The Arabidopsis E3 ubiquitin ligase PUB4 regulates BIK1 and is targeted by a bacterial type-III effector.

Plant immunity is tightly controlled by a complex and dynamic regulatory network, which ensures optimal activation upon detection of potential pathogens. Accordingly, each component of this network is a potential target for manipulation by pathogens. Here, we report that RipAC, a type III-secreted effector from the bacterial pathogen Ralstonia solanacearum, targets the plant E3 ubiquitin ligase PUB4 to inhibit pattern-triggered immunity (PTI). PUB4 plays a positive role in PTI by regulating the homeostasis of the central immune kinase BIK1. Before PAMP perception, PUB4 promotes the degradation of non-activated BIK1, while after PAMP perception, PUB4 contributes to the accumulation of activated BIK1. RipAC leads to BIK1 degradation, which correlates with its PTI-inhibitory activity. RipAC causes a reduction in pathogen-associated molecular pattern (PAMP)-induced PUB4 accumulation and phosphorylation. Our results shed light on the role played by PUB4 in immune regulation, and illustrate an indirect targeting of the immune signalling hub BIK1 by a bacterial effector.

A Regulatory Module Controlling Homeostasis of a Plant Immune Kinase.

Plant pattern recognition receptors (PRRs) perceive microbial and endogenous molecular patterns to activate immune signaling. The cytoplasmic kinase BIK1 acts downstream of multiple PRRs as a rate-limiting component, whose phosphorylation and accumulation are central to immune signal propagation. Previous work identified the calcium-dependent protein kinase CPK28 and heterotrimeric G proteins as negative and positive regulators of BIK1 accumulation, respectively. However, mechanisms underlying this regulation remain unknown. Here we show that the plant U-box proteins PUB25 and PUB26 are homologous E3 ligases that mark BIK1 for degradation to negatively regulate immunity. We demonstrate that the heterotrimeric G proteins inhibit PUB25/26 activity to stabilize BIK1, whereas CPK28 specifically phosphorylates conserved residues in PUB25/26 to enhance their activity and promote BIK1 degradation. Interestingly, PUB25/26 specifically target non-activated BIK1, suggesting that activated BIK1 is maintained for immune signaling. Our findings reveal a multi-protein regulatory module that enables robust yet tightly regulated immune responses.

Microbiota and metabolite alterations in pancreatic head and body/tail cancer patients.

Pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) have distinct clinical and biological behaviors. The microbial and metabolic differences in PHC and PBTC have not been studied. The pancreatic microbiota and metabolome of 15 PHC and 8 PBTC tissues and their matched nontumor tissues were characterized using 16S rRNA amplicon sequencing and untargeted metabolomics. At the genus level, Bradyrhizobium was increased while Corynebacterium and Ruminococcus were decreased in the PHC tissues (Head T) compared with the matched nontumor tissues (Head N) significantly. Shuttleworthia, Bacillus, and Bifidobacterium were significantly decreased in the PBTC tissues (Body/Tail T) compared with the matched nontumor tissues (Body/Tail N). Significantly, Ileibacterium was increased whereas Pseudoxanthomonas was decreased in Head T and Body/Tail T, and Lactobacillus was increased in Head T but decreased in Body/Tail T. A total of 102 discriminative metabolites were identified between Head T and Head N, which were scattered through linoleic acid metabolism and purine metabolism pathways. However, there were only four discriminative metabolites between Body/Tail T and Body/Tail N, which were related to glycerophospholipid metabolism and autophagy pathways. The differential metabolites in PHC and PBTC were commonly enriched in alpha-linolenic acid metabolism and choline metabolism in cancer pathways. Eubacterium decreased in Head T was positively correlated with decreased linoleic acid while negatively correlated with increased arachidyl carnitine and stearoylcarnitine. Bacillus decreased in Body/Tail T was negatively correlated with increased L-carnitine. These microbiota and metabolites deserve further investigations to reveal their roles in the pathogenesis of PHC and PBTC, providing clues for future treatments.

