CLCuMuV subverts the processing of hydroxyproline-rich systemin to suppress tobacco defenses against insect vectors.

The interactions of insect vector-virus-plant have important ecological and evolutionary implications. The constant struggle of plants against viruses and insect vectors has driven the evolution of multiple defense strategies in the host as well as counter-defense strategies in the viruses and insect vectors. Cotton leaf curl Multan virus (CLCuMuV) is a major causal agent of cotton leaf curl disease in Asia and is exclusively transmitted by the whitefly Bemisia tabaci. Here, we report that plants infected with CLCuMuV and its betasatellite, cotton leaf curl Multan betasatellite (CLCuMuB) enhance the performance of B. tabaci vector, and ßC1 encoded by CLCuMuB plays an important role in begomovirus-whitefly-tobacco tripartite interactions. We showed that CLCuMuB ßC1 suppresses the jasmonic acid signaling pathway by interacting with the subtilisin-like protease 1.7 (NtSBT1.7) protein, thereby enhancing whitefly performance on tobacco plants. Further studies revealed that in the wild type plants, NtSBT1.7 could process tobacco preprohydroxyproline-rich systemin B (NtpreproHypSysB). After CLCuMuB infection, CLCuMuB ßC1 could interfere with the processing of NtpreproHypSysB by NtSBT1.7, thereby impairing plant defenses against whitefly. These results contribute to our understanding of the tripartite interactions among virus, plant, and whitefly, thus offering ecological insights into the spread of vector insect populations and the prevalence of viral diseases.

Bayesian genome-wide TWAS with reference transcriptomic data of brain and blood tissues identified 141 risk genes for Alzheimer's disease dementia.

BACKGROUND: Transcriptome-wide association study (TWAS) is an influential tool for identifying genes associated with complex diseases whose genetic effects are likely mediated through transcriptome. TWAS utilizes reference genetic and transcriptomic data to estimate effect sizes of genetic variants on gene expression (i.e., effect sizes of a broad sense of expression quantitative trait loci, eQTL). These estimated effect sizes are employed as variant weights in gene-based association tests, facilitating the mapping of risk genes with genome-wide association study (GWAS) data. However, most existing TWAS of Alzheimer's disease (AD) dementia are limited to studying only cis-eQTL proximal to the test gene. To overcome this limitation, we applied the Bayesian Genome-wide TWAS (BGW-TWAS) method to leveraging both cis- and trans- eQTL of brain and blood tissues, in order to enhance mapping risk genes for AD dementia. METHODS: We first applied BGW-TWAS to the Genotype-Tissue Expression (GTEx) V8 dataset to estimate cis- and trans- eQTL effect sizes of the prefrontal cortex, cortex, and whole blood tissues. Estimated eQTL effect sizes were integrated with the summary data of the most recent GWAS of AD dementia to obtain BGW-TWAS (i.e., gene-based association test) p-values of AD dementia per gene per tissue type. Then we used the aggregated Cauchy association test to combine TWAS p-values across three tissues to obtain omnibus TWAS p-values per gene. RESULTS: We identified 85 significant genes in prefrontal cortex, 82 in cortex, and 76 in whole blood that were significantly associated with AD dementia. By combining BGW-TWAS p-values across these three tissues, we obtained 141 significant risk genes including 34 genes primarily due to trans-eQTL and 35 mapped risk genes in GWAS Catalog. With these 141 significant risk genes, we detected functional clusters comprised of both known mapped GWAS risk genes of AD in GWAS Catalog and our identified TWAS risk genes by protein-protein interaction network analysis, as well as several enriched phenotypes related to AD. CONCLUSION: We applied BGW-TWAS and aggregated Cauchy test methods to integrate both cis- and trans- eQTL data of brain and blood tissues with GWAS summary data, identifying 141 TWAS risk genes of AD dementia. These identified risk genes provide novel insights into the underlying biological mechanisms of AD dementia and potential gene targets for therapeutics development.

Phylogenetic placement and comparative analysis of the mitochondrial genomes of Idiostoloidea (Hemiptera: Heteroptera).

