Objective: The therapeutic efficacy of the classic antibiotic combination trimethoprim/sulfamethoxazole (TMP/SMZ) is often limited by the significant pharmacokinetic mismatch. In this study, a polyethylene glycol-polylactic-co-glycolic acid (PEG-PLGA) nanodelivery system was employed to improve the pharmacokinetic matching of TMP and SMZ. The investigation also evaluated the enhanced in vivo antibacterial efficacy of this formulation. Methods: Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) was employed to systematically characterize the absorption, distribution, and excretion profiles of PEG-PLGA-loaded TMP nanoparticles (NPs) in rats. In vitro antibacterial activity was assessed against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vivo efficacy and biosafety of the TMP NPs/SMZ regimen were evaluated using a murine E. coli infection model via survival monitoring, biochemical assays, and histopathology. Results: Pharmacokinetic analysis revealed that TMP NPs achieved a relative bioavailability of 193.05% and extended the elimination half-life by 3.37-fold compared to free TMP. Tissue distribution showed significantly increased drug accumulation in the liver, spleen, and kidneys, with renal clearance as the primary excretion pathway (73.89%). In vitro, the nano-formulation reduced the minimum inhibitory concentration (MIC) by 2-4-fold and shortened the bactericidal duration from 12 to 8 h. In vivo, the TMP NPs/SMZ combination significantly improved survival rates, accelerated recovery, and alleviated infection-induced organ damage without systemic toxicity. Conclusions: This nanotechnology-based strategy effectively aligns the pharmacokinetics of TMP and SMZ, prolongs their synergistic window, and enhances biosafety, offering a viable approach to revitalize classic antibiotic combinations.

This study aimed to clarify the neuroprotective effect of Acer truncatum Bunge seed oil (ASO) and its interactions with the gut microbiota in transgenic mice with 5 × Familial Alzheimer's disease (5 × FAD). The AD-transgenic mice were fed with standard diet supplemented with 4% ASO from one to six months of age. The result show that ASO intervention can alleviate learning and memory impairment, enhance motor coordination and endurance, and reduce Aβ deposition in the brains. It also inhibit the proliferation of microglia and astrocytes, decrease the levels of IL-1β, IL-6, and TNF-α in the hippocampus and serum. Then, ASO could increase the Chao1 index and Shannon index, alter the gut microbiota composition, specifically, enhance the growth of gut bacteria correlated with the production of SCFAs, including Ruminococcaceae, Butyricicoccus, Sutterella and others, particularly those related to butyrate production. Additionally, ASO can increase the concentrations of SCFAs in fresh feces and serum, particularly butyric acid. ASO could primarily modulate the biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, and sphingolipids metabolism in serum. At the same time, Fecal microbiota transplantation (FMT) could reduce Aβ deposition, enhance learning and memory. Finally, Supplementation of sodium Buty also mitigate learning and memory impairments. This study highlights the gut microbiota might be a potential therapeutic target for AD and provides a scientific foundation for developing novel pharmaceuticals or nutraceuticals.

The bovine corpus luteum (CL) is critical for pregnancy establishment and maintenance via progesterone (P4) secretion. Primary bovine luteal cells (PBLC), the core in vitro model for reproductive and steroidogenesis research, are severely limited by high isolation cost, cellular heterogeneity, and restricted proliferative capacity. In this study, we established an immortalized bovine luteal cell line with stable in vitro proliferative capacity, termed SV40 T-immortalized bovine luteal cells (SV40T-IBLC), via lentiviral transduction of the Simian virus 40 (SV40) T antigen gene. The immortalized cells displayed a typical epithelial-like morphology with abundant small cytoplasmic lipid droplets. They secreted multiple functional hormones including P4 and oxytocin, expressed synaptophysin, a key marker protein of mature functional luteal cells, and maintained stable expression of core steroidogenic genes and proteins such as STAR, 3β-hydroxysteroid dehydrogenase (3β-HSD), CYP11A1, and PTGFR, with mRNA levels of these key genes showing no significant difference from those of parallel-cultured PBLC. Functionally, SV40T-IBLC exhibited time-dependent P4 secretion, with P4 concentration in the culture supernatant reaching 1.89 ± 0.14 ng/mL at 60 h, which was fully consistent with the secretory level and dynamic pattern of PBLC. After continuous in vitro culture up to the 50th passage, the cells maintained a normal diploid karyotype (29 pairs of autosomes and 1 pair of XX sex chromosomes), and no evidence of malignant transformation was observed in the anchorage-independent growth assay and in vivo tumorigenicity assay in nude mice. Furthermore, Co-culture with SV40T-IBLC significantly enhanced the viability of bovine endometrial epithelial cells (BEEC) by 34.2% after 72 h of co-incubation (p < 0.01), increased intracellular lipid droplet abundance of BEEC, and upregulated the mRNA expression of endometrial receptivity-related genes including EGF and LIF, with no significant alteration in BEEC apoptosis rate. In conclusion, this immortalized cell line retains core functional characteristics of PBLC, providing a stable, homogeneous in vitro model for bovine reproductive research.