Development of Recoverable Magnetic Bimetallic ZIF-67 (Co/Cu) Adsorbent and Its Enhanced Selective Adsorption of Organic Dyes in Wastewater.

In the critical domain of wastewater treatment, the development of cost-effective, durable, and recyclable adsorbents with high adsorption capacities remains a significant challenge. This study introduces a novel magnetic bimetallic Metal-Organic Framework (MOF) adsorbent, MZIF-67-Co/Cu, doped with copper ions. The MZIF-67-Co/Cu adsorbent was successfully synthesized and structurally characterized, demonstrating remarkable selectivity for removing methyl orange (MO) from water. This high selectivity is attributed to the adsorbent's high porosity and Lewis base properties at the coordinating metal ion center. The incorporation of Cu ions significantly enhances the porous architecture and increases the number of metal adsorption sites, leading to an impressive maximum MO adsorption capacity of 39.02 mg/g under optimized conditions (0.5 g/L adsorbent concentration, pH 3.0, 250 rpm agitation speed, adsorption time > 10 min). The adsorption kinetics closely follow the pseudo-second-order model, and the isotherm data fit well with the Langmuir model. The primary adsorption mechanisms involve electrostatic attraction and mesoporous interaction. This study highlights MZIF-67-Co/Cu as a highly efficient adsorbent with magnetic recovery capabilities, positioning it as a promising candidate for addressing critical issues in wastewater treatment.

[Comprehensive therapy of traditional Chinese medicine for erectile dysfunction with damp-heat stasis: A clinical observation of 103 cases].

OBJECTIVE: To assess the clinical effect and safety of comprehensive therapy of traditional Chinese medicine (TCM) in the treatment of erectile dysfunction (ED) with damp-heat stasis. METHODS: We selected 108 cases of ED with damp-heat stasis meeting the inclusion criteria and treated with tadalafil (the control group, n = 54) or tadalafil + comprehensive TCM therapy (the trial group, n = 54) in the First Affiliated Hospital of Henan University of Chinese Medicine in the same period. After 8 weeks of treatment, we recorded the patients' scores on IIEF-5, TCM syndrome, erectile quality (EQS), 9-Item Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Scale 7 (GAD-7). At 16 weeks of our study, we collected the efficacy parameters, safety indicators and adverse reactions by telephone follow-up and compared the data obtained between the two groups of patients. RESULTS: Totally, 103 of the patients completed the study, 51 in the control and 52 in the trial group. Compared with the baseline, the IIEF-5 and EQS scores were both markedly increased after 8 weeks of treatment in the trial group (12.35±3.00 vs 18.36±2.82, P< 0.05; 39.5 ï¼»30.25－43ï¼½ vs 67.5 ï¼»54.5－76.75ï¼½, P< 0.05) and the control (11.96±2.79 vs 15.88±3.86, P< 0.05; 38.0 ï¼»29－42ï¼½ vs 56 ï¼»49－64ï¼½, P< 0.05), even more significantly in the former than in the latter (P< 0.05); the TCM syndrome and GAD-7 scores were remarkably decreased in the trial (9.5 ï¼»8－12ï¼½ vs 4.0 ï¼»2.25－5ï¼½, P< 0.05; 5 ï¼»2.25－6.75ï¼½ vs 2.5 ï¼»1－4.75ï¼½, P< 0.05) and the control group (10.0 ï¼»8－12ï¼½ vs 5.0 ï¼»3－6ï¼½, P< 0.05; 5.0 ï¼»3－6ï¼½ vs 4.0 ï¼»2－5ï¼½, P< 0.05), even more significantly in the former than in the latter (P< 0.05), so were the PHQ-9 scores (P< 0.05), but with no statistically significant difference between the two groups (P > 0.05). The IIEF-5 scores of the two groups remained significantly higher than the baseline during the follow-up (P< 0.05), even higher in the trial than in the control group (17.04±2.60 vs 14.16±3.34, P< 0.05). No obvious abnormal safety indicators or adverse events were observed during the study. CONCLUSION: Comprehensive TCM therapy combined with tadalafil is superior to tadalafil alone in the treatment of ED with damp-heat stasis, and has a better long-term efficacy and a higher safety.

