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.

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.

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.

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.

Real-Time Detection Algorithm for Kiwifruit Canker Based on a Lightweight and Efficient Generative Adversarial Network.

Disease diagnosis and control play important roles in agriculture and crop protection. Traditional methods of identifying plant disease rely primarily on human vision and manual inspection, which are subjective, have low accuracy, and make it difficult to estimate the situation in real time. At present, an intelligent detection technology based on computer vision is becoming an increasingly important tool used to monitor and control crop disease. However, the use of this technology often requires the collection of a substantial amount of specialized data in advance. Due to the seasonality and uncertainty of many crop pathogeneses, as well as some rare diseases or rare species, such data requirements are difficult to meet, leading to difficulties in achieving high levels of detection accuracy. Here, we use kiwifruit trunk bacterial canker (Pseudomonas syringae pv. actinidiae) as an example and propose a high-precision detection method to address the issue mentioned above. We introduce a lightweight and efficient image generative model capable of generating realistic and diverse images of kiwifruit trunk disease and expanding the original dataset. We also utilize the YOLOv8 model to perform disease detection; this model demonstrates real-time detection capability, taking only 0.01 s per image. The specific contributions of this study are as follows: (1) a depth-wise separable convolution is utilized to replace part of ordinary convolutions and introduce noise to improve the diversity of the generated images; (2) we propose the GASLE module by embedding a GAM, adjust the importance of different channels, and reduce the loss of spatial information; (3) we use an AdaMod optimizer to increase the convergence of the network; and (4) we select a real-time YOLOv8 model to perform effect verification. The results of this experiment show that the Fréchet Inception Distance (FID) of the proposed generative model reaches 84.18, having a decrease of 41.23 compared to FastGAN and a decrease of 2.1 compared to ProjectedGAN. The mean Average Precision (mAP@0.5) on the YOLOv8 network reaches 87.17%, which is nearly 17% higher than that of the original algorithm. These results substantiate the effectiveness of our generative model, providing a robust strategy for image generation and disease detection in plant kingdoms.

Occurrence Regionalization of Kiwifruit Brown Spot in Sichuan.

Kiwifruit brown spot caused by Corynespora cassiicola is the most significant fungal disease in Sichuan, resulting in premature defoliation, which had a significant impact on yield and fruit quality. The objective of the study was to determine the occurrence regularity and suitability of kiwifruit brown spot in Sichuan. The occurrence of the disease in the main producing region was continuously monitored, the maximum entropy (MaxEnt) model was used to predict its potential distribution, and the key environmental variables were identified using the jackknife method. The results indicated that kiwifruit brown spot was widely distributed across the entire producing region in Sichuan, predominantly affecting the variety "Hongyang". The incidence (p < 0.01) and disease index (p < 0.05) showed a significant positive correlation with the cultivar, and decreased with the altitude increasing. The average area under the ROC curve (AUC) of 10 replicates was 0.933 ± 0.012, with an accuracy of 84.44% in a field test, confirming the reliability of the predicted results. The highly suitable distribution areas of kiwifruit brown spot were mainly located in the Chengdu and Ya'an regions. The entire Panzhihua region was an unsuitable distribution area, and the entire Pujiang County and Mingshan District were highly suitable distribution areas. The key environmental variables affecting the potential distribution of kiwifruit brown spot included isothermality (24.3-33.7%), minimum temperature in August (16.3-23.6 °C), maximum temperature in July (25.5-31.2 °C), minimum temperature in June (15.6-20.9 °C), precipitation in August (158-430 mm), and average temperature in October (15.6-18.8 °C). This study provides a theoretical basis for the reasonable layout of the cultivar and the precise prevention and control of the disease.

Superhydrophilic Interconnected Biomass-Based Absorbers Toward High-Speed Evaporation for Solar Steam Generation.

Taking abundant and sustainable solar energy as the only energy source, solar-powered interface evaporation has been regarded as a promising method to alleviate the pressure of freshwater shortage. However, the uptake of clean water from brine is constantly accompanied by evaporation of water and condensation of vapor, which inevitably generates salt solid, preventing further continuous and stable evaporation. The most direct method is to fabricate a photothermal material with salt self-resistance by using the reflux of salt ions. Here, a superhydrophilic interconnected biomass carbon absorber (SBCA) is prepared by freeze-drying and carbonization, realizing strong liquid pumping, and self-blocking salt. In combination with superior broadband light absorption (94.91%), high porosity (95.9%), superhydrophilicity, and excellent thermal localization, an evaporation device with excellent evaporation rate (2.45 kg m-2 h-1 under 1 kW m-2) is successfully proposed. In the meantime, the porous skeleton and rapid water transport can enhance the diffusion of salt ions and slow down the rate of salt deposition. As a result, no salt deposition is found on the SBCA surface after continuous irradiation at 1 kW m-2 for 15 h. The design can provide a convenient and low-cost efficient strategy for solar steam generators to address clean water acquisition.

CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer.

In search of an effective therapeutic target for bladder urothelial carcinoma (BLCA), the present study aimed to investigate the expression of cyclin B1 (CCNB1) and its putative mechanism in BLCA. BLCA sequencing data from Gene Expression Omnibus and The Cancer Genome Atlas were used to analyze expression of CCNB1 mRNA and high CCNB1 expression had a poorer prognosis compared with those with low expression. Immunohistochemistry (IHC) samples collected from the Human Protein Atlas database were analyzed for CCNB1 protein expression. Short hairpin (sh) CCNB1-transfected BLCA T24 and 5637 cells were used to investigate the effects of CCNB1 and inhibit the proliferation, migration and invasion of BLCA cells, affect the cell cycle distribution and promote apoptosis of 5637 cells. A sh-CCNB1 BLCA chicken embryo chorioallantoic membrane (CAM) transplantation model was established to observe the impacts of sh-CCNB1 on the tumorigenesis of BLCA in vivo. Analysis of sequencing data showed that CCNB1 mRNA was significantly elevated in tumor and BLCA compared with normal tissues [standardized mean difference (SMD)=1.21; 95% CI: 0.26-2.15; I²=95.9%]. IHC indicated that CCNB1 protein was localized in the nucleus and cytoplasm and was significantly increased in BLCA tumor tissues. The in vitro tests demonstrated that proliferation of T24 and 5637 cells transfected with sh-CCNB1 was significantly inhibited and cell migration and invasion ability were significantly decreased. sh-CCNB1 decreased the percentage of T24 cells in G0/G1, 5637 cells in the G0/G1 phase and S phase and increased percentage of 5637 cells in the G2/M phase and increased early apoptosis of 5637 cells. The in vivo experiments demonstrated that the mass of transplanted tumors was significantly decreased compared with the control group following silencing of CCNB1. The present results suggested that CCNB1 was involve in the development and prognosis of BLCA and silencing of CCNB1 may be a promising targeted therapy for BLCA.

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.

Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancer.

OBJECTIVE: This study aims to evaluate the prognostic value of m6A-associated long noncoding RNAs (lncRNAs) and their interaction with tumour microenvironment in thyroid cancer (THCA). METHODS: The clinical and gene expression data of tumours from 502 patients with THCA and 58 adjacent normal tissues were retrieved from The Cancer Genome Atlas (TCGA)-THCA dataset. The Pearson test was utilized to identify potential m6A-associated lncRNAs (p < 0.001 and Pearson correlation coefficient > 0.4). Quantitative real-time polymerase chain reaction was performed to verify the expression levels of lncRNAs in tissues. MTT, EdU, colony formation and wound-healing assays were performed to determine the functions of m6A-associated lncRNAs in THCA cell proliferation and metastasis. RESULTS: M6A-associated lncRNAs were identified in three cluster groups. A significant survival difference was found among them, with cluster 1 patients showing worse survival. Moreover, lower immune and estimate scores were correlated to poorer prognosis, and CD8+ T cell and memory CD4+ T cell levels were increased in cluster 1. Cluster 2, with better overall survival, had high expression of PD-L1 and CTLA-4. Eleven of the m6A-associated lncRNAs were screened to establish the risk model, including AC007365.1, AC008555.1, AC040160.1, AC064807.1, AC126773.4, AL023583.1, AL512306.2, EIF2AK3-DT, LINC00667, LYPLAL1-DT and MIR181A2HG. Based on the median risk score, THCA patients were stratified into low-risk and high-risk groups. Overall survival analysis showed a dramatic difference between the two groups. qRCR was performed to verify the expression levels of lncRNA (LYPLAL1-DT, EIF2AK3-DT and MIR181A2HG) in THCA and adjacent normal tissues. Furthermore, functional experiments showed that knockdown of MIR181A2HG obviously inhibited the proliferation and migration of papillary thyroid cancer (PTC) cells in vitro, whereas LYPLAL1-DT overexpression promoted PTC cell proliferation and migration. CONCLUSIONS: Eleven of the m6A-associated lncRNAs were identified as a risk model to predict clinical outcomes and provide a novel and efficient immunotherapeutic strategy for THCA patients.Key messagesm6A-associated lncRNAs can be used to predict the clinical outcomes of thyroid cancer patients.An m6A-associated lncRNAs risk model, which can accurately evaluate the immune status and risk stratification in individual thyroid cancer patients, was established.Knockdown/overexpression of representative lncRNAs in the risk model significantly affected the proliferation and migration of papillary thyroid cancer cells.

