Weak magnetic field promotes denitrification by stimulating ferromagnetic ion-containing metalloprotein expression.

Weak magnetic field (WMF) has been recognized to promote biological denitrification processes; however, the underlying mechanisms remain largely unexplored, hindering the optimization of its effectiveness. Here, we systematically investigated the effects of WMF on denitrification performance, enzyme activity, microbial community, and metaproteome in packed bed bioreactors treating high nitrate wastewater under different WMF intensities and C:N ratios. Results showed that WMFs significantly promoted denitrification by consistently stimulating the activities of denitrifying reductases and NAD+/NADH biosynthesis across decreasing C:N ratios. Reductases and electron transfer enzymes involved in denitrification were overproduced due to the significantly enriched overexpression of ferromagnetic ion-containing (FIC) metalloproteins. We also observed WMFs' intensity-dependent selective pressure on microbial community structures despite the effects being limited compared to those caused by changing C:N ratios. By coupling genome-centric metaproteomics and structure prediction, we found the dominant denitrifier, Halomonas, was outcompeted by Pseudomonas and Azoarcus under WMFs, likely due to its structural deficiencies in iron uptake, suggesting that advantageous ferromagnetic ion acquisition capacity was necessary to satisfy the substrate demand for FIC metalloprotein overproduction. This study advances our understanding of the biomagnetic effects in the context of complex communities and highlights WMF's potential for manipulating FIC protein-associated metabolism and fine-tuning community structure.

Predicting the potential risks posed by antidepressants as emerging contaminants in fish based on network pharmacological analysis.

This study conducted a network pharmacology-based analysis to simultaneously discern a broad spectrum of potential environmental risks and health effects of antidepressants, a common class of pharmaceutical emerging contaminants (PECs) possessing a complex pharmacological profile, and in silico predict the adverse phenotypes potentially occurring in fish associated with exposure to antidepressants and their mixtures under realistic exposure scenarios. Results showed that 24 of the included 39 antidepressants had been detected worldwide in water environment across 50 countries. Using the environmentally realistic exposure scenario for China as an example, the predicted blood concentrations of antidepressant residues that were generated based on the Fish Plasma Model ranged from 37.89 (Alprazolam) to 16,772.05 (Sertraline) ng/L in exposed fish. Hazard-based bioactivity network without regard to concentration data was composed of 148 potential targets and 701 antidepressant-target interactions. After filtering each antidepressant-target interaction node using the predicted drug concentrations in the blood of fish under realistic exposure scenarios in China, an environmental risk-based network was refined and showed that 11 targets, including muscarinic acetylcholine receptor M1, alpha-2B adrenergic receptor, serotonin 2 A receptor, etc. might be modulated by antidepressants at concentrations equal to or below the environmental exposure levels and their mixtures in fish. Environmentally relevant concentrations of antidepressants in water samples from China might perturb the behavior, stress response, phototaxis, and development in exposed fish.

The safety and efficacy of sugammadex for reversing neuromuscular blockade in younger children and infants.

INTRODUCTION: Sugammadex, a novel selective antagonist of non-depolarizing neuromuscular blocking agents, has been shown to rapidly and effectively reverse moderate and deep paralysis in adults and pediatric patients over age 2, improving patient recovery and reducing the risk of postoperative complications. AREAS COVERED: Since the use of sugammadex in patients under age 2 is not widely studied, we aim to provide an overview on the drug's application and potential use in infants and neonates. There is a limited but growing body of evidence for the safe, efficacious use of sugammadex in children under age 2. Relevant studies were identified from the most updated data including case reports, clinical trials, systematic reviews, and meta analyses. EXPERT OPINION: The results suggest that at a dose of 2 to 4 mg/kg of sugammadex can be safely used to rapidly and effectively reverse neuromuscular blockade in neonates and infants; it is non-inferior based on incidence of adverse events compared to neostigmine. Additionally, sugammadex doses between 8 and 16 mg/kg may be used as a rescue agent for infants during 'can't intubate, can't ventilate' crisis. Overall, sugammadex offers new value in the perioperative care of patients under age 2, with further studies warranted to better understand its application and full effect in the pediatric population.

