Prognostic value of morning blood pressure surge in chronic kidney disease.

This was a retrospective study. This study investigated the occurrence of a composite endpoints (cardiovascular and cerebrovascular events, end-stage renal disease, and death) in 153 patients (aged ≥ 18 years) with a diagnosis of in chronic kidney disease (CKD). Based on morning blood pressure surge (MBPS) defined as ≥35 mm Hg, patients were divided into two groups: with MBPS (n = 50) and without MBPS (n = 103). All patients were followed up for at least 1 year. Baseline demographic, laboratory and follow-up data were collected. The clinical characteristics of the two groups were compared. The relationships between MBPS and endpoint events were analyzed using the Kaplan-Meier method and Cox regression model. In total, 153 patients (mean age 41.8 years; 56.86% males) were included in this study. During the follow-up period (mean 4.3 years), 34 endpoint events occurred. After adjustment for the covariates, the risk of cardiovascular and cerebrovascular events, end-stage renal disease and death remained significantly higher in patients with MBPS (hazard ratio [HR] and 95% confidence interval [CI] 3.124 [1.096-9.130]]) Among the other variables, systolic blood pressure, and night-time and daytime pulse pressures remained significantly associated with outcome in patients of CKD (1.789 [1.205-2.654], 1.710 [1.200-2.437], and 1.318 [1.096-1.586], respectively]. In conclusions, MBPS was identified as an independent prognostic factor for composite endpoint events (cardiovascular and cerebrovascular events, end-stage renal disease and death) patients with chronic kidney disease patients.

Drug-induced liver injury in children: A nationwide cohort study from China.

Background & Aims: Currently, there is limited knowledge on the clinical profile of drug-induced liver injury (DILI) in Chinese children. We aimed to assess the clinical characteristics, suspected drugs, and outcomes associated with pediatric DILI in China. Methods: This nationwide, multicenter, retrospective study, conducted between 2012 and 2014, analyzed 25,927 cases of suspected DILI at 308 medical centers using the inpatient medical register system. Utilizing the Roussel Uclaf causality assessment method score, only patients with scores ≥6 or diagnosed with DILI by three experts after scoring <6 were included in the analysis. Among them, 460 cases met the EASL biochemical criteria. The study categorized children into three age groups: toddlers (≥30 days to <6 years old), school-age children (6 to <12 years old), and adolescents (12 to <18 years old). Results: Hepatocellular injury was the predominant clinical classification, accounting for 63% of cases, with 34% of these cases meeting Hy's law criteria. Adolescents comprised the majority of children with moderate/severe DILI (65%). Similarly, adolescents faced a significantly higher risk of severe liver injury compared to younger children (adjusted odd ratios 4.75, p = 0.002). The top three most frequently prescribed drug classes across all age groups were antineoplastic agents (25.9%), antimicrobials (21.5%), and traditional Chinese medicine (13.7%). For adolescents, the most commonly suspected drugs were antitubercular drugs (22%) and traditional Chinese medicine (23%). Conclusion: Adolescents are at a greater risk of severe and potentially fatal liver injury compared to younger children. Recognizing the risk of pediatric DILI is crucial for ensuring safe medical practices. Impact and implications: Drug-induced liver injury, a poorly understood yet serious cause of pediatric liver disease, encompasses a spectrum of clinical presentations, ranging from asymptomatic liver enzyme elevation to acute liver failure. This retrospective study, utilizing a large Chinese cohort of pediatric liver injury cases from 308 centers nationwide, characterized the major clinical patterns and suspected drugs in detail, revealing that adolescents are at a greater risk of severe liver injury compared to younger children. Vigilant care and careful surveillance of at-risk pediatric patients are crucial for physicians, researchers, patients, caregivers, and policymakers. Additional multicenter prospective studies are needed to evaluate the risk of hepatotoxicity in outpatients and hospitalized pediatric patients.

Development of a microbial dewaxing agent using three spore forming bacteria.

Microbial enhanced oil recovery (MEOR) is a cost effective and efficient method for recovering residual oil. However, the presence of wax (paraffin) in residual oil can substantially reduce the efficiency of MEOR. Therefore, microbial dewaxing is a critical process in MEOR. In this study, a bacterial dewaxing agent of three spore-forming bacteria was developed. Among these bacteria, Bacillus subtilis GZ6 produced the biosurfactant surfactin. Replacing the promoter of the surfactin synthase gene cluster (srfA), increased the titer of surfactin in this strain from 0.33 g/L to 2.32 g/L. The genetically modified strain produced oil spreading rings with diameters increasing from 3.5 ± 0.1 to 4.1 ± 0.2 cm. The LadA F10L/N133R mutant was created by engineering an alkane monooxygenase (LadA) using site-directed mutagenesis in the Escherichia coli host. Compared to the wild-type enzyme, the resulting mutant exhibited an 11.7-fold increase in catalytic efficiency toward the substrate octadecane. When the mutant (pIMPpladA2mu) was expressed in Geobacillus stearothermophilus GZ178 cells, it exhibited a 2.0-fold increase in octadecane-degrading activity. Cultures of the two modified strains (B. subtilis GZ6 (pg3srfA) and G. stearothermophilus GZ178 (pIMPpladA2mu)) were mixed with the culture of Geobacillus thermodenitrificans GZ156 at a ratio of 5:80:15. The resulting composition increased the rate of wax removal by 35% compared to the composition composed of three native strains. This study successfully developed a multi-strain bacterial agent with enhanced oil wax removal capabilities by genetically engineering two bacterial strains.

