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High temperature requirement protein A2 (HtrA2/Omi), a key regulator of mitochondrial quality control, plays a pivotal role in determining cell fate through its subcellular localization, whether mitochondrial or cytosolic. Growing evidence links the absence or dysfunction of HtrA2 to the pathogenesis of neurodegenerative diseases. This review examines the structure and function of HtrA2, highlights its transcriptional regulators, explores its involvement in neurodegeneration, and outlines the currently identified agonists and inhibitors, offering new insights for developing HtrA2/Omi as a potential therapeutic target for neurodegenerative disorders.

Habitat quality (HQ) is of great significance to regional sustainable development, which is a key link for regional ecological security and human welfare. Assessing the temporal and spatial evolution of HQ caused by land-use change could provide a scientific basis for regional ecological protection and land management. Here, based on the ArcGIS platform and the InVEST model, this study quantified the spatial and temporal evolutions of land use, landscape patterns, and HQ from 1985 to 2015, in Taihu Lake Basin (TLB). Hotspot analysis tools were used to identify the spatial agglomeration and evolution characteristics of HQ in TLB. The results showed that, (1) the land use and landscape pattern in TLB experienced dramatic change process during 1985–2015, with the dominating conversion being from farmland to construction land, which led to an increase in landscape heterogeneity and fragmentation. (2) The HQ was generally reduced in the past 30 years. In particular, the decline of HQ was extremely severe in the peripheral area of cities and roads, due to urban sprawl. (3) Regarding the spatial distribution of HQ, the northern and eastern areas were generally higher, while the western and southern areas were generally lower. The hotspots areas were mainly located in the southwestern mountain area and west-central lake area, while the cold spots areas were mainly located in urban areas in the north and the east. (4) The area and degree of habitat degradation were both increased significantly due to land-use change, and the degradation of the Taihu Lake was highlighted. Strengthening the ecological environment management and reducing the threat of urban expansion to the HQ is urgently required. This study could help understand HQ of the TLB and provide a scientific basis for decision-makers.

The cuttlefish, Sepia pharaonis , is characterized by rapid growth and strong disease resistance, making it an important commercially farmed cephalopod species in the southeastern coastal regions of China. However, in the reproductive process of S. pharaonis , there are challenges such as a low output of eggs, poor quality, and low survival rates of newly hatched juveniles. Therefore, there is an urgent need to study the molecular mechanisms underlying ovarian development in this species. In this study, we conducted the first transcriptomic analysis of the ovary at four developmental stages: the undeveloped stage, developing stage, nearly-ripe stage, and ripe stage, and compared the transcriptomics among these four stages using Illumina sequencing technology. The total numbers of clean reads of the four stages ranged from 40,890,772 to 52,055,714 reads. A total of 136,829 DEGs were obtained, GC base ratios of raw data were between 38.44 and 44.59%, and the number of uniquely mapped reads spanned from 88.08 to 95.90%. The Pearson correlation coefficient demonstrated a strong correlation among different samples within the same group, PCA and Anosim analysis also revealed that the grouping of these four stages was feasible, and each stage could be distinguished from the others. GO enrichment analysis demonstrated that ovarian follicle growth, sex differentiation, and transforming growth factor beta receptor, played a foreshadowing role at the early ovarian development stage, and the terms of small molecule metabolic process, peptide metabolic process, and catalytic activity were prominent at the mature stage. Meanwhile, KEGG analysis showed that the early ovarian development of S. pharaonis was mainly associated with the cell cycle, DNA replication, and carbon metabolism, while the mid-late ovarian development was involved with the signal transduction, endocrine system, and reproduction pathway. RT-qPCR further confirmed the consistent expression patterns of genes such as 17β-HSD , GH , VGS , NFR , and NYR in the ovaries of S. pharaonis , exhibiting elevated levels of expression during the maturation stage. Conversely, ER and OM exhibited high expression levels during the early stages of ovarian development. These transcriptomic data provide insights into the molecular mechanisms of S. pharaonis ovarian development. The findings of this study will contribute to improving the reproduction and development of cuttlefish and enriching the bioinformatics knowledge of cephalopods.