Efficacy of traditional Chinese medicine versus angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and their combinations in the treatment of IgA nephropathy: a systematic review and network meta-analysis.

Background: IgA nephropathy (IgAN), a condition posing a significant threat to public health, currently lacks a specific treatment protocol. Research has underscored the potential benefits of traditional Chinese medicine (TCM) for treating IgAN. Nevertheless, the effectiveness of various intervention strategies, such as combining TCM with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), lacks a comprehensive systematic comparison. Therefore, this study aimed to conduct a network meta-analysis to assess the clinical efficacy of ACEIs, ARBs, TCM, and their combinations in treating IgAN to offer novel insights and approaches for the clinical management of IgAN. Methods: A systematic review conducted until November 2023 included relevant literature from databases such as PubMed, Embase, Cochrane, Web of Science, Scopus, CNKI, and Wanfang. Two independent researchers screened and assessed the data for quality. Network and traditional meta-analyses were performed using Stata 18.0 and RevMan 5.3 software, respectively. Outcome measures included 24-h urinary protein quantification (24 hpro), estimated glomerular filtration rate (eGFR), serum creatinine (Scr), blood urea nitrogen (BUN), and adverse event incidence rates (ADRs). Forest plots, cumulative ranking probability curves (SUCRA), and funnel plots generated using Stata 18.0 facilitated a comprehensive analysis of intervention strategies' efficacy and safety. Results: This study included 72 randomized controlled trials, seven interventions, and 7,030 patients. Comparative analysis revealed that ACEI + TCM, ARB + TCM combination therapy, and TCM monotherapy significantly reduced the levels of 24 hpro, eGFR, Scr, and BUN compared to other treatment modalities (p < 0.05). TCM monotherapy demonstrated the most favorable efficacy in reducing eGFR levels (SUCRAs: 78%), whereas the combination of ARB + TCM reduced Scr, 24 hpro, and BUN levels (SUCRAs: 85.7%, 95.2%, and 87.6%, respectively), suggesting that ARB + TCM may represent the optimal intervention strategy. No statistically significant differences were observed among the various treatment strategies in terms of ADR (p > 0.05). Conclusion: The combination of ACEI or ARB with TCM demonstrated superior efficacy compared to ACEI/ARB monotherapy in the treatment of IgAN without any significant ADRs. Therefore, combination therapies can be used to enhance therapeutic outcomes based on individual patient circumstances, highlighting the use of TCM as a widely applicable approach in clinical practice. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023476674.

Structural characterization of the polysaccharide from the black crystal region of Inonotus obliquus and its effect on AsPC-1 and SW1990 pancreatic cancer cell apoptosis.

In this study, one water soluble polysaccharide (IOP1-1) with a weight average molecular weight of 6886 Da was obtained from the black crystal region of Inonotus obliquus by hot water extraction, DEAE-52 cellulose extraction and Sephadex-100 column chromatography purification. Structural analysis indicated that IOP1-1 was a glucan with a main chain composed of α-Glcp-(1 â†’ 4)-α-Glcp-(1 â†’ 4)-ß-Glcp-(1 â†’ 4)-ß-Glcp-(1 â†’ 4)-α-Glcp-(1 â†’ 6)-ß-Glcp-(1 â†’ 4)-α-Glcp-(1 â†’ 3)-ß-Glcp-(1→. The CCK-8 assay results showed that IOP1-1 inhibited AsPC-1 and SW1990 pancreatic cancer cell proliferation in a concentration-dependent manner. Flow cytometric analysis revealed that IOP1-1 induced cell cycle arrest in AsPC-1 and SW1990 cells. Hoechst 33342 staining and Annexin V-FITC/PI double staining analysis showed that IOP1-1 could induce apoptosis in AsPC-1 and SW1990 cells. Furthermore, western blot analysis confirmed that IOP1-1 could induce apoptosis in AsPC-1 and SW1990 pancreatic cancer cells through three pathways: the mitochondrial pathway, the death receptor pathway, and endoplasmic reticulum stress. According to these research data, IOP1-1 may be utilized as an adjuvant treatment to anticancer medications, opening up new application prospects and opportunities.

