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Abstract Background Saline-alkaline water aquaculture has become a key way to mitigate the reduction of freshwater aquaculture space and meet the increasing global demand for aquatic products. To enhance the comprehensive utilization capability of saline-alkaline water, it is necessary to understand the regulatory mechanisms of aquatic animals coping with saline-alkaline water. In this study, our objective was to elucidate the function of proline metabolism in the alkaline adaptation of Nile tilapia (Oreochromis niloticus). Results Expose Nile tilapia to alkaline water of different alkalinity for 2 weeks to observe changes in its growth performance and proline metabolism. Meanwhile, to further clarify the role of proline metabolism, RNA interference experiments were conducted to disrupt the normal operation of proline metabolic axis by knocking down pycr (pyrroline-5-carboxylate reductases), the final rate-limiting enzyme in proline synthesis. The results showed that both the synthesis and degradation of proline were enhanced under carbonate alkalinity stress, and the environmental alkalinity impaired the growth performance of tilapia, and the higher the alkalinity, the greater the impairment. Moreover, environmental alkalinity caused oxidative stress in tilapia, enhanced ion transport, ammonia metabolism, and altered the intensity and form of energy metabolism in tilapia. When the expression level of the pycr gene decreased, the proline metabolism could not operate normally, and the ion transport, antioxidant defense system, and energy metabolism were severely damaged, ultimately leading to liver damage and a decreased survival rate of tilapia under alkalinity stress. Conclusions The results indicated that proline metabolism plays an important role in the alkaline adaptation of Nile tilapia and is a key regulatory process in various biochemical and physiological processes.

Abstract Endothelial cell (EC) senescence and vascular aging are important hallmarks of chronic metabolic diseases. An improved understanding of the precise regulation of EC senescence may provide novel therapeutic strategies for EC and vascular aging-related diseases. This study examined the potential functions of Spinster homolog 2 (SPNS2) in EC senescence and vascular aging. We discovered that the expression of SPNS2 was significantly lower in older adults, aged mice, hydrogen peroxide-induced EC senescence models and EC replicative senescence model, and was correlated with the expression of aging-related factors. in vivo experiments showed that the EC-specific knockout of SPNS2 markedly aggravated vascular aging by substantially, impairing vascular structure and function, as evidenced by the abnormal expression of aging factors, increased inflammation, reduced blood flow, pathological vessel dilation, and elevated collagen levels in a naturally aging mouse model. Moreover, RNA sequencing and molecular biology analyses revealed that the loss of SPNS2 in ECs increased cellular senescence biomarkers, aggravated the senescence-associated secretory phenotype (SASP), and inhibited cell proliferation. Mechanistically, silencing SPNS2 disrupts pyruvate metabolism homeostasis via pyruvate kinase M (PKM), resulting in mitochondrial dysfunction and EC senescence. Overall, SPNS2 expression and its functions in the mitochondria are crucial regulators of EC senescence and vascular aging.

Abstract Background Rimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is indicated for acute and preventive migraine treatment in the United States and other countries. However, there is a lack of prospective real-world evidence for the use of rimegepant in Chinese migraine patients. Methods This was a single-arm, prospective, real-world study. While taking rimegepant to treat migraine attacks as needed, eligible participants were asked to record their pain intensity, functional ability, and accompanying symptoms for a single attack at predose and 0.5, 1, 2, 24, and 48 h postdose via a digital platform. Adverse events (AEs) during the rimegepant treatment period were recorded and analysed. The percentages of participants who experienced moderate to severe pain at predose and 0.5, 1, 2, 24, and 48 h postdose were assessed. Additionally, the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose were analysed. In addition, the total cohort (full population, FP) was stratified into a prior nonresponder (PNR) group to observe the effectiveness and safety of rimegepant for relatively refractory migraine and a rimegepant and eptinezumab (RE) group to observe the effectiveness and safety of the combination of these drugs. Results By November 24th, 2023, 133 participants (FP, n = 133; PNR group, n = 40; RE group, n = 28) were enrolled, and 99 participants (FP, n = 99; PNR group, n = 30; RE group, n = 23) were included in the analysis. Rimegepant was effective in treating migraine in the FP and both subgroups, with a significant decreasing trend in the percentages of participants experiencing moderate to severe pain postdose (p

Abstract Intestinal epithelial cells (IECs) are pivotal for maintaining intestinal homeostasis through self-renewal, proliferation, differentiation, and regulated cell death. While apoptosis and necroptosis are recognized as distinct pathways, their intricate interplay remains elusive. In this study, we report that Mettl3-mediated m6A modification maintains intestinal homeostasis by impeding epithelial cell death. Mettl3 knockout induces both apoptosis and necroptosis in IECs. Targeting different modes of cell death with specific inhibitors unveils that RIPK1 kinase activity is critical for the cell death triggered by Mettl3 knockout. Mechanistically, this occurs via the m6A-mediated transcriptional regulation of Atf3, a transcription factor that directly binds to Cflar, the gene encoding the anti-cell death protein cFLIP. cFLIP inhibits RIPK1 activity, thereby suppressing downstream apoptotic and necroptotic signaling. Together, these findings delineate the essential role of the METTL3-ATF3-cFLIP axis in homeostatic regulation of the intestinal epithelium by blocking RIPK1 activity.

Abstract Oomycete pathogens deliver many effectors to enhance virulence or suppress plant immunity. Plant immune networks are interconnected, in which a few effectors can trigger a strong defense response when recognized by immunity-related proteins. How effectors activate plant defense response remains poorly understood. Here we report Phytophthora capsici effector RxLR23KM can induce plant cell death and plant immunity. RxLR23KM specifically binds to ERD15La, a regulator of abscisic acid and salicylic acid pathway, and the binding intensity depends on the amino acid residues (K93 and M320). NbNAC68, a downstream protein of ERD15La, can stimulate plant immunity that is compromised after binding with ERD15La. Silencing of NbNAC68 substantially prevents the activation of plant defense response. RxLR23KM binds to ERD15La, releasing NbNAC68 to activate plant immunity. These findings highlight a strategy of plant defense response that ERD15La as a central regulator coordinates RxLR23KM to regulate NbNAC68-triggered plant immunity.

In aquaculture, co-culturing rice with fish may mitigate greenhouse-gas emissions. In this study, co-culture of four rice cultivars in a laboratory-scale rice–fish system reduced CH4 and N2O emissions relative to fish monoculture. Differences in CH4 and N2O emissions among rice cultivars primarily stem from the differential effects of rice plants on plant-mediated CH4 transport, CH4 oxidation and nitrogen absorption.

Abstract Clarifying migration timing and its link with underlying drivers is fundamental to understanding the evolution of bird migration. However, previous studies have focused mainly on environmental drivers such as the latitudes of seasonal distributions and migration distance, while the effect of intrinsic biological traits remains unclear. Here, we compile a global dataset on the annual cycle of migratory birds obtained by tracking 1531 individuals and 177 populations from 186 species, and investigate how body mass, a key intrinsic biological trait, influenced timings of the annual cycle using Bayesian structural equation models. We find that body mass has a strong direct effect on departure date from non-breeding and breeding sites, and indirect effects on arrival date at breeding and non-breeding sites, mainly through its effects on migration distance and a carry-over effect. Our results suggest that environmental factors strongly affect the timing of spring migration, while body mass affects the timing of both spring and autumn migration. Our study provides a new foundation for future research on the causes of species distribution and movement.