Ischemic stroke ranks as the second leading cause of global mortality. The limited time for effective thrombolytic treatment has prompted the exploration of alternative prevention approaches. Eucommia ulmoides (E. ulmoides) Oliv. bark has shown multiple pharmacological effects, including neuroprotection, anti-inflammation and autophagy modulation. This study aims to elucidate the neuroprotective effects of water extract of E. ulmoides (WEU) supplementation in a middle cerebral artery occlusion (MCAO) mouse model and to further explore the underlying molecular mechanisms. Seven bioactive compounds in WEU—aucubin, chlorogenic acid, geniposidic acid, quercetin, protocatechuic acid, betulin and pinoresinol diglucoside—were identified using HPLC-MS. Our results showed that WEU supplementation significantly decreased infarct volume and ameliorated neurological dysfunction in mice following MCAO/reperfusion (MCAO/R) injury. Furthermore, the administration of WEU significantly attenuated microglia activation induced by cortical ischemia in mice and inhibited the production of pro-inflammatory mediators, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Importantly, in contrast with the vehicle group, the protein expression levels of Toll-like receptor 4 (TLR4), phospho-p38 (p-p38) and nuclear factor kappa B (NF-κB) were reduced in the WEU group. Therefore, this present study provides evidence that E. ulmoides improves neurological behaviors by suppressing neuroinflammation and inhibiting the activation of the TLR4/ p38 MAPK and NF-κB pathways in mice after ischemia, which indicates that E.ulmoides is a promising candidate for alleviating gray matter ischemic change.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which effective treatment options are still lacking. Xanthoceras sorbifolium oil (XSO), which contains rich nervonic acid and unsaturated fatty acids, shows anti-AD potential. However, its underlying mechanisms remain unclear. This study investigated the neuroprotective effects of XSO and its interactions with the gut microbiota in transgenic mice with 5×Familial Alzheimer's disease (5×FAD). The AD-transgenic mice were fed a standard diet supplemented with 5% XSO from 3 to 6 months of age. Behavioral tests revealed that XSO intervention markedly improved learning and memory in AD mice. Immunofluorescence staining further revealed that XSO-administration effectively reduced β-amyloid (Aβ) deposition in the hippocampus of AD mice. Moreover, XSO supplementation alleviated neuroinflammation by suppressing microglial over-activation and decreasing the pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in the hippocampus of AD mice. In addition, XSO intervention modulated the gut microbiota structure and enhanced microbial richness and diversity in AD mice. Serum metabolomics showed that XSO intervention primarily modulated the unsaturated fatty acid metabolism. Subsequently, a fecal microbiota transplantation (FMT) experiment showed that FMT from XSO-administrated mice regulated the gut microbiota and unsaturated fatty acid metabolism, reduced Aβ deposition, and improved learning and memory in AD mice. This study highlights the gut microbiota might be a potential therapeutic target for AD and demonstrates that XSO holds promise as a natural agent for the treatment of AD and related neurodegenerative diseases.

