Protective effect of dihydromyricetin on intestinal epithelium in weaned pigs upon enterotoxigenic Escherichia coli challenge.

Dihydromyricetin (DMY), a natural flavonoid compound, are believed to prevent inflammatory response, dealing with pathogens and repairing the intestinal barrier. The objective of this study was to investigate whether DMY supplementation could attenuate intestinal damage in the context of enterotoxigenic Escherichia coli K88 (ETEC F4+) infection. After weaning, different litters of pigs were randomly assigned to one of the following treatments: (1) non-challenged control (CON, fed with basal diet); (2) ETEC-challenged control (ECON, fed with basal diet); and (3) ETEC challenge + DMY treatment (EDMY, fed with basal diet plus 300 mg kg-1 DMY). We observed a significant reduction in fecal Escherichia coli shedding and diarrhea incidence, but an increase in ADG in pigs of EDMY group compared to the pigs of ECON group. Relative to the pigs of ECON group, dietary DMY treatment decreased (P < 0.05) concentrations of the serum D-xylose, D-lactate and diamine oxidase (DAO), but increased the abundance of zonula occludens-1 (ZO-1) in the jejunum of pigs. In addition, DMY also decreased (P < 0.05) the number of S-phase cells and the percentage of total apoptotic epithelial cells of jejunal epithelium in pigs of the EDMY group compared to the pigs of the ECON group. Furthermore, DMY decreased the mRNA expression levels of critical immune-associated genes TLR4, NFκB, Caspase3, Caspase9, IL-1ß, IL-6, TNF-α and the protein p-NFκB and p-IκBα expressions of intestinal epithelium in pigs of the EDMY group compared to the pigs of the ECON group. Compared to the ECON group, DMY elevated (P < 0.05) the expression levels of ß-defensins PBD1, PBD2, PBD3, PBD129, as well as the abundance of secreted IgA in intestinal mucosae of the EDMY group. Thus, our results indicate that DMY may relieve intestinal integrity damage due to Escherichia coli F4.

[Genetic diversity of SP1 population of space mutagenized Pueraria montana].

To explore the mutagenic effect of the space environment on Pueraria montana and select the elite germplasm with good growth conditions and high isoflavone content, this study observed the agronomic traits, determined the flower isoflavone content, and labeled amplified fragment length polymorphism(AFLP) fluorescent molecular markers of 79 P. montana plants exposed to space mutagenesis(SP1 group) and 10 control plants of P. montana(CK group). Excel 2019, SPSS 25.0, NTSYSpc-2.11F, and Popgen 32 were employed to analyze the genetic diversity and perform the cluster analysis. The results showed that the SP1 group presented changed leaf hairy attitude and flower structure and higher CV and H' of quantitative traits than the CK group. The cluster analysis screened out five plants in the SP1 group. Ten P. montana plants in the SP1 group had higher content of 6″-O-xylosyl-tectoridin and tectoridin in the flowers than the control group, with the total content of both exceeding 11%. After clustering, 9 plants in the SP1 group were separated. Nine pairs of polymorphic primers were screened out frrom 64 pairs of primers. A total of 1 620 polymorphic loci were detected, with the average percentage of polymorphic loci(PPL) of 83.33%. The average Nei's gene diversity index(H) and Shannon's information index(I) were 0.192 2 and 0.305 2, respectively. After clustering, 4 plants in the SP1 group were screened out. According to the above results, plants No. 30, No. 66, and No. 89 in the SP1 group were subjected to greater mutagenic effect by the space environment and presented better growth and higher flower isoflavone content. Moreover, plant No. 30 showed the flower structure variation and flower weight two times of that in the CK group. These plants can be used as key materials for the subsequent experiments.

Ultrasound-guided nitinol stent implantation to treat early restenosis of arteriovenous fistula: A 69-case study with 1-year outcome.

