Mechanism-based Inactivation of Cytochromes P450: Implications in Drug Interactions and Pharmacotherapy.

Cytochrome P40 (CYP) enzymes dominate the metabolism of numerous endogenous and xenobiotic substances. While it is commonly believed that CYP-catalyzed reactions result in the detoxication of foreign substances, these reactions can also yield reactive intermediates that can bind to cellular macromolecules to cause cytotoxicity or irreversibly inactivate CYPs that create them.Mechanism-based inactivation (MBI) produces either irreversible or quasi-irreversible inactivation and is commonly caused by CYP metabolic bioactivation to an electrophilic reactive intermediate. Many drugs that have been known to cause MBI in CYPs have been discovered as perpetrators in drug-drug interactions throughout the last 20-30 years.This review will highlight the key findings from the recent literature about the mechanisms of CYP enzyme inhibition, with a focus on the broad mechanistic elements of MBI for widely used drugs linked to the phenomenon. There will also be a brief discussion of the clinical or pharmacokinetic consequences of CYP inactivation with regard to drug interaction and toxicity risk.Gaining knowledge about the selective inactivation of CYPs by common therapeutic drugs helps with the assessment of factors that affect the systemic clearance of co-administered drugs and improves comprehension of anticipated interactions with other drugs or xenobiotics.

Application of artificial intelligence in the diagnosis and treatment of Kawasaki disease.

This editorial provides commentary on an article titled "Potential and limitations of ChatGPT and generative artificial intelligence (AI) in medical safety education" recently published in the World Journal of Clinical Cases. AI has enormous potential for various applications in the field of Kawasaki disease (KD). One is machine learning (ML) to assist in the diagnosis of KD, and clinical prediction models have been constructed worldwide using ML; the second is using a gene signal calculation toolbox to identify KD, which can be used to monitor key clinical features and laboratory parameters of disease severity; and the third is using deep learning (DL) to assist in cardiac ultrasound detection. The performance of the DL algorithm is similar to that of experienced cardiac experts in detecting coronary artery lesions to promoting the diagnosis of KD. To effectively utilize AI in the diagnosis and treatment process of KD, it is crucial to improve the accuracy of AI decision-making using more medical data, while addressing issues related to patient personal information protection and AI decision-making responsibility. AI progress is expected to provide patients with accurate and effective medical services that will positively impact the diagnosis and treatment of KD in the future.

A Comprehensive Analysis of LYAR in Colorectal Cancer: Prognostic Marker and Therapeutic Target.

Background: Colorectal cancer (CRC) is a major global health challenge with a need for new biomarkers and therapeutic targets. This work aimed to investigate the biological mechanisms and clinical value of Ly1 antibody reactive (LYAR) in CRC. Methods: We analyzed LYAR mRNA expression across multiple public databases, including genotype-tissue expression, gene expression omnibus, Oncomine, and the cancer genome atlas, alongside in-house immunohistochemical data to evaluate LYAR protein expression in CRC and non-CRC colorectal tissues. Gene set enrichment analysis (GSEA) was used to elucidate LYAR's biological functions, and its impact on the tumor immune microenvironment was assessed using CIBERSORT, ESTIMATE, and single-cell RNA sequencing techniques. In addition, LYAR's association with clinicopathological features and patient prognosis was explored, and its influence on drug sensitivity was investigated using the Connectivity Map database. Results: LYAR was significantly upregulated in CRC tissues compared with non-CRC colorectal counterparts, associated with altered immune cell composition and enhanced RNA processing, splicing, and cell cycle regulation. High LYAR expression correlated with poor disease-free and overall survival, underscoring its prognostic value. GSEA revealed LYAR's involvement in critical cellular processes and pathways, including DNA repair, cell cycle, and mTORC1 signaling. Correlation analysis identified genes positively and negatively associated with LYAR, leading to the discovery of temsirolimus and WYE-354, mTOR inhibitors, as potential therapeutic agents for CRC. Furthermore, LYAR expression predicted increased sensitivity to cetuximab in RAS wild-type metastatic CRC, indicating its utility as a biomarker for treatment responsiveness. Conclusions: LYAR's upregulation in CRC highlights its potential as a biomarker for prognosis and therapeutic targeting, offering insights into CRC pathology and suggesting new avenues for treatment optimization.

Rh(III)-Catalyzed C(sp3)-H Thiolation of 8-Methylquinolines Promoted by Benzoic Anhydride.