Leydig cells (LCs) are the primary testosterone-producing cells. Their steroidogenic capacity is heavily influenced by the postnatal development of the LC lineage. The final developmental stage of LCs involves transition from immature LCs (ILCs) to adult LCs (ALCs) during puberty. However, the morphological and functional changes that occur during this transition in most mammals remain unclear. In this study, we conducted a comparative analysis of morphological and functional changes in developing LCs in dairy goats. The results revealed that during the transition from ILC to ALC, the ovoid LC transformed into an irregular round shape with a well-developed smooth endoplasmic reticulum (sER), numerous mitochondria, and small lipid droplets (LDs) distributed in the cytoplasm. Subsequently, the isolated primary ILCs were matured using chorionic gonadotropin (CG). CG stimulation increases the expression of steroidogenic genes and decreases the levels of testosterone-metabolizing enzymes. In vitro studies have shown that small LDs are the preferred source of cholesterol substrates in steroidogenesis, and that their interaction with mitochondria facilitates free cholesterol transport. Further analyses using confocal microscopy, ultrastructural analysis, and co-immunoprecipitation consistently demonstrated that vimentin filaments contributed to the interaction between LDs and mitochondria. Specifically, the knockdown of vimentin using siRNA substantially reduced the physical contact between LDs and mitochondria, resulting in inadequate cholesterol transport and ultimately impaired steroidogenesis. Overall, our findings indicate that significant morphological and functional changes occurred during the transition from ILCs to ALCs in goats. The cytoskeleton, primarily composed of vimentin filaments, is an important component of the interactions between LDs and mitochondria and contributes to cholesterol transport during testosterone synthesis.

Diet-related maternal obesity has been implicated in neurodevelopmental disorders in progeny. Although the precise mechanisms and effective interventions remain uncertain, our research elucidates some of these complexities. We established that a prenatal high-fat diet triggered maternal immune activation (MIA), marked by elevated serum lipopolysaccharide levels and inflammatory-cytokine overproduction, which dysregulated the maternal tryptophan metabolism promoting the accumulation of neurotoxic kynurenine metabolites in the embryonic brain. Interventions aimed at mitigating MIA or blocking the kynurenine pathway effectively rescued the male mice social performance. Furthermore, excessive kynurenine metabolites initiated oxidative stress response causing neuronal migration deficits in the fetal neocortex, an effect that was mitigated by administering the glutathione synthesis precursor N-Acetylcysteine, underscoring the central role of maternal immune-metabolic homeostasis in male mice behavioral outcomes. Collectively, our study accentuated the profound influence of maternal diet-induced immuno-metabolic dysregulation on fetal brain development and provided the preventive strategies for addressing neurodevelopmental disorders.

Background/Objectives: Trimethoprim (TMP), a sulfonamide antibacterial synergist, is widely used in antimicrobial therapy owing to its broad-spectrum activity and clinical efficacy in treating respiratory, urinary tract, and gastrointestinal infections. However, its application is limited due to poor aqueous solubility, a short elimination half-life (t1/2), and low bioavailability. In this study, we proposed TMP loaded by PEG-PLGA polymer nanoparticles (NPs) to increase its efficacy. Methods: We synthesized and thoroughly characterized PEG-PLGA NPs loaded with TMP using an oil-in-water (O/W) emulsion solvent evaporation method, denoted as PEG-PLGA/TMP NPs. Drug loading capacity (LC) and encapsulation efficiency (EE) were quantified by ultra-performance liquid chromatography (UPLC). Comprehensive investigations were conducted on the stability of PEG-PLGA/TMP NPs, in vitro drug release profiles, and in vivo pharmacokinetics. Results: The optimized PEG-PLGA/TMP NPs displayed a high LC of 34.0 ± 1.6%, a particle size of 245 ± 40 nm, a polydispersity index (PDI) of 0.103 ± 0.019, a zeta potential of −23.8 ± 1.2 mV, and an EE of 88.2 ± 4.3%. The NPs remained stable at 4°C for 30 days and under acidic conditions. In vitro release showed sustained biphasic kinetics and enhanced cumulative release, 86% at pH 6.8, aligning with first-order models. Pharmacokinetics in rats revealed a 2.82-fold bioavailability increase, prolonged half-life 2.47 ± 0.19 h versus 0.72 ± 0.08 h for free TMP, and extended MRT 3.10 ± 0.11 h versus 1.27 ± 0.11 h. Conclusions: PEG-PLGA NPs enhanced the solubility and oral bioavailability of TMP via high drug loading, stability, and sustained-release kinetics, validated by robust in vitro-in vivo correlation, offering a promising alternative for clinical antimicrobial therapy.