BACKGROUND: To investigate the feasibility, methods and effects of interventional ultrasound in nitinol stent implantation to treat early restenosis after percutaneous transluminal angioplasty (PTA) in autogenous arteriovenous fistula (AVF). METHODS: From April 2018 to December 2021, 69 patients with early restenosis of AVF received ultrasound-guided nitinol stent implantation (UNSI) and were followed-up. Imaging features of the stent and procedure by ultrasound were observed. The technical success rate, clinical success rate and incidence of complications were recorded and counted. Target lesion primary patency (TLPP), access circuit primary patency (ACPP) and access circuit secondary patency (ACSP) were estimated. RESULTS: Ultrasonography can show the structure of the stent and guide the stenting process clearly. Both the technical and clinical success rates were 100%. Thirty-one patients had in-stent restenosis (ISR), which was treated by plain balloon (PB) PTA or drug coated balloon (DCB) PTA. The TLPP at 3, 6, 12 and 24 months were 100.0%, 94.2%, 63.4% and 39.6%, respectively. The ACPP at 3, 6, 12 and 24 months were 98.6%, 91.6%, 60.2% and 35.2%, respectively. The ACSP at 3, 6, 12 and 24 months were 98.6%, 98.6%, 95.6% and 93.8%, respectively. The TLPP of ISR after DCB PTA at 3, 6 and 12 months were 100.0%, 100.0% and 93.6%, respectively. CONCLUSIONS: This pilot study indicates ultrasonography can accurately guide nitinol stent implantation in AVF and this technique is a feasible and minimally invasive treatment for early restenosis after PTA with good short- and medium-term patency. DCB PTA may be used to deal with the ISR and is a way to prolong the patency of nitinol stent.

Inverse association between serum chloride levels and the risk of atrial fibrillation in chronic kidney disease patients.

Background: Electrolyte abnormalities are common symptoms of chronic kidney disease (CKD), but previous studies have mainly focussed on serum potassium and sodium levels. Chloride is an important biomarker for the prognosis of various diseases. However, the relationship between serum chloride levels and atrial fibrillation (AF) in CKD patients is unclear. Objective: In this study, we sought to determine the association between serum chloride homeostasis and AF in CKD patients. Methods: In this retrospective cohort study, we included patients who met the diagnostic criteria for CKD in China between 2000 and 2021. Competing risk regression for AF was performed. The associations of the baseline serum chloride concentration with heart failure (HF) and stroke incidence were also calculated by competing risk regression. The association of baseline serum chloride levels with all-cause death was determined by a Cox regression model. Results: The study cohort comprised 20 550 participants. During a median follow-up of 350 days (interquartile range, 123-730 days), 211 of the 20 550 CKD patients developed AF. After multivariable adjustment, every decrease in the standard deviation of serum chloride (5.02 mmol/l) was associated with a high risk for AF [sub-hazard ratio (sHR) 0.78, 95% confidence interval (CI) 0.65-0.94, P = .008]. These results were also consistent with those of the stratified and sensitivity analyses. According to the fully adjusted models, the serum chloride concentration was also associated with a high risk for incident HF (sHR 0.85, 95% CI 0.80-0.91, P < .001), a high risk for incident stroke (sHR 0.87, 95% CI 0.81-0.94, P < .001), and a high risk for all-cause death [hazard ratio (HR) 0.82, 95% CI 0.73-0.91, P < .001]. Conclusion: In this CKD population, serum chloride levels were independently and inversely associated with the incidence of AF. Lower serum chloride levels were also associated with an increased risk of incident HF, stroke, and all-cause death.

Unlocking the Therapeutic Potential: Harnessing miR-125a-5p To Enhance Autophagy and Apoptosis in Pancreatic Cancer through Targeting STAT3.