Nonylphenol (NP), an endocrine disruptor, has been demonstrated to be a harmful environmental contaminant and toxic to organisms. In this study, to address concerns regarding the immunotoxicity of NP, we treated clam Ruditapes philippinarum hemocytes with NP in vitro and explored the underlying mechanisms of NP-induced extracellular traps (ETs). NP could induce the formation of hemocytes ETs in a dose-dependent manner. Transcriptomics analysis revealed changes of signaling pathway involved in immunity and energy metabolism in hemocytes after NP stimulation. In this process, both reactive oxygen species (ROS) and myeloperoxidase (MPO) were up-regulated. Moreover, mitogen-activated protein kinase (MAPK) signaling pathway was proved to be activated in the formation of NP-induced ETs, manifested as enhanced phosphorylation of extracellular signal-regulated kinase (ERK) but not p38 or c-Jun N-terminal kinase (JNK). In the presence of U0126, an ERK phosphorylation inhibitor, the NP-induced expression of NADPH oxidase enzyme (NOX) was significantly decreased, which further alleviated the ROS production and ultimately limited the release of ETs. NP exposure increased glucose uptake, along with enhanced activities of glycolysis-related enzymes such as hexokinase (HK) and pyruvate kinase (PK). After inhibiting glycolysis by the inhibitor 2-DG, the formation of NP-induced ETs was significantly suppressed. ERK could regulate mTOR signaling and the PI3K/AKT pathway, potentially directing ETs formation by orchestrating the glycolysis through the activation of key transcription factors c-Myc and HIF-1α. Collectively, the results preliminary confirm that the ERK-NOX-ROS axis and glycolysis are involved in NP-induced ETs formation, contributing to the cellular immunotoxicity in clam.

This study aims to investigate the nutritional needs and physiological functions of dietary cholesterol in juvenile Chinese mitten crabs (Eriocheir sinensis). In the 8-week feeding experiment, we evaluated the effects of various cholesterol levels (0 control, 0.6, 1.3, 2.6, 5.9, 12.0 g/kg diet) on growth, immune capacity, lipid metabolism, molting, and cholesterol and bile acid metabolism. Crabs (1.06 ± 0.04 g) were divided into six groups with four replicates of 40 crabs per tank. The highest weight gain was found in crabs fed 5.9 g/kg cholesterol (P < 0.05), while the highest molting frequency was observed in the 0.6 g/kg group (P < 0.05). Cholesterol significantly changed fatty acid composition in the hepatopancreas, and 5.9 g/kg cholesterol increased immune enzyme activities (acid phosphatase, alkaline phosphatase, and polyphenol oxidase) (P < 0.05). A 5.9 g/kg cholesterol significantly upregulated lipogenesis- and catabolism-related genes, while higher levels of cholesterol (12.0 g/kg) downregulated lipogenesis-related genes significantly (P < 0.05). Low cholesterol levels upregulated chitinase expression, while ecdysone receptor and molt-inhibiting hormone expressions were upregulated with cholesterol levels (P < 0.05). Cholesterol also upregulated the gene in bile acid metabolism. The total bile acids, the proportion of primary bile acids, and the content of primary bile acids increased significantly compared to the control. Based on quadratic regression model analysis, the optimal dietary cholesterol level for juvenile E. sinensis is 5.74–5.77 g/kg. The study suggests that cholesterol promotes growth and immunity in juvenile E. sinensis by regulating molting frequency, improving lipid and HUFA utilization, and increasing bile acids.

Dilated cardiomyopathy (DCM) remains an enigmatic myocardial disorder characterized either by enlargement of either the left or right ventricle or both and reduced contractility, posing a significant burden on pediatric populations as a leading cause of cardiac-related mortality and morbidity. This paper presents a compelling case of DCM in a Han Chinese child whose genomic analysis unveiled a novel LMNA-C.185G>C (p.Arg62Pro) variant. Over a meticulous 3-year clinical follow-up, spanning ten outpatient consultations and hospital admissions since the initial diagnosis, the patient exhibited a progressive emergence of various cardiac conduction anomalies closely mirroring LMNA-associated phenotypes. Delving into a comprehensive review of the patient's 14-year medical journey and familial history, antecedent signs of muscular dystrophy (MD) predated DCM onset. Familial scrutiny revealed a lineage marred by muscular atrophy, with the patient's maternal grandmother having a history of muscular dystrophy and an episode of DCM, necessitating cardiac transplantation in the patient's uncle at age 37. This scenario illuminates the intricate interplay between LMNA-associated diseases and genetic predisposition. Timely identification of etiological triggers stands paramount in DCM management. Beyond conventional genetic scrutiny, leveraging novel serum biomarkers such as anti-heart muscle antibodies (AHA) remarkably enhanced diagnostic precision. Notably, personalized therapeutic interventions comprising prednisolone regimens and intravenous immunoglobulin infusions precipitated marked amelioration in heart failure symptoms and serum biomarker profiles. It is noteworthy to identify this novel genetic locus within the Han Chinese populace, underscoring the imperative of expanding the LMNA mutation repository within this demographic cohort. Early recognition of clinical manifestations and etiological cues in pediatric DCM heralds a paradigm shift in risk prognostication and individualized therapeutic interventions, underscoring the profound significance of precision medicine in combating rare familial cardiomyopathies.

Summary: Neurovascular coupling (NVC) and neurometabolic coupling (NMC) provide the basis for functional magnetic resonance imaging and positron emission tomography to map brain neurophysiology. While increases in neuronal activity are often accompanied by increases in blood oxygen delivery and oxidative metabolism, these observations are not the rule. This decoupling is important when interpreting brain network organization (e.g., resting-state functional connectivity [RSFC]) because it is unclear whether changes in NMC/NVC affect RSFC measures. We leverage wide-field optical imaging in Thy1-jRGECO1a mice to map cortical calcium activity in pyramidal neurons, flavoprotein autofluorescence (representing oxidative metabolism), and hemodynamic activity during wake and ketamine/xylazine anesthesia. Spontaneous dynamics of all contrasts exhibit patterns consistent with RSFC. NMC/NVC relative to excitatory activity varies over the cortex. Ketamine/xylazine profoundly alters NVC but not NMC. Compared to awake RSFC, ketamine/xylazine affects metabolic-based connectomes moreso than hemodynamic-based measures of RSFC. Anesthesia-related differences in NMC/NVC timing do not appreciably alter RSFC structure.

This study investigated the effects of dietary glutamine on growth performance, antioxidant capacity, and osmoregulation in euryhaline fish (Oreochromis niloticus) under hyperosmotic stress. Nile tilapia was fed four diets with varying glutamine concentrations (0 %, 0.75 %, 1.5 %, and 3 %) at 0 or 16 ppt for 42 days. The results demonstrated that dietary supplementation of 0.75 % glutamine significantly enhanced the growth performance of Nile tilapia under both 0 ppt and 16 ppt salinity. Hyperosmotic stress significantly reduced the crude protein and crude lipid contents while elevated the ash content of the fish. Under hyperosmotic stress, dietary glutamine supplementation significantly increased the antioxidant and immune capacities, and attenuated apoptosis in the liver of tilapia. The expression of ion transporter genes in the gills and kidneys were both significantly increased by dietary glutamine. Meanwhile, glutamine supplementation significantly reduced the levels of inorganic ions in serum while increased serum osmolality. Hyperosmotic stress significantly activated the glycolysis, gluconeogenesis, and pentose phosphate pathways in the liver of tilapia. However, supplementation of glutamine under hyperosmotic stress would significantly enhance the ability of gluconeogenesis of tilapia in the liver. The results of this research suggested that dietary glutamine might promote the growth performance of fish by enhancing their antioxidant capacity and osmoregulation capacity under chronic hyperosmotic stress. This work investigates the role of glutamine in osmolarity regulation and extends the understanding of its mechanism of action, which could provide a reference for hyperosmotic adaptation in aquatic animals.