The steroidogenic acute regulatory protein (STAR) plays a crucial role in facilitating cholesterol transfer across the inner mitochondrial membrane during the process of steroidogenesis. However, the transcriptional regulation of the bovine STAR gene and its function of progesterone synthesis in luteal cells remain poorly understood. The objective of this study was to analyze the bovine STAR gene structure, identify its active promoter region, and explore its potential roles in progesterone synthesis. Bioinformatics analysis revealed that the bovine STAR gene encodes an 858-bp mRNA transcript, which translates into a protein consisting of 285 amino acids. The phylogenetic tree analysis showed that its genetic distance was closest to that of sheep. Notably, the promoter region of bovine STAR lacks CpG islands, and the core promoter is located within the - 1990/-1 region, which containes potential binding sites for transcription factors such as NF-κB, Sp1, NF-1, and LyF-1. Dual-luciferase reporter assays confirmed the core promoter activity within this region, aligning with the prediction results. Overexpression of the STAR gene in bovine luteal cells significantly enhanced progesterone production and upregulated the expression of steroidogenic enzymes, particularly 3βHSD and CYP11A1. In conclusion, this study identifies the core promoter region of the bovine STAR gene is positioned at -1990/-1. By regulating key steroidogenic enzymes, particularly 3βHSD and CYP11A1, STAR is involved in the synthesis of progesterone in corpus luteum cells.

Reverse transcription–quantitative real-time polymerase chain reaction (RT-qPCR) is widely used to accurately assess target gene expression. Evaluating gene expression requires the selection of appropriate reference genes. To identify reliable reference genes for Toxoplasma gondii (T. gondii) under varying concentrations of broxaldine (BRO), we employed the ΔCt method, BestKeeper, NormFinder, GeNorm, and the comprehensive web-based platform RefFinder to assess the expression stability of ten candidate reference genes in T. gondii. Herein, our findings reveal that the stability of these candidate reference genes is influenced by different experimental conditions. Under normal conditions, the most stable genes were TGME49_205470 and TGME49_226020. However, the most stable genes differed when BRO concentrations were at 1, 2, and 4 μg/mL. Across all samples, TGME49_247220 and TGME49_235930 were identified as the most stable reference genes. Moreover, we also confirmed the stability of TGME49_247220 and TGME49_235930 as reference genes through RT-qPCR assays. The present study provides a foundation for applying the RT-qPCR method to investigate target gene expression following BRO treatment in T. gondii.

There is an urgent need to find new solutions for the global dilemma of increasing antibiotic resistance in humans and animals. Modifying the performance of existing antibiotics using the nanocarrier drug delivery system (DDS) is a good option considering economic costs, labor costs, and time investment compared to the development of new antibiotics. Numerous studies on nanomedicine carriers that can be used for humans are available in the literature, but relatively few studies have been reported specifically for veterinary pharmaceutical products. Polymer-based nano-DDS are becoming a research hotspot in the pharmaceutical industry owing to their advantages, such as stability and modifiability. This review presents current research progress on polymer-based nanodelivery systems for veterinary antimicrobial drugs, focusing on the role of polymeric materials in enhancing drug performance. The use of polymer-based nanoformulations improves treatment compliance in livestock and companion animals, thereby reducing the workload of managers. Although promising advances have been made, many obstacles remain to be addressed before nanoformulations can be used in a clinical setting. Some crucial issues currently facing this field, including toxicity, quality control, and mass production, are discussed in this review. With the continuous optimization of nanotechnology, polymer-based DDS has shown its potential in reducing antibiotic resistance to veterinary medicines.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious viral disease that causes significant economic losses to the swine industry worldwide. PRRS virus (PRRSV) infection is a receptor-mediated endocytosis and replication process. The purpose of this study was to determine the localization and expression of four important PRRSV receptors in immunological organs of piglets. After piglets were infected with PRRSV, Hematoxylin and Eosin staining, immunofluorescence, and Western blot were used to perform histopathological examination and receptors distribution analysis. The results showed that PRRSV caused severe damage to the piglets’ immune organs, including atrophy of the thymus and swelling of lymph node. Histopathological lesions were mainly observed in the lung and lymph node and were characterized by interstitial pneumonia, collapsed follicles, exhaustion of germinal centers, and extensive hemorrhage. Immunofluorescence staining and Western blot results showed that the receptors of CD163 and NMHCII-A were mainly distributed in the thymus, hilar lymph nodes, and mesenteric lymph nodes. However, Sn and vimentin receptors were expressed at low levels in the immune organs of piglets. The distribution of the four receptors in the immune organs was more concentrated in the cortex but was more scattered in the medulla. Compared to the control group, the relative expression of the four receptors increased significantly in most immune organs after viral infection. In conclusion, our study examined the distribution and expression of four PRRSV receptors in immunological organs. We observed a significant increase in the expression of Sn, CD163, and vimentin following viral infection. These findings may provide potential targets for future antiviral reagent design or vaccine development.