Objectives: miR-125a-5p's role in various cancers has been recognized, yet its specific function in pancreatic cancer (PCa) demands further exploration. This study aimed to reveal the potential function of miR-125a-5p in PCa. Methods: With publicly available databases, we explored the expression pattern and prognostic relevance of miR-125a-5p and STAT3 in PCa. We measured miR-125a-5p levels in PCa tissues, plasma and cell lines using RT-qPCR. To assess functional effects, PANC-1 cells were transfected with miR-125a-5p mimics and inhibitors, as well as siRNA-STAT3 and STAT3 vectors. Cell proliferation was estimated using Cell Counting Kit-8, while autophagy and apoptosis were examined by transmission electron microscopy and TUNEL assay, respectively. Western blot analysis was also performed to detect proteins associated with autophagy and apoptosis. The regulatory relationship of miR-125a-5p on STAT3 was verified using a dual luciferase reporter assay. The influence of miR-125a-5p on tumor development was evaluated in xenograft models. Results: Decreased expression of miR-125a-5p was found in PCa samples, and low expression of miR-125a-5p was associated with a poorer prognosis in PCa patients. Functional assays indicated miR-125a-5p suppressed cell growth while enhancing apoptosis and autophagy in PCa cells. STAT3 represents a specific target of miR-125a-5p, inhibiting STAT3 reversed the inhibitory effect of overexposed miR-125a-5p. Additionally, miR-125a-5p significantly restrained tumor development in mice. Conclusions: miR-125a-5p functions as a tumor suppressor in PCa by targeting STAT3, thereby inducing autophagy and apoptosis. Its regulatory role underscores its potential as a valuable biomarker for PCa diagnosis and therapy, warranting further clinical investigation.

Association of Questionnaire-Based Physical Activity Analysis and Body Composition Dynamics in Type 2 Diabetes: A Cross-Sectional Study.

Background: Physical activity (PA) exerts an important influence on glycemic control in type 2 diabetes (T2D) patients. Alterations in body composition in patients with T2D may be involved in the overall pathophysiologic process, but PAs and alterations in body composition have been poorly studied. Methods: A total of 615 patients with T2D were selected by convenient sampling. The patients were investigated with the International Physical Activity Questionnaire (IPAQ-S). Moreover, biochemical indices were collected, and the progression of the body composition of the subjects was determined via dual-energy X-ray absorptiometry (DXA). The variables included lumbar bone mineral density (LSBMD), femoral neck bone mineral density (FNBMD), hip bone mineral density (HBMD), whole-body bone mineral density (TBMD), limb skeletal muscle mass index (ASMI), whole-body fat percentage (B-FAT) and trunk fat percentage (T-FAT). Moreover, the levels of physical activity (high level of physical activity [H-PA], medium level of physical activity [M-PA] and low level of physical activity [L-PA]) were divided into three groups to analyze the changes in patient body composition with changes in physical activity level. Results: One-way analysis of variance showed that ß-CTX, TP1NP, HbA1c, B-FAT and T-FAT increased significantly (p<0.05), while 25(OH)D, LSBMD, FNBMD, HBMD, TBMD and ASMI decreased significantly (p<0.001) with the decrease of physical activity. However, there was no significant difference in serum lipids between lnHOMA-ir and lnHOMA-ß (p>0.05). Multiple linear regression model was established to gradually adjust for clinical confounding factors. It was found that physical activity level was independently positively correlated with LSBMD, FNBMD, HBMD, TBMD, and ASMI, and was independently negatively correlated with B-FAT and T-FAT in patients with type 2 diabetes. Conclusion: A lack of physical activity is an independent risk factor for decreased bone mineral density, decreased skeletal muscle content and increased fat content in patients with T2D.

A machine learning-based predictive model for biliary stricture attributable to malignant tumors: a dual-center retrospective study.