The prognostic significance and clinical relevance of stem cell characteristic in bladder cancer.

Background: Bladder cancer (BLCA) is a common malignant tumor of urinary system and prognostic biomarkers are needed for better clinical decision-making and patient management. Cancer stem cells (CSCs) are involved in carcinogenesis, development, metastasis and recurrence of BLCA. This study explored the prognostic and predictive value of CSCs-related genes and laid the groundwork for precision treatment development in BLCA. Methods: The mRNA data and corresponding clinical information obtained from TCGA-BLCA cohort was used to discover biomarkers and develop CSCs-related prognostic model, which was further validated in GSE32548 and GSE32894 datasets. In addition, the association between CSCs-related risk score and therapeutic efficacy was analyzed to explore the potential predictive value of the prognostic model. Results: We identified four CSCs-related subtypes and 900 differentially expressed genes (DEGs) among subtypes. Then the CSCs-related prognostic model was built based on 16 CSCs-related DEGs with the most significant prognostic value. Patients in the low-risk group had better overall survival than those in high-risk group (P < 0.001; HR, 0.42; 95 %CI, 0.31-0.57). Multivariable Cox analysis in training and test sets confirmed the independence of CSCs-related risk score as a prognostic factor (P < 0.05). The difference of survival between two risk groups were probably due to the significantly varied immune microenvironment based on the analysis of infiltrated immune cells. Additionally, the risk score was significantly associated with chemotherapy sensitivity and the response to anti-PD-L1 therapy (P < 0.05) which suggested a potential predictive value of CSCs-related risk model. Conclusion: We established a risk classifier based on 16 CSCs-related genes for predicting survival in patients with BLCA. The CSCs-related risk model has both prognostic value and potential predictive value for therapeutic efficacy, which brings us closer to understanding the important role of CSCs in BLCA and may provide guidance for clinical treatment decision-making and patient management. The clinical utility of the CSCs-related risk classifier warrants further studies.

Chemical characteristics of dissolved organic matter in effluent from sludge alkaline fermentation liquid-fed sequencing batch reactors.

Sludge alkaline fermentation liquid (SAFL) is a promising alternative to acetate for improving biological nitrogen removal (BNR) from wastewater. SAFL inevitably contains some refractory compounds, while the characteristics of dissolved organic matter (DOM) in effluent from SAFL-fed BNR process remain unclear. In this study, the molecular weight distribution, fluorescent composition and molecular profiles of DOM in effluent from SAFL and acetate-fed sequencing batch reactors (S-SBRs and A-SBRs, respectively) at different hydraulic retention time (12 h and 24 h) was comparatively investigated. Two carbon sources resulted in similar effluent TN, but a larger amount of DOM, which was bio-refractory or microorganisms-derived, was found in effluent of S-SBRs. Compared to acetate, SAFL increased the proportion of large molecular weight organics and humic-like substances in effluent DOM by 74.87%-101.3% and 37.52%-48.35%, respectively, suggesting their bio-refractory nature. Molecular profiles analysis revealed that effluent DOM of S-SBRs exhibited a more diverse composition and a higher proportion of lignin-like molecules. Microorganisms-derived molecules were found to be the dominant fraction (71.51%-72.70%) in effluent DOM (<800 Da) of S-SBRs. Additionally, a prolonged hydraulic retention time enriched Bacteroidota, Haliangium and unclassified_f_Comamonadaceae, which benefited the degradation of DOM in S-SBRs. The results help to develop strategies on reducing effluent DOM in SAFL-fed BNR process.