Rationale: Consumption of a high-fat diet (HFD) has been implicated in cognitive deficits and gastrointestinal dysfunction in humans, with the gut microbiota emerging as a pivotal mediator of these diet-associated pathologies. The introduction of plant-based polysaccharides into the diet as a therapeutic strategy to alleviate such conditions is gaining attention. Nevertheless, the mechanistic paradigm by which polysaccharides modulate the gut microbiota remains largely undefined. This study investigated the mechanisms of action of Eucommiae cortex polysaccharides (EPs) in mitigating gut dysbiosis and examined their contribution to rectifying diet-related cognitive decline. Methods: Initially, we employed fecal microbiota transplantation (FMT) and gut microbiota depletion to verify the causative role of changes in the gut microbiota induced by HFD in synapse engulfment-dependent cognitive impairments. Subsequently, colonization of the gut of chow-fed mice with Escherichia coli (E. E. coli) ) from HFD mice confirmed that inhibition of Proteobacteria by EPs was a necessary prerequisite for alleviating HFD-induced cognitive impairments. Finally, supplementation of HFD mice with butyrate and treatment of EPs mice with GW9662 demonstrated that EPs inhibited the expansion of Proteobacteria in the colon of HFD mice by reshaping the interactions between the gut microbiota and colonocytes. Results: Findings from FMT and antibiotic treatments demonstrated that HFD-induced cognitive impairments pertaining to neuronal spine loss were contingent on gut microbial composition. Association analysis revealed strong associations between bacterial taxa belonging to the phylum Proteobacteria and cognitive performance in mice. Further, introducing E. coli from HFD-fed mice into standard diet-fed mice underscored the integral role of Proteobacteria proliferation in triggering excessive synaptic engulfment-related cognitive deficits in HFD mice. Crucially, EPs effectively counteracted the bloom of Proteobacteria and subsequent neuroinflammatory responses mediated by microglia, essential for cognitive improvement in HFD-fed mice. Mechanistic insights revealed that EPs promoted the production of bacteria-derived butyrate, thereby ameliorating HFD-induced colonic mitochondrial dysfunction and reshaping colonocyte metabolism. This adjustment curtailed the availability of growth substrates for facultative anaerobes, which in turn limited the uncontrolled expansion of Proteobacteria. . Conclusions: Our study elucidates that colonocyte metabolic disturbances, which promote Proteobacteria overgrowth, are a likely cause of HFD-induced cognitive deficits. Furthermore, dietary supplementation with EPs can rectify behavioral dysfunctions associated with HFD by modifying gut microbiota-colonocyte interactions. These insights contribute to the broader understanding of the modulatory effects of plant prebiotics on the microbiota-gut-brain axis and suggest a potential therapeutic avenue for diet-associated cognitive dysfunction.

Toxoplasma gondii (T. gondii) is a highly successful global parasite, infecting about one-third of the world's population and significantly affecting human life and the economy. However, current drugs for toxoplasmosis treatment have considerable side effects, and there is no specific drug to meet current needs. This study aims to evaluate the anti-T. gondii activity of broxaldine (BRO) in vitro and in vivo and explore its mechanism of action. Our results showed that compared to the control group, the invasion rate of tachyzoites in the 4 μg/mL BRO group was only 14.31%, and the proliferation rate of tachyzoites in host cells was only 1.23%. Furthermore, BRO disrupted the lytic cycle of T. gondii and reduced the size and number of cysts in vitro. A mouse model of acute toxoplasmosis reported a 41.5% survival rate after BRO treatment, with reduced parasite load in tissues and blood. The subcellular structure of T. gondii was observed, including disintegration of T. gondii, mitochondrial swelling, increased liposomes, and the presence of autophagic lysosomes. Further investigation revealed enhanced autophagy, increased neutral lipids, and decreased mitochondrial membrane potential in T. gondii treated with BRO. The results also showed a significant decrease in ATP levels. Overall, BRO demonstrates good anti-T. gondii activity in vitro and in vivo; therefore, it has the potential to be used as a lead compound for anti-T. gondii treatment.