Background: Biliary stricture caused by malignant tumors is known as Malignant Biliary Stricture (MBS). MBS is challenging to differentiate clinically, and accurate diagnosis is crucial for patient prognosis and treatment. This study aims to identify the risk factors for malignancy in all patients diagnosed with biliary stricture by Endoscopic Retrograde Cholangiopancreatography (ERCP), and to develop an effective clinical predictive model to enhance diagnostic outcomes. Methodology: Through a retrospective study, data from 398 patients diagnosed with biliary stricture using ERCP between January 2019 and January 2023 at two institutions: the First People's Hospital affiliated with Jiangsu University and the Second People's Hospital affiliated with Soochow University. The study began with a preliminary screening of risk factors using univariate regression. Lasso regression was then applied for feature selection. The dataset was divided into a training set and a validation set in an 8:2 ratio. We analyzed the selected features using seven machine learning algorithms. The best model was selected based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUROC) and other evaluation indicators. We further evaluated the model's accuracy using calibration curves and confusion matrices. Additionally, we used the SHAP method for interpretability and visualization of the model's predictions. Results: RF model is the best model, achieved an AUROC of 0.988. Shap result indicate that age, stricture location, stricture length, carbohydrate antigen 199 (CA199), total bilirubin (TBil), alkaline phosphatase (ALP), (Direct Bilirubin) DBil/TBil, and CA199/C-Reactive Protein (CRP) were risk factors for MBS, and the CRP is a protective factor. Conclusion: The model's effectiveness and stability were confirmed, accurately identifying high-risk patients to guide clinical decisions and improve patient prognosis.

IVF laboratory management through workflow-based RFID tag witnessing and real-time information entry.

BACKGROUND: Dual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records. METHODS: This study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups. RESULTS: The study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn't affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups. CONCLUSIONS: RFID tag witnessing doesn't negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist's confidence.

Kaempferol inhibited invasion and metastasis of gastric cancer cells by targeting AKT/GSK3ß pathway based on network pharmacology and molecular docking.

This study aims to explore the mechanisms of the inhibitory effect of kaempferol on the invasion and metastasis of gastric cancer (GC) cells through network pharmacology prediction and experimental verification. It identifies core targets via PPI network analysis and finds that kaempferol binds to these targets well. In vitro experiments showed that kaempferol could inhibit the proliferation, colony formation, migration and invasion of GC cells. Western blotting indicated kaempferol may reduce AKT and GSK3ß phosphorylation, leading to lower expression of invasion-related genes SRC, MMP9, CXCR4, KDR, and MMP2. Overall, kaempferol may prevent migration and invasion of GC cells via the AKT/GSK3ß signaling pathway.

Long-term clinical efficacy of drug-coated balloon angioplasty for TASCII C/D femoropopliteal lesions in older patients with chronic limb-threatening ischemia: A retrospective study.

This study aimed to evaluate the long-term clinical outcomes of drug-coated drug (DCB) angioplasty for long femoropopliteal lesions in older patients with chronic limb-threatening ischemia (CLTI). In this multi-center retrospective study, we enrolled 119 patients with CLTI due to Trans-Atlantic Inter-Society Consensus (TASCII) C/D femoropopliteal lesions who underwent DCB angioplasty. A total of 119 patients with 122 limbs (TASCII C = 67, 54.9%; TASCII D = 55, 45.1%) were enrolled. At 36-month follow-up, primary patency, assisted primary patency, secondary patency, and freedom from target lesion revascularization were 47.3%, 49.8%, 59.5%, and 62.7%, respectively, and there was a significant improvement over baseline in Rutherford class (P < .001) and ankle-brachial index measurements (P < .001). Complex target lesions (P = .017) and 1 stenosis-free outflow vessel (P = .001) were risk predictors of freedom from clinically driven target lesion revascularization. Complex target lesions (P = .044), diabetes (P = .007), and 1 stenosis-free outflow vessel (P = .003) were risk predictors of restenosis. At 2 months, the ulcer healing rate was 96.3% (26/27). At 36 months, the limb salvage and survival rates were 85.8% and 83.3%, respectively. DCB angioplasty were safe and effective for older patients with CLTI attributable to femoropopliteal TASCII C/D lesions.