This study aimed to investigate the effects of arginine (Arg) on the vitellogenesis and ovarian maturation of Chinese mitten crab. Six isonitrogenous and isolipidic diets (1.83, 2.52, 3.26, 3.96, 4.81 and 5.52 % Arg) were fed to adult female Chinese mitten crab (60.05 ± 4.33 g). The feeding period lasted for eleven weeks. The results showed that gonadosomatic index of crabs increased with increasing dietary Arg concentrations from 1.83 % to 2.52 % and significantly decreased from 2.52 % to 5.52 %. The quadratic regression analysis based on gonadosomatic index estimated that the optimal Arg requirement for adult female crabs was 2.60 %. Dietary supplementation with 2.52 % Arg significantly increased the crude protein concentration in the ovary. A dose of 2.52 % Arg significantly decreased the vitellogenesis-inhibiting hormone (VIH) content in the hemolymph. Arg (2.52 %) significantly upregulated the Vg and protein kinase A (PKA) gene expressions and increased the cyclic adenosine monophosphate (cAMP) concentration in the hepatopancreas. Moreover, dietary supplementation with 2.52 % Arg significantly decreased the cyclic guanosine monophosphate (cGMP) concentration and downregulated protein kinase G (PKG) and p38 mitogen-activated protein kinase (p38 MAPK) gene expression. Arg at 2.52 % significantly increased hemolymph Vg content and the gene expression of the vitellogenin receptor (VgR). In conclusion, Arg at 2.52 % improved vitellogenesis and ovarian maturation by reducing the VIH content and regulating Vg expression via the cGMP/cAMP pathway.

Study region: The Daliang Mountain region, characterized by its widespread debris flow-pone catchments, is the primary sediment source area for the upper reaches of the Yangtze River, and has experienced intensive human activity over the past half-century. Study focus: Here, we combined lake deposits with sediment source areas to quantify the sediment source and corresponding sediment yield (SY) in response to recent human impacts in a typical debris flow-prone catchment located in the Daliang Mountain region, Southwest China. The fingerprinting techniques, incorporating geochemical elements and their specific ratios, were used to characterize the sediment provenances and corresponding SY. New hydrological insight for the region: The results indicated that gully erosion was the major sediment provenance (90.10 %) in the catchment, followed by cultivated land (6.76 %) and forested land (3.14 %) for the studied period. The temporal variations of SY showed two distinctive erosional stages in response to different human activities over the past 70 years, namely 1950−2004 and 2004−2020. Greater SY values, dominated by gully erosion, occurred from 1950 to 2004, implying that both critical national activities and revegetation projects have limited effects on surface sediment generation. In contrast, gully activity and resulting SY have sharply decreased since 2004 following the implementation of check dams. These comparisons indicate a central role of the check dam in reducing gully activity. The findings have important implications for policymakers to optimize the spatial layout of future soil conservation strategies in the region.

Abstract The elevation gradient has long been known to be vital in shaping the structure and function of terrestrial ecosystems, but little is known about the elevation-dependent pattern of net CO2 uptake, denoted by net ecosystem productivity (NEP). Here, by analyzing data from 203 eddy covariance sites across China, we report a negative linear elevation-dependent pattern of NEP, collectively shaped by varying hydrothermal factors, nutrient supply, and ecosystem types. Furthermore, the NEP shows a higher temperature sensitivity in high-elevation environments (3000–5000 m) compared with the lower-elevation environments (

Abstract Plant cells perceive pathogen invasion by recognizing microbial patterns using plasma-membrane-localized pattern-recognition receptors (PRRs) to initiate pattern-triggered immunity (PTI), which confers a moderate immunity to most microbes. For instance, the PRR FLS2 (FLAGELLIN SENSING 2) recognizes bacterial flagellin in the presence of the co-receptor BAK1 and activates a series of PTI responses, such as reactive oxygen species (ROS) burst and mitogen-activated protein kinase (MAPK) activation. We previously showed that soybean malectin/malectin-like domain-containing receptor-like kinase (MRLK) protein GmLMM1 negatively regulates PTI by suppressing FLS2-BAK1 interaction. GmLMM1 replicates in tandem with five other GmMRLKs on chromosome 13. Here, we show that GmMRLK32, the closest homolog to GmLMM1 among the tandem genes of GmLMM1, negatively regulates PTI and disease resistance against bacterial and oomycete pathogens. The Gmmrlk32 mutant showed enhanced flg22-induced ROS burst and MAPK activation. We revealed that GmMRLK32 interacts with GmFLS2 and GmBAK1, and suppresses flg22-induced GmFLS2-GmBAK1 dimerization in a manner similar to that of GmLMM1. We further showed that GmMRLK32 specifically interacts with GmLMM1 to regulate PTI. In Nicotiana benthamiana plants, co-expression of GmMRLK32 and GmLMM1 showed a stronger PTI inhibitory effect on PTI activation than expression of GmMRLK32 or GmLMM1 alone. We uncovered a novel mechanism by which GmMRLK32 and GmLMM1 coordinately regulate PTI by forming hetero-oligomer.

Abstract Plant pH is an emerging functional trait that plays important roles in physiological processes and nutrient cycling. However, how root pH varies among plant functional groups (PFGs) and the regulatory factors on a large scale remain unclear. Therefore, we quantified root pH variation of herbaceous plants in four PFGs from 20 sites on the Tibetan Plateau along a 1600 km transect and explored the correlations between root pH and different PFGs, climate and soil conditions. The results showed that the root pH of herbaceous plants was slightly acidic (6.46 ± 0.05). Grasses had the highest root pH (6.91 ± 0.10) across all functional groups (p

An 8-week experiment was conducted to study the effect of dietary enzymatic hydrolysis of full-fat soybean (ESB) in combination with fish meal (FM) on the growth performance, oxidation resistance, immunity and intestinal health of juvenile Chinese mitten crab Eriocheir sinensis. The crabs (0.74±0.01 g) were randomly divided into six groups. Six diets were formulated by replacing 0, 15, 30, 45, 60 and 75% of FM (350 g/kg) with ESB (ESB0-control, ESB15, ESB30, ESB45, ESB60 and ESB75, respectively). The weight gain rate and specific gain rate of the crabs were significantly greater in the ESB15 group than in the control group, while they decreased significantly with replacement levels up to 60%. A replacement level of 15% significantly improved the hepatopancreas antioxidant capacity and hemolymph acid phosphatase indices. However, the glutathione peroxidase activity and total antioxidant capacity in the hepatopancreas decreased significantly when the replacement concentration reached 45% and 75%, respectively. The replacement level could increase to 45% without affecting the hepatopancreas malondialdehyde content. Hemolymph acid phosphatase and alkaline phosphatase activities decreased significantly with replacement levels up to 60%. Aspartate aminotransferase activity in the hemolymph increased significantly when the replacement dose reached 75%. Moreover, different replacement levels did not affect the gene expression of the hepatopancreas ALF1/2, crustin, relish, or LITAF. The hepatic mRNA levels of TLR2 and Myd88 were significantly elevated in the ESB45 and ESB60 groups, respectively. Unlike those in the ESB0 group, intestinal PM1 and PM2 expressions were significantly higher in the ESB15 group. In contrast, intestinal PM1, PM2 and PT expressions were significantly lower in the ESB60 and ESB75 groups. The present study suggests that 15% of the optimal replacement level of FM with ESB enhanced growth performance, antioxidation, immunity and intestinal health. To maintain normal growth performance, the replacement level of FM with ESB could not exceed 45%.