Cerebral malaria (CM) is a severe encephalopathy caused by Plasmodium parasite infection, resulting in thousands of annual deaths and neuro-cognitive sequelae even after anti-malarial drugs treatment. Despite efforts to dissect the mechanism, the cellular transcriptomic reprogramming within the spatial context remains elusive. Here, we constructed single-cell and spatial transcriptome atlases of experimental CM (ECM) male murine brain tissues with or without artesunate (ART) treatment. We identified activated inflammatory endothelial cells during ECM, characterized by a disrupted blood-brain barrier, increased antigen presentation, and leukocyte adhesion. We also observed that inflammatory microglia enhance antigen presentation pathway such as MHC-I to CD8 + cytotoxic T cells. The latter underwent an inflammatory state transition with up-regulated cytokine expression and cytotoxic activity. Multi-omics analysis revealed that the activated interferon-gamma response of injured neurons during ECM and persisted after ART treatment. Overall, our research provides valuable resources for understanding malaria parasite-host interaction mechanisms and adjuvant therapy development. By integrating single-cell and spatial transcriptomic analysis, Chen et al. profile the cellular disruptions in the murine brain during cerebral malaria and after artemisinin treatment.

Fungal pathogens typically use secreted effector proteins to suppress host immune activators to facilitate invasion. However, there is rarely evidence supporting the idea that fungal secretory proteins contribute to pathogenesis by transactivating host genes that suppress defense. We previously found that pathogen Magnaporthe oryzae induces rice Bsr-d1 to facilitate infection and hypothesized that a fungal effector mediates this induction. Here, we report that MoSPAB1 secreted by M. oryzae directly binds to the Bsr-d1 promoter to induce its expression, facilitating pathogenesis. Amino acids 103-123 of MoSPAB1 are required for its binding to the Bsr-d1 promoter. Both MoSPAB1 and rice MYBS1 compete for binding to the Bsr-d1 promoter to regulate Bsr-d1 expression. Furthermore, MoSPAB1 homologues are highly conserved among fungi. In particular, Colletotrichum fructicola CfSPAB1 and Colletotrichum sublineola CsSPAB1 activate kiwifruit AcBsr-d1 and sorghum SbBsr-d1  respectively, to facilitate pathogenesis. Taken together, our findings reveal a conserved module that may be widely utilized by fungi to enhance pathogenesis. Magnaporthe oryzae effector MoSPAB1 enters rice nuclei to bind to the promoter of the immunity-brake gene Bsr-d1 and activates its expression by competing with rice MYBS1, which constitute a conserved module that facilitates fungal pathogenesis.

Nitrogen fertilizer application is an important method for the production of high-quality maize. However, nitrogen fertilizer addition patterns vary according to regional climate, field management practices, and soil conditions. In this study, a meta-analysis was used to quantify the yield effects of nitrogen addition on maize, and meta-regression analysis and a random forest model were used to study the main factors affecting the yield effects of nitrogen addition on maize. The results showed that nitrogen addition significantly increased maize yield by 50.26%–55.72%, and a fluctuating increasing trend was observed with the advancement of the experimental year. The increase in maize yield upon nitrogen addition was the highest in Gansu Province, and showed a decreasing trend with the rise in average annual temperature, but did not change significantly with the average annual precipitation. Among the field management factors, the increase in maize yield was better with the variety Qiangsheng 51, topdressing at the jointing and tasseling stages (JS, TS), nitrogen application rate of 175–225 kg·ha -1 , and controlled release of nitrogen fertilizer and urea (CRNFU) or the application of a combination of organic and inorganic nitrogen (OIF). Moreover, the positive effects of nitrogen fertilizer application on maize yield improved with soil pH, organic matter, available potassium, available phosphorus, and total nitrogen content; decreased with soil carbon and nitrogen ratio and available nitrogen (AN) content; and were enhanced in chestnut soil, clay, and at a bulk density of 1.2–1.4 g·cm -3 . Random forest model and multifactorial optimization revealed that the effects of nitrogen addition on maize yield in Northwest China were primarily influenced by experimental year, variety, soil type, AN, and soil pH.

This study aims to analyze the risk factors associated with delayed postoperative bleeding (DPPB) following colorectal polyp surgery, develop a dynamic nomogram and evaluate the model efficacy, provide a reference for clinicians to identify the patients at high risk of DPPB. Retrospective study was done on patients who underwent endoscopic colorectal polypectomy at the First Hospital of Lanzhou University from January 2020 to March 2023. Differences between the group with and without DPPB were compared, and independent risk factors for DPPB occurrence were identified through univariate analysis and combination LASSO and logistic regression. A dynamic nomogram was constructed based on multiple logistic regression to predict DPPB following colorectal polyp surgery. Model evaluation included receiver operating characteristic (ROC), Calibration curve, Decision curve analysis (DCA). DPPB occurred in 38 of the 1544 patients included. multivariate analysis showed that direct oral anticoagulants (DOACs), polyp location in the right hemi colon, polyp diameter, drink, and prophylactic hemoclips were the independent risk factors for DPPB and dynamic nomogram were established. Model validation indicated area under the ROC curve values of 0.936, 0.796, and 0.865 for the training set, validation set, and full set, respectively. The calibration curve demonstrated a strong alignment between the predictions of the column-line diagram model and actual observations. The decision curve analysis (DCA) displayed a significant net clinical benefit across the threshold probability range of 0–100%. The dynamic nomogram aids clinicians in identifying high-risk patients, enabling personalized diagnosis and treatment.