HIF-2α-dependent TGFBI promotes ovarian cancer chemoresistance by activating PI3K/Akt pathway to inhibit apoptosis and facilitate DNA repair process.

Hypoxia-mediated chemoresistance plays a crucial role in the development of ovarian cancer (OC). However, the roles of hypoxia-related genes (HRGs) in chemoresistance and prognosis prediction and theirs underlying mechanisms remain to be further elucidated. We intended to identify and validate classifiers of hub HRGs for chemoresistance, diagnosis, prognosis as well as immune microenvironment of OC, and to explore the function of the most crucial HRG in the development of the malignant phenotypes. The RNA expression and clinical data of HRGs were systematically evaluated in OC training group. Univariate and multivariate Cox regression analysis were applied to construct hub HRGs classifiers for prognosis and diagnosis assessment. The relationship between classifiers and chemotherapy response and underlying pathways were detected by GSEA, CellMiner and CIBERSORT algorithm, respectively. OC cells were cultured under hypoxia or transfected with HIF-1α or HIF-2α plasmids, and the transcription levels of TGFBI were assessed by quantitative PCR. TGFBI was knocked down by siRNAs in OC cells, CCK8 and in vitro migration and invasion assays were performed to examine the changes in cell proliferation, motility and metastasis. The difference in TGFBI expression was examined between cisplatin-sensitive and -resistant cells, and the effects of TGFBI interference on cell apoptosis, DNA repair and key signaling molecules of cisplatin-resistant OC cells were explored. A total of 179 candidate HRGs were extracted and enrolled into univariate and multivariate Cox regression analysis. Six hub genes (TGFBI, CDKN1B, AKAP12, GPC1, TGM2 and ANGPTL4) were selected to create a HRGs prognosis classifier and four genes (TGFBI, AKAP12, GPC1 and TGM2) were selected to construct diagnosis classifiers. The HRGs prognosis classifier could precisely distinguish OC patients into high-risk and low-risk groups and estimate their clinical outcomes. Furthermore, the high-risk group had higher percentage of Macrophages M2 and exhibited higher expression of immunecheckpoints such as PD-L2. Additionally, the diagnosis classifiers could accurately distinguish OC from normal samples. TGFBI was further verified as a specific key target and demonstrated that its high expression was closely correlated with poor prognosis and chemoresistance of OC. Hypoxia upregulated the expression level of TGFBI. The hypoxia-induced factor HIF-2α but not HIF-1α could directly bind to the promoter region of TGFBI, and facilitate its transcription level. TGFBI was upregulated in cisplatin-sensitive and resistant ovarian cancer cells in a cisplatin time-dependent manner. TGFBI interference downregulated DNA repair-related markers (p-p95/NBS1, RAD51, p-DNA-PKcs, DNA Ligase IV and Artemis), apoptosis-related marker (BCL2) and PI3K/Akt pathway-related markers (PI3K-p110 and p-Akt) in cisplatin-resistant OC cells. In summary, the HRGs prognosis risk classifier could be served as a predictor for OC prognosis and efficacy evaluation. TGFBI, upregulated by HIF-2α as an HRG, promoted OC chemoresistance through activating PI3K/Akt pathway to reduce apoptosis and enhance DNA damage repair pathway.

2-Hydroxy-1,4-Naphthoquinone: A Promising Redox Mediator for Minimizing Dissolved Organic Nitrogen and Eutrophication Effects of Wastewater Effluent.

