Advancing the predictive accuracy of PNTML in rectal prolapse: An ongoing quest.

Fecal incontinence is a common symptom among patients with rectal prolapse. Pudendal nerve terminal motor latency (PNTML) testing can serve as a reference indicator for predicting the outcomes of rectal prolapse surgery, thereby assisting surgeons in formulating more appropriate surgical plans. The direct correlation between preoperative PNTML testing results and postoperative fecal incontinence in patients with rectal prolapse remains a contentious issue, necessitating further clarification. Thus, we analyze the existing publications from both clinical and statistical perspectives to comprehensively evaluate the accuracy of preoperative PNTML testing in rectal prolapse and provide some feasible statistical solutions.

Frontier role of extracellular vesicles in kidney disease.

Kidney diseases represent a diverse range of conditions that compromise renal function and structure which characterized by a progressive deterioration of kidney function, may ultimately necessitate dialysis or kidney transplantation as end-stage treatment options. This review explores the complex landscape of kidney diseases, highlighting the limitations of existing treatments and the pressing need for innovative strategies. The paper delves into the role of extracellular vesicles (EVs) as emerging biomarkers and therapeutic agents in the context of kidney pathophysiology. Urinary extracellular vesicles (uEVs), in particular, offer a non-invasive means of assessing renal injury and monitoring disease progression. Additionally, mesenchymal stem cell-derived EVs (MSC-EVs) are examined for their immunomodulatory and tissue repair capabilities, presenting a promising avenue for novel therapeutic interventions. And discusses the potential of engineering EVs to enhance their targeting and therapeutic efficacy. This paper systematically integrates the latest research findings and aims to provide a comprehensive overview of the role of EVs in kidney disease, providing cutting-edge insights into their potential as a diagnostic and therapeutic tool.

Exosomal miR-4745-5p/3911 from N2-polarized tumor-associated neutrophils promotes gastric cancer metastasis by regulating SLIT2.

Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in human health and diseases including cancer. So far, the biological roles of exosomes from N2 TANs in gastric cancer have not been well characterized. Herein, we represented the first report that exosomes from N2 TANs promoted gastric cancer metastasis in vitro and in vivo. We found that exosomes from N2 TANs transferred miR-4745-5p/3911 to gastric cancer cells to downregulate SLIT2 (slit guidance ligand 2) gene expression. Adenovirus-mediated overexpression of SLIT2 reversed the promotion of gastric cancer metastasis by N2 TANs derived exosomes. We further revealed that gastric cancer cells induced glucose metabolic reprogramming in neutrophils through exosomal HMGB1 (high mobility group protein B1)/NF-κB pathway, which mediated neutrophil N2 polarization and miR-4745-5p/3911 upregulation. We further employed ddPCR (droplet digital PCR) to detect the expression of miR-4745-5p/3911 in N2 TANs exosomes from human serum samples and found their increased levels in gastric cancer patients compared to healthy controls and benign gastric disease patients. Conclusively, our results indicate that N2 TANs facilitate cancer metastasis via regulation of SLIT2 in gastric cancer cells by exosomal miR-4745-5p/3911, which provides a new insight into the roles of TME cells derived exosomes in gastric cancer metastasis and offers a potential biomarker for gastric cancer diagnosis.

A clinical evaluation of robotic-assisted radical prostatectomy (RARP) in located prostate cancer: A systematic review and network meta-analysis.

Prostate cancer (PCa) is a prevalent malignant tumor affecting the male reproductive system and there are mainly three widely accepted PCa surgery types in current clinical treatment: open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP). Here, we aimed to evaluate the clinical effect of RARP for PCa patients compared with ORP and LRP based on the context of PCa encompass two dimensions: oncological outcomes (biochemical recurrence (BCR) and positive surgical margin (PSM)) and functional outcomes (urinary continence and recovery of erectile function) in this network meta-analysis (NMA). PubMed, Embase and Cochrane databases were systematically searched in January 7, 2024. 4 randomized controlled trials (RCTs) and 72 non-RCTs were included. RARP displayed significant positive effect on lower BCR and better recovery of erectile function but no significant differences existed among three surgery types for PSM and urinary continence.

[Anti-breast cancer effect of a mitochondrion-targeted derivative of ergosterol peroxide in vitro and in vivo].