Tetramethylpyrazine (TTMP) is considered a crucial flavor component in Moutai-flavored liquor. Laceyeella sacchari FBKL4.010 (L. sacchari) is the dominant species found in Moutai-flavor Daqu, and this study aims to determine the mechanism by which L. sacchari produces TTMP during liquid fermentation of Moutai-flavor Daqu. The results of the liquid fermentation performance demonstrated a gradual increase in biomass over time, while there was a gradual decline in residual glucose content and pH value. Furthermore, analysis of volatile components revealed that liquid fermentation significantly enhanced the production of TTMP in Moutai-flavor Daqu, with the relative content of TTMP reaching 14.24 mg/L after 96 h of liquid fermentation. Additionally, to explore the synthesis mechanism of TTMP, we compared differentially expressed genes (DEGs) of L. sacchari between 24 and 96 h using comparative transcriptomic techniques. The results indicated that DEGs involved in isoleucine, valine, and leucine biosynthesis pathway were upregulated, while those associated with isoleucine, valine, and leucine degradation pathway were downregulated, suggesting that the valine, leucine, and isoleucine biosynthesis pathway primarily contributes ammonia for TTMP synthesis. The findings of this study present an opportunity for further elucidating the production process of TTMP in Moutai-flavor Daqu during liquid fermentation.

In this study, Senescence Accelerated Mice (SAMP8) were supplemented with exogenous DHA milk, endogenous DHA milk, normal milk, or 0.9 % saline solution. Enzyme-linked immunosorbent assay (ELISA), gas chromatography (GC), ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI MS/MS), and Morris water maze were used to characterize the effects of diet on oxidative stress and cognition in SAMP8 mice. Supplementation endogenous DHA milk or exogenous DHA milk can enhance the antioxidant capacity of mice organs. Endogenous DHA milk increased the superoxide dismutase (SOD) activity of mice brain and serum than normal milk and 0.9 % saline solution (P ≤ 0.05), as well as increased SOD activity of mice liver and glutathione peroxidase (GSH-Px) activity of mice brain than normal milk (P ≤ 0.05). Exogenous DHA milk increased SOD activity of mice brain than normal milk and 0.9 % saline solution, as well as increased SOD activity of mice serum than 0.9 % saline solution (P ≤ 0.05). Several polar lipid relative content, such as 18:0/18:2 PS, 17:0 Ceramide, and 20:4 LPC in mice brain was affected by dietary supplementation with DHA-containing milk. Lipid oxidation metabolites in mice brain were not affected by DHA-containing milk. Endogenous DHA milk increased the number of platform location crossing times of mice in the Morris water maze test, compared with Exogenous DHA milk, normal milk, and 0.9 % saline solution (P ≤ 0.05).

Abstract Background Potato late blight, caused by Phytophthora infestans, is the most devastating disease on potato. Dissecting critical immune components in potato will be supportive for engineering P. infestans resistance. Upon pathogens attack, plant Ca2+ signature is generated and decoded by an array of Ca2+ sensors, among which calcineurin B-like proteins (CBLs) coupled with plant specific CBL-interacting protein kinases (CIPKs) are much less explored in plant immunity. Results In this study, we identified that two differential potato CBL-CIPK modules regulate plant defense responses against Phytophthora and ROS production, respectively. By deploying virus-induced gene silencing (VIGS) system-based pathogen inoculation assays, StCBL3 was shown to negatively regulate Phytophthora resistance. Consistently, StCBL3 was further found to negatively regulate PTI and ETI responses in Nicotiana benthamiana. Furthermore, StCIPK7 was identified to act together with StCBL3 to negatively regulate Phytophthora resistance. StCIPK7 physically interacts with StCBL3 and phosphorylates StCBL3 in a Ca2+-dependent manner. StCBL3 promotes StCIPK7 kinase activity. On the other hand, another StCBL3-interacting kinase StCIPK24 negatively modulating flg22-triggered accumulation of reactive oxygen species (ROS) by interacting with StRBOHB. Conclusions Together, these findings demonstrate that the StCBL3-StCIPK7 complex negatively modulates Phytophthora resistance and StCBL3-StCIPK24 complex negatively regulate ROS production. Our results offer new insights into the roles of potato CBL-CIPK in plant immunity and provide valuable gene resources to engineer the disease resistance potato in the future.

Grazing enclosure has been extensively employed as a direct and effective management measure for grassland restoration on the Qinghai-Xizang Plateau.Enclosures significantly increased vegetation coverage and affected the water and heat exchange between the land surface and the atmosphere.However， there is still a lack of quantitative research on how enclosures regulates water and heat fluxes in typical alpine ecosystems.Based on continuous data observed from eddy covariance system from July 2019 to June 2021 at alpine steppe and alpine wetland of the Northern Xizang， the changes of surface energy flux after enclosure was analyzed by using the eddy covariance method.The results show that： The water and heat fluxes in alpine steppe and alpine wetland shows significant unimodal diurnal variations.The exchange of land-atmosphere in alpine steppe is mainly dominated by sensible heat （Bowen ratio： 1.60） except in Summer， while wetland mainly transfers energy to the atmosphere by latent heat （Bowen ratio： 0.31） whole year.Grazing enclosure decreased the surface fluxes in alpine steppe， the sensible heat flux reduced by 5.99 W·m-2 and the latent heat flux increased by 4.84 W·m-2.Grazing enclosures increased the surface fluxes in alpine wetland， the sensible and latent heat raised by 3.04 W·m-2 and 30.95 W·m-2， respectively.The daily and average sensible and latent heat fluxes decreased in alpine steppe but increased in alpine wetland.The effect of enclosure on surface energy fluxes was stronger during the day and weaker at night.The collected literature data demonstrated that fencing decreased soil temperature and increased soil water holding capacity.Given the data of soil temperature， soil moisture， latent heat flux， and sensible heat flux， our study shows the cooling potential of enclosure on alpine steppe and alpine wetland.

Abstract Ballistic missile defense systems require accurate target recognition technology. Effective feature extraction is crucial for this purpose. The deep convolutional neural network (CNN) has proven to be an effective method for recognizing high-resolution range profiles (HRRPs) of ballistic targets. It excels in perceiving local features and extracting robust features. However, the standard CNN's fully connected manner results in high computational complexity, which is unsuitable for deployment in real-time missile defense systems with stringent performance requirements. To address the issue of computational complexity in HRRP recognition based on the standard one-dimensional CNN (1DCNN), we propose a lightweight network called group-fusion 1DCNN with layer-wise auxiliary classifiers (GFAC-1DCNN). GFAC-1DCNN employs group convolution (G-Conv) instead of standard convolution to effectively reduce model complexity. Simply using G-Conv, however, may decrease model recognition accuracy due to the lack of information flow between feature maps generated by each G-Conv. To overcome this limitation, we introduce a linear fusion layer to combine the output features of G-Convs, thereby improving recognition accuracy. Additionally, besides the main classifier at the deepest layer, we construct layer-wise auxiliary classifiers for different hierarchical features. The results from all classifiers are then fused for comprehensive target recognition. Extensive experiments demonstrate that GFAC-1DCNN with such simple and effective techniques achieves higher overall testing accuracy than state-of-the-art ballistic target HRRP recognition models, while significantly reducing model complexity. It also exhibits a higher recall rate for warhead recognition compared to other methods. Based on these compelling results, we believe this work is valuable in reducing workload and enhancing missile interception rates in missile defense systems.

This study introduces a deep learning framework based on SMILES representations of chemical structures to predict drug–drug interactions (DDIs). The model extracts Morgan fingerprints and key molecular descriptors, transforming them into raw graphical features for input into a modified ResNet18 architecture. The deep residual network, enhanced with regularization techniques, efficiently addresses training issues such as gradient vanishing and exploding, resulting in superior predictive performance. Experimental results show that StructNet-DDI achieved an AUC of 99.7%, an accuracy of 94.4%, and an AUPR of 99.9%, demonstrating the model’s effectiveness and reliability. These findings highlight that StructNet-DDI can effectively extract crucial features from molecular structures, offering a simple yet robust tool for DDI prediction.