The classification system and the higher level phylogenetic relationships of Pentatomomorpha, the second largest infraorder of Heteroptera (Insecta: Hemiptera), have been debated and remain controversial over decades. In particular, the placement and phylogenetic relationship of Idiostoloidea are not well resolved, which hampers a better understanding of the evolutionary history of Pentatomomorpha. In this study, for the first time, we reported the complete mitochondrial genome for two narrowly distributed families of Idiostoloidea (including Idiostolidae and Henicocoridae), respectively. The length of the mitochondrial genome of Monteithocoris hirsutus and Henicocoris sp. is 16,632 and 16,013 bp, respectively. The content of AT is ranging from 75.15% to 80.48%. The mitogenomic structure of Idiostoloidea is highly conservative and there are no gene arrangements. By using the Bayesian inference, maximum likelihood, and Bayesian site-heterogeneous mixture model, we inferred the phylogenetic relationships within Pentatomomorpha and estimated their divergence times based on concatenated mitogenomes and nuclear ribosomal genes. Our results support the classification system of six superfamilies within Pentatomomorpha and confirm the monophyletic groups of each superfamily, with the following phylogenetic relationships: (Aradoidea + (Pentatomoidea + (Idiostoloidea + (Coreoidea + (Pyrrhocoroidea + Lygaeoidea))))). Furthermore, estimated divergence times revealed that most pentatomomorphan superfamilies and families diverged during the Late Jurassic to Early Cretaceous, which coincides with the explosive radiation of angiosperms.

Characterization of extrachromosomal circular DNAs in plasma of patients with clear cell renal cell carcinoma.

BACKGROUND AND PURPOSE: Extrachromosomal circular DNAs (eccDNAs) have been recognized for their significant involvement in numerous biological processes. Nonetheless, the existence and molecular characteristics of eccDNA in the peripheral blood of patients diagnosed with clear cell renal cell carcinoma (ccRCC) have not yet been reported. Our aim was to identify potentially marked plasma eccDNAs in ccRCC patients. METHODS AND MATERIALS: The detection of plasma eccDNA in ccRCC patients and healthy controls was performed using the Tn5-tagmentation and next-generation sequencing (NGS) method. Comparisons were made between ccRCC patients and healthy controls regarding the distribution of length, gene annotation, pattern of junctional nucleotide motif, and expression pattern of plasma eccDNA. RESULTS: We found 8,568 and 8,150 plasma eccDNAs in ccRCC patients and healthy controls, respectively. There were no statistical differences in the length distribution, gene annotation, and motif signature of plasma eccDNAs between the two groups. A total of 701 differentially expressed plasma eccDNAs were identified, and 25 plasma eccDNAs with potential diagnostic value for ccRCC have been successfully screened. These up-regulated plasma eccDNAs also be indicated to originate from the genomic region of the tumor-associated genes. CONCLUSION: This work demonstrates the characterization of plasma eccDNAs in ccRCC and suggests that the up-regulated plasma eccDNAs could be considered as a promising non-invasive biomarker in ccRCC.

Genome-wide study of gene-by-sex interactions identifies risks for cleft palate.

Structural birth defects affect 3-4% of all live births and, depending on the type, tend to manifest in a sex-biased manner. Orofacial clefts (OFCs) are the most common craniofacial structural birth defects and are often divided into cleft lip with or without cleft palate (CL/P) and cleft palate only (CP). Previous studies have found sex-specific risks for CL/P, but these risks have yet to be evaluated in CP. CL/P is more common in males and CP is more frequently observed in females, so we hypothesized there would also be sex-specific differences for CP. Using a trio-based cohort, we performed sex-stratified genome-wide association studies (GWAS) based on proband sex followed by a genome-wide gene-by-sex (GxS) interaction testing. There were 13 loci significant for GxS interactions, with the top finding in LTBP1 (RR=3.37 [2.04 - 5.56], p=1.93x10 -6 ). LTBP1 plays a role in regulating TGF-B bioavailability, and knockdown in both mice and zebrafish lead to craniofacial anomalies. Further, there is evidence for differential expression of LTBP1 between males and females in both mice and humans. Therefore, we tested the association between the imputed genetically regulated gene expression of genes with significant GxS interactions and the CP phenotype. We found significant association for LTBP1 in cell cultured fibroblasts in female probands (p=0.0013) but not in males. Taken altogether, we show there are sex-specific risks for CP that are otherwise undetectable in a combined sex cohort, and LTBP1 is a candidate risk gene, particularly in females.