Herein, we developed a ligand-promoted Rh(III)-catalyzed C(sp3)-H thiolation of 8-methylquinolines. The effect of ligands on improving the activity of the catalytic centers has been studied in detail and proven to be significant. Various substituents are well tolerated under this reaction condition to provide potential precursors for organic synthesis. The mechanistic study suggests that the reaction may proceed through a five-membered rhodacycle intermediate via thiolation twice.

Structural characterization of Li2(MgxZn1-x)2W2O9 for bluish-white luminescence in rare earth-free tungstate phosphors.

Self-activated phosphors have attracted considerable attention due to their low synthesis temperature, high excitation threshold, and broad emission spectrum. And self-activated tungstate phosphors are distinguished by their low cost and stable chemical properties. Generally, it is difficult to observe luminescence from tungstate phosphors at room temperature. Furthermore, blue-emitting tungstate phosphors with high quantum efficiency are rarely reported. In this study, we succeeded in discovering high quantum-efficiency bluish-white-emitting Li2(MgxZn1-x)2W2O9 phosphors and investigating their detailed crystal structures. Upon near-ultraviolet excitation at 266 nm, these phosphors exhibit a broadband emission peak. The red shift of emission is slight with increasing Zn content in Li2(MgxZn1-x)2W2O9. A highly compact octahedral [WO6] unit is observed in the Li2(MgxZn1-x)2W2O9 phosphors. The phosphors exhibit high internal quantum efficiencies (IQEs) of 68.70% (M = Mg), 43.90% (M = Mg0.5Zn0.5), and 22.90% (M = Zn), respectively. This study provides a bluish-white-emitting tungstate phosphor with high quantum efficiency.

The anti-tumor effects of cosmosiin through regulating AhR/CYP1A1-PPARγ in breast cancer.

Breast cancer is one of the threatening malignant tumors with the highest mortality and incidence rate over the world. There are a lot of breast cancer patients dying every year due to the lack of effective and safe therapeutic drugs. Therefore, it is highly necessary to develop more effective drugs to overcome breast cancer. As a glycoside derivative of apigenin, cosmosiin is characterized by low toxicity, high water solubility, and wide distribution in nature. Additionally, cosmosiin has been shown to perform anti-tumor effects in cervical cancer, hepatocellular carcinoma and melanoma. However, its pharmacological effects on breast cancer and its mechanisms are still unknown. In our study, the anti-breast cancer effect and mechanism of cosmosiin were investigated by using breast cancer models in vivo and in vitro. The results showed that cosmosiin inhibited the proliferation, migration, and adhesion of breast cancer cells in vitro and suppressed the growth of tumor in vivo through binding with AhR and inhibiting it, thus regulating the downstream CYP1A1/AMPK/mTOR and PPARγ/Wnt/ß-catenin signaling pathways. Collectively, our findings have made contribution to the development of novel drugs against breast cancer by targeting AhR and provided a new direction for the research in the field of anti-breast cancer therapy.

A versatile fluorescent probe for the ratiometric detection of hydrazine (N2H4) in water, soil, plant, and food samples.

Hydrazine (N2H4) is a crucial chemical raw material extensively utilized in chemical production. However, due to its volatility, water solubility, and high toxicity, both the gaseous form and aqueous solution of N2H4 pose significant environmental risks by causing severe pollution that can adversely impact plants, microorganisms, and human health. Therefore, accurate detection of N2H4 in the environment is imperative for safeguarding public health. In this study, we synthesized a ratiometric fluorescent probe (BCaz-Cy2) based on Carbazole and Hemicyanine groups. This probe exhibits simple synthesis procedure, rapid response time, high sensitivity and selectivity as well as remarkable detection signals. It enables effective detection of N2H4 in various matrices such as water, food, soil and plant samples thereby significantly expanding the scope of applications for N2H4 probes.

Isolation and identification of a novel porcine-related recombinant mammalian orthoreovirus type 3 strain from cattle in Guangxi Province, China.