An Integrated Multi-Omics Analysis Identifying Immune Subtypes of Pancreatic Cancer.

Limited studies have explored novel pancreatic cancer (PC) subtypes or prognostic biomarkers based on the altered activity of relevant signaling pathway gene sets. Here, we employed non-negative matrix factorization (NMF) to identify three immune subtypes of PC based on C7 immunologic signature gene set activity in PC and normal samples. Cluster 1, the immune-inflamed subtype, showed a higher response rate to immune checkpoint blockade (ICB) and had the lowest tumor immune dysfunction and exclusion (TIDE) scores. Cluster 2, the immune-excluded subtype, exhibited strong associations with stromal activation, characterized by elevated expression levels of transforming growth factor (TGF)-ß, cell adhesion, extracellular matrix remodeling, and epithelial-to-mesenchymal transition (EMT) related genes. Cluster 3, the immune-desert subtype, displayed limited immune activity. For prognostic prediction, we developed an immune-related prognostic risk model (IRPM) based on four immune-related prognostic genes in pancreatic cancer, RHOF, CEP250, TSC1, and KIF20B. The IRPM demonstrated excellent prognostic efficacy and successful validation in an external cohort. Notably, the key gene in the prognostic model, RHOF, exerted significant influence on the proliferation, migration, and invasion of pancreatic cancer cells through in vitro experiments. Furthermore, we conducted a comprehensive analysis of somatic mutational landscapes and immune landscapes in PC patients with different IRPM risk scores. Our findings accurately stratified patients based on their immune microenvironment and predicted immunotherapy responses, offering valuable insights for clinicians in developing more targeted clinical strategies.

CPR5 positively regulates pattern-triggered immunity via a mediator protein.

Plant cells possess a two-layered immune system consisting of pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), mediated by cell surface pattern-recognition receptors and intracellular nucleotide-binding leucine-rich repeat receptors (NLRs), respectively. The CONSTITUTIVE EXPRESSION OF PR GENES 5 (CPR5) nuclear pore complex protein negatively regulates ETI, including ETI-associated hypersensitive response. Here, we show that CPR5 is essential for the activation of various PTI responses in Arabidopsis, such as resistance to the non-adapted bacterium Pseudomonas syringae pv. tomato DC3000 hrcC- . In a forward-genetic screen for suppressors of cpr5, we identified the mediator protein MED4. Mutation of MED4 in cpr5 greatly restored the defective PTI of cpr5. Our findings reveal that CPR5 plays opposite roles in regulating PTI and ETI, and genetically regulates PTI via MED4.

PuHox52 promotes coordinated uptake of nitrate, phosphate, and iron under nitrogen deficiency in Populus ussuriensis.

It is of great importance to better understand how trees regulate nitrogen (N) uptake under N deficiency conditions which severely challenge afforestation practices, yet the underlying molecular mechanisms have not been well elucidated. Here, we functionally characterized PuHox52, a Populus ussuriensis HD-ZIP transcription factor, whose overexpression greatly enhanced nutrient uptake and plant growth under N deficiency. We first conducted an RNA sequencing experiment to obtain root transcriptome using PuHox52-overexpression lines of P. ussuriensis under low N treatment. We then performed multiple genetic and phenotypic analyses to identify key target genes of PuHox52 and validated how they acted against N deficiency under PuHox52 regulation. PuHox52 was specifically induced in roots by N deficiency, and overexpression of PuHox52 promoted N uptake, plant growth, and root development. We demonstrated that several nitrate-responsive genes (PuNRT1.1, PuNRT2.4, PuCLC-b, PuNIA2, PuNIR1, and PuNLP1), phosphate-responsive genes (PuPHL1A and PuPHL1B), and an iron transporter gene (PuIRT1) were substantiated to be direct targets of PuHox52. Among them, PuNRT1.1, PuPHL1A/B, and PuIRT1 were upregulated to relatively higher levels during PuHox52-mediated responses against N deficiency in PuHox52-overexpression lines compared to WT. Our study revealed a novel regulatory mechanism underlying root adaption to N deficiency where PuHox52 modulated a coordinated uptake of nitrate, phosphate, and iron through 'PuHox52-PuNRT1.1', 'PuHox52-PuPHL1A/PuPHL1B', and 'PuHox52-PuIRT1' regulatory relationships in poplar roots.