Amphiregulin secreted by umbilical cord Multipotent Stromal Cells protects against ferroptosis of macrophages via the Activating Transcription Factor 3-CD36 axis to alleviate endometrial fibrosis.

Endometrium fibrosis is the leading cause of uterine infertility. Macrophages participated in the occurrence and development of endometrial fibrosis. We previously reported that human umbilical cord multipotent stromal cells (hUC-MSCs) exerted their therapeutic effect in a macrophage-dependent manner in endometrial fibrosis. However precise mechanisms by which hUC-MSCs may influence macrophages in endometrial fibrosis remain largely unexplored. Here, we demonstrated that abnormal iron and lipid metabolism occurred in intrauterine adhesions (IUA) patients and murine models. Ferroptosis has been proven to contribute to the progression of fibrotic diseases. Our results revealed that pharmacological activation of ferroptosis by Erastin aggravated endometrial fibrosis, while inhibition of ferroptosis by Ferrostatin-1 ameliorated endometrial fibrosis in vivo. Moreover, ferroptosis of macrophages was significantly upregulated in endometria of IUA murine models. Of note, transcriptome profiles revealed that CD36 gene expression was significantly increased in IUA patients and immunofluorescence analysis showed CD36 protein was mainly located in macrophages. Silencing CD36 in macrophages could reverse cell ferroptosis. Dual luciferase reporter assay revealed that CD36 was the direct target of activation transcription factor 3 (ATF3). Furthermore, through establishing coculture system and IUA murine models, we found that hUC-MSCs had a protective role against macrophage ferroptosis and alleviated endometrial fibrosis related to decreased CD36 and ATF3. The effect of hUC-MSCs on macrophage ferroptosis was attributed to the upregulation of amphiregulin (AREG). Our data highlighted that macrophage ferroptosis occurred in endometrial fibrosis via the ATF3-CD36 pathway and hUC-MSCs protected against macrophage ferroptosis to alleviate endometrial fibrosis via secreting AREG. These findings provided a potential target for therapeutic implications of endometrial fibrosis.

Comparison of Craniotomy versus Decompressive Craniectomy for Acute Subdural Hematoma: a Systematic Review and Meta-Analysis.

OBJECTIVE: Acute Subdural Hematoma (ASDH) is a common critical neurosurgical condition, often requiring immediate surgical intervention. Craniotomy and decompressive craniectomy are the two mainstay surgical approaches. This comprehensive review and meta-analysis aims to summarize the existing evidence and compare the outcomes of these two procedures. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL electronic databases were searched for relevant studies, published between inception of databases till June 2023. Eligible studies reported data of patients diagnosed with ASDH who underwent craniotomy or decompressive craniectomy for ASDH. Outcome measures included the Glasgow Coma Scale score, residual subdural hematoma (SDH), requirement of revision surgery, poorer outcomes, and mortality. Data were presented as pooled odds ratios (ORs) with 95% confidence intervals (CIs). Quality assessment and risk of bias were performed for each study. RESULTS: Fourteen studies with a total of 3095 patients were included. The results showed that patients who underwent craniotomy had significantly lower mortality, lower odds of poorer outcomes, and a higher rate of residual SDH, compared to patients who underwent decompressive craniectomy. There was no significant difference in the requirement of revision surgery between the two groups. Heterogeneity was high for most outcomes, and the quality of evidence ranged from moderate to low. CONCLUSION: Our findings suggest that craniotomy is associated with better clinical outcomes and lower mortality compared to decompressive craniectomy for ASDH, but a higher rate of residual SDH. Further high-quality randomized controlled trials are needed to validate our findings.

Carbon slow-release and enhanced nitrogen removal performance of plant residue-based composite filler and ecological mechanisms in constructed wetland application.

Stable carbon release and coupled microbial efficacy of external carbon source solid fillers are the keys to enhanced nitrogen removal in constructed wetlands. The constructed wetland plant residue Acorus calamus was cross-linked with poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) to create composite solid carbon source fillers (Ac-BDPs). The study demonstrated the slow release of carbon sources from Ac-BDPs with 35.27 mg/g under an average release rate of 0.88 mg/(g·d). Excellent denitrification was also observed in constructed wetlands with Ac-BDPs. Moreover, the average removal rate of nitrate nitrogen (NO3--N) was increased by 1.94 and 3.85 times of the blank groups under initial NO3--N inputs of 5 and 15 mg/L, respectively. Furthermore, the relatively high abundances of nap, narG, nirKS, norB, qnorZ and nosZ guaranteed efficient denitrification performance in constructed wetlands with Ac-BDPs. The study introduced a reliable technique for biological nitrogen removal by using composite carbon source fillers in constructed wetlands.