The Mammalian orthoreovirus (MRV) infects various mammals, including humans, and is linked to gastrointestinal, respiratory, and neurological diseases. A recent outbreak in Liuzhou, Guangxi, China, led to the isolation of a new MRV strain, GXLZ2301, from fecal samples. This strain replicates in multiple cell lines and forms lattice-like structures. Infected cells exhibit single-cell death and syncytia formation. The virus's titers peaked at 107.2 TCID50/0.1 mL in PK-15 and BHK cells, with the lowest at 103.88 TCID50/0.1 mL in A549 cells. Electron microscopy showed no envelope with a diameter of about 70 nm. Genetic analysis revealed GXLZ2301 as a recombinant strain with gene segments from humans, cows, and pigs, similar to type 3 MRV strains from Italy (2015-2016). Pathogenicity tests indicated that while the bovine MRV strain did not cause clinical symptoms in mice, it caused significant damage to the gut, lungs, liver, kidneys, and brain. The emergence of this MRV strain may pose a threat to the health of animals and humans, and it is recommended that its epidemiology and recombination be closely monitored.

Predictive value of blood coagulation and routine blood indices for rebleeding after endoscopic treatment in hepatitis B-related cirrhotic patients with esophagogastric fundal varices: a logistic regression model analysis.

OBJECTIVE: To evaluate the predictive value of blood coagulation and routine blood indices for rebleeding after endoscopic treatment of ruptured esophagogastric fundal varices (EGVB) in cirrhotic patients with hepatitis B infection. METHODS: This retrospective analysis included 248 patients with hepatitis B-related cirrhosis and EGVB who received initial endoscopic treatment from October 2019 to March 2022 and were followed up for 12 months. Patients were divided into rebleeding and non-rebleeding groups. Laboratory indices were analyzed, and univariate and multivariate analyses identified predictors of rebleeding. The efficacy of a logistic regression model was evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA), and a risk factor nomogram was constructed for assessing the predictive efficiency of those risk factors. RESULTS: Univariate analysis showed significant differences in portal vein diameters and lower Child-Pugh scores in the rebleeding group in contrast to those in the non-rebleeding group. Key laboratory markers such as platelet count (PLT), albumin (ALB), alanine aminotransferase (ALT), lymphocytes (LYM), and prognostic nutritional index (PNI) were lower, while prothrombin time (PT) and lactate levels (LN) were higher in the rebleeding group than those in the non-rebleeding group. Multivariate analysis identified portal vein diameter, PLT, ALT, PT, LYM, and PNI as significant predictors of rebleeding. The logistic model demonstrated high accuracy (AUC=0.986) and clinical value, validated by ROC curves, calibration curves (C-index =0.986), and DCA results. A risk factor predictive nomogram was successfully constructed. CONCLUSION: This study developed a logistic regression model with a nomogram for predicting EGVB-related rebleeding in patients with hepatitis B-related cirrhosis, achieving an AUC of 0.986, indicating high accuracy and significant clinical relevance.

A ratiometric fluorescent probe for selective detection of hypochlorite (ClO-) and gallium (III) (Ga3+) ions in environmental and food samples.

Hypochlorite (ClO-) and gallium (Ⅲ) ions (Ga3+) have extensive applications in various human industries and daily activities. However, their inherent toxicity poses significant risks to environmental preservation and human well-being. Hence, the development of reliable and handy detection tools for ClO- and Ga3+ in the environment and food is crucial. In this study, a ratiometric fluorescent probe was prepared based on benzothiazolaldehyde and pyridine-2-carboxylic acid hydrazide, which exhibited exceptional performance characteristics for the selective detection of ClO- and Ga3+. These features include high specificity, low detection limits (0.28 µM for ClO-, 0.13 µM for Ga3+), mild pH conditions (pH 4-11 for ClO-, pH 6-11 for Ga3+), fast response time (within 30 s), as well as versatile applicability across different matrices such as water, soil, food, and plant samples. Additionally, this probe can be used with a smartphone color recognition app. The probe offers a convenient and effective tool for the detection of ClO- and Ga3+, demonstrating its potential application value in environmental monitoring and food safety.

A deep learning system for myopia onset prediction and intervention effectiveness evaluation in children.

The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p < 0.001) in both test sets. In an emulated randomized controlled trial (eRCT) on the Shanghai outdoor cohort (n = 3303) where DeepMyopia showed effectiveness in myopia prevention compared to NonCyc-based model, with an adjusted relative reduction (ARR) of -17.8%, 95% CI: -29.4%, -6.4%. DeepMyopia-assisted interventions attained quality-adjusted life years (QALYs) of 0.75 (95% CI: 0.53, 1.04) per person and avoided blindness years of 13.54 (95% CI: 9.57, 18.83) per 1 million persons compared to natural lifestyle with no active intervention. Our findings demonstrated DeepMyopia as a reliable and efficient AI-based decision support system for intervention guidance for children.