Rice extra-large G proteins play pivotal roles in controlling disease resistance and yield-related traits.

To better explore the potential of rice extra-large G (XLG) proteins in future breeding, we characterised the function of OsXLG1, OsXLG2 and OsXLG3 in disease resistance. Loss-of-function Osxlg2 and Osxlg3 mutants showed reduced resistance to the fungal pathogen Magnaporthe oryzae, whereas Osxlg1 mutants were specifically compromised in resistance to the bacterial pathogen Xanthomonas oryzae pv oryzae. Consistent with their effects on rice blast resistance, mutations in OsXLG2 and OsXLG3 caused greater defects than did mutations in OsXLG1 for chitin-induced defence responses. All three OsXLGs interacted with components of a surface immune receptor complex composed of OsCERK1, OsRLCK176 and OsRLCK185. Further characterisation of yield-related traits showed that the Osxlg3 mutants displayed reduced plant height, panicle length and 1000grain weight, whereas Osxlg1 mutants exhibited increased plant height, panicle length and 1000-grain weight. Together the study shows the differential contributions of the three OsXLG proteins to disease resistance to fungal and bacterial pathogens, their yield-related traits and provides insights for future improvement of rice production.

Anti-Psoriatic Effects of Middle Fragment of Chlamydial Plasmid-Encoded Protein pGP3 in an Imiquimod-Induced Psoriasis Mouse Model.

BACKGROUND Previously, we demonstrated that the chlamydial protein pGP3 forms a stable complex with LL-37 to neutralize its proinflammatory activity during the pathogenesis of psoriasis. The middle domain of pGP3 (pGP3M) is critical for the binding and neutralization of LL-37. Here, we further examined the mechanism underlying pGP3-mediated inhibition of psoriasis progression and evaluated the inhibitory effect of pGP3M on the development of psoriasis-like skin lesions in mice. MATERIAL AND METHODS Stock solutions of pGP3M and pGP3 (100 µg/mL) were prepared using sterile ultrapure water and intramuscularly injected into the left leg of the imiquimod (IMQ)-induced psoriasis mouse model. The severity of skin lesions was evaluated based on the psoriasis area and severity index score and ear skin thickness. The skin biopsy and blood samples were collected on the 8th day for histological analysis and inflammatory cytokines detection. RESULTS Erythema, scaling, and thickening were observed on the dorsal skin and the right ear skin of IMQ-treated mice. Treatment with pGP3 and pGP3M alleviated the IMQ-induced erythema, inflammatory cell infiltration, and scaly plaques. Compared with IMQ-treated and PBS-treated mice, pGP3- and PGP3M-treated mice had less inflammatory cell infiltration in skin tissues and had significantly reduced IL-17A, IFN-γ, and IL-22 levels in serum. CONCLUSIONS The anti-psoriatic efficacy of exogenous pGP3M was similar to that of pGP3. This indicated that pGP3M attenuated the IMQ-induced inflammatory and psoriatic symptoms in mice by binding and inhibiting LL-37. Further research is needed to examine the toxicity of pGP3 and pGP3M before clinical trial evaluation.

Chlamydial-Secreted Protease Chlamydia High Temperature Requirement Protein A (cHtrA) Degrades Human Cathelicidin LL-37 and Suppresses Its Anti-Chlamydial Activity.