Researchers and engineers are committed to finding effective approaches to reduce dissolved organic nitrogen (DON) to meet more stringent effluent total nitrogen limits and minimize effluent eutrophication potential. Here, we provided a promising approach by adding specific doses of 2-hydroxy-1,4-naphthoquinone (HNQ) to postdenitrification bioreactors. This approach of adding a small dosage of 0.03-0.1 mM HNQ effectively reduced the concentrations of DON in the effluent (ANOVA, p < 0.05) by up to 63% reduction of effluent DON with a dosing of 0.1 mM HNQ when compared to the control bioreactors. Notably, an algal bioassay indicated that DON played a dominant role in stimulating phytoplankton growth, thus effluent eutrophication potential in bioreactors using 0.1 mM HNQ dramatically decreased compared to that in control bioreactors. The microbe-DON correlation analysis showed that HNQ dosing modified the microbial community composition to both weaken the production and promote the uptake of labile DON, thus minimizing the effluent DON concentration. The toxic assessment demonstrated the ecological safety of the effluent from the bioreactors using the strategy of HNQ addition. Overall, HNQ is a promising redox mediator to reduce the effluent DON concentration with the purpose of meeting low effluent total nitrogen levels and remarkably minimizing effluent eutrophication effects.

Cytoskeleton Rearrangement in Podocytopathies: An Update.

Podocyte injury can disrupt the glomerular filtration barrier (GFB), leading to podocytopathies that emphasize podocytes as the glomerulus's key organizer. The coordinated cytoskeleton is essential for supporting the elegant structure and complete functions of podocytes. Therefore, cytoskeleton rearrangement is closely related to the pathogenesis of podocytopathies. In podocytopathies, the rearrangement of the cytoskeleton refers to significant alterations in a string of slit diaphragm (SD) and focal adhesion proteins such as the signaling node nephrin, calcium influx via transient receptor potential channel 6 (TRPC6), and regulation of the Rho family, eventually leading to the disorganization of the original cytoskeletal architecture. Thus, it is imperative to focus on these proteins and signaling pathways to probe the cytoskeleton rearrangement in podocytopathies. In this review, we describe podocytopathies and the podocyte cytoskeleton, then discuss the molecular mechanisms involved in cytoskeleton rearrangement in podocytopathies and summarize the effects of currently existing drugs on regulating the podocyte cytoskeleton.

Weak magnetic carriers reduce nitrite accumulation and boost denitrification at high nitrate concentrations by enriching functional bacteria and enhancing electron transfer.

Biological denitrification is the dominant method for NO3- removal from wastewater, while high NO3- leads to NO2- accumulation and inhibits denitrification performance. In this study, different weak magnetic carriers (0, 0.3, 0.6, 0.9 mT) were used to enhance biological denitrification at NO3- of 50-2400 mg/L. The effect of magnetic carriers on the removal and mechanism of denitrification of high NO3- was investigated. The results showed that 0.6 and 0.9 mT carriers significantly enhanced the TN removal efficiency (>99%) and reduced the accumulation of NO2- (by > 97%) at NO3- of 1200-2400 mg/L 0.6 and 0.9 mT carriers stimulated microbial electron transport by improving the abundances of coenzyme Q-cytochrome C reductase (by 4.44-23.30%) and cytochrome C (by 2.90-16.77%), which contributed to the enhanced elimination of NO3- and NO2-. 0.6 and 0.9 mT carriers increased the activities of NAR (by 3.74-37.59%) and NIR (by 5.01-8.24%). The abundance of narG genes in 0.6 and 0.9 mT was 1.47-2.35 and 1.38-1.75 times that of R1, respectively, and the abundance of nirS genes was 1.49-2.83 and 1.55-2.39 times that of R1, respectively. Denitrifying microorganisms, e.g., Halomonas, Thauera and Pseudomonas were enriched at 0.6 and 0.9 mT carriers, which benefited to the advanced denitrification performance. This study suggests that weak magnetic carriers can help to enhance the biological denitrification of high NO3- wastewater.

Pharmacological potential of Astragali Radix for the treatment of kidney diseases.