A meta-analysis on the prevalence of Charcot-Marie-Tooth disease and related inherited peripheral neuropathies.

BACKGROUND: Charcot-Marie-Tooth disease and related inherited peripheral neuropathies (CMT&RIPNs) brings great suffering and heavy burden to patients, but its global prevalence rates have not been well described. METHODS: We searched major English and Chinese databases for studies reporting the prevalence of CMT&RIPNs from the establishment of the databases to September 26, 2022. Based on the age, gender, study design, study region, and disease subtype, the included studies were correspondingly synthesized for meta-analyses on the overall prevalence and/or the subgroup analyses by using pool arcsine transformed proportions in the random-effects model. RESULTS: Of the finally included 31 studies, 21 studied the whole age population and various types of CMT&RIPNs, and the others reported specific disease subtype(s) or adult or non-adult populations. The pooled prevalence was 17.69/100,000 (95% CI 12.32-24.33) for the whole age population and significantly higher for CMT1 [10.61/100,000 (95% CI 7.06-14.64)] than for other subtypes (P' < 0.001). Without statistical significance, the prevalence seemed higher in those aged ≥ 16 or 18 years (21.02/100,000) than in those aged < 16 years (16.13/100,000), in males (22.50/100,000) than in females (17.95/100,000), and in Northern Europe (30.97/100,000) than in other regions. CONCLUSION: CMT&RIPNs are relatively more prevalent as CMT1 in the disease subtypes, and probably prevalent in older ages, males, and Northern Europe. More studies on the epidemiological characteristics of CMT&RIPNs with well-defined diagnosis criteria are needed to improve the prevalence evaluation and to arouse more attention to health care support.

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.

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.

Clinical study of comprehensive TCM therapy in the treatment of damp and hot stasis erectile dysfunction.

BACKGROUND: The dilemma of male sexual dysfunction has been the focus of the whole society. Erectile dysfunction (ED) is one of the common sexual dysfunctions, and traditional Chinese medicine therapy has shown potential benefits in the treatment of ED. Comprehensive therapy of traditional Chinese medicine (CTTCM) is a comprehensive application of Chinese medicine therapy for auxiliary intervention. Through preliminary clinical observations, we found that CTTCM is simple, safe, and has good efficacy; however, there is a lack of rigorous clinical trials to support its application. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of CTTCM for patients with ED of damp-heat stasis type, and to provide evidence for the clinical application of CTTCM and the construction of a traditional Chinese medicine andrology rehabilitation system. METHODS: In this randomized controlled study, 108 eligible patients were assigned 1:1 to the CTTCM group or the tadalafil group. The treatment period was 8 weeks and the follow-up period was 8 weeks. The primary outcome will be the International Erectile Function Score and traditional Chinese medicine Syndrome Score. Secondary outcomes will include the Erection Quality Score, Patient Health Questionnaire-9, and the 7-item Generalized Anxiety Scale. Safety results will include electrocardiogram, blood tests (including blood, liver and kidney function), urine and stool. International Erectile Function Score-5, traditional Chinese medicine Syndrome Score, Erectile Quality Score, Patient Health Questionnaire-9, 7-item Generalized Anxiety Scale and all Safety outcomes will be conducted at baseline, 2th, 4th, 6th, and 8th week. Follow-up results will be assessed at 8th week after 8 weeks' treatment. DISCUSSION: This study will provide preliminary evidence for the efficacy and safety of traditional Chinese medicine integrated therapy in the treatment of damp-heat stasis ED. In addition, it also provides a basis for the clinical application of Chinese medicine comprehensive therapy and the construction of Chinese medicine andrology rehabilitation system. TRIAL REGISTRATION: Chinese clinical trial registration identifier, ChiCTR2200062016, registered on July 19, 2022.

A surface-receptor-coupled G protein regulates plant immunity through nuclear protein kinases.