BACKGROUND Chlamydia trachomatis is an obligate intracellular pathogen that can cause severe reproductive tract complications while ascending infection occurs. When spreading from cell to cell in a host, C. trachomatis utilizes various survival strategies to offset host defense mechanisms. One such strategy is to degrade host antimicrobial defense proteins before they can attack the invading C. trachomatis cells. MATERIAL AND METHODS We expressed and purified recombinant chlamydia high temperature requirement protein A (cHtrA) including 2 cHtrA mutants (MT-H143A and MT-S247A), and also extracted endogenous cHtrA. Proteins were identified and their purity evaluated by SDS-PAGE and Western blot. The anti-chlamydial activity and degradation of 5 antimicrobial peptides (cathelicidin LL-37, alpha-defensin-1 and -3, and ß-defensin-2 and -4) by cHtrA and 2 cHtrA mutants (MT-H143A and MT-S247A) were tested by immunoassay and Western blot. RESULTS Of the 5 antimicrobial peptides (cathelicidin LL-37, alpha-defensin-1 and -3, and ß-defensin-2 and -4) tested, cathelicidin LL-37 showed the strongest anti-chlamydial activity. Interestingly, cHtrA effectively and specifically degraded LL-37, suppressing its anti-chlamydial activity. The 2 cHtrA mutants (MT-H143A and MT-S247A) were unable to degrade LL-37. Comparison of cHtrA activity from C. trachomatis D, L2, and MoPn strains on LL-37 showed similar responses. CONCLUSIONS cHtrA may contribute to C. trachomatis pathogenicity by clearing the passage of invasion by specific LL-37 degradation.

[Effects of norepinephrine on proliferation and apoptosis of neonatal cardiac fibroblasts in rats].

OBJECTIVE: To investigate the effects of different concentrations of norepinephrine (NE) on proliferation and apoptosis of cultured cardiac fibroblasts (CFBs) from neonatal mice and to elucidate related mechanisms. METHODS: CFBs of Sprague-Dawley (SD) rats were isolated and cultured and divided into normal control group and different concentration of NE intervention groups (0.1, 1, 10, 50, and 100 µmol/L). Water soluble tetrazolium-1 (WST-1) assay was carried out to detect the viability of CFBs. Morphology of apoptosis cells was evaluated by fluorescence microscope with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expressions of collagen I, collagen III, pro-oncogene c-myc in CFBs were detected by reverse transcription-polymerase chain reaction (RT-PCR). The phospho-mitogen activated protein kinase (p-p38MAPK) and caspase3 protein levels were examined by Western blot. RESULTS: Proliferation was significantly increased in 1 µmol/L and 10 µmol/L groups compared with the normal control group (1.05 ± 0.05 and 1.09 ± 0.02 vs. 1.00 ± 0.03, all P < 0.05).CFBs apoptosis was significantly enhanced in 50 µmol/L and 100 µmol/L groups ((22.69 ± 2.18)% and (36.40 ± 6.80)% vs.(4.50 ± 1.08)%, all P < 0.05). Expression of Collagen I peaked in 10 µmol/L group, expression of collagen III and c-myc increased dose-dependently in proportion to increasing NE concentrations (all P < 0.05 vs. control group). The expression of p-p38MAPK and caspase3 was also significantly upregulated in a dose-dependent manner in NE groups (all P < 0.05 vs. control group). CONCLUSIONS: Low concentration NE induces CFBs proliferation and high concentration NE promotes CFBs apoptosis. p38MAPK phosphorylation may be a major mediator of NE-induced effects on CFBs.

New energy vehicles' technology innovation coordination strategy based on alliance negotiation under dual credit policy.

The development of new energy vehicles (NEVs) is one of the effective ways to alleviate carbon emissions, environmental pollution, and energy scarcity in the transportation sector. The Chinese government has innovatively proposed the "dual credit policy," but it is still a hot topic whether it can promote the NEVs' technological innovation. In this study, we construct game models and obtain the technological innovation strategies for NEVs under the dual credit policy, considering that the NEV supply chain contains one manufacturer and N suppliers. Further, we construct bargaining game models and study how to encourage manufacturers and suppliers to enhance technological innovation, realize supply chain coordination, and give the alliance strategy to maximize suppliers' profit. We found that the dual credit policy can effectively stimulate technological innovation, and the higher the credit price or technological innovation credit factor, the higher the technical level of NEVs. The findings could guide the government to adjust and revise the policy. Second, we found that the bargaining games could coordinate the NEV supply chain so that decentralized enterprises can achieve optimal technological innovation under centralized decision-making. Third, we found that suppliers can improve their profits by choosing a suitable alliance strategy under the manufacturer's different negotiating power.