BACKGROUND: With the increasing prevalence of hypertension, diabetes, and obesity, the incidence of kidney diseases is also increasing, resulting in a serious public burden. Conventional treatments for kidney diseases have unsatisfactory effects and are associated with adverse reactions. Traditional Chinese medicines have good curative effects and advantages over conventional treatments for preventing and treating kidney diseases. Astragali Radix is a Chinese herbal medicine widely used to treat kidney diseases. PURPOSE: To review the potential applications and molecular mechanisms underlying the renal protective effects of Astragali Radix and its components and to provide direction and reference for new therapeutic strategies and future research and development of Astragali Radix. STUDY DESIGN AND METHODS: PubMed, Google Scholar, and Web of Science were searched using keywords, including "Astragali Radix," "Astragalus," "Astragaloside IV" (AS-IV), "Astragali Radix polysaccharide" (APS), and "kidney diseases." Reports on the effects of Astragali Radix and its components on kidney diseases were identified and reviewed. RESULTS: The main components of Astragali Radix with kidney-protective properties include AS-IV, APS, calycosin, formononetin, and hederagenin. Astragali Radix and its active components have potential pharmacological effects for the treatment of kidney diseases, including acute kidney injury, diabetic nephropathy, hypertensive renal damage, chronic glomerulonephritis, and kidney stones. The pharmacological effects of Astragali Radix are manifested through the inhibition of inflammation, oxidative stress, fibrosis, endoplasmic reticulum stress, apoptosis, and ferroptosis, as well as the regulation of autophagy. CONCLUSION: Astragali Radix is a promising drug candidate for treating kidney diseases. However, current research is limited to animal and cell studies, underscoring the need for further verifications using high-quality clinical data.

Optimizing waste molasses utilization to enhance electron transfer via micromagnetic carriers: Mechanisms and high-nitrate wastewater denitrification performance.

The biological denitrification of high-nitrate wastewater (HNW) is primarily hindered by insufficient carbon sources and excessive nitrite accumulation. In this study, micromagnetic carriers with varying micromagnetic field (MMF) strengths (0.0, 0.3, 0.6, 0.9 mT) were employed to enhance the denitrification of HNW using waste molasses (WMs) as a carbon source. The results revealed that 0.6 mT MMF significantly improved the total nitrogen removal (TN) efficiency at 96.3%. A high nitrate (NO3--N) removal efficiency at 99.3% with a low nitrite (NO2--N) accumulation at 25.5 mg/L was achieved at 0.6 mT MMF. The application of MMF facilitated the synthesis of adenosine triphosphate (ATP) and stimulated denitrifying enzymes (e.g., nitrate reductase (NAR), nitrite reductase (NIR), and nitric oxide reductase (NOR)), which thereby promoting denitrification. Moreover, the effluent chemical oxygen demand (COD), tryptophan and fulvic-like substances exhibited their lowest levels at 0.6 mT MMF. Analysis through 16S ribosomal ribonucleic acid gene sequencing indicated a significant enrichment of denitrifying bacteria including Castellaniella Klebsiella under the influence of MMF. Besides, the proliferation of Acholeplasma, Klebsiella and Proteiniphilum at 0.6 mT MMF promoted the hydrolysis and acidification of WMs. This study offers new insights into the enhanced utilization of WMs and the denitrification of HNW through the application of MMF.

Ameliorative effects of Modified Huangqi Chifeng decoction on podocyte injury via autophagy mediated by PI3K/AKT/mTOR and AMPK/mTOR pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Proteinuria is recognized as a risk factor for the exacerbation of chronic kidney disease. Modified Huangqi Chifeng decoction (MHCD) has distinct advantages in reducing proteinuria. Our previous experimental results have shown that MHCD can inhibit excessive autophagy. However, the specific mechanism by which MHCD regulates autophagy needs to be further explored. AIM OF THE STUDY: In this study, in vivo and in vitro experiments were conducted to further clarify the protective mechanism of MHCD on the kidney and podocytes by regulating autophagy based on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK)/mTOR signaling pathways. MATERIALS AND METHODS: By a single injection via the tail vein, Sprague-Dawley rats received Adriamycin (5 mg/kg) to establish a model of proteinuria nephropathy. They were divided into control, model, MHCD, 3-methyladenine (3 MA), 3 MA + MHCD, and telmisartan groups and were administered continuously for 6 weeks. The MHCD-containing serum was prepared, and a model of podocyte injury induced by Adriamycin (0.2 µg/mL) was established. RESULTS: MHCD reduced the 24-h urine protein levels and relieved pathological kidney damage. During autophagy in the kidneys of rats with Adriamycin-induced nephropathy, the PI3K/AKT/mTOR signaling pathway is inhibited, while the AMPK/mTOR signaling pathway is activated. MHCD antagonized these effects, thereby inhibiting excessive autophagy. MHCD alleviated Adriamycin-induced podocyte autophagy, as demonstrated using Pik3r1 siRNA and an overexpression plasmid for Prkaa1/Prkaa2. Furthermore, MHCD could activate the PI3K/AKT/mTOR signaling pathway while suppressing the AMPK/mTOR signaling pathway. CONCLUSIONS: This study demonstrated that MHCD can activate the interaction between the PI3K/AKT/mTOR and the AMPK/mTOR signaling pathways to maintain autophagy balance, inhibit excessive autophagy, and play a role in protecting the kidneys and podocytes.