Gasdermin D could be lost in the brain parenchyma infarct core and a pyroptosis-autophagy inhibition effect of Jie-Du-Huo-Xue decoction after stroke.

Background: The Chinese ethnic medicine Jie-Du-Huo-Xue Decoction (JDHXD) is used to alleviate neuroinflammation in cerebral ischemia (CI). Our previous studies have confirmed that JDHXD can inhibit microglial pyroptosis in CI. However, the pharmacological mechanism of JDHXD in alleviating neuroinflammation and pyroptosis needs to be further elucidated. New research points out that there is an interaction between autophagy and inflammasome NLRP3, and autophagy can help clear NLRP3. The NLRP3 is a key initiator of pyroptosis and autophagy. The effect of JDHXD promoting autophagy to clear NLRP3 to inhibit pyroptosis on cerebral ischemia-reperfusion inflammatory injury is currently unknown. We speculate that JDHXD can inhibit pyroptosis in CI by promoting autophagy to clear NLRP3. Methods: Chemical characterization of JDHXD was performed using LC-MS. Model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established in SD rats. Neurological deficits, neuron damage, and cerebral infarct volume were evaluated. Western Blot and immunofluorescence were used to detect neuronal pyroptosis and autophagy. Results: 30 possible substance metabolites in JDHXD medicated serum were analyzed by LC-MS (Composite Score > 0.98). Furthermore, JDHXD protects rat neurological function and cerebral infarct size after CI. JDHXD inhibited the expression of pyroptosis and autophagy after CI. Our western blot and immunofluorescence results showed that JDHXD treatment can reduce the expression of autophagy-related factors ULK1, beclin1, and LC3-Ⅱ. The expression of NLRP3 protein was lower in the JDHXD group than in the I/R group. Compared with the I/R group, the expressions of pyroptosis-related factors caspase-1 P 10, GSDMD-NT, IL-18, and IL-1ß decreased in the JDHXD group. Furthermore, we observed an unexpected result: immunofluorescence demonstrated that Gasdermin D (GSDMD) was significantly absent in the infarct core, and highly expressed in the peri-infarct and contralateral cerebral hemispheres. This finding challenges the prevailing view that GSDMD is elevated in the ischemic cerebral hemisphere. Conclusion: JDHXD inhibited pyroptosis and autophagy after MCAO/R. JDHXD suppressed pyroptosis and autophagy by inhibiting NLRP3, thereby alleviating CI. In addition, we present a different observation from previous studies that the expression of GSDMD in the infarct core was lower than that in the peri-infarct and contralateral non-ischemic hemispheres on day 3 of CI.

Mendelian randomization study reveals causal effects of specific gut microbiota on the risk of interstitial cystitis/bladder pain syndrome (IC/BPS).

Evidence from previous studies have demonstrated that gut microbiota are closely associated with occurrence of interstitial cystitis/bladder pain syndrome (IC/BPS), yet the causal link between the two is not well known. In this study, we performed a two-sample Mendelian randomization (MR) analysis to determine the possible causal association between gut microbiota with IC/BPS. Gut microbiota summary level data were derived from the genome-wide association study (GWAS) conducted by MiBioGen and the IC/BPS GWAS summary level data were obtained from the GWAS Catalog. Next, we performed an MR study to investigate the causal link between gut microbiota and IC/BPS. The primary method for causal analysis was the inverse variance weighted (IVW), and the MR results were validated through multiple sensitivity analyses. A positive association was found between IC/BPS and eight gut microbial taxa, including genus Bacteroides, genus Haemophilus, genus Veillonella, genus Coprococcus1, genus Butyricimonas, family Bacteroidaceae, family Christensenellaceae, and order Lactobacillales. Sensitivity analysis revealed lack of significant pleiotropy or heterogeneity in the obtained results. This MR analysis reveals that a causal association exists between some gut microbiota with IC/BPS. This finding may is expected to guide future research and development of IC/BPS preventions and treatments based on the bladder-gut axis. However, given the clinical complexity and diagnostic challenges of IC/BPS, along with the limitations of using large-scale GWAS summary data for analysis, our MR results require further validation through additional research.