This study aims to explore the effect and mechanism of a mitochondrion-targeted derivative of ergosterol peroxide(Mito-EP) on breast cancer. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of MDA-MB-231 cells treated with different concentrations(0, 0.075, 0.15, 0.3, 0.6, 1.2, and 2.4 µmol·L~(-1)) of Mito-EP. Cells were grouped for treatment with water(blank control), low, medium, and high concentrations(0.15, 0.3, and 0.6 µmol·L~(-1)) of Mito-EP, and ergosterol peroxide(EP)(0.6 µmol·L~(-1)). After the cells were treated for 48 h, flow cytometry was employed to examine the apoptosis rate, reactive oxygen species(ROS) level, mitochondrial membrane potential, and cell cycle distribution, and the apoptosis, ROS, and mitochondrial membrane potential were observed by laser confocal microscopy. A mouse model bearing subcutaneous xenograft tumor was established by injecting 4T1 cell suspension and used to study the inhibitory effect of Mito-EP on breast cancer. Western blot was employed to determine the protein levels of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cytochrome C(Cyt C), cleaved caspase-7, and cleaved caspase-9 in cells and the tumor tissue. The results showed that Mito-EP reduced the proliferation rate of MDA-MB-231 cells in a concentration-dependent manner. Compared with the blank control group, EP(0.6 µmol·L~(-1)) caused slight changes in the apoptosis rate, ROS level, and mitochondrial membrane potential. However, Mito-EP increased the apoptosis rate, elevated the ROS level, decreased mitochondrial membrane potential, up-regulated the protein levels of Bax, Cyt C, cleaved caspase-7, and cleaved caspase-9, and down-regulated the protein level of Bcl-2(all P<0.05). Moreover, Mito-EP reduced the tumor volume and weight. In summary, Mito-EP may promote apoptosis in breast cancer cells by activating the mitochondrial apoptosis pathway.

Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial.

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Mesenchymal stem cell-derived extracellular vesicles ameliorate renal interstitial fibrosis via the miR-13474/ADAM17 axis.

Renal interstitial fibrosis (RIF) is a prevalent consequence of chronic renal diseases, characterized by excessive extracellular matrix (ECM) deposition. A Disintegrin and Metalloprotease 17 (ADAM17), a transmembrane metalloproteinase, plays a central role in driving renal fibrosis progression by activating Notch 1 protein and the downstream TGF-ß signaling pathway. Our study investigated potential therapeutic interventions for renal fibrosis, focusing on human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs). We found that hucMSC-EVs inhibit ADAM17, thereby impeding renal fibrosis progression. Analysis of hucMSC-EVs miRNA profiles revealed significant enrichment of miR-13474, which effectively targeted and inhibited ADAM17 mRNA expression, subsequently suppressing Notch1 activation, TGF-ß signaling, and collagen deposition. Overexpression of miR-13474 enhanced hucMSC-EVs' inhibitory effect on renal fibrosis, while its downregulation abolished this protective effect. Our findings highlight the efficacy of hucMSC-EVs overexpressing miR-13474 in mitigating renal fibrosis via ADAM17 targeting. These insights offer potential therapeutic strategies for managing renal fibrosis.

Silica nanoparticle design for colorectal cancer treatment: Recent progress and clinical potential.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.

Comparative analysis of the analgesic effects of intercostal nerve block, ultrasound-guided paravertebral nerve block, and epidural block following single-port thoracoscopic lung surgery.