Depressive symptom mediates the association between the number of chronic diseases and cognitive impairment: a multi-center cross-sectional study based on community older adults.

Objective: The purpose of this study was to understand the relationship between the multiple chronic conditions (MCC), mental health and cognitive function of older adults in the community, and to propose a hypothesis that depressive symptom mediate the number of chronic diseases and cognitive impairment in older adults. Method: Participants aged 65 years and older from 35 communities in 14 cities in Guangxi, China were recruited. The residents' depressive symptom (PHQ-9) and cognitive status (AD-8) were evaluated, Chi-square test was used to explore the effects of different socio-demographic characteristics on depressive symptom and cognitive impairment. Pearson correlation analysis and the process model 4 were used to explore the relationship between the number of chronic diseases, depressive symptom and cognitive impairment. Result: A total of 11,582 older adults were included in our analysis. The rate of MCC reaching 26.53%. Hypertension combined with diabetes accounts for the highest proportion of two chronic diseases (13.2%). Among the combination of three chronic diseases, the highest incidence of coexisting hypertension combined with cervical/lumbar spondylosis, and rheumatoid arthritis (7.1%). In this study, depression symptoms accounted for 12.9% of older adults aged 65 and above, and cognitive impairment accounted for 27.4%. Female, older age, reside in urban areas, lower educational levels, no spouse, live alone, and MCC were risk factors for depressive symptom and cognitive impairment in older adults (P<0.05). Depressive symptom had a mediating effect in the number of chronic diseases and cognitive impairment, and the mediating effect (1.109) accounted for 44.13% of the total effect (0.247). Conclusion: The mental health of the older adult needs to be taken seriously, and improving depressive symptom can reduce the occurrence of cognitive impairment in older patients with MCC to a certain extent.

Potential association of rheumatic diseases with bone mineral density and fractures: a bi-directional mendelian randomization study.

BACKGROUND: Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures. METHODS: The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) (n = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) (n = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) (n = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture. RESULTS: The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p = 0.516). CONCLUSIONS: RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD.

Efficacy and safety analysis of PD-1 combined with regorafenib in the treatment of advanced hepatocellular carcinoma.

OBJECTIVE: To investigate the therapeutic efficacy and safety of programmed death-1 (PD-1) inhibitors combined with regorafenib in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was performed on 82 patients diagnosed with advanced HCC at Lanzhou Petrochemical General Hospital and the Second People's Hospital of Lanzhou City from October 2021 to October 2022. Patients were divided into two groups: the observation group (42 patients) received combined therapy with regorafenib and a PD-1 inhibitor, while the control group (40 patients) received only regorafenib monotherapy. Treatment efficacy, changes in serum tumor markers pre- and post-treatment, incidence of adverse reactions, progression-free survival (PFS), 1-year survival rate, and independent prognostic factors were evaluated for both groups. RESULTS: The treatment efficacy in the observation group was significantly better than that in the control group (P<0.05). Post-treatment levels of VEGF, sIL-2R, and CEA were significantly lower in the observation group compared to the control group (all P<0.05). The incidence of adverse reactions was similar between the two groups (P>0.05). However, the observation group demonstrated a significantly higher median PFS and 1-year survival rate than the control group (both P<0.05). Vascular invasion, degree of differentiation, and treatment regimen were identified as independent prognostic factors affecting outcomes (all P<0.05). CONCLUSION: For patients with advanced HCC, integrating PD-1 inhibitors with regorafenib treatment not only enhances clinical efficacy but also maintains safety. This combination therapy significantly improves progression-free survival and 1-year survival rates, supporting its further clinical application.

DOA Estimation on One-Bit Quantization Observations through Noise-Boosted Multiple Signal Classification.

Due to the low-complexity implementation, direction-of-arrival (DOA) estimation-based one-bit quantized data are of interest, but also, signal processing struggles to obtain the demanded estimation accuracy. In this study, we injected a number of noise components into the receiving data before the uniform linear array (ULA) composed of one-bit quantizers. Then, based on this designed noise-boosted quantizer unit (NBQU), we propose an efficient one-bit multiple signal classification (MUSIC) method for estimating the DOA. Benefiting from the injected noise, the numerical results show that the proposed NBQU-based MUSIC method outperforms existing one-bit MUSIC methods in terms of estimation accuracy and resolution. Furthermore, with the optimal root mean square (RMS) of the injected noise, the estimation accuracy of the proposed method for estimating DOA can approach that of the MUSIC method based on the complete analog data.