A Novel Germline Mutation of BRCA1 and Integrated Analysis With Somatic Mutation in a Chinese Multi-Cancer Family.

The presence of mutations in the BRCA1 gene (MIM: 113705) is widely recognized as a significant genetic predisposition for ovarian cancer. This study investigated the genomic mutations in a Chinese family with a history of ovarian, breast, and rectal adenocarcinoma. A novel germline mutation (Phe1695Val) in BRCA1 was identified through whole-exome sequencing. Subsequently, we performed whole-genome sequencing to identify somatic mutations and analyze mutational signatures in individuals carrying the novel germline mutation. Our findings revealed a correlation between somatic mutational signatures and the BRCA1 germline mutation in the proband with ovarian cancer, while no such association was observed in the tumor tissue from the patient with breast cancer. Furthermore, distinct somatic driver mutations were identified, a truncated mutation in the TP53 gene in the ovarian tumor tissue, and a hotspot mutation in the PIK3CA gene in the breast cancer. According to our findings, the BRCA1 F1695V mutation is linked to ovarian cancer susceptibility in the family and causes specific somatic mutational profiles.

New strategy of personalized tissue regeneration: when autologous platelet concentrates encounter biomaterials.

Components in blood play an important role in wound healing and subsequent tissue regeneration processes. The fibrin matrix and various bioactive molecules work together to participate in this complex yet vital biological process. As a means of personalized medicine, autologous platelet concentrates have become an integral part of various tissue regeneration strategies. Here, we focus on how autologous platelet concentrates play a role in each stage of tissue healing, as well as how they work in conjunction with different types of biomaterials to participate in this process. In particular, we highlight the use of various biomaterials to protect, deliver and enhance these libraries of biomolecules, thereby overcoming the inherent disadvantages of autologous platelet concentrates and enabling them to function better in tissue regeneration.

Inhibition of excessive autophagy alleviates renal injury and inflammation in a rat model of immunoglobulin A nephropathy.

The pathogenesis of immunoglobulin A nephropathy (IgAN) is closely related to immunity and inflammation. The clinical process of IgAN varies greatly, making the assessment of prognosis challenging and limiting progress on effective treatment measures. Autophagy is an important pathway for the development of IgAN. However, the role of autophagy in IgAN is complex, and the consequences of autophagy may change during disease progression. In the present study, we evaluated the dynamic changes in autophagy during IgAN. Specifically, we examined autophagy in the kidney of a rat model of IgAN at different time points. We found that autophagy was markedly and persistently induced in IgAN rats, and the expression level of inflammation was also persistently elevated. The autophagy enhancer rapamycin and autophagy inhibitor 3-methyladenine were used in this study, and the results showed that 3-methyladenine can alleviate renal injury and inflammation in IgAN rats. Our study provides further evidence for autophagy as a therapeutic target for IgAN.

The cardioprotective effect of Shengmai Zhenwu decoction on patients with chronic heart failure based on the levels of soluble interleukin 1 receptor-like 1.