OBJECTIVE: In this study, we compared the analgesic effects of intercostal nerve block (ICNB), ultrasound-guided paravertebral nerve block (PVB), and epidural block (EB) following single-port thoracoscopic lung surgery. METHOD: A total of 120 patients who underwent single-hole thoracoscopic lung surgery were randomly and equally divided into three groups: ICNB group, the PVB group, and the EB group. ICNB was performed under direct thoracoscopic visualization before the conclusion of the surgery in the ICNB group, while PVB and EB were performed after general anesthesia in the PVB and EB groups, respectively. Patient-controlled intravenous analgesia (PCIA) was used following the surgery in all the groups. The following indicators were recorded: Intraoperative sufentanil dosage, anesthesia awakening time, postoperative intubation time, nerve block operation time, postoperative visual analog scale (VAS) pain scores during resting and coughing at regular intervals of 0, 2, 4, 8, 24, and 48 h, the time until first PCIA, number of effective compressions within 24 h postoperatively, number of rescue analgesia interventions, and the side effects. RESULTS: In comparison to the ICNB group, the PVB and EB groups had a lower intraoperative sufentanil dosage, significantly shorter anesthesia awakening time, and postoperative intubation time, but longer nerve block operation time, lower VAS scores when resting and coughing within 24 h postoperatively (all p-values less than 0.05). Conversely, there were no statistically significant differences in VAS scores during resting and coughing after 24 h (all p-values greater than 0.05). Time to first PCIA, number of effective compressions and number of rescue analgesia at the 24-hour mark postoperatively were significantly better in the PVB and EB groups than that in the ICNB group (P < 0.05). However, there was a higher incidence of side effects observed in the EB group (P < 0.05). CONCLUSION: The analgesic effect of PVB and EB following single-port thoracoscopic lung surgery is better than that of ICNB. PVB causes fewer side effects and complications and is safer and more effective.

The impact of mild and moderate COVID-19 infection on the progression of kidney dysfunction in patients with IgA nephropathy.

Background: Previous research indicates that coronavirus disease 2019 (COVID-19) infection may have a role in triggering immunoglobulin A (IgA) nephropathy. However, limited research has explored the clinical implications of COVID-19 infection in individuals already diagnosed with IgA nephropathy. This study aimed to determine whether COVID-19 infection independently affects the subsequent trajectory of kidney function in IgA nephropathy patients. Methods: This was a single-center cohort study. The study included 199 patients diagnosed with IgA nephropathy. The COVID-19 infection status was determined using a combined method: a questionnaire and the Health Code application, both administered at the end of 2022 in northern China. Kidney function trajectory was assessed by the estimated glomerular filtration rate (eGFR), calculated based on serum creatinine levels measured during follow-up outpatient visits. The primary endpoint of interest was the eGFR trajectory. Results: Out of the 199 participants, 75% (n = 181) reported a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, determined through antigen or polymerase chain reaction tests, accounting for 79% (n = 143) of the infected patients. A significant majority (98%) experienced mild to moderate symptoms. Over a median follow-up period of 10.7 months post-COVID-19 infection, notable clinical events included gross hematuria in 30 patients (16.6%), which normalized within an average of 3 days. Additionally, a 2-fold increase in proteinuria or progression to the nephrotic range was observed in 10 individuals (5.5%). No cases of acute kidney injury were noted. COVID-19 exposure was associated with an absolute change in eGFR of 2.98 mL/min/1.73 m2 per month (95% confidence interval 0.46 to 5.50). However, in a fully adjusted model, the estimated changes in eGFR slope post-COVID-19 were -0.39 mL/min/1.73 m2 per month (95% confidence interval -0.83 to 0.06, P = .088) which included the possibility of no significant effect. Notably, a higher rate of kidney function decline was primarily observed in patients with a baseline eGFR <45 mL/min/1.73 m2 [-0.56 mL/min/1.73 m2 (-1.11 to -0.01), P = .048]. In the cohort, there were few instances of severe COVID-19 cases. The absence of long-term follow-up outcomes was observed. Conclusions: Overall, mild to moderate COVID-19 infection does not appear to significantly exacerbate the subsequent decline in kidney function among IgA nephropathy patients, particularly in those with preserved baseline kidney function.

Single-cell RNA transcriptomic reveal the mechanism of MSC derived small extracellular vesicles against DKD fibrosis.

Diabetic kidney disease (DKD), a chronic kidney disease, is characterized by progressive fibrosis caused due to persistent hyperglycemia. The development of fibrosis in DKD determines the patient prognosis, but no particularly effective treatment. Here, small extracellular vesicles derived from mesenchymal stem cells (MSC-sEV) have been used to treat DKD fibrosis. Single-cell RNA sequencing was used to analyze 27,424 cells of the kidney, we have found that a novel fibrosis-associated TGF-ß1+Arg1+ macrophage subpopulation, which expanded and polarized in DKD and was noted to be profibrogenic. Additionally, Actin+Col4a5+ mesangial cells in DKD differentiated into myofibroblasts. Multilineage ligand-receptor and cell-communication analysis showed that fibrosis-associated macrophages activated the TGF-ß1/Smad2/3/YAP signal axis, which promotes mesangial fibrosis-like change and accelerates renal fibrosis niche. Subsequently, the transcriptome sequencing and LC-MS/MS analysis indicated that MSC-sEV intervention could restore the levels of the kinase ubiquitin system in DKD and attenuate renal interstitial fibrosis via delivering CK1δ/ß-TRCP to mediate YAP ubiquitination degradation in mesangial cells. Our findings demonstrate the unique cellular and molecular mechanisms of MSC-sEV in treating the DKD fibrosis niche at a single-cell level and provide a novel therapeutic strategy for renal fibrosis.