Plants employ cell-surface-localized pattern recognition receptors (PRRs) to recognize immunogenic patterns and activate defenses. How these receptors regulate immune signaling in the nucleus is not well understood. Our previous studies showed that BIK1, a central kinase associated with PRRs, phosphorylates a plant-specific Gα protein called extra-large G protein 2 (XLG2) to positively regulate immunity. Here, we show that this phosphorylation promotes XLG2 nuclear translocation, which is essential for antibacterial immunity. XLG2 interacts with nuclear-localized MUT9-like kinases (MLKs) to regulate transcriptome programming. MLKs negatively regulate plant immunity in a kinase activity-dependent manner, whereas XLG2 promotes defense gene expression and antibacterial immunity likely by inhibiting MLK kinase activity. A C-terminal motif in MLKs is essential for the interaction with XLG2, and this motif is required for the XLG2-mediated defense activation. Together, our findings reveal a previously unknown pathway and mechanisms by which cell surface receptors regulate transcriptome during pathogen invasion.

Clinical study on the treatment of male infertility with Wuwei Fuzheng Yijing decoction based on microplastics: Study protocol for a randomized controlled trial.

BACKGROUND: Environmental pollution and male infertility have become global public health problems. The presence of microplastics (MPs) has been detected in the human body, and it has also been demonstrated that MPs can cause damage to the reproductive system. Wuwei Fuzheng Yijing Decoction (WWFZYJ) is effective in treating male infertility. Therefore, we designed a clinical randomized controlled trial to observe the effect of WWFZYJ on the content of MPs and semen quality in male infertility patients, and to evaluate its security. METHODS: In this randomized controlled study, 66 eligible patients were randomly assigned in a 1:1 ratio to a treatment group (WWFZYJ Decoction) and a control group (Coenzyme Q10 tablets combined with vitamin E soft capsules) for 8 weeks. The content of MPs in semen, sperm DNA Fragmentation Index (DFI), and semen analysis (including sperm density, sperm count, forward motile sperm, sperm motility, etc) will be used as primary indicators, and Traditional Chinese Medicine (TCM) syndrome scores will be used as secondary indicators. Vital signs (such as respiration, heart rate, body temperature, blood pressure, electrocardiogram, etc), blood routine, urine routine, stool routine, liver function, and renal function will be used as safety indicators. The primary and secondary indicators will be performed at 0th and 8th week, and the safety indicators will be performed at 0th, 4th, and 8th week. DISCUSSION: This study will provide evidence for the efficacy and safety of WWFZYJ in treating male infertility and reducing the content of MPs in semen, and further explore the effects of MPs on male fertility.

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.

Three Cases of Familial Moyamoya Disease with RASA1 Mutations-A Case Report.

OBJECTIVE: The prevalence of moyamoya disease (MMD) is relatively high in East Asia, whereas the susceptibility genes of MMD have not been identified. METHODS: Here, we reported 3 patients diagnosed with MMD from 1 single family, including a 53-year-old mother (case 1) and her 32-year-old and 29-year-old daughters (cases 2 and 3). The younger daughter was diagnosed with cerebral hemorrhage. Computed tomographic angiogram showed the typical signs of MMD in 3 patients. RESULTS: Clinical whole-exome sequencing was performed in 3 daughters of case 1, and RASA1 mutations in chr5: 87,376,389 and NM_002890.2: c.2012-4C > T were determined to have the strongest correlation with MMD. RASA1 mutations were verified in case 1, husband of case 1 and the descendant of case 3 by using Sanger sequencing. CONCLUSIONS: According to the findings of literature review, this is the first study indicating the association between RASA1 mutations and MMD.

Associations between Circulating SELENOP Level and Disorders of Glucose and Lipid Metabolism: A Meta-Analysis.

Selenoprotein P (SELENOP) is an extracellular antioxidant, selenium transporter, and hepatokine interfering with glucose and lipid metabolism. To study the association between the circulating SELENOP concentration and glucose and lipid metabolic diseases (GLMDs), including gestational diabetes (GD), metabolic syndrome (MetS), non-alcoholic fatty liver disease, obesity, and type 2 diabetes, as well as the individual markers, a meta-analysis was conducted by searching multiple databases from their establishment through March 2022 and including 27 articles published between October 2010 and May 2021, involving 4033 participants. Participants with GLMDs had higher levels of SELENOP than those without GLMDs (standardized mean difference = 0.84, 95% CI: 0.16 to 1.51), and the SELENOP levels were positively correlated with the markers of GLMDs (pooled effect size = 0.09, 95% CI: 0.02 to 0.15). Subgroup analyses showed that the SELENOP concentrations were higher in women with GD and lower in individuals with MetS than their counterparts, respectively. Moreover, SELENOP was positively correlated with low-density lipoprotein cholesterol, but not with the other markers of GLMDs. Thus, the heterogenicity derived from diseases or disease markers should be carefully considered while interpreting the overall positive association between SELENOP and GLMDs. Studies with a larger sample size and advanced design are warranted to confirm these findings.