Detection Methods for Pine Wilt Disease: A Comprehensive Review.

Pine wilt disease (PWD), caused by the nematode Bursaphelenchus xylophilus, is a highly destructive forest disease that necessitates rapid and precise identification for effective management and control. This study evaluates various detection methods for PWD, including morphological diagnosis, molecular techniques, and remote sensing. While traditional methods are economical, they are limited by their inability to detect subtle or early changes and require considerable time and expertise. To overcome these challenges, this study emphasizes advanced molecular approaches such as real-time polymerase chain reaction (RT-PCR), droplet digital PCR (ddPCR), and loop-mediated isothermal amplification (LAMP) coupled with CRISPR/Cas12a, which offer fast and accurate pathogen detection. Additionally, DNA barcoding and microarrays facilitate species identification, and proteomics can provide insights into infection-specific protein signatures. The study also highlights remote sensing technologies, including satellite imagery and unmanned aerial vehicle (UAV)-based hyperspectral analysis, for their capability to monitor PWD by detecting asymptomatic diseases through changes in the spectral signatures of trees. Future research should focus on combining traditional and innovative techniques, refining visual inspection processes, developing rapid and portable diagnostic tools for field application, and exploring the potential of volatile organic compound analysis and machine learning algorithms for early disease detection. Integrating diverse methods and adopting innovative technologies are crucial to effectively control this lethal forest disease.

Comparative effectiveness of chemotherapy in different histological types of pancreatic cancer: a PSM-based study using the SEER database.

This study aimed to compare the effectiveness of chemotherapy in different histological types of pancreatic cancer using data collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients who were diagnosed with pancreatic cancer between 2004 and 2015 were selected from the SEER database. Propensity score matching (PSM) was employed to minimize the selection bias. The Kaplan-Meier survival curves and the log-rank test were utilized to compare the overall survival (OS) and cancer-specific survival (CSS) among different groups. Of the 7,653 pancreatic cancer patients, both OS and CSS were higher in the chemotherapy group than those in the non-chemotherapy group (p < 0.001). After PSM, 2381 pairs were generated. The Kaplan-Meier survival curved indicated that both OS and CSS for pancreatic ductal adenocarcinoma (PDAC), pancreatic adenosquamous carcinoma (PASC), and pancreatic mucin-producing adenocarcinoma (PMPAC) (p < 0.001) in the chemotherapy group were superior to those in the non-chemotherapy group, while there was no significant difference in pancreatic mucinous adenocarcinoma (PMAC) (p = 0.2586). Compared with PASC and PMPAC, PDAC exhibited longer OS and CSS. The results of statistical analysis showed that PASC tumors were mainly poorly differentiated, and the majority of patients with PMPAC had distant metastasis. Chemotherapy could prolong pancreatic cancer patients' survival, especially for patients with advanced disease. PMPAC patients had a higher rate of metastasis, accompanying with the worse survival.

A Study of Sperm DNA Damage Mechanism Based on miRNA Sequencing.

