Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Peanut, a major economic and oil crop known for the high protein and oil content, is extensively cultivated in China. Peanut plants have the ability to form nodules with rhizobia, where the nitrogenase converts atmospheric nitrogen into ammonia nitrogen that can be utilized by the plants. Analysis of nodule fixation is of positive significance for avoiding overapplication of chemical fertilizer and developing sustainable agriculture. In this study, AhNIGT1.2, a member of the NIGT family predominantly expressed in peanut nodules, was identified by bioinformatics analysis. Subsequent spatiotemporal expression analysis revealed that AhNIGT1.2 was highly expressed in nodules and showed significant responses to high nitrogen, low nitrogen, high phosphorus, low phosphorus, and rhizobia treatments. Histochemical staining indicated that the gene was primarily expressed in developing nodules and at the connection region between mature nodules and peanut roots. The fusion protein AhNIGT1.2-GFP was located in the nucleus of tobacco epidermal cells. The AhNIGT1.2-OE significantly increased the number of peanut nodules, while AhNIGT1.2-RNAi reduced the number of nodules, which suggested a positive regulatory role of AhNIGT1.2 in peanut nodulation. The AhNIGT1.2-OE in roots down-regulated the expression levels of NRT1.2, NRT2.4, NLP1, and NLP7, which indicated that AhNIGT1.2 influenced peanut nodulation by modulating nitrate transport and the expression of NLP genes. The transcriptome analysis of AhNIGT1.2-OE and control roots revealed that overexpressing AhNIGT1.2 significantly enriched the differentially expressed genes associated with nitrate response, nodulation factor pathway, enzymes for triterpene biosynthesis, and carotenoid biosynthesis. These findings suggest that AhNIGT1.2 play a key role in peanut nodulation by regulating nitrate transport and response and other related pathways. This study gives insights into the molecular mechanisms of nitrogen and phosphorus in regulating legume nodulation and nitrogen fixation, and sheds light on the development of legume crops that can efficiently fix nitrogen in high nitrogen environments.
Arachis/physiology* ; Nitrates/metabolism* ; Plant Proteins/physiology* ; Transcription Factors/metabolism* ; Plant Root Nodulation/physiology* ; Gene Expression Regulation, Plant ; Root Nodules, Plant/metabolism* ; Nitrogen Fixation

Rice is the world's largest food crop, and its yield and quality are directly related to food security and human health. Grain size, as one of the important factors determining the rice yield, has been widely concerned by breeders and researchers for a long time. To decipher the regulatory mechanism of rice grain size, we obtained a multi-tiller, dwarf, and small-grain mutant htd1 by ethyl methanesulfonate (EMS) mutation from the Japonica rice cultivar 'Zhonghua 11' ('ZH11'). Genetic analysis indicated that the phenotype of htd1 was controlled by a single recessive gene. Using the mutation site map (Mutmap) method, we identified the candidate gene OsHTD1, which encoded a carotenoid cleavage dioxygenase involved in the biosynthesis of strigolactone (SL). The SL content in htd1 was significantly lower than that in 'ZH11'. Cytological analysis showed that the grain size of the mutant decreased due to the reductions in the length and width of glume cells. The function of htd1 was further verified by the CRISPR/cas9 gene editing technology. The plants with the gene knockout exhibited similar grain size to the mutant. In addition, gene expression analysis showed that the expression levels of multiple grain size-related genes in the mutant changed significantly, suggesting that HTD1 may interact with other genes regulating grain size. This study provides a new theoretical basis for research on the regulatory mechanism of rice grain size and potential genetic resources for breeding the rice cultivars with high yields.
Oryza/growth & development* ; Mutation ; Edible Grain/growth & development* ; Alleles ; Plant Proteins/genetics* ; Dioxygenases/genetics* ; Lactones/metabolism* ; Gene Expression Regulation, Plant ; Genes, Plant ; Gene Editing ; CRISPR-Cas Systems ; Phenotype