Guideline for the diagnosis and treatment of incomplete Kawasaki disease in children in China.

BACKGROUND: Kawasaki disease (KD) is a pyretic ailment predominantly observed in children aged below 5 years. There is currently a dearth of precise markers for timely identification of incomplete Kawasaki disease (IKD). It is imperative to develop updated, comprehensive, and evidence-based guidelines to effectively direct clinical practice. METHODS: The guideline development group comprised individuals with diverse expertise in both content and methodology and carried out an extensive exploration of the following digital repositories: CNKI, VIP, Wanfang Data, UpToDate, BMJ, Clinical Evidence, National Guideline Clearinghouse, Joanna Briggs Institute Library, Cochrane Library, and PubMed. The entire period from the establishment of these databases until January 1, 2024 was covered. To evaluate IKD, systematic reviews and randomised controlled trials were assessed using the risk of prejudice instrument specified in the Cochrane Handbook, along with the evidence robustness framework established by the GRADE group. The recommendations were formulated based on the findings, considering the evidence strength. After several iterations of expert consensus, the relevant professional committees in China endorsed the ultimate guideline. RESULTS: These guidelines address clinical questions regarding the classification and definition of KD, diagnosis of IKD, treatment during the acute phase of IKD, and follow-up of IKD. CONCLUSIONS: To provide healthcare professionals with guidance and decision-making bases for the diagnosis and treatment of IKD in China, 13 recommendations were formulated based on expert consensus and evidence of best practices.

Regulatory T cells inhibit FoxP3 to increase the population of tumor initiating cells in hepatocellular carcinoma.

PURPOSE: Tumor initiating cells (TICs) or cancer stem cells (CSCs) are considered to be the main culprit of hepatocellular carcinoma (HCC) initiation and progression, nevertheless the mechanism by which tumor microenvironment maintains the HCC 'stemness' is not fully understood. This study aims to investigate the effect of regulatory T cells (Tregs) on the TICs characteristics of HCC. METHODS: Immunocytochemistry, flow cytometry, real-time PCR, western blot, in vitro sphere-formation, and in vivo tumorigenesis assay were used to detect HCC 'stemness'. Additionally, after forced expression or inhibition of FoxP3, ß-catenin expression and HCC 'stemness' were investigated. RESULTS: Tregs enhanced the 'stemness' of HCC cells by upregulating TIC-related markers CD133, Oct3/4, Sox2, c-Myc, Klf4, Nanog, CD13, EpCAM, and inducting epithelial to mesenchymal transition (EMT), increasing TICs ratio, as well as promoting tumorigenic ability. Moreover, ß-catenin and c-Myc were upregulated in HCC cells after co-cultured with Tregs. HCC 'stemness' was inhibited after treatment with Wnt/ß-catenin pathway inhibitor. Furthermore, forced expression of FoxP3 resulted in increased GSK3ß, decreased ß-catenin and TIC ratio in HCC. In contrast, FoxP3 interference reduced GSK3ß, enhanced ß-catenin and TIC ratio of HCC. CONCLUSION: This study, for the first time, demonstrated that Tregs increased the population of TICs in HCC by inhibiting FoxP3 as well as promoting ß-catenin expression.

Transcriptome-wide m6A methylation profile reveals its potential role underlying drought response in wheat (Triticum aestivum L.).

MAIN CONCLUSION: This study revealed the transcriptome-wide m6A methylation profile under drought stress and found that TaETC9 might regulate drought tolerance through mediating RNA methylation in wheat. Drought is one of the most destructive environmental constraints limiting crop growth and development. N6-methyladenosine (m6A) is a prevalent and important post-transcriptional modification in various eukaryotic RNA molecules, playing the crucial role in regulating drought response in plants. However, the significance of m6A in wheat (Triticum aestivum L.), particularly its involvment in drought response, remains underexplored. In this study, we investigated the transcriptome-wide m6A profile under drought stress using parallel m6A immunoprecipitation sequencing (MeRIP-seq). Totally, 4221 m6A peaks in 3733 m6A-modified genes were obtained, of which 373 methylated peaks exhibited differential expression between the control (CK) and drought-stressed treatments. These m6A loci were significantly enriched in proximity to stop codons and within the 3'-untranslated region. Integration of MeRIP-seq and RNA-seq revealed a positive correlation between m6A methylation and mRNA abundance and the genes displaying both differential methylation and expression were obtained. Finally, qRT-PCR analyses were further performed and the results found that the m6A-binding protein (TaETC9) showed significant up-regulation, while the m6A demethylase (TaALKBH10B) was significantly down-regulated under drought stress, contributing to increased m6A levels. Furthermore, the loss-of-function mutant of TaECT9 displayed significantly higher drought sensitivity compared to the wild type, highlighting its role in regulating drought tolerance. This study reported the first wheat m6A profile associated with drought stress, laying the groundwork for unraveling the potential role of RNA methylation in drought responses and enhancing stress tolerance in wheat through epigenetic approaches.