Tunneling Proton Grotthuss Transfer Channels by Hydrophilic-Zincophobic Heterointerface Shielding for High-Performance Zn-MnO2 Batteries.

Hollandite-type manganese dioxide (α-MnO2) is recognized as a promising cathode material upon high-performance aqueous zinc-ion batteries (ZIBs) owing to the high theoretical capacities, high working potentials, unique Zn2+/H+ co-insertion chemistry, and environmental friendliness. However, its practical applications limited by Zn2+ accommodation, where the strong coulombic interaction and sluggish kinetics cause significant lattice deformation, fast capacity degradation, insufficient rate capability, and undesired interface degradation. It remains challenging to accurately modulate H+ intercalation while suppressing Zn2+ insertion for better lattice stability and electrochemical kinetics. Herein, proton Grotthuss transfer channels are first tunneled by shielding MnO2 with hydrophilic-zincophobic heterointerface, fulfilling the H+-dominating diffusion with the state-of-the-art ZIBs performance. Local atomic structure and theoretical simulation confirm that surface-engineered α-MnO2 affords to the synergy of Mn electron t2g-eg activation, oxygen vacancy enrichment, selective H+ Grotthuss transfer, and accelerated desolvation kinetics. Consequently, fortified α-MnO2 achieves prominent low current density cycle stability (≈100% capacity retention at 1 C after 400 cycles), remarkable long-lifespan cycling performance (98% capacity retention at 20 C after 12 000 cycles), and ultrafast rate performance (up to 30 C). The study exemplifies a new approach of heterointerface engineering for regulation of H+-dominating Grotthuss transfer and lattice stabilization in α-MnO2 toward reliable ZIBs.

Immediate and delayed placement of the intrauterine device after abortion: a systematic review and meta-analysis.

This article aims to report the comprehensive and up-to-date analysis and evidence of the insertion rate, expulsion rate, removal rate, and utilization rate of immediate placement of intrauterine devices (IUDs) versus delayed placement after artificial abortion. PubMed, Embase, Cochrane, Web of Science, CNKI, and Wanfang databases were comprehensively searched up to January 12, 2024 for studies that compared immediate versus delayed insertion of IUDs after abortion. The evaluation metrics included the number of IUD insertion after surgical or medical abortions, the frequency of expulsion and removal at 6 months or 1 year, the number of continued usage, pain intensity scores, the number of infections, the duration of bleeding, and instances of uterine perforation during or after IUD insertion. Ten randomized controlled articles were eligible, comprising 11 research projects, of which 3 projects involved the placement of an IUD after surgical abortion, and 8 projects involved the placement of an IUD after medical abortion. This included 2025 patients (977 in the immediate insertion group and 1,048 in the delayed insertion group). We summarized all the extracted evidence. The meta-analysis results indicated that for post-surgical abortions, the immediate insertion group exhibited a higher IUD placement rate than the delayed insertion group. After medical abortions, the immediate insertion group showed higher rates of IUD placement, utilization, and expulsion at 6 months or 1 year. The two groups showed no statistically significant differences in the removal rate, post-insertion infection rate, pain scores during insertion, and days of bleeding during the follow-up period. Compared to delayed placement, immediate insertion of IUDs can not only increase the usage rate at 6 months or 1 year but also enhance the placement rate.

Protective Interphases of Advanced Znic Anodes: Structure, Mechanisms, Fabrication Strategies and Characterization Techniques.