Design and construction of high strength double network hydrogel with flow-induced orientation.

The design and construction of high strength hydrogels is a widely discussed topic in hydrogel research. In this study, we combined three toughening strategies, including dual network, oriented structure construction and nanophase doping, to develop an alginate/polyacrylamide (PAM)/modified titanium dioxide fiber (TiO2 NF@PAM) dual network composite hydrogel prepared via syringe. The effects of different preparation methods, AM/Alginate ratios, inorganic doping phases and TiO2 NF@PAM/AM ratios on the mechanical properties of composite hydrogels were investigated. The study found that the alginate hydrogel prepared by syringe exhibited superior axial orientation and achieved a tensile strength of (1091 ± 46) kPa. And the composite hydrogel doped with 0.2 wt% TiO2 NF@PAM had a tensile strength of (1006 ± 64) kPa, which was higher than that of the composite hydrogel doped with 0.2 wt% TiO2 nanoparticles (976 ± 66) kPa. The highest tensile strength (1120 ± 67) kPa and elongation at break (182 ± 8) % were achieved when the ratio of TiO2 NF@PAM/AM was 0.6 wt%. The force applied to the gel solution in the syringe affects the orientation of the polymer chains and TiO2 NF@PAM within the gel, which subsequently impacts the mechanical properties of the hydrogel. Therefore, we further investigated the mechanical properties of composite hydrogels under varying propulsion speeds, syringe diameters, and syringe lengths. It was observed that the gel solution's shear strength increased as the syringe diameter decreased. The resulting composite hydrogels were better oriented and had improved mechanical properties. The composite hydrogels' tensile strength peaked at (1117 ± 47) kPa when the syringe advance rate was between 1-7 mL/min. The mechanical properties of the hydrogels were optimal when the syringe length was 30 mm, with a maximum tensile strength of (1131 ± 67) kPa and a tensile ratio of (166 ± 5) %. This study demonstrates the viability of integrating three distinct strengthening methodologies to generate hydrogels of considerable strength. Furthermore, the Alginate/PAM/TiO2 NF@PAM composite hydrogels possess remarkable potential as adaptable, wearable sensors due to their exemplary mechanical properties, knittability, and conductivity.

Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol.

Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and low-density lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPARα signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild-type and AdipoR2 overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild-type and hepatic-specific AdipoR2 overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPARα signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver.

Risk assessment model based on nucleotide metabolism-related genes highlights SLC27A2 as a potential therapeutic target in breast cancer.

PURPOSE: Breast cancer (BC) is the most prevalent malignant tumor worldwide among women, with the highest incidence rate. The mechanisms underlying nucleotide metabolism on biological functions in BC remain incompletely elucidated. MATERIALS AND METHODS: We harnessed differentially expressed nucleotide metabolism-related genes from The Cancer Genome Atlas-BRCA, constructing a prognostic risk model through univariate Cox regression and LASSO regression analyses. A validation set and the GSE7390 dataset were used to validate the risk model. Clinical relevance, survival and prognosis, immune infiltration, functional enrichment, and drug sensitivity analyses were conducted. RESULTS: Our findings identified four signature genes (DCTPP1, IFNG, SLC27A2, and MYH3) as nucleotide metabolism-related prognostic genes. Subsequently, patients were stratified into high- and low-risk groups, revealing the risk model's independence as a prognostic factor. Nomogram calibration underscored superior prediction accuracy. Gene Set Variation Analysis (GSVA) uncovered activated pathways in low-risk cohorts and mobilized pathways in high-risk cohorts. Distinctions in immune cells were noted between risk cohorts. Subsequent experiments validated that reducing SLC27A2 expression in BC cell lines or using the SLC27A2 inhibitor, Lipofermata, effectively inhibited tumor growth. CONCLUSIONS: We pinpointed four nucleotide metabolism-related prognostic genes, demonstrating promising accuracy as a risk prediction tool for patients with BC. SLC27A2 appears to be a potential therapeutic target for BC among these genes.