Rice (Oryza sativa L.) is an important food crop. The appearance of lesion mimics in rice leads to phytohormone disorders, which affects rice adaptation to environmental stresses and ultimately reduces the yield and quality. To explore whether the changes in the adaptability of rice lesion-mimic mutants to stressful environments are caused by the disorder of phytohormone metabolism in plants. In this study, we screened an ethyl methane sulfonate-treated population of the japonica cultivar 'Taipei 309' for a mutant with rust-like spots on leaves at the early tillering stage and brown-red spots at maturity and named it rsl1 (rust spotted leaf 1). Compared with the wild type, rsl1 showed decreases in plant height, panicle length, primary branch number, secondary branch number, filled grains per panicle, seed-setting rate, and 1 000-grain weight, and an increase in number of effective panicles. Genetic analysis indicated that rsl1 was controlled by a single recessive nuclear gene. RSL1 was localized between two molecular markers, B7-7 and B7-9, on rice chromosome 7 by map-based cloning. PCR sequencing of the annotated genes in this interval revealed a mutation of C1683A on the eighth exon of SPL5 (LOC_Os07g10390) in rsl1, which resulted in premature termination of protein translation. Exogenous phytohormone treatments showed that rsl1 was less sensitive to salicylic acid (SA), abscisic acid (ABA), and indo-3-acetic acid (IAA) and more sensitive to methyl jasmonate (MeJA) and gibberellin acid (GA) than the wild type. In addition, the survival rate of rsl1 was lower than that of the wild type under salt, alkali, drought, and high temperature stresses, and it was higher than that of the wild type under cold stress. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that RSL1 was involved in the regulation of ABA, SA, MeJA, IAA, and GA-related genes under abiotic stresses. The present study showed that the RSL1 mutation led to the appearance of lesion mimics and affected the growth, development, and stress resistance of rsl1 under abiotic stresses. The study of the functional mechanism of this gene can provide theoretical guidance for the research on rice stress resistance.
Oryza/microbiology* ; Stress, Physiological/genetics* ; Plant Diseases/genetics* ; Cloning, Molecular ; Chromosome Mapping ; Plant Growth Regulators/metabolism* ; Plant Proteins/genetics* ; Mutation ; Cyclopentanes ; Genes, Plant ; Plant Leaves/genetics* ; Oxylipins

Synthetic biology, recognized as one of the most revolutionary interdisciplinary fields in the 21st century, has established innovative strategies for the genetic improvement of rice through the integration of multidisciplinary technologies including genome editing, genetic circuit design, metabolic engineering, and artificial intelligence. This review systematically summarizes recent research advancements and breakthrough achievements in the application of synthetic biology in the genetic improvement of rice, focusing on three critical domains: yield improvement, nutritional quality fortification, and reinforcement of disease resistance and abiotic stress tolerance. It elucidates that synthetic biology enables precise genomic and metabolic pathway engineering through modular, standard, and systematic approaches, effectively overcoming the limitations of conventional breeding methods characterized by prolonged cycles and restricted trait modification capabilities. The implementation of synthetic biology has facilitated synergistic improvement of multi-traits, thereby providing critical technical references for developing elite rice cultivars with superior productivity and nutritional value. These technological breakthroughs hold significant implications for ensuring global food security and promoting green and sustainable development of agriculture.
Oryza/growth & development* ; Synthetic Biology/methods* ; Metabolic Engineering ; Plant Breeding/methods* ; Gene Editing ; Genetic Engineering/methods* ; Plants, Genetically Modified/genetics* ; Disease Resistance/genetics*

Objective:To investigate the effect of astragaloside IV (AS-IV) regulating the signal axis of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) on the mobilization of bone marrow endothelial progenitor cells (EPCs) to peripheral blood in diabetes skin ulcer (DSU) rats.Methods:Twenty four SPF grade male Sprague Dawley (SD) rats were selected to make the model of type 2 diabetes rats by intraperitoneal injection of 30 mg/kg 1% (plastid ratio) streptozotocin, and then round full-thickness skin with a diameter of 2 cm was cut on both sides of the waist and back to make the skin ulcer model of diabetes rats. After that, they were randomly divided into AS-IV group (50 mg/kg AS-IV), blocker group (50 mg/kg AS-IV+ 5 mg/kg AMD3100) and model group. At the same time, a blank group ( n=8) was set up, The drug was administered via intraperitoneal injection, and the model group and blank group were treated with 0.9% NaCl of equal volume. On the 10th day, peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats were collected. The number of EPCs in peripheral blood of each group of rats was measured by flow cytometry, and the protein expression of SDF-1α and CXCR4 in peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats was detected by enzyme-linked immunosorbent assay (ELISA); At the same time, the wound healing rates of each group were tested. Results:On the 10th and 21st day after modeling, the wound healing rate of each group of rats was compared. The blank group healed the fastest, while the model group healed the slowest. The AS-IV group had better healing than the model group and the blocker group, and the difference was statistically significant (all P<0.05). On the 10th day after modeling, the positive rates of peripheral blood EPCs in the white group, AS-IV group, and blocker group were significantly higher than those in the model group (all P<0.05), while the positive rates of peripheral blood EPCs in the blocker group were significantly lower than those in the AS-IV group (all P<0.05). On the 10th day after modeling, the protein expression of SDF-1α and CXCR4 in the wound, serum, and bone marrow of the model group was the lowest, while the protein expression in the blank group was the highest (all P<0.05). The protein expression of SDF-1α and CXCR4 in the wound, serum, bone marrow of the AS-IV group was significantly higher than that of the blocker group and model group, and the difference was statistically significant (all P<0.05). Conclusions:Astragaloside IV can promote the mobilization and migration of endothelial progenitor cells from bone marrow to peripheral blood in diabetes ulcer rats by regulating SDF-1α/CXCR4 signal axis, and can participate in angiogenesis of diabetes ulcer wounds as seed cells to promote the healing of diabetes skin ulcers.