To analyze the differential expression profiles of microRNAs (miRNAs) in spermatozoa of patients with sperm DNA damage and to investigate the role of miRNAs in sperm DNA damage. Male infertility patients with sperm DNA damage who attended the First Affiliated Hospital of Henan University of Chinese Medicine from October 2023 to December 2023 were selected and included in this study as a case group. Fertile healthy men who were seen at the health check-up center during the same period and diagnosed by examination were also included as a control group. Sperm miRNA expression was detected in patients with sperm DNA damage (case group, n = 5) and healthy medical check-ups (control group, n = 5) using high-throughput sequencing technology. The differentially expressed miRNAs between the two groups were bioinformatically analyzed to explore the main biological functions of the target genes. We found that 63 miRNAs were significantly changed in the spermatozoa of patients with sperm DNA damage,|log2 (foldchange)| ≥ 1, p < .05. Gene Ontology (GO) enrichment analysis indicated that these differential miRNAs might be involved in developmental process, anatomical structure development, cellular macromolecule metabolic process, multicellular organism development, system development, and so on. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that that they mainly affect the PI3K-AKT signaling pathway. The present study suggests that the altered expression of miR-1255a, miR-921, and miR-3156-5p may play an important role in the sperm DNA damage process, and the mechanism may involve the phosphatidylinositol-3'-kinase-AKT (PI3K-AKT) signaling pathway.

Does erectile dysfunction predict cardiovascular risk? A cross-sectional study of clinical characteristics in patients with erectile dysfunction combined with coronary heart disease.

Background: Erectile Dysfunction (ED) is a common sexual dysfunction in men who are unable to consistently obtain and maintain sufficient penile erection to accomplish a satisfactory sexual life. ED is currently considered to be a predictor of cardiovascular disease (CVD), but few studies have observed the association between ED and clinical features of coronary heart disease (CHD). An investigation of the association between ED and clinical characteristics of CHD was carried out using a cross-sectional study design. Methods: This cross-sectional single-center study was conducted in the Department of Cardiology and included 248 patients. Associations between patients' general information, underlying disease information, coronary heart disease information, and ED severity were statistically and analytically analyzed using SPSS 26.0 software. Patients with comparable clinical characteristics were grouped together using K-means clustering. Finally, ordered logistic regression analysis was performed for general and underlying disease information. Results: In the comparison of general data, age, education, and weekly exercise were associated with the distribution of ED severity. In the comparison of underlying disease information, the number of underlying diseases, hypertension, diabetes, hyperlipidemia, anxiety state, and depressive state were associated with the distribution of ED severity. In the comparison of CHD information, the degree of ED severity was associated with CHD subtypes, lesion sites, number of stenoses, degree of stenosis, and interventional interventions. The time from ED to CHD onset was associated with the subtypes of CHD and the number of stenoses. We clustered the main characteristics of low-risk and high-risk patients and ordered logistic regression analysis found that BMI, smoking, alcoholism, number of underlying diseases, diabetes, anxiety state, and depression state were all risk factors for CHD severity (P < 0.05); the higher the value of the above factors, the more severe the degree of CHD. Age was a protective factor for CHD severity; the younger the patient, the lower the likelihood of myocardial infarction. Conclusion: ED severity and the time from ED to CHD onset may be predictive of coronary heart disease severity. Reducing smoking and alcohol consumption, maintaining a healthy body weight, and regular physical activity are important in preventing CVD in ED patients.

Exploring the Mechanisms of Yishen Tongluo Decoction on Repairing DNA Damage in Mouse Spermatogonia Cells Based on Whole Transcriptome Sequencing.

The aim of this study was to investigate the potential mechanism through which Yishen Tongluo decoction (YSTL) repairs DNA damage caused by benzo(a)pyrene diol epoxide (BPDE) in mouse spermatocytes (GC-2). The GC-2 cells were divided randomly into the control group, BPDE group, and low-, medium-, and high-dose YSTL groups of YSTL decoction. A comet assay was used to detect the DNA fragment index (DFI) of cells in each group. Based on the DFI results, whole transcriptome sequencing was conducted, followed by trend analysis, gene ontology (GO) enrichment analysis, kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and ceRNA network analysis. Compared with the control group, the BPDE group reported a significant increase in the DNA fragmentation index (DFI) (p < .05). Compared with the BPDE group, the low-, high- and medium-dose YSTL groups had a significantly reduced DFI (p < .05). Whole-transcriptome sequencing revealed seven differentially expressed circRNAs, 203 differentially expressed miRNAs, and 3,662 differentially expressed mRNAs between the control group and the BPDE group. There was a total of 12 differentially expressed circRNAs, 204 miRNAs, and 2150 mRNAs between the BPDE group and the traditional Chinese medicine group. The pathways involved include DNA repair pathway, nucleotide excision repair pathway, base excision repair pathway, etc. The ceRNA network reported that Hmga2 was the core protein involved, novel_cir_000117 and mmu-miR-466c-3p were located upstream of Hmga2, and they were regulatory factors associated with Hmga2. Finally, we conclude that YSTL decoction may repair sperm DNA damage caused by BPDE through the novel_cir_000117-mmu-miR-466c-3p-Hmga2 pathway.