Osthole exhibits the remedial potential for polycystic ovary syndrome mice through Nrf2-Foxo1-GSH-NF-κB pathway.

Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro-inflammatory cytokine interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF-κB) subunit p65 by DHEA and weakened the transcriptional activity of NF-κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF-κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2-Foxo1-GSH-NF-κB pathway.

Arene-Arene Coupled Disulfamethazines (or Sulfadiazine)-Phenanthroline-Metal(II) Complexes were Synthesized by In Situ Reactions and Inhibited the Growth and Development of Triple-Negative Breast Cancer through the Synergistic Effect of Antiangiogenesis, Anti-Inflammation, Pro-Apoptosis, and Cuproptosis.

The novel metal(II)-based complexes HA-Cu, HA-Co, and HA-Ni with phenanthroline, sulfamethazine, and aromatic-aromatic coupled disulfamethazines as ligands were synthesized and characterized. HA-Cu, HA-Co, and HA-Ni all showed a broad spectrum of cytotoxicity and antiangiogenesis. HA-Cu was superior to HA-Co and HA-Ni, and even superior to DDP, showing significant inhibitory effect on the growth and development of tripe-negative breast cancer in vivo and in vitro. HA-Cu exhibited observable synergistic effects of antiproliferation, antiangiogenesis, anti-inflammatory, pro-apoptosis, and cuproptosis to effectively inhibited tumor survival and development. The molecular mechanism was confirmed that HA-Cu could downregulate the expression of key proteins in the VEGF/VEGFR2 signaling pathway and the expression of inflammatory cytokines, enhance the advantage of pro-apoptotic protein Bax, and enforce cuproptosis by weakening the expression of FDX1 and enhancing the expression of HSP70. Our research will provide a theoretical and practical reference for the development of metal-sulfamethazine and its derivatives as chemotherapy drugs for cancer treatment.

MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4.

BACKGROUND: Diabetic kidney disease (DKD) is a major complication of diabetes mellitus. Renal tubular epithelial cell (TEC) damage, which is strongly associated with the inflammatory response and mesenchymal trans-differentiation, plays a significant role in DKD; However, the precise molecular mechanism is unknown. The recently identified microRNA-630 (miR-630) has been hypothesized to be closely associated with cell migration, apoptosis, and autophagy. However, the association between miR-630 and DKD and the underlying mechanism remain unknown. AIM: To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats. METHODS: Streptozotocin was administered to six-week-old male rats to create a hyperglycemic diabetic model. In the second week of modeling, the rats were divided into control, DKD, negative control of lentivirus, and miR-630 overexpression groups. After 8 wk, urine and blood samples were collected for the kidney injury assays, and renal tissues were removed for further molecular assays. The target gene for miR-630 was predicted using bioinformatics, and the association between miR-630 and toll-like receptor 4 (TLR4) was confirmed using in vitro investigations and double luciferase reporter gene assays. Overexpression of miR-630 in DKD rats led to changes in body weight, renal weight index, basic blood parameters and histopathological changes. RESULTS: The expression level of miR-630 was reduced in the kidney tissue of rats with DKD (P < 0.05). The miR-630 and TLR4 expressions in rat renal TECs (NRK-52E) were measured using quantitative reverse transcription polymerase chain reaction. The mRNA expression level of miR-630 was significantly lower in the high-glucose (HG) and HG + mimic negative control (NC) groups than in the normal glucose (NG) group (P < 0.05). In contrast, the mRNA expression level of TLR4 was significantly higher in these groups (P < 0.05). However, miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Furthermore, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were significantly higher in the HG and HG + mimic NC groups than in NG group (P < 0.05). However, the levels of these cytokines were significantly lower in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Notably, changes in protein expression were observed. The HG and HG + mimic NC groups showed a significant decrease in E-cadherin protein expression, whereas TLR4, α-smooth muscle actin (SMA), and collagen IV protein expression increased (P < 0.05). Conversely, the HG + miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4, α-SMA, and collagen IV protein expression than in the HG + mimic NC group (P < 0.05). The miR-630 targets TLR4 gene expression. In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC. Additionally, rats treated with miR-630 agomir showed significant reductions in urinary albumin, blood glucose, TLR4, and proinflammatory markers (TNF-α, IL-1ß, and IL-6) expression levels (P < 0.05). Moreover, these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells. CONCLUSION: MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4, and has a protective effect on DKD.