Aflatoxin B1 (AFB1) a mycotoxin found in chicken feed that possess a global hazard to poultry health. However different potent compounds like bovine lactoferrin (bLF) may prove to be protective effects against AFB1. This study aims to explore the protective effect of bLF against AFB1-induced injury in the liver and kidney in broiler. For this purpose, 600 broilers chicks were randomly alienated into 5 groups (n = 120 each): negative control; positive control (3 mg/kg AFB1), and bLF high, medium, and low dosage groups (600 mg/kg, 300 mg/kg, and 150 mg/kg, respectively). The results highlight that AFB1 toxicity in birds exhibited low feed intake, reduction in weight gain, and a decrease in FCR while, bLF regulated these adverse effects. Meanwhile, AFB1 group showed higher levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and lower levels of superoxide dismutase (SOD) and glutathione (GSHpx) in liver, while urea and creatinine were decline in kidney. Supplementation with bLF effectively controlled these biomarkers and control the negative effects of toxicity. Furthermore, hematoxylin and eosin (H&E) staining exhibited normal morphological structures within liver and kidney in the bLF treated groups, while degenerative changes were observed in AFB1 group. Similarly, bLF, decreased oxidative stress and thus prevented apoptosis in the liver and kidney cells of the birds. Whereas, mRNA level of mitochondrial apoptosis related gene including Bcl-2 (Bak and Bax), caspase-3 and caspase-9 was upregulated, while bcl2 gene were downregulated in AFB1 group. Dietary supplementation of bLF effectively normalizes the expression of these genes. AFB1 exposed birds shown to decrease gene expression level of the crucial component of Nrf2 pathway, responsible to regulate antioxidant defense. Interestingly, bLF reverse these detrimental effects of and restore the normal expression levels of Nrf2 pathway. Conclusively, our findings demonstrate that bLF mitigates the detrimental effects of AFB1, besides regulation of the apoptosis-related genes via mitochondrial pathways. These findings validate that the bLF (600 mg/kg) could be used as protective agent against AFB1-induced liver and kidney damage.

所有类固醇激素的合成均始于胞内胆固醇,类固醇激素合成急性调节蛋白(StAR)专一性地负责将底物胆固醇从线粒体外膜转运至内膜,该过程是类固醇激素合成的限速步骤.StAR在不同物种中具有高度的保守性,其表达主要分布于肾上腺、卵巢及睾丸组织.StAR基因的表达对动物机体生殖过程存在直接或间接影响,表达异常会导致生殖内分泌功能紊乱,影响胚胎发育及精子发生.论文探讨了 StAR的基本结构特点及表达分布特征,基于StAR对胆固醇转运的作用机制,综述了 StAR对动物和人类生殖内分泌的调控作用,为StAR在生殖应用方面的深入研究提供理论参考.

【Objective】Screening wheat varieties not only with speed grain-filling and dehydration, but also with good yielding potential and favorable grain quality is beneficial to avoid “heat-forced maturity” under late sowing conditions. 【Method】11 varieties from 5 ecological wheat regions were examined the corresponding traits.【Result】The results revealed that both maximum grain-filling rate and filling duration were significantly positively correlated with grain weight at physiological maturity stage, which could ultimately predominate grain yield in the harvest stage. For instance, among the 11 tested varieties, Jimai 22 had the largest amount of grain yield with 6 195 kg·hm -2 , followed by Yunmai 53 with an output of 5 898 kg·hm -2 ; while Zhengmai 7698 and Mianmai 367 ranked the third and fourth, respectively. Furthermore, Jimai 22 had a characteristic of speed grain filling, long time of maximum grain-filling duration and high speed of dehydration rate, which could meet with the demand of the medium-gluten and the weak-gluten wheat in the middle and lower reaches of the Yangtze River. Mianmai 367 reaches the standard of the high-quality weak-gluten. In addition, grain weight instability happened during the dehydration stage indicating the possible existence of grain re-stocking.【Conclusion】The present study here implied that grain yield could be improved in case the maximum grain-filling rate and duration were coordinatedas well as the dehydration rate, so that yield potential and stability could be achieved.With regard to grain quality, breeding accuracy can be improved through optimized cultivation practice to improve and secure grain quality of medium-and weak-strength wheat combined with grain quality test and screening.