Objective To investigate the effect and mechanism of Di'ao Xinxuekang(hereinafter referred to as Xinxuekang)combined with Simvastatin on atherosclerosis(AS)mice.Methods Eight C57BL/6J mice were used as control group,and 32 ApoE-/-mice were randomly divided into model group,Xinxuekang group(160 mg·kg-1),Simvastatin group(1.3 mg·kg-1)and combined treatment group(Xinxuekang 160 mg·kg-1+Simvastatin 1.3 mg·kg-1),with eight mice in each group.The control group was fed with conventional diet,and the other four groups were fed with high-fat diet.At the same time,each administration group was given intragastric administration according to the above dose,and the volume of intragastric administration was 10 mL·kg-1,once a day for 18 weeks.After administration,the levels of serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)were detected.Oil red O staining was used to observe the formation of aortic plaque and liver lipid accumulation in mice.Serum PCSK9 level was detected by ELISA.The mRNA and protein expression levels of LDLR,HNF1α and SREBP2 in liver tissues were detected by qRT-PCR and Western Blot.Results(1)Compared with the control group,the levels of serum TC,TG and LDL-C in the model group were significantly increased(P＜0.01),and the level of HDL-C was significantly decreased(P＜0.01).The percentage of aortic root plaque area,the percentage of total aortic plaque area and the percentage of liver lipid droplet area were significantly increased(P＜0.01).The mRNA and protein expression levels of LDLR in liver tissue were significantly decreased(P＜0.01),and the serum PCSK9 level was significantly increased(P＜0.01).The mRNA and protein expression levels of HNF1α and SREBP2 in liver tissues were significantly increased(P＜0.05,P＜0.01).(2)Compared with the model group,the levels of serum TC,TG and LDL-C in the Xinxuekang group and the combined treatment group were significantly decreased(P＜0.05,P＜0.01),and the level of HDL-C was significantly increased(P＜0.05).The level of serum LDL-C in Simvastatin group was significantly decreased(P＜0.01).The percentage of aortic root plaque area and the percentage of total aortic plaque area in the Xinxuekang group and the combined treatment group were significantly decreased(P＜0.05,P＜0.01),and the percentage of liver lipid droplet area in each administration group was significantly decreased(P＜0.01).The protein expression level of LDLR in liver tissue of mice in Xinxuekang group and combined treatment group was significantly increased(P＜0.05),the serum PCSK9 level was significantly decreased(P＜0.05,P＜0.01),and the mRNA and protein expression levels of HNF1 α and SREBP2 in liver tissue were significantly decreased(P＜0.05,P＜0.01).(3)Compared with the Simvastatin group,the serum HDL-C level in the combined treatment group was significantly increased(P＜0.05).The percentage of aortic root plaque area and the percentage of liver lipid droplet area were significantly decreased(P＜0.05,P＜0.01).The protein expression level of LDLR in liver tissue was significantly increased(P＜0.01),and the serum PCSK9 level was significantly decreased(P＜0.01).The expression levels of HNF1α protein and SREBP2 mRNA in liver tissues were significantly decreased(P＜0.05,P＜0.01).Conclusion Xinxuekang may play a synergistic effect on lipid-lowering and anti-AS effects of Simvastatin by inhibiting the expressions of SREBP2 and HNF1α and regulating the PCSK9/LDLR signaling pathway.

Objective To explore the effect of the nursing intervention for Internet+whole course breastfeeding support based on lactation physiology on exclusive breastfeeding of cesarean section women.Methods Using the convenience sampling method,198 women who were from prenatal examination to delivery in the Obstetrical Department of a tertiary hospital in Nanning city from July 2022 to February 2023 were selected,with 99 women in each group.The experimental group adopted the nursing intervention for Internet+whole course breastfeeding support based on lactation physiology,while the control group adopted routine nursing care.The rates of exclusive breastfeeding within 6 months,breastfeeding or milking frequency within 3 days postpartum,incidence of nipple pain,breastfeeding knowledge scores,and breastfeeding self-efficacy scores were compared between the 2 groups.Results No shedding occurred in both groups.The exclusive breastfeeding rates in the experimental group at postpartum 3 days,14 days,42 days,4 months,and 6 months were higher than that in the control group.The comparison of the rates of exclusive breastfeeding between 2 groups at different time points showed that the intergroup effect,time effect and interaction effect were statistically significant(P＜0.05).The 2 groups were stratified by maternal and child separation,and the rates of exclusive breastfeeding of the experimental group at postpartum 42 days,4 months and 6 months were higher than that of the control group(P＜0.05).The frequency of breastfeeding or milking within 3 days postpartum,incidence of nipple pain,breastfeeding knowledge scores,and breastfeeding self-efficacy scores were higher in the experimental group than those in the control group(P＜0.05).Conclusion The nursing intervention for Internet+whole course breastfeeding support based on lactation physiology can improve the compliance of lactation behavior in cesarean section women and promote the establishment of lactation,which can significantly improve the rate of exclusive breastfeeding within 6 months.