortical neurons or PC12 cells in vitro subjected to 4 or 6 h of OGD followed by 24 h of reperfusion. We showed that HIBD induced mitochondrial damage, ROS overproduction, intracellular iron accumulation, lipid peroxidation and ferroptosis, which were significantly reduced by the pretreatment with Tat-SPK2 peptide, and aggravated by the treatment with Mdivi-1 or BNIP3 knockdown. Ferroptosis inhibitors Fer-1 and deferoxamine B (DFO) reversed the accumulation of iron and lipid peroxides caused by Mdivi-1, hence reducing ferroptosis triggered by HI. We demonstrated that Tat-SPK2 peptide-activated BNIP3-mediated mitophagy did not alleviate neuronal ferroptosis through the GPX4-GSH pathway. BNIP3-mediated mitophagy drove the P62-KEAP1-NRF2 pathway, which conferred ferroptosis resistance by maintaining iron and redox homeostasis via the regulation of FTH1, HO-1, and DHODH/FSP1-CoQ10-NADH. This study may provide a new perspective and a therapeutic drug for the treatment of neonatal HIE.

Numerical simulation processes in scientific and engineering applications require efficient solutions of large sparse linear systems, and variants of Krylov subspace solvers with various preconditioning techniques have been developed. However, it is time-consuming for practitioners with trial and error to find a high-performance Krylov solver in a candidate solver set for a given linear system. Therefore, it is instructive to select an efficient solver intelligently among a solver set rather than exploratory application of all solvers to solve the linear system. One promising direction of solver selection is to apply machine learning methods to construct a mapping from the matrix features to the candidate solvers. However, the computation of some matrix features is quite difficult. In this paper, we design a new selection strategy of matrix features to reduce computing cost, and then employ the selected features to construct a machine learning classifier to predict an appropriate solver for a given linear system. Numerical experiments on two attractive GMRES-type solvers for solving linear systems from the University of Florida Sparse Matrix Collection and Matrix Market verify the efficiency of our strategy, not only reducing the computing time for obtaining features and construction time of classifier but also keeping more than 90% prediction accuracy.