Genome-Wide Identification and Expression Analysis of SlNRAMP Genes in Tomato under Nutrient Deficiency and Cadmium Stress during Arbuscular Mycorrhizal Symbiosis.

Arbuscular mycorrhizal (AM) fungi are well known for enhancing phosphorus uptake in plants; however, their regulating roles in cation transporting gene family, such as natural resistance-associated macrophage protein (NRAMP), are still limited. Here, we performed bioinformatics analysis and quantitative expression assays of tomato SlNRAMP 1 to 5 genes under nutrient deficiency and cadmium (Cd) stress in response to AM symbiosis. These five SlNRAMP members are mainly located in the plasma or vacuolar membrane and can be divided into two subfamilies. Cis-element analysis revealed several motifs involved in phytohormonal and abiotic regulation in their promoters. SlNRAMP2 was downregulated by iron deficiency, while SlNRAMP1, SlNRAMP3, SlNRAMP4, and SlNRAMP5 responded positively to copper-, zinc-, and manganese-deficient conditions. AM colonization reduced Cd accumulation and expression of SlNRAMP3 but enhanced SlNRAMP1, SlNRAMP2, and SlNRMAP4 in plants under Cd stress. These findings provide valuable genetic information for improving tomato resilience to nutrient deficiency and heavy metal stress by developing AM symbiosis.

Diagnostic efficacy of the contrast-enhanced ultrasound thyroid imaging reporting and data system classification for benign and malignant thyroid nodules.

Background: The contrasted-enhanced ultrasound thyroid imaging reporting and data system (CEUS TI-RADS) is the first international risk stratification system for thyroid nodules based on conventional ultrasound (US) and CEUS. This study aimed to evaluate the diagnostic efficacy of CEUS TI-RADS for benign and malignant thyroid nodules and to assess the related interobserver agreement. Methods: The study recruited 433 patients who underwent thyroid US and CEUS between January 2019 and June 2023 at the Affiliated Hospital of Guangdong Medical University. A retrospective analysis of 467 thyroid nodules confirmed by fine-needle aspiration (FNA) and/or surgery was performed. Further, a CEUS TI-RADS classification was assigned to each thyroid nodule based on the CEUS TI-RADS scoring criteria for the US and CEUS features of the nodule. The nodules were grouped based on their sizes as follows: size ≤1 cm, group A; size >1 and ≤4 cm, group B; and size >4 cm, group C. Multivariate logistic regression was used to analyze independent risk factors for malignant thyroid nodules. Pathological assessment was the reference standard for establishing the sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) of CEUS TI-RADS in diagnosing malignant thyroid nodules. The area under the curve (AUC) in the receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficacy of the scoring system in predicting malignancy in three groups of nodules. The intragroup correlation coefficient (ICC) was adopted to assess the interobserver agreement of the CEUS TI-RADS score. Results: Out of the 467 thyroid nodules, 262 were malignant and 205 were benign. Logistic regression analysis revealed that the independent risk factors for malignant thyroid nodules included punctate echogenic foci (P<0.001), taller-than-wide shape (P=0.015), extrathyroidal invasion (P=0.020), irregular margins/lobulation (P=0.036), hypoechoicity on US (P=0.038), and hypoenhancement on CEUS (P<0.001). The AUC for the CEUS TI-RADS in diagnosing malignant thyroid nodules was 0.898 for all nodules, 0.795 for group A, 0.949 for group B, and 0.801 for group C, with the optimal cutoff values of the CEUS TI-RADS being 5 points, 6 points, 5 points, and 5 points, respectively. Among these groups of nodules, group B had the highest AUC, with the SEN, SPE, ACC, PPV, and NPV for diagnosing malignant nodules being 95.9%, 88.1%, 92.8%, 92.6%, and 93.2%, respectively. The ICC of the CEUS TI-RADS classification between senior and junior physicians was 0.862 (P<0.001). Conclusions: In summary, CEUS TI-RADS demonstrated significant efficacy in distinguishing thyroid nodules. Nonetheless, there were variations in its capacity to detect malignant nodules across diverse sizes, and it demonstrate optimal performance in 1- to 4-cm nodules. These findings may serve as important insights for clinical diagnoses.

PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality.

Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.

Harmine promotes megakaryocyte differentiation and thrombopoiesis by activating the Rac1/Cdc42/JNK pathway through a potential target of 5-HTR2A.

Harmine (HM), a ß-carboline alkaloid extracted from plants, is a crucial component of traditional Chinese medicine (TCM) known for its diverse pharmacological activities. Thrombocytopenia, a common and challenging hematological disorder, often coexists with serious illnesses. Previous research has shown a correlation between HM and thrombocytopenia, but the mechanism needs further elucidation. The aim of this study was to clarify the mechanisms underlying the effects of HM on thrombocytopenia and to develop new therapeutic strategies. Flow cytometry, Giemsa staining, and Phalloidin staining were used to assess HM's impact on Meg-01 and HEL cell differentiation and maturation in vitro. A radiation-induced thrombocytopenic mouse model was employed to evaluate HM's effect on platelet production in vivo. Network pharmacology, molecular docking, and protein blotting were utilized to investigate HM's targets and mechanisms. The results demonstrated that HM dose-dependently promoted Meg-01 and HEL cell differentiation and maturation in vitro and restored platelet levels in irradiated mice in vivo. Subsequently, HM was found to be involved in the biological process of platelet production by upregulating the expressions of Rac1, Cdc42, JNK, and 5-HTR2A. Furthermore, the targeting of HM to 5-HTR2A and its correlation with downstream Rac1/Cdc42/JNK were also confirmed. In conclusion, HM regulates megakaryocyte differentiation and thrombopoiesis through the 5-HTR2A and Rac1/Cdc42/JNK pathways, providing a potential treatment strategy for thrombocytopenia.

Combined effects of nitrogen limitation and overexpression of malic enzyme gene on lipid accumulation in Dunaliella parva.

Overexpression of Dunaliella parva (D. parva) malic enzyme (ME) gene (DpME) significantly increased DpME expression and ME enzyme activity in transgenic D. parva. Nitrogen limitation had an inhibitory effect on protein content, and DpME overexpression could improve protein content. Nitrogen limitation increased carbohydrate content, and Dunaliella parva overexpressing malic enzyme gene under nitrogen limitation (DpME-N-) group showed the lowest starch content among all groups. Dunaliella parva overexpressing malic enzyme gene under nitrogen sufficient condition (DpME) and DpME-N- groups showed considerably high mRNA levels of DpME. ME activity was significantly enhanced by DpME overexpression, and nitrogen limitation caused a smaller increase. DpME overexpression and nitrogen limitation obviously enhanced lipid accumulation, and DpME overexpression had more obvious effect. Compared with control (wild type), lipid content (68.97%) obviously increased in DpME-N- group. This study indicated that the combination of DpME overexpression and nitrogen limitation was favorable to the production of microalgae biodiesel.

Synergy of oxygen reduction for H2O2 production and electro-fenton induced by atomic hydrogen over a bifunctional cathode towards water purification.