Diabetes serves as a severe chronic disease that severely affects the normal life of human beings. Diabetes causes the complication of diabetic wound dysfunction, which is characterized by sustained inflammation, altered angiogenesis, delayed epithelialization and abnormal secretion of protease. Dang-Gui-Bu-Xue decoction (DBD) is a Chinese traditional medicine that comprises Radix Astragali and Radix Angelicae sinensis and is widely applied in treatment of multiple diseases owing to its functions against inflammation, lipid peroxidation and oxidative stress. Nevertheless, the impact of DBD on diabetic wound healing remains elusive. In this study, we aimed to explore the function of DBD in the regulation of wound healing. We observed that the gavage administration of DBD reduced the wound area, inflammatory infiltration, inflammatory factor levesl, and enhanced granulation tissue formation, wound extracellular matrix (ECM) production, and CD31 accumulation in the diabetic rat wound model, and the co-treatment of gavage administration and the external administration of gauze containing DBD further improved the wound healing effect, while the combination of Notch signaling inhibitor DAPT ((N- [N- (3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester)) could attenuate the improvement. Regarding to the mechanism, the expression levels of Notch1, Delta-like canonical Notch ligand 4 (Dll4), Jagged1, and Hairy Enhancer of Split-1 (Hes1) were increased by DBD, while the treatment of DAPT impaired the effect in the rats. Furthermore, we found that the high glucose (HG)-inhibited viability and tube formation were induced by DBD in human umbilical vein endothelial cells (HUVECs), in which DAPT could reverse this effect. Therefore, we concluded that DBD contributed to wound healing by the activation of Notch signaling. Our finding provides new insight into the potential role of DBD in promoting diabetic wound healing.

ABSTRACT: In this study, we aimed to detect the physicochemical properties of distilled products (residue and distillate) obtained from anhydrous milk fat (AMF) and its dry fractionation products (liquid and solid fractions at 25°C [25 L and 25 S]). The results showed that the saturated fatty acids and low- and medium molecular–weight triglycerides were easily accumulated in the distillate, and the percentage of unsaturated fatty acid and high molecular–weight triglycerides in the residue were higher, and these components in 25 S and 25 L were influenced more significantly than those in the AMF. In addition, the distillate had larger melting ranges in comparison with the distilled substrate, while the melting ranges of residue was smaller. The triglycerides were presented as the mixture crystal forms (α, βʹ, and β crystal) in 25 S, AMF, and their distilling products, and it was transformed gradually to a single form as the increasing of distilling temperature. Moreover, the accumulated pattern of triglycerides was double chain length in 25 S, AMF, and their distilling products. These results provide a new approach to obtain the milk fat fractions with different properties, and the findings of this study enrich the theoretical basis of milk fat separation in practical production.

Abstract Potato late blight caused by Phytophthora infestans is a devastating disease worldwide. Unlike other plant pathogens, double-stranded RNA (dsRNA) is poorly taken up by P. infestans, which is a key obstacle in using dsRNA for disease control. Here, a self-assembled multicomponent nano-bioprotectant for potato late blight management is designed based on dsRNA and a plant elicitor. Nanotechnology overcomes the dsRNA delivery bottleneck for P. infestans and extends the RNAi protective window. The protective effect of nano-enabled dsRNA against infection arises from a synergistic mechanism that bolsters the stability of dsRNA and optimizes its effective intracellular delivery. Additionally, the nano-enabled elicitor enhances endocytosis and amplifies the systemic defense response of the plants. Co-delivery of dsRNA and an elicitor provides a protective effect via the two aspects of pathogen inhibition and elevated plant defense mechanisms. The multicomponent nano-bioprotectant exhibits superior control efficacy compared to a commercial synthetic pesticide in field conditions. This work proposes an eco-friendly strategy to manage devastating plant diseases and pests.

Abstract As an important part of the stomach, gastric antrum secretes gastrin which can regulate acid secretion and gastric emptying. Although most cell types in the gastric antrum are identified, the comparison of cell composition and gene expression in the gastric antrum among different species are not explored. In this study, we collected antrum epithelial tissues from human, pig, rat and mouse for scRNA-seq and compared cell types and gene expression among species. In pig antral epithelium, we identified a novel cell cluster, which is marked by high expression of AQP5, F3, CLCA1 and RRAD. We also discovered that the porcine antral epithelium has stronger immune function than the other species. Further analysis revealed that this may be due to the insufficient function of porcine immune cells. Together, our results replenish the information of multiple species of gastric antral epithelium at the single cell level and provide resources for understanding the homeostasis maintenance and regeneration of gastric antrum epithelium.

Southern stem canker (SSC) of soybean, attributable to the fungal pathogen Diaporthe aspalathi, results in considerable losses of soybean in the field and has damaged production in several of the main soybean-producing countries worldwide. Early and precise identification of the causal pathogen is imperative for effective disease management. In this study, we performed an RPA-CRISPR/Cas12a, as well as LAMP, PCR and real-time PCR assays to verify and compare their sensitivity, specificity and simplicity and the practicality of the reactions. We screened crRNAs targeting a specific single-copy gene, and optimized the reagent concentrations, incubation temperatures and times for the conventional PCR, real-time PCR, LAMP, RPA and Cas12a cleavage stages for the detection of D. aspalathi. In comparison with the PCR-based assays, two thermostatic detection technologies, LAMP and RPA-CRISPR/Cas12a, led to higher specificity and sensitivity. The sensitivity of the LAMP assay could reach 0.01 ng μL−1 genomic DNA, and was 10 times more sensitive than real-time PCR (0.1 ng μL−1) and 100 times more sensitive than conventional PCR assay (1.0 ng μL−1); the reaction was completed within 1 h. The sensitivity of the RPA-CRISPR/Cas12a assay reached 0.1 ng μL−1 genomic DNA, and was 10 times more sensitive than conventional PCR (1.0 ng μL−1), with a 30 min reaction time. Furthermore, the feasibility of the two thermostatic methods was validated using infected soybean leaf and seeding samples. The rapid, visual one-pot detection assay developed could be operated by non-expert personnel without specialized equipment. This study provides a valuable diagnostic platform for the on-site detection of SSC or for use in resource-limited areas.

We aimed to obtain the optimal formula for human milk fat substitute (HMFS) through a combination of software and an evaluation model and further verify its practicability through an animal experiment. The results showed that a total of 33 fatty acid (FA) and 63 triglyceride (TAG) molecular species were detected in vegetable oils. Palmitic acid, oleic acid, linoleic acid, 18:1/16:0/18:1, 18:2/16:0/18:2, 18:1/18:1/18:1 and 18:1/18:2/18:1, were the main molecular species among the FAs and TAGs in the vegetable oils. Based on the HMFS evaluation model, the optimal mixed vegetable oil formula was blended with 21.3% palm oil, 2.8% linseed oil, 2.6% soybean oil, 29.9% rapeseed oil and 43.4% maize oil, with the highest score of 83.146. Moreover, there was no difference in the weight, blood routine indices or calcium and magnesium concentrations in the feces of the mice between the homemade mixed vegetable oil (HMVO) group and the commercial mixed vegetable oil (CMVO) group, while nervonic acid (C24:1) and octanoic acid (C8:0) were absorbed easily in the HMVO group. Therefore, these results demonstrate that the mixing of the different vegetable oils was feasible via a combination of computer software and an evaluation model and provided a new way to produce HMFS.