Aqueous zinc ion batteries (AZIBs) with metallic Zn anode have the potential for large-scale energy storage application due to their cost-effectiveness, safety, environmental-friendliness, and ease of preparation. However, the concerns regarding dendrite growth and side reactions on Zn anode surface hamper AZIB's commercialization. This review aims to give a comprehensive evaluation of the protective interphase construction and provide guildance to further improve the electrochemical performance of AZIBs. The failure behaviors of Zn metal anode including dendrite growth, corrosion, and hydrogen evolution are analyzed. Then, the applications and mechanisms of the constructed interphases are introduced, classified by the material species. The fabrication methods of the artificial interfaces are summarized and evaluated, including the in-situ strategy and ex-situ strategy. Finally, the characterization means of the interphases are discussed to give a full view for the study of Zn anode protection. Based on the analysis of this review, a stable and high-performance Zn anode could be designed by carefully choosing applied material, corresponding protective mechanism, and appropriate construction technique. Additionally, this review for Zn anode modification and construction techniques for anode protection in AZIBs may be helpful in other aqueous metal batteries with similar problems.

Development and validation of a nomogram for predicting in-hospital survival rates of patients with COVID-19.

Objective: Our aim was to develop and validate a nomogram for predicting the in-hospital 14-day (14 d) and 28-day (28 d) survival rates of patients with coronavirus disease 2019 (COVID-19). Methods: Clinical data of patients with COVID-19 admitted to the Renmin Hospital of Wuhan University from December 2022 to February 2023 and the north campus of Shanghai Ninth People's Hospital from April 2022 to June 2022 were collected. A total of 408 patients from Renmin Hospital of Wuhan University were selected as the training cohort, and 151 patients from Shanghai Ninth People's Hospital were selected as the verification cohort. Independent variables were screened using Cox regression analysis, and a nomogram was constructed using R software. The prediction accuracy of the nomogram was evaluated using the receiver operating characteristic (ROC) curve, C-index, and calibration curve. Decision curve analysis was used to evaluate the clinical application value of the model. The nomogram was externally validated using a validation cohort. Result: In total, 559 patients with severe/critical COVID-19 were included in this study, of whom 179 (32.02 %) died. Multivariate Cox regression analysis showed that age >80 years [hazard ratio (HR) = 1.539, 95 % confidence interval (CI): 1.027-2.306, P = 0.037], history of diabetes (HR = 1.741, 95 % CI: 1.253-2.420, P = 0.001), high APACHE II score (HR = 1.083, 95 % CI: 1.042-1.126, P < 0.001), sepsis (HR = 2.387, 95 % CI: 1.707-3.338, P < 0.001), high neutrophil-to-lymphocyte ratio (NLR) (HR = 1.010, 95 % CI: 1.003-1.017, P = 0.007), and high D-dimer level (HR = 1.005, 95 % CI: 1.001-1.009, P = 0.028) were independent risk factors for 14 d and 28 d survival rates, whereas COVID-19 vaccination (HR = 0.625, 95 % CI: 0.440-0.886, P = 0.008) was a protective factor affecting prognosis. ROC curve analysis showed that the area under the curve (AUC) of the 14 d and 28 d hospital survival rates in the training cohort was 0.765 (95 % CI: 0.641-0.923) and 0.814 (95 % CI: 0.702-0.938), respectively, and the AUC of the 14 d and 28 d hospital survival rates in the verification cohort was 0.898 (95 % CI: 0.765-0.962) and 0.875 (95 % CI: 0.741-0.945), respectively. The calibration curves of 14 d and 28 d hospital survival showed that the predicted probability of the model agreed well with the actual probability. Decision curve analysis (DCA) showed that the nomogram has high clinical application value. Conclusion: In-hospital survival rates of patients with COVID-19 were predicted using a nomogram, which will help clinicians in make appropriate clinical decisions.

Mito-Specific Nutri-Hijacker Synergizing Mitochondrial Metabolism and Glycolysis Intervention for Enhanced Antitumor Bioenergetic Therapy.

Metabolic rewiring, a dynamic metabolic phenotype switch, confers that tumors exist and proliferate after fitness (or preadaptation) in harsh environmental conditions. Glycolysis deprivation was considered to be a tumor's metabolic Achilles heel. However, metabolic configuration can flexibly retune the mitochondrial metabolic ability when glycolysis is scared, potentially resulting in more aggressive clones. To address the challenge of mitochondrial reprogramming, an antiglycolytic nanoparticle (GRPP NP) containing a novel mitochondrial-targeted reactive oxygen species (ROS) generator (diIR780) was prepared to hijack glucose and regulate mitochondria, thus completely eliminating tumorigenic energy sources. In this process, GRPP NPs@diIR780 can catalyze endogenous glucose, leading to significantly suppressed glycolysis. Moreover, diIR780 can be released and selectively accumulated around mitochondria to generate toxic ROS. These combined effects, in turn, can hamper mitochondrial metabolism pathways, which are crucial for driving tumor progression. This synchronous intervention strategy enables utter devastation of metabolic rewiring, providing a promising regiment to eradicate tumor lesions without recurrence.