Acute lung injury (ALI) is a fatal respiratory disease caused by excessive inflammation. Chelerythrine chloride (CH), an isoquinoline alkaloid, exhibits diverse biological activities. The research focused on assessing CH’s therapeutic effects against LPS-mediated ALI in mice and its underlying mechanisms. The anti-inflammatory effects of CH were evaluated both in LPS-induced RAW264.7 cells and ALI mouse model. An amount of 2.5 μM CH significantly inhibited the secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in RAW264.7 cells. CH treatment notably mitigated the thickened alveolar septa and reduced edema in LPS-induced ALI in mice. Activity-based protein profiling (ABPP) technology was employed to identify the targets of CH. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was one of the direct targets of CH identified by ABPP. CH could downregulate the production of pyruvate. Furthermore, CH reduced the extracellular acidification rate (ECAR) while increasing the oxygen consumption rate (OCR) in LPS-stimulated RAW264.7 cells. All results suggest that CH mitigates LPS-induced ALI by targeting GAPDH and inhibiting glycolysis. This study reveals preliminary anti-inflammatory mechanisms of CH and its therapeutic potential for ALI.

The study on the association between aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio and the risk of type 2 diabetes mellitus (T2DM) was limited. Therefore, we conducted a secondary analysis based on online data to explore whether there was an association between the AST/ALT ratio and incident T2DM among a large number of Japanese people. The study was a retrospective cohort study. We downloaded the NAGALA (NAfld in Gifu area) data from DATADRYAD website between 2004 and 2015. This present study included 15,291 participants. Cox proportional-hazards regression, generalized additive models and subgroup analyses were used to find out the association between the AST/ALT ratio and T2DM events. The negative relationship was shown between AST/ALT ratio and incident T2DM (HR = 0.617, 95% CI: 0.405-0.938) in our study. A non-linear relationship and saturation effect were found between them, and the inflection point was 0.882. It indicated that the AST/ALT ratio was negatively correlated with incident T2DM when the AST/ALT ratio was less than the inflection point (HR = 0.287, 95% CI: 0.126-0.655, p = 0.0030). We found that exercise modified their relationship (P for interaction = 0.0024), and people who did not exercise associated strongly (HR = 0.464 95% CI: 0.290-0.741). AST/ALT ratio was negatively associated with T2DM risk, and their relationship was non-linear and had a saturation effect. When the AST/ALT ratio was less than 0.882, they showed a significant negative correlation.

(−)-Epigallocatechin 3-gallate (EGCG) is a potent natural antioxidant, but its strong bitterness and poor palatability limit its application in animal production. This study aimed to evaluate the protective effects and underlying mechanisms of chemically synthesized EGCG derivatives against oxidative stress using a diquat-induced mouse model. A total of 36 male ICR mice were randomly assigned into six groups (n = 6): Control (T0), Diquat (T1), EGCG + Diquat (T2), Epigallocatechin octanoate (EGCO) + Diquat (T3), Epigallocatechin p-chloromethylbenzoate (EGCP) + Diquat (T4), and Epigallocatechin ibuprofen ester (EGCI) + Diquat (T5). Oxidative stress was induced by intraperitoneal injection of diquat at day 27 of the experiment, while EGCG or its derivatives were administered via dietary supplementation. At day 28, the mice were weighed, killed, and the tissues were sampled. Diquat challenge significantly impaired growth, increased serum injury markers (ALT, AST, DAO, and D-LA) (p < 0.05), suppressed hepatic and jejunal antioxidant enzymes (GPx, SOD, and TAOC) while elevating MDA (p < 0.05), damaged jejunal morphology (villus atrophy) (p < 0.05), and downregulated tight junction proteins (ZO-1 and Occludin) (p < 0.05). Chemically synthesized EGCG derivatives, especially EGCI, effectively alleviated diquat-induced growth impairment and hepatic and intestinal oxidative damage by improving intestinal barrier function and enhancing systemic antioxidant capacity, possibly in part through activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Compared with EGCG, EGCI exhibited reduced bitterness and improved palatability, which favored normal feed intake. These findings provide strong theoretical support for the future application of EGCG derivatives, especially EGCI, as functional antioxidant additives in broiler production.