High oleic acid rapeseed oil offers superior nutritional and health benefits, but its mass production is limited due to poor resistance and slightly lower yield. Photosynthesis serves as the foundation of biological survival and closely correlates with crop resistance to stresses, yield, and quality. To identify photosynthesis-related genes, transcriptome sequencing was conducted on high oleic acid rapeseed Gaoyousuan No. 1 and low oleic acid rapeseed Xiangyou 15 resulting in the identification of a total of 9396 differentially expressed genes (4669 up-regulated and 4727 down-regulated). From these genes nine candidate genes were screened using GO and KEGG analysis with BnGLO4 being selected for cloning purposes. The BnGLO4 gene fragment has a length of 1161 bp with an ORF sequence of 1092 bp encoding a theoretical isoelectric point of pI 7.60; it encodes an unstable lipid-soluble protein localized in peroxisomes without transmembrane structural domains or signal peptides. Its amino acid sequence homology was highest with that of BnaA01G0355200ZS, BnaA01G0355600ZS, BnaA05G0410400ZS, BnaC01G0441800ZS, and Brassica rapa (XP_0091171 45.1), Brassica napus (CDY39100.1), Brassica cretica (KAF3533604.1) and Brassica oleracea var. oleracea (XP_0136106 44.1) belonging to the same cruciferous family.The BnGLO4 gene may be associated with responses to abiotic stresses such as salt, drought, and temperature extremes along with photosynthesis and growth in rapeseed plants. The expression levels of the GLO4 gene (BnaA01G0355200 ZS) were highest in filaments while being higher at each stage in seeds and siliques with the highest expression level at day 14 in seeds. Expression was significantly upregulated after 3 ​h of salt stress treatment, reaching a maximum at 12 ​h before slightly decreasing at 24 ​h. The findings of this study lay a foundation for further investigation on photosynthesis and stress response in high oleic rapeseed.

Abstract Background Diabetic kidney disease (DKD) is a severe complication of diabetes. Currently, no effective measures are available to reduce the risk of DKD progression. This study aimed to establish a weighted risk model to determine DKD progression and provide effective treatment strategies. Methods This was a hospital-based, cross-sectional study. A total of 1104 patients with DKD were included in this study. The random forest method was used to develop weighted risk models to assess DKD progression. Receiver operating characteristic curves were used to validate the models and calculate the optimal cutoff values for important risk factors. Results We developed potent weighted risk models to evaluate DKD progression. The top six risk factors for DKD progression to chronic kidney disease were hemoglobin, hemoglobin A1c (HbA1c), serum uric acid (SUA), plasma fibrinogen, serum albumin, and neutrophil percentage. The top six risk factors for determining DKD progression to dialysis were hemoglobin, HbA1c, neutrophil percentage, serum albumin, duration of diabetes, and plasma fibrinogen level. Furthermore, the optimal cutoff values of hemoglobin and HbA1c for determining DKD progression were 112 g/L and 7.2%, respectively. Conclusion We developed potent weighted risk models for DKD progression that can be employed to formulate precise therapeutic strategies. Monitoring and controlling combined risk factors and prioritizing interventions for key risk factors may help reduce the risk of DKD progression.

Abstract Plant pathogens cause severe losses to crop yields and economic returns in agriculture. Despite plant tissue DNA extraction of typically constituting a preliminary step in nucleic acid-based molecular diagnostics, such lab-based methods can be time-consuming and arduous to complete many samples. To mitigate these challenges, we developed an inexpensive portable DNA extraction technique that is lightweight and suitable for deployment in sampling locations, such as fields. It includes a DNA extraction device fabricated with a Steel Microneedle Array (SMA) and a simple high-efficiency DNA extraction buffer. As a result, DNA extraction times can be reduced to within ~ 1 min, and the eluted DNA is demonstrated to be suitable for subsequent molecular biological analyses without requiring additional purification. Cross-priming amplification (CPA) technology was first established to detect Phytophthora infestans, which achieves sensitivity attainment of 10–7 ng/µL. The detection result can be conveniently estimated with naked-eye visual inspection using fluorescent dsDNA binding dye. CPA was demonstrated to be more feasible than PCR-based approaches and performed well in species-specific and practicability tests. This study elucidates a novel integrated pathogen detection technique coupled with SMA-Device extraction and a modified visual CPA assay to establish and verify various field-based samples infected with multiple pathogens. Altogether, the total sample-to-answer time for pathogen detection was reduced to ~ 1.5 h, making field-based analysis affordable and achievable for farmers or extension workers inside and outside the laboratory.

A 56-day feeding trial assessed the effects of black soldier fly larvae meal (BSFLM) on the growth performance and hepatopancreas health of juvenile Eriocheir sinensis. Six isoproteic and isolipidic diets with 0% (FM), 10% (BSFLM10), 20% (BSFLM20), 30% (BSFLM30), 40% (BSFLM40), or 50% (BSFLM50) replacement of fish meal by BSFLM were formulated. Compared to FM, replacing 10%–40% of fish meal with BSFLM did not significantly affect the weight gain rate (WGR) or specific growth rate (SGR), while BSFLM50 significantly decreased the WGR and SGR. Crabs fed BSFLM50 had significantly lower T-AOC activity than those fed other diets, and crabs fed BSFLM30, BSFLM40, or BSFLM50 had significantly lower activities of antioxidant enzymes (SOD and GSH-Px) in the hepatopancreas than those fed FM or BSFLM10. Compared to FM, BSFLM10, BSFLM20, and BSFLM30 did not affect the relative expression of genes related to the nonspecific immunity, while BSFLM40 and BSFLM50 upregulated the relative expression of these genes. Furthermore, histological analysis showed that the hepatopancreas was deformed in the BSFLM50 group, with widened lumens and loss of basal membrane integrity. In summary, BSFLM replacing 50% of fish meal reduced growth and structural damage to the hepatopancreas. An immune response was activated when the replacement level was over 30%. Therefore, the replacement level of dietary fish meal by BSFLM is recommended to be not more than 30% of the juvenile E. sinensis feed.

Ecosystem services (ESs) are the cornerstone of human well-being. On the Tibetan Plateau and in its subregions, understanding the effects of the spatiotemporal continuity in the trade-offs/synergies of ESs, and identifying their drivers, is crucial for ecosystem conservation and sustainable development. In this study, we investigated the spatiotemporal variation of four ESs (WY, water yield; SR, soil retention; HQ, habitat quality; CS, carbon sequestration) on the Tibetan Plateau, in 2000–2020. We introduced a new indicator (RESI, Index of the relationships between ESs) to measure the trade-offs/synergies among ESs and their magnitudes, and used GeoDetector to analyze the drivers of ESs and their relationships. The following results were obtained: (1) The four ESs exhibited similar geographical characteristics, being higher in the southeast and lower in the northwest. The spatiotemporal variation of WY and SR was similar to the precipitation trend. WY, SR and CS increased significantly (p

Summary: Protein homeostasis is vital for organisms and requires chaperones like the conserved Bcl-2-associated athanogene (BAG) co-chaperones that bind to the heat shock protein 70 (HSP70) through their C-terminal BAG domain (BD). Here, we show an unconventional BAG subfamily exclusively found in oomycetes. Oomycete BAGs feature an atypical N-terminal BD with a short and oomycete-specific α1 helix (α1′), plus a C-terminal small heat shock protein (sHSP) domain. In oomycete pathogen Phytophthora sojae, both BD-α1′ and sHSP domains are required for P. sojae BAG (PsBAG) function in cyst germination, pathogenicity, and unfolded protein response assisting in 26S proteasome-mediated degradation of misfolded proteins. PsBAGs form homo- and heterodimers through their unique BD-α1′ to function properly, with no recruitment of HSP70s to form the common BAG-HSP70 complex found in other eukaryotes. Our study highlights an oomycete-exclusive protein homeostasis mechanism mediated by atypical BAGs, which provides a potential target for oomycete disease control.