Cis- and trans-eQTL TWASs of breast and ovarian cancer identify more than 100 susceptibility genes in the BCAC and OCAC consortia.

Transcriptome-wide association studies (TWASs) have investigated the role of genetically regulated transcriptional activity in the etiologies of breast and ovarian cancer. However, methods performed to date have focused on the regulatory effects of risk-associated SNPs thought to act in cis on a nearby target gene. With growing evidence for distal (trans) regulatory effects of variants on gene expression, we performed TWASs of breast and ovarian cancer using a Bayesian genome-wide TWAS method (BGW-TWAS) that considers effects of both cis- and trans-expression quantitative trait loci (eQTLs). We applied BGW-TWAS to whole-genome and RNA sequencing data in breast and ovarian tissues from the Genotype-Tissue Expression project to train expression imputation models. We applied these models to large-scale GWAS summary statistic data from the Breast Cancer and Ovarian Cancer Association Consortia to identify genes associated with risk of overall breast cancer, non-mucinous epithelial ovarian cancer, and 10 cancer subtypes. We identified 101 genes significantly associated with risk with breast cancer phenotypes and 8 with ovarian phenotypes. These loci include established risk genes and several novel candidate risk loci, such as ACAP3, whose associations are predominantly driven by trans-eQTLs. We replicated several associations using summary statistics from an independent GWAS of these cancer phenotypes. We further used genotype and expression data in normal and tumor breast tissue from the Cancer Genome Atlas to examine the performance of our trained expression imputation models. This work represents an in-depth look into the role of trans eQTLs in the complex molecular mechanisms underlying these diseases.

Atmospheric drought dominates changes in global water use efficiency.

Water use efficiency (defined as the ratio of gross primary productivity to plant transpiration, WUET) describes the tradeoff between ecosystem carbon uptake and water loss. However, a comprehensive understanding of the impact of soil and atmospheric moisture deficits on WUET across large regions remains incomplete. Solar-induced chlorophyll fluorescence (SIF) serves as an effective signal for measuring both terrestrial vegetation photosynthesis and transpiration, thereby enabling a rapid response to changes in the physiological status of plants under water stress. The objectives of this study were to: 1) mechanistically calculate WUET using top-of-canopy SIF data and meteorological information by using the revised mechanistic light response model and the Penman-Monteith equation; 2) analyze the effects of atmospheric and soil water deficits on SIF-based WUET by using decoupled soil water content (SWC) and vapor pressure deficit (VPD); 3) evaluate estimated SIF-based WUET against data from 28 eddy covariance (EC) flux sites representing eight different vegetation types. Results indicated that the model performed well in ecosystems with dense canopies, explaining 56 % of the daily variability in EC tower-based WUET. For the years 2019-2020, the global average WUET derived from SIF was 3.49 g C/kg H2O. Notably, this value exceeded 4 g C/kg H2O in tropical rainforest regions near the equator and went beyond 5 g C/kg H2O in the high-latitude regions of the Northern Hemisphere. We found that SIF-based WUET was primarily influenced by VPD rather than SWC in over 90 % of the global vegetated area. The model used in this study increased our ability to mechanistically estimate WUET with SIF at the global scale, thereby highlighting the significance of the global response of SIF-based WUET to water stress, and also enhancing our understanding of the water­carbon cycle in terrestrial ecosystems.

[Effect of Xuming Decoction in Records of Proved Prescriptions, Ancient a nd Modern on cerebral ischemic injury and angiogenesis in rat model of acute cerebral infarction].