Clinical Features and Pathology of PLA2R and THSD7A-Associated Membranous Nephropathy: A Single-Center Study from China.

Objective: Serum-specific antibodies as a non-invasive means to effectively diagnose idiopathic membranous nephropathy and assess clinicopathology. Methods: Immunofluorescence of anti-PLA2R and THSD7A antibodies and kidney tissue PLA2R, THSD7A and IgG4 expression in IMN and non-IMN (2020-2021) was detected to assess the efficacy of diagnosing IMN. IMN patients were divided into two groups, anti-PLA2R antibody positive (161 cases) and negative (26 cases), and two groups, kidney tissue PLA2R (40 cases) and PLA2R+THSD7A (6 cases), to compare the clinical and pathological features, and to carry out a prognostic analysis of THSD7A-positive patients, with a focus on correlation with malignancy. Results: The positive rate of anti-PLA2R antibodies was significantly higher in IMN (P<0.05); anti-PLA2R antibodies, kidney tissue PLA2R and IgG4 and THSD7A had some diagnostic value. Anti-PLA2R antibodies correlated with proteinuria levels in IMN patients, and their levels were negatively correlated with blood albumin (r=-0.146, P=0.042); correlated with pathological stage and C3 and IgG4 immunodeposition; there was no significant difference in clinical pathology between kidney tissue THSD7A+PLA2R positive compared to kidney tissue PLA2R positive patients, but the probability of achieving complete remission was low and time longer, and no malignancy events were detected during follow-up. Conclusion: Anti-PLA2R antibodies, kidney tissue PLA2R, THSD7A and IgG4 have high diagnostic efficacy for IMN; anti-PLA2R antibodies can be used as diagnostic markers to assist in the assessment of clinical and pathological features; co-expression of kidney tissue PLA2R and THSD7A is not significantly different from kidney tissue PLA2R in assessing the clinical features, pathological manifestations and prognosis, but requires long-term. However, long-term follow-up is needed to monitor the potential risk, and a larger multicentre study with long-term follow-up is expected to be conducted to comprehensively assess IMN characteristics.

State- and frequency-dependence in autonomic rebalance mediated by intradermal auricular electroacupuncture stimulation.

Background: Vagus nerve stimulation (VNS) improves diseases such as refractory epilepsy and treatment-resistant depression, likely by rebalancing the autonomic nervous system (ANS). Intradermal auricular electro-acupuncture stimulation (iaES) produces similar effects. The aim of this study was to determine the effects of different iaES frequencies on the parasympathetic and sympathetic divisions in different states of ANS imbalance. Methods: We measured heart rate variability (HRV) and heart rate (HR) of non-modeled (normal) rats with the treatment of various frequencies to determine the optimal iaES frequency. The optimized iaES frequency was then applied to ANS imbalance model rats to elucidate its effects. Results: 30 Hz and 100 Hz iaES clearly affected HRV and HR in normal rats. 30 Hz iaES increased HRV, and decreased HR. 100 Hz iaES decreased HRV, and increased HR. In sympathetic excited state rats, 30 Hz iaES increased HRV. 100 Hz iaES increased HRV, and decreased HR. In parasympathetic excited state rats, 30 Hz and 100 Hz iaES decreased HRV. In sympathetic inhibited state rats, 30 Hz iaES decreased HRV, while 100 Hz iaES decreased HR. In parasympathetic inhibited rats, 30 Hz iaES decreased HR and 100 Hz iaES increased HRV. Conclusion: 30 Hz and 100 Hz iaES contribute to ANS rebalance by increasing vagal and sympathetic activity with different amplifications. The 30 Hz iaES exhibited positive effects in all the imbalanced states. 100 Hz iaES suppressed the sympathetic arm in sympathetic excitation and sympathetic/parasympathetic inhibition and suppressed the vagal arm and promoted the sympathetic arm in parasympathetic excitation and normal states.