Radar high‐resolution range profile (HRRP) is widely used in radar automatic target recognition due to its advantages such as easy availability, convenient processing, and small storage space. Current recognition methods for HRRP sequences mainly focus on the temporal information of HRRP sequences, which cannot fully utilize the temporal and spatial information contained in HRRP sequences. Moreover, most of these methods fail in long‐range modeling and global information extraction of HRRP sequences. To solve above problems, a HRRP sequence recognition method based on transformer with temporal–spatial fusion and label smoothing (TSF–transformer–LS) is proposed. TSF–transformer–LS contains temporal transformer blocks and spatial transformer blocks, which are used to extract deep global features of HRRP sequences in the time domain and space domain, respectively. Then, an attention fusion mechanism is developed to realize the adaptive fusion of temporal and spatial features. Moreover, label smoothing is used to add noise to sample labels, which can solve the overfitting problem of transformer caused by a large amount of noise hidden in HRRP in real scenes. Experiments on MSTAR, a standard dataset, show that the proposed method outperforms other methods in recognition performance. Furthermore, the effectiveness and interpretability of the method are explored.

Although telomerase has low activity in somatic quiescent cells, it plays an significant roles in regenerative cells such as endothelial cells, hepatocytes, epithelial cells, and hemocytes. Telomerase activity and telomere length are critical factors in age-related chronic diseases as they are closely related to cell senescence. However, whether telomerase activity plays a key role in disease progression or whether the role of telomerase is unified among different diseases are unresolved. Considering that aging is the most important risk factor for neurodegenerative and metabolic diseases, this article will analyze the evidence, mechanism, and therapeutic potential of telomerase activity in several chronic disease, including type 2 diabetes, neurodegenerative diseases, atherosclerosis, heart failure and non-alcoholic fatty liver disease, in order to provide clues for the use of telomerase activity to target the treatment of age-related chronic diseases.

Purpose – To cope with climate change and achieve the dual carbon goal, China has actively promoted the implementation of carbon trading pilot policy, among which the power industry plays an important role in China’s carbon emission reduction work. The purpose of this paper is to study the influence of carbon trading policy on the energy efficiency of power industry and achieve the comprehensive goal of carbon emission reduction, carbon peak and carbon neutralization. Design/methodology/approach – This paper constructs the difference-in-differences model based on 2012–2019 provincial data to study the impact of carbon trading policy on energy efficiency in the power industry and its effect path. Heterogeneity analysis was conducted to compare the effects of carbon trading policy in eastern, central and western regions as well as at different levels of power structures. Findings – Carbon trading policy can significantly improve the energy efficiency of the power industry, and the policy effect is more significant in eastern and western regions and areas with high power structure. Mechanism analysis shows that carbon trading policy mainly influences the energy efficiency of power industry by environmental protection investment, power consumption demand and industrial structure. Originality/value – This paper uses provincial panel data to deeply study the influence of carbon trading policy on energy efficiency of the power industry and its effect path. By constructing the difference-in-differences model, this paper empirically analyzes the governance effect of carbon trading policy. Meanwhile, it controls individual and time effects to solve the endogeneity problem prevalent in previous literature.

Methotrexate (MTX) has an antitumor effect when used for the treatment of acute lymphoblastic leukemia (ALL). This study aims at evaluating the associations between 14 polymorphisms of six genes involved in MTX metabolism with serum MTX concentration and toxicity accompanying high-dose MTX. Polymorphisms in 183 Chinese patients with ALL were analyzed using TaqMan single nucleotide polymorphism genotyping assay. The serum MTX concentration was determined using homogeneous enzyme immunoassay. MTX-related toxicities were also evaluated. Renal toxicity was significantly associated with higher serum MTX concentrations at 24, 48, and 72 hours, and MTX elimination delay (P = 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively), whereas SLCO1B1 rs4149056 was associated with serum MTX concentrations at 48 and 72 hours, and MTX elimination delay in candidate polymorphisms (P = 0.014, P = 0.019, and P = 0.007, respectively). SLC19A1 rs2838958 and rs3788200 were associated with serum MTX concentrations at 24 hours (P = 0.016, P = 0.043, respectively). MTRR rs1801394 was associated with serum MTX concentrations at 72 hours (P = 0.045). Neutropenia was related to SLC19A1 rs4149056 (odds ratio [OR]: 3.172, 95% confidence interval [CI]: 1.310–7.681, P = 0.011). Hepatotoxicity was associated with ABCC2 rs2273697 (OR: 3.494, 95% CI: 1.236–9.873, P = 0.018) and MTRR rs1801394 (OR: 0.231, 95% CI: 0.084–0.632, P = 0.004). Polymorphisms of SLCO1B1, SLC19A1, ABCC2, and MTRR genes help predict higher risk of increased MTX levels or MTX-related toxicities in adult ALL patients.

Dendrobium nobile Lindl. polysaccharide (DNP1) showed good anti-inflammatory activity in our previous study. In this study, the structural characterization of DNP1 and its mode of action on TLR4 were investigated. Structural characterization suggested that DNP1 was a linear glucomannan composed of (1 → 4)-β-Manp and (1 → 4)-β-Glcp residues, and the acetyl group was linked to the C-2 of Manp. The possible repeating structural units of DNP1 were [→4)-2-OAc-β-Manp-(1→]3 →4)-β-Glcp-(1→. Surface plasmon resonance (SPR) binding test results showed that DNP1 did not bind directly to TLR4. The TLR4 and MD2 receptor blocking tests confirmed that DNP1 needs MD2 and TLR4 to participate in its anti-inflammatory effect. The binding energy of DNP1 to TLR4-MD2 was −7.9 kcal/mol, indicating that DNP1 could bind to the TLR4-MD2 complex stably. Therefore, it is concluded that DNP1 may play an immunomodulatory role by binding to the TLR4-MD2 complex and inhibiting the TLR4-MD2-mediated signaling pathway.

During early lactation, dairy cows have a negative energy balance since their energy demands exceed their energy intake: in this study, we aimed to investigate the association between diet and plasma metabolomics profiles and how these relate to energy unbalance of course in the early-lactation stage. Holstein-Friesian cows were randomly assigned to a glucogenic (n = 15) or lipogenic (n = 15) diet in early lactation. Blood was collected in week 2 and week 4 after calving. Plasma metabolite profiles were detected using liquid chromatography–mass spectrometry (LC-MS), and a total of 39 metabolites were identified. Two plasma metabolomic profiles were available every week for each cow. Metabolite abundance and metabolite ratios were used for the analysis using the XGboost algorithm to discriminate between diet treatment and lactation week. Using metabolite ratios resulted in better discrimination performance compared with the metabolite abundances in assigning cows to a lipogenic diet or a glucogenic diet. The quality of the discrimination of performance of lipogenic diet and glucogenic diet effects improved from 0.606 to 0.753 and from 0.696 to 0.842 in week 2 and week 4 (as measured by area under the curve, AUC), when the metabolite abundance ratios were used instead of abundances. The top discriminating ratios for diet were the ratio of arginine to tyrosine and the ratio of aspartic acid to valine in week 2 and week 4, respectively. For cows fed the lipogenic diet, choline and the ratio of creatinine to tryptophan were top features to discriminate cows in week 2 vs. week 4. For cows fed the glucogenic diet, methionine and the ratio of 4-hydroxyproline to choline were top features to discriminate dietary effects in week 2 or week 4. This study shows the added value of using metabolite abundance ratios to discriminate between lipogenic and glucogenic diet and lactation weeks in early-lactation cows when using metabolomics data. The application of this research will help to accurately regulate the nutrition of lactating dairy cows and promote sustainable agricultural development.