This paper aims to explore the effect of Xuming Decoction in the Records of Proved Prescriptions, Ancient and Modern on cerebral ischemic injury and angiogenesis in the rat model of acute cerebral infarction. SD rats were randomized into 6 groups: sham group, model group, low-, medium-, and high-dose(5.13, 10.26, and 20.52 g·kg~(-1), respectively) Xuming Decoction groups, and butylphthalide(0.06 g·kg~(-1)) group. After the successful establishment of the rat model by middle cerebral artery occlusion(MCAO), rats in the sham and model groups were administrated with distilled water and those in other groups with corresponding drugs for 7 consecutive days. After the neurological function was scored, all the rats were sacrificed, and the brain tissue samples were collected. The degree of cerebral ischemic injury was assessed by the neurological deficit score and staining with 2,3,5-triphenyltetrazolium chloride. Hematoxylin-eosin staining was performed to observe the pathological changes in the brain. Transmission electron microscopy was employed to observe the ultrastructures of neurons and microvascular endothelial cells(ECs) on the ischemic side of the brain tissue. Immunofluorescence assay was employed to detect the expression of von Willebrand factor(vWF) and hematopoietic progenitor cell antigen CD34(CD34) in the ischemic brain tissue. Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of Runt-related transcription factor 1(RUNX1), vascular endothelial growth factor(VEGF), angiopoietin-1(Ang-1), angiopoietin-2(Ang-2), and VEGF receptor 2(VEGFR2) in the ischemic brain tissue. The results showed that compared with the sham group, the model group showed increased neurological deficit score and cerebral infarction area(P<0.01), pathological changes, and damaged ultrastructure of neurons and microvascular ECs in the ischemic brain tissue. Furthermore, the modeling up-regulated the mRNA levels of RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01) and the protein levels of vWF, CD34, RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.05 or P<0.01). Compared with the model group, high-dose Xuming Decoction and butylphthalide decreased the neurological deficit score and cerebral infarction area(P<0.01) and alleviated the pathological changes and damage of the ultrastructure of neurons and microvascular ECs in the ischemic brain tissue. Moreover, they up-regulated the mRNA levels of RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01) and the protein levels of vWF, CD34, RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01). The results suggest that Xuming Decoction in the Records of Proved Prescriptions, Ancient and Modern can promote the angiogenesis and collateral circulation establishment to alleviate neurological dysfunction of the ischemic brain tissue in MCAO rats by regulating the RUNX1/VEGF pathway.

Exogenous application of 5-NGS increased osmotic stress resistance by improving leaf photosynthetic physiology and antioxidant capacity in maize.

Background: Drought is a critical limiting factor affecting the growth and development of spring maize (Zea mays L.) seedlings in northeastern China. Sodium 5-nitroguaiacol (5-NGS) has been found to enhance plant cell metabolism and promote seedling growth, which may increase drought tolerance. Methods: In the present study, we investigated the response of maize seedlings to foliar application of a 5-NGS solution under osmotic stress induced by polyethylene glycol (PEG-6000). Four treatment groups were established: foliar application of distilled water (CK), foliar application of 5-NGS (NS), osmotic stress + foliar application of distilled water (D), and osmotic stress + foliar application of 5-NGS (DN). Plant characteristics including growth and photosynthetic and antioxidant capacities under the four treatments were evaluated. Results: The results showed that under osmotic stress, the growth of maize seedlings was inhibited, and both the photosynthetic and antioxidant capacities were weakened. Additionally, there were significant increases in the proline and soluble sugar contents and a decrease in seedling relative water content (RWC). However, applying 5-NGS alleviated the impact of osmotic stress on maize seedling growth parameters, particularly the belowground biomass, with a dry mass change of less than 5% and increased relative water content (RWC). Moreover, treatment with 5-NGS mitigated the inhibition of photosynthesis caused by osmotic stress by restoring the net photosynthetic rate (Pn) through an increase in chlorophyll content, photosynthetic electron transport, and intercellular CO2 concentration (Ci). Furthermore, the activity of antioxidant enzymes in the aboveground parts recovered, resulting in an approximately 25% decrease in both malondialdehyde (MDA) and H2O2. Remarkably, the activity of enzymes in the underground parts exhibited more significant changes, with the contents of MDA and H2O2 decreasing by more than 50%. Finally, 5-NGS stimulated the dual roles of soluble sugars as osmoprotectants and energy sources for metabolism under osmotic stress, and the proline content increased by more than 30%. We found that 5-NGS played a role in the accumulation of photosynthates and the effective distribution of resources in maize seedlings. Conclusions: Based on these results, we determined that foliar application of 5-NGS may improve osmotic stress tolerance in maize seedlings. This study serves as a valuable reference for increasing maize yield under drought conditions.