Aberrant tryptophan (Trp)-kynurenine (Kyn) metabolism has been implicated in the pathogenesis of human disease. In particular, populations with long-term western-style diets are characterized by an excess of Kyn in the plasma. Host-gut microbiota interactions are dominated by diet and are essential for maintaining host metabolic homeostasis. However, the role of western diet-disturbed gut microbiota-colonocyte interactions in Trp metabolism remains to be elucidated. Here, 4-week-old mice were fed with a high-fat diet (HFD), representing a typical western diet, for 4 weeks, and multi-omics approaches were adopted to determine the mechanism by which HFD disrupted gut microbiota-colonocyte interplay causing serum Trp-Kyn metabolism dysfunction. Our results showed that colonocyte-microbiota interactions dominated the peripheral Kyn pathway in HFD mice. Mechanistically, persistent HFD-impaired mitochondrial bioenergetics increased colonic epithelial oxygenation and caused metabolic reprogramming in colonites to support the expansion of Proteobacteria in the colon lumen. Phylum Proteobacteria-derived lipopolysaccharide (LPS) stimulated colonic immune responses to upregulate the indoleamine 2,3-dioxygenase 1 (IDO1)-mediated Kyn pathway, leading to Trp depletion and Kyn accumulation in the circulation, which was further confirmed by transplantation of Escherichia coli (E.coli) indicator strains and colonic IDO1 depletion. Butyrate supplementation promoted mitochondrial functions in colonocytes to remodel the gut microbiota in HFD mice, consequently ameliorating serum Kyn accumulation. Our results highlighted that HFD disrupted the peripheral Kyn pathway in a gut microbiota-dependent manner and that the continuous homeostasis of gut bacteria-colonocytes interplay played a central role in the regulation of host peripheral Trp metabolism. Meanwhile, this study provided new insights into therapies against western diet-related metabolic disorders.

利用网络药理学分析方法,经过动物试验验证,探究杜仲改善小鼠睡眠障碍的作用机制.通过TCMSP数据库获得杜仲的潜在作用靶点,利用OMIM和GeneCards数据库获得睡眠障碍潜在靶点.将两个靶点合集交集后构建蛋白互作网络,筛选核心靶点.通过David在线平台进行基因本体功能(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析.使用Cytoscape软件构建杜仲成分-睡眠障碍靶点-通路网络,之后采用分子对接技术进行检验.最终通过PCPA小鼠睡眠障碍模型进行体内试验验证.网络药理学和分子对接结果显示,杜仲有效成分烟碱单宁、表奎宁定等通过调节多巴胺D2受体基因(DRD2)和GABAA受体α亚基基因(GABRA1)的表达,发挥镇静安神、抗焦虑的作用.动物试验结果显示,杜仲显著减少了睡眠障碍小鼠的运动量(P<0.05),下调睡眠障碍小鼠下丘脑组织中DRD2基因的表达(P<0.01),上调GABRA1基因的表达(P<0.01).预测并验证了杜仲改善睡眠障碍的作用机制,为其临床应用提供了一定的参考依据.

Scope This study aims to investigate the role of gut microbiota regulation with ketogenic diet (KD) in hypoglycemia‐induced neuroinflammation. Methods and results Immunofluorescence staining and western blotting show that KD alleviates blood‐brain barrier injury induced by hypoglycemia by increasing Podxl and zonula occludens‐1 (ZO‐1) levels. KD‐fed mice show reduced brain edema by decreasing aquaporin‐4 (AQP4) content and maintaining its polarized expression. 16S rRNA gene amplicon sequencing results show that KD reduces the Chao 1 index of gut microbiota α‐diversity, and significant separation is detected in the β‐diversity analysis between the control and KD‐fed mice. KD increases the relative abundance of Firmicutes and Proteobacteria and decreases that of Bacteroidetes . Hypoglycemia can reduce SOD and GSH‐PX levels while increasing TNF‐α, IL‐1β, and IL‐6 mRNA levels in the brain tissues of mice. KD alleviates hypoglycemia‐induced neuroinflammation by inhibiting microglia activation and TLR4/p38MAPK/NF‐κB signaling pathway. Importantly, antibiotic cocktail depletion of the gut microbiota weakens anti‐inflammatory and antioxidation responses in KD‐fed mice. Conclusion Collectively, these findings suggest that KD alleviates hypoglycemia‐induced brain injury via gut microbiota modulation, which may provide novel insights into the therapy for hypoglycemia.