Bovine diarrhea is a multi-factorial disease and remains one of the biggest health problems in animal husbandry. The endemic trends of the main pathogens responsible for bovine diarrhea in Inner Mongolia have not been analyzed systematically before. Therefore, the purpose of this study was to estimate the prevalence of bovine diarrhea pathogens found in the scattered households of Inner Mongolia in China. Additionally, we assessed for differences in the prevalence of infection based on age and region, as well as determined local prevalence rates and the rates of mixed infections. Using a two-stage random sampling strategy, 3,050 serum samples were collected from 72 bovine herds in 11 leagues and cities in Inner Mongolia, and the positive rates of BVDV, BRV, BCoV, K99, and Mycobacterium paratuberculosis (M. paratuberculosis) antibodies in the samples were detected by ELISA to determine the epidemic trends and epidemic differences of the five pathogens in Inner Mongolia. The positive rates of antibodies based on serum samples were: BVDV, 18.79% (95% CI [17.44–20.22]); BRV, 12.39% (95% CI [11.27–13.61]); BCoV, 12.82% (95% CI [11.68–14.05]); K99, 13.80% (95% CI [12.62–15.07]); and M. paratuberculosis, 10.79% (95% CI [9.74–11.94]). The prevalence rates of BRV, BCoV and K99 at 0–2 months were significantly different from that at 2–6 months, 6–18 months and adult cattle (P < 0.05). The prevalence of BVDV and M. paratuberculosis was the highest in adult cattle, which was significantly different from that in other age groups (P < 0.05). Furthermore, obvious regional epidemiological differences among the five diseases were observed. There was a mixed infection of BRV+BCoV in each age stage, the highest mixed infection being BVDV+BRV+K99 at 0–2 months of age. Our results showed that the cattle of scattered households in the Inner Mongolia of China were endemicly infected with several important cattle pathogens. Most of the pathogens studied occurred between 0–2 months of age and were mixed infections, which greatly influences the health of the cattle and leads to economic loss. These findings are of practical significance for the future prevention and control of bovine diarrhea in the Inner Mongolia or other regions of China.

Abstract The failing heart is characterized by an increase in glucose uptake and glycolytic rates that is not accompanied by a concomitant increase in glucose oxidation. Lower coupling of glucose oxidation to glycolysis possibly owes to unchanged or reduced pyruvate oxidation in mitochondria. Therefore, increasing pyruvate oxidation may lead to new therapies for heart disease. Dihydrolipoamide dehydrogenase (DLD) is a component of the pyruvate dehydrogenase complex (PDH). DLD mutations or defects are closely associated with metabolic diseases. However, few studies explore the effects of DLD mutants or acylation status on PDH activity and pyruvate metabolism. P300 is protein 2-hydroxyisobutyryltransferases in cells, and P300-dependent lysine 2-hydroxyisobutyrylation of glycolytic enzymes affects glucose metabolism. However, there are no relevant reports on the effect of 2-hydroxyisobutyrylation on the energy metabolism of heart failure, and it is worth further in-depth study. In this study, we showed that 2-hydroxyisobutyrylation is an essential protein translational modification (PTM) that regulates the activity of pyruvate dehydrogenase complex (PDHc). In a mouse model of transverse aortic constriction (TAC)-induced cardiac hypertrophy, the 2-hydroxyisobutylation of DLD was significantly increased, related to the decrease in PDH activity. In addition, our data provide clear evidence that DLD is a direct substrate of P300. As one of the main active ingredients of ginseng, ginsenoside Rg3 (Rg3) can reduce the 2-hydroxyisobutylation levels of DLD and restore the PDH activity by inhibiting the acyltransferase activity of P300, thereby producing beneficial effects whenever the heart is injured. Therefore, this study suggests a novel strategy for reversing myocardial hypertrophy.

Abstract Heterotrimeric G proteins, comprising Gα, Gβ, and Gγ subunits, are key regulators of eukaryotic intracellular signaling. Extra-large G (XLG) proteins are a subfamily of plant-specific Gα proteins interacting with plasma membrane-localized receptors to regulate multiple biological processes. The Nicotiana benthamiana genome encodes seven XLG proteins, NbXLG1–7, whose functions in disease resistance and underlying mechanisms are unknown. In this study, we silenced all the seven genes and found that disease susceptibility was enhanced when both NbXLG3 and NbXLG5 or NbXLG4 was silenced. Then, we generated N. benthamiana xlg3xlg5 double- and xlg4 single-mutant lines using the CRISPR-Cas9 approach. All the mutants showed reduced resistance to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000, the fungal pathogen Sclerotinia sclerotiorum, and a series of oomycete pathogens, including Phytophthora capsici, Phytophthora infestans, and Phytophthora parasitica. We further demonstrated that NbXLG3/4/5 positively regulated microbial pattern-induced reactive oxygen species burst and defense gene expression by directly coupling to the tested plant immune receptors. In addition, we examined the role of NbXLG3/4/5 in abiotic stress tolerance and observed that NbXLG3 and NbXLG5 negatively regulated plant resistance to high-salt, mannitol, and PEG. Our study demonstrates the possible role of NbXLG3/4/5 in response to biotic and abiotic stresses and provides insights for the improvement of plant resistance to environmental changes.

Abstract Convolution neural networks (CNNs) represent one of the workhorses of artificial intelligence applications. As a typical artificial intelligence application, a high‐resolution range profile (HRRP) target recognition method based on CNNs has aroused a lot of research interest. Most CNNs use a relatively small and single‐scale convolution kernel size to control the number of parameters and computational complexity, but recent studies indicate that CNNs with a small kernel size cannot extract enough spatial information, which hurts the recognition performance. Aiming at this problem, this paper proposes a multi‐scale group‐fusion one‐dimensional convolution neural network (MSGF‐1D‐CNN) for HRRP target recognition. MSGF‐1D‐CNN utilises multi‐scale group one‐dimensional convolution (MSG 1D‐Conv) and point‐wise convolution (PW‐Conv) to replace the standard convolution. Multi‐scale group one‐dimensional convolution can significantly reduce complexity and capture the information of targets within HRRP in different levels of detail to enhance feature extraction, while PW‐Conv can realise the fusion of multi‐scale features to help boosting recognition performance. Experiments on five mid‐course ballistic targets in the HRRP dataset show that MSGF‐1D‐CNN has superior recognition performance, and the parameter number of the model is reduced by more than 2.4 times than standard 1D‐CNN. Furthermore, MSGF‐1D‐CNN shows better performance on fine‐grained HRRP target recognition and anti‐noise robustness in most cases.

Abstract As a special deep learning algorithm, the multilayer extreme learning machine (ML-ELM) has been extensively studied to solve practical problems in recent years. The ML-ELM is constructed from the extreme learning machine autoencoder (ELM-AE), and its generalization performance is affected by the representation learning of the ELM-AE. However, given label information, the unsupervised learning of the ELM-AE is difficult to build the discriminative feature space for classification tasks. To address this problem, a novel Fisher extreme learning machine autoencoder (FELM-AE) is proposed and is used as the component for the multilayer Fisher extreme leaning machine (ML-FELM). The FELM-AE introduces the Fisher criterion into the ELM-AE by adding the Fisher regularization term to the objective function, aiming to maximize the between-class distance and minimize the within-class distance of abstract feature. Different from the ELM-AE, the FELM-AE requires class labels to calculate the Fisher regularization loss, so that the learned abstract feature contains sufficient category information to complete classification tasks. The ML-FELM stacks the FELM-AE to extract feature and adopts the extreme leaning machine (ELM) to classify samples. Experiments on benchmark datasets show that the abstract feature extracted by the FELM-AE is more discriminative than the ELM-AE, and the classification results of the ML-FELM are more competitive and robust in comparison with the ELM, one-dimensional convolutional neural network (1D-CNN), ML-ELM, denoising multilayer extreme learning machine (D-ML-ELM), multilayer generalized extreme learning machine (ML-GELM), and hierarchical extreme learning machine with L21‑norm loss and regularization (H-LR21-ELM).