Preliminary investigation on the causes of red tides in Qinhuangdao coastal areas in 2022.

To explore the causes of red tides in Qinhuangdao coastal water, we conducted surveys on both water quality and red tides during April to September of 2022 and analyzed the relationships between main environmental factors and red tide organisms through the factor analysis and canonical correspondence analysis. The results showed that there were eight red tides along the coast of Qinhuangdao in 2022, with a cumulative blooming area of 716.1 km2. The red tides could be divided into three kinds based on the major blooming organisms and occurrence time, Noctiluca scintillans bloom, diatom-euglena (Skeletonema costatum, Eutreptiella gymnastica, Pseudo-nitzschia spp.) bloom, and dinoflagellate (Scrippsiella trochoidea and Ceratium furca) bloom. Seasonal factor played roles mainly during July to September, while inorganic nutrients including nitrogen and phosphorus influenced the blooms mainly in April and July. The canonical correspondence analysis suggested that N. scintillans preferred low temperature, and often bloomed with high concentrations of ammonium nitrogen and dissolved inorganic phosphorus. S. costatum, E. gymnastica, and Pseudo-nitzschia spp. could tolerate broad ranges of various environmental factors, but favored high temperature and nitrogen-rich seawater. C. furca and S. trochoidea had higher survival rate and competitiveness in phosphate-poor waters. Combined the results from both analyses, we concluded that the causes for the three kinds of red tide processes in Qinhuangdao coastal areas in 2022 were different. Adequate diet algae and appropriate water temperature were important factors triggering and maintaining the N. scintillans bloom. Suitable temperature, salinity and eutrophication were the main reasons for the diatom-euglena bloom. The abundant nutrients and seawater disturbance promoted the germination of S. trochoidea cysts, while phosphorus limitation caused the blooming organism switched to C. furca and maintained the bloom hereafter.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

Puerarin Ameliorated PCOS through Preventing Mitochondrial Dysfunction Dependent on the Maintenance of Intracellular Calcium Homeostasis.

Polycystic ovarian syndrome (PCOS) is the major cause of infertility in reproductive women, but no universal drug is feasible. Although puerarin clinically treats cerebrovascular and cardiovascular diseases, its curative effect on PCOS remains elusive. The present study discovered that administration of puerarin restored estrous cycle of PCOS mice and diminished the number of cystic follicles with the concomitant recovery for circulating testosterone, LH and FSH levels, and LH/FSH ratio, indicating the therapeutic role of puerarin in PCOS. KEGG analysis of differential genes between PCOS and control revealed the enrichment in MAPK and calcium signaling pathway. Application of puerarin restricted the phosphorylation of ERK1/2 and JNK, whose activation neutralized the improvement of puerarin on the secretory function and apoptosis of ovarian granulosa cells (GCs). Meanwhile, puerarin alleviated the accumulation of cytosolic Ca2+ through restricting the opening of Ryr and Itpr channels, but this effectiveness was counteracted by the activatory ERK1/2 and JNK. Attenuation of cytosolic Ca2+ counteracted the antagonistic effects of ERK1/2 and JNK activation on puerarin's role in rescuing the calcineurin and Nfatc. Further analysis manifested that Mcu had been authenticated as a direct downstream target of Nfatc to mediate the amelioration of puerarin on mitochondrial Ca2+ uptake. Moreover, puerarin prevented the disorder of ATP content, mitochondrial membrane potential, and mitochondrial permeability transition pore opening through maintaining mitochondrial Ca2+ homeostasis. Collectively, puerarin might ameliorate the symptoms of PCOS mice through preventing mitochondrial dysfunction that is dependent on the maintenance of intracellular Ca2+ homeostasis after inactivation of ERK1/2 and JNK.