Development of a "Signal-On" Fluorescent Aptasensor for Highly Selective and Sensitive Detection of ZEN in Cereal Products Using Nitrogen-Doped Carbon Dots Based on the Inner Filter Effect.

This study aimed to develop a novel fluorescent aptasensor for the quantitative detection of zearalenone (ZEN), addressing the limitations of conventional detection techniques in terms of speed, sensitivity, and ease of use. Nitrogen-doped carbon dots (N-CDs) were synthesized via the hydrothermal method, resulting in spherical particles with a diameter of 3.25 nm. These N-CDs demonstrated high water solubility and emitted a bright blue light at 440 nm when excited at 355 nm. The fluorescence of N-CDs was quenched by dispersed gold nanoparticles (AuNPs) through the inner filter effect, while aggregated AuNPs induced by NaCl did not affect the fluorescence of N-CDs. The aptamer could protect AuNPs from NaCl-induced aggregation, but the presence of ZEN weakened this protective effect. Based on this principle, optimal conditions for ZEN detection included 57 mM NaCl, 12.5 nM aptamer concentration, incubation of AuNPs with NaCl for 15 min in Tris-EDTA(TE) buffer, and incubation of aptamer with ZEN and NaCl for 30 min. Under these optimized conditions, the "signal-on" fluorescent aptasensor for ZEN detection showed a linear range of 0.25 to 200 ng/mL with a low detection limit of 0.0875 ng/mL. Furthermore, the developed aptasensor exhibited excellent specificity and could rapidly detect ZEN in corn flour samples or corn oil, achieving satisfactory recovery rates ranging from 84.7% to 108.6%. Therefore, this study presents an economical, convenient, sensitive, and rapid method for accurately quantifying ZEN in cereal products.

Effects of Active Dry Yeast Supplementation in In Vitro and In Vivo Nutrient Digestibility, Rumen Fermentation, and Bacterial Community.

This study assessed the impact of active dry yeast (ADY) on nutrient digestibility and rumen fermentation, using both in vitro and in vivo experiments with lambs. In vitro, ADYs were incubated with rumen fluid and a substrate mixture to assess gas production, pH, volatile fatty acid (VFA) profiles, and lactate concentration. In vivo, Hu lambs were randomly assigned to five dietary treatments: a control group and four groups receiving one of two dosages of either Vistacell or Procreatin7. Growth performance, nutrient digestibility, rumen fermentation parameters, and bacterial community composition were measured. Pro enhanced the propionate molar proportion while it decreased the n-butyrate molar proportion. Vis reduced the lactate concentration in vitro. In the in vivo experiment, Vis increased the propionate molar proportion and the Succinivibrionaceae_UCG-001 abundance while it decreased the n-butyrate molar proportion and the Lachnospiraceae_ND3007 abundance. Additionally, Vis showed a greater impact on improving the NDF digestibility and total VFA concentration in vivo compared to Pro. Overall, the effects of ADYs on rumen fermentation were found to vary depending on the specific ADY used, with Vis being the most suitable for lamb growth. It was observed that Vis promoted propionate fermentation and Succinivibrionaceae_UCG-001 abundance at the expense of reduced n-butyrate fermentation and Lachnospiraceae_ND3007 abundance. Importantly, differences were noted between the outcomes of the in vitro and in vivo experiments concerning the effects of ADYs on rumen fermentation, highlighting the need for caution when generalizing batch culture results to the in vivo effects of ADYs.