In the Electro-Fenton (EF) process, hydrogen peroxide (H2O2) is produced in situ by a two-electron oxygen reduction reaction (2e ORR), which is further activated by electrocatalysts to generate reactive oxygen specieces (ROS). However, the selectivity of 2e transfer from catalysts to O2 is still unsatisfactory, resulting in the insufficient H2O2 availability. Carbon based materials with abundant oxygen-containing functional groups have been used as excellent 2e ORR electrocatalysts, and atomic hydrogen (H*) can quickly transfer one electron to H2O2 in a wide pH range and avoiding the restrict of traditional Fenton reaction. Herein, nickel nanoparticles growth on oxidized carbon deposited on modified carbon felt (Ni/Co@CFAO) was prepared as a bifunctional catalytic electrode coupling 2e ORR to form H2O2 with H* reducing H2O2 to produce ROS for highly efficient degradation of antibiotics. Electrochemical oxidation and thermal treatment were used to modulate the structure of carbon substrates for increasing the electro-generation of H2O2, while H* was produced over Ni sites through H2O/H+ reduction constructing an in-situ EF system. The experimental results indicated that 2e ORR and H* induced EF processes could promote each other mutually. The optimized Ni/Co@CFAO with a Ni:C mass ratio of 1:9 exhibited a high 2e selectivity and H2O2 yield of 49 mg L-1. As a result, the designed Ni/Co@CFAO exhibited excellent electrocatalytic ability to degrade tetracycline (TC) under different aqueous environmental conditions, and achieved 98.5% TC removal efficiency within 60 min H2O2 and H* were generated simultaneously at the bifunctional cathode and react to form strong oxidizing free radicals •OH. At the same time, O2 gained an electron to form •O2-, which could react with •OH and H2O to form 1O2, which had relatively long life (10-6∼10-3 s), further promoting the efficient removal of antibiotics in water.

Activation of GABAergic neurons in the dorsal raphe nucleus alleviates hyperalgesia induced by ovarian hormone withdrawal.

ABSTRACT: Menopausal and postmenopausal women, characterized by a significant reduction in ovarian hormones, have a high prevalence of chronic pain with great pain intensity. However, the underlying mechanism of hyperalgesia induced by ovarian hormone withdrawal remains poorly understood. Here, we report that decreases in the activity and excitability of GABAergic neurons in the dorsal raphe nucleus (DRN) are associated with hyperalgesia induced by ovariectomy in mice. Supplementation with 17ß-estradiol, but not progesterone, is sufficient to increase the mechanical pain threshold in ovariectomized (OVX) mice and the excitability of DRN GABAergic (DRNGABA) neurons. Moreover, activation of the DRNGABA neurons projecting to the lateral parabrachial nucleus was critical for alleviating hyperalgesia in OVX mice. These findings show the essential role of DRNGABA neurons and their modulation by estrogen in regulating hyperalgesia induced by ovarian hormone withdrawal, providing therapeutic basis for the treatment of chronic pain in physiological or surgical menopausal women.

Balancing the benefits and risks of China's national salt iodization policy over 30 years using disability-adjusted life years (DALYs): a systematic review and meta-analysis.

Both insufficient and excessive iodine intake can lead to thyroid-related disorders. Although China has made progress in eliminating iodine deficiency over the past few decades, the incidence of thyroid cancer is increasing. Currently, there is a lack of relevant research on the tradeoff between the benefits and risks of salt iodization in China. In this study, we developed a method that combines the total probability algorithm and disease burden to evaluate the appropriate amount of salt iodization. Following the principle of minimizing the comprehensive disease burden and using the metabolic model of human iodine nutrition. Based on the average national iodine level in water, the optimal iodine content in Chinese salt is determined to be 17 mg/kg. However, iodine content in water is not evenly distributed in China. Approximately 3.23% of administrative villages have water iodine concentrations exceeding 80 ug/L, eliminating the need for iodine fortification in salt. Approximately 83.51% of administrative villages need to continue implementing the salt iodization policy, with the optimal iodine content in salt ranging from 15 to 18 mg/kg. In 13.16% of administrative villages, the iodine content in salt is determined based on the local water iodine concentration, ranging from 0 to 15 mg/kg. Our study cracks open a window of insight suggesting that the optimal iodine content for salt is lower than the existing benchmark dictated by the prevailing policy in China. Hence, there is an urgent need to refine and advance the iodine supplementation strategy in salt to pave the way for precision medicine and health-centric iodine supplementation strategies.