Objective: The purpose of this study was to evaluate the protective effect of Shengmai Zhenwu decoction on patients with chronic heart failure (CHF) based on the levels of soluble interleukin 1 receptor-like 1 (ST2). Methods: We included a total of 80 outpatients and inpatients with CHF who were undergoing treatment at the Shanghai Municipal Hospital of Traditional Chinese Medicine between March 2020 and March 2022. We randomly divided them into the observation group (n = 40) and the control group (n = 40). Patients in the control group received treatments as per conventional Western medicine, while those in the observation group were treated with the Shengmai Zhenwu decoction in conjunction with Western medicine for eight consecutive weeks. We then compared the pre- and post-treatment levels of ST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) of the patients in the two groups. Results: There were no significant differences in the pre-treatment levels of ST2 and NT-proBNP indexes between the two groups (P > 0.05), while the post-treatment comparison between the two groups in terms of ST2 and NT-proBNP levels suggested that the effect in the observation group was better, with statistical significance (P < 0.05). Conclusion: Shengmai Zhenwu decoction was beneficial in patients with CHF, suggesting that it could be a promising and effective method for the treatment of CHF.

UBE2C serves as a prognosis biomarker of uterine corpus endometrial carcinoma via promoting tumor migration and invasion.

The biological functions of ubiquitin-conjugating enzymes E2 (UBE2) family members in uterine corpus endometrial carcinoma (UCEC) remains unclear. Our study aimed to systematically analyze the expression patterns, prognostic value, biological functions and molecular regulatory mechanisms of UBE2 family in UCEC. Among nine screened UBE2 family members associated with UCEC, UBE2C was the most significantly overexpressed gene with poor prognosis. High expression levels of UBE2C in UCEC was correlated with stages, histological subtypes, patient's menopause status and TP53 mutation. Three molecules (CDC20, PTTG1 and AURKA), were identified as the key co-expression proteins of UBE2C. The generic alterations (mutation, amplification) and DNA hypomethylation might contribute to UBE2C's high expression in UCEC. Furthermore, in vitro experiments showed that the interference of UBE2C inhibited the migration and invasion of endometrial cancer cells, while partially impact cell proliferation and didn't impact the expression of epithelial-mesenchymal transition (EMT) markers. Using comprehensive bioinformatics analysis and in vitro experiments, our study provided a novel insight into the oncogenic role of UBE2 family, specifically UBE2C in UCEC. UBE2C might serve as an effective biomarker to predict poor prognosis and a potential therapeutic target in clinical practice.

Immunomodulatory Effect of Flammulina rossica Fermentation Extract on Healthy and Immunosuppressed Mice.

Flammulina rossica fermentation extract (FREP) was obtained by ethanol precipitation of the fermentation broth. The molecular weight of FREP is 28.52 kDa, and it mainly contains active ingredients such as polysaccharides, proteins, reducing sugars, and 16 amino acids. Among them, the polysaccharides were mannose, glucose, galactose, arabinose, and fucose and possessed ß-glycosidic bonds. Furthermore, the immunoregulatory activities of FREP were investigated in vivo. The results demonstrated that FREP could increase the counts of CD4+ T lymphocytes and the ratio of CD4+/CD8+ in a dose-dependent manner in healthy mice. In addition, FREP significantly increased serum cytokines, including IL-2, IL-8, IL-10, IL-12, IL-6, IL-1ß, INF-γ, C-rection protein, and TNF-α, and promoted splenocyte proliferation in healthy mice. Finally, FREP could restore the counts of white blood cells, red blood cells, secretory immunoglobulin A, and antibody-forming cells and significantly promote the serum haemolysin level in mice treated with cyclophosphamide. The findings indicated that FREP possessed immunoregulatory activity in healthy mice and could improve the immune functions in immunosuppressive mice. Therefore, FREP could be exploited as an immunomodulatory agent and potential immunotherapeutic medicine for patients with inadequate immune function.