Constructing CoP/Ni2P Heterostructure Confined Ru Sub-Nanoclusters for Enhanced Water Splitting in Wide pH Conditions.

Developing efficient electrocatalysts for water splitting is of great significance for realizing sustainable energy conversion. In this work, Ru sub-nanoclusters anchored on cobalt-nickel bimetallic phosphides (Ru-CoP/Ni2P) are constructed by an interfacial confinement strategy. Remarkably, Ru-CoP/Ni2P with low noble metal loading (33.1 µg cm-2) shows superior activity for hydrogen evolution reaction (HER) in all pH values, whose turnover frequency (TOF) is 8.7, 15.3, and 124.7 times higher than that of Pt/C in acidic, alkaline, and neutral conditions, respectively. Meanwhile, it only requires the overpotential of 171 mV@10 mA cm-2 for oxygen evolution reaction (OER) and corresponding TOF is 20.3 times higher than that of RuO2. More importantly, the Ru-CoP/Ni2P||Ru-CoP/Ni2P displays superior mass activity of 4017 mA mgnoble metal -1 at 2.0 V in flowing alkaline water electrolyzer, which is 105.1 times higher than that of Pt/C||IrO2. In situ Raman spectroscopy demonstrates that the Ru sites in Ru-CoP/Ni2P play a key role for water splitting and follow the adsorption evolution mechanism toward OER. Further mechanism studies disclose the confined Ru atom contributes to the desorption of H2 during HER and the formation of O-O bond during OER, leading to fast reaction kinetics. This study emphasizes the importance of interface confinement for enhancing electrocatalytic activity.

Sanguinarine Induces Necroptosis of HCC by Targeting PKM2 Mediated Energy Metabolism.

BACKGROUNDS: Abnormal metabolism is the hallmark of hepatocellular carcinoma. Targeting energy metabolism has become the major focus of cancer therapy. The natural product, sanguinarine, displays remarkable anti-tumor properties by disturbing energy homeostasis; however, the underlying mechanism has not yet been elucidated. METHODS: The anticancer activity of sanguinarine was determined using CCK-8 and colony formation assay. Morphological changes of induced cell death were observed under electron microscopy. Necroptosis and apoptosis related markers were detected using western blotting. PKM2 was identified as the target by transcriptome sequencing. Molecular docking assay was used to evaluate the binding affinity of sanguinarine to the PKM2 molecule. Furthermore, Alb-CreERT2; PKM2loxp/loxp; Rosa26RFP mice was used to construct the model of HCC-through the intervention of sanguinarine in vitro and in vivo-to accurately explore the regulation effect of sanguinarine on cancer energy metabolism. RESULTS: Sanguinarine inhibited tumor proliferation, metastasis and induced two modes of cell death. Molecular docking of sanguinarine with PKM2 showed appreciable binding affinity. PKM2 kinase activity and aerobic glycolysis rate declined, and mitochondrial oxidative phosphorylation was inhibited by sanguinarine application; these changes result in energy deficits and lead to necroptosis. Additionally, sanguinarine treatment prevents the translocation of PKM2 into the nucleus and suppresses the interaction of PKM2 with ß-catenin; the transcriptional activity of PKM2/ß-catenin signaling and its downstream genes were decreased. CONCLUSIONS: Sanguinarine showed remarkable anti-HCC activity via regulating energy metabolism by PKM2/ß-catenin signaling. On the basis of these investigations, we propose that sanguinarine might be considered as a promising compound for discovery of anti-HCC drugs.

Metagenomic analysis reveals altered gut virome and diagnostic potential in pancreatic cancer.

Pancreatic cancer (PC) is a highly aggressive malignancy with a poor prognosis, making early diagnosis crucial for improving patient outcomes. While the gut microbiome, including bacteria and viruses, is believed to be essential in cancer pathogenicity, the potential contribution of the gut virome to PC remains largely unexplored. In this study, we conducted a comparative analysis of the gut viral compositional and functional profiles between PC patients and healthy controls, based on fecal metagenomes from two publicly available data sets comprising a total of 101 patients and 82 healthy controls. Our results revealed a decreasing trend in the gut virome diversity of PC patients with disease severity. We identified significant alterations in the overall viral structure of PC patients, with a meta-analysis revealing 219 viral operational taxonomic units (vOTUs) showing significant differences in relative abundance between patients and healthy controls. Among these, 65 vOTUs were enriched in PC patients, and 154 were reduced. Host prediction revealed that PC-enriched vOTUs preferentially infected bacterial members of Veillonellaceae, Enterobacteriaceae, Fusobacteriaceae, and Streptococcaceae, while PC-reduced vOTUs were more likely to infect Ruminococcaceae, Lachnospiraceae, Clostridiaceae, Oscillospiraceae, and Peptostreptococcaceae. Furthermore, we constructed random forest models based on the PC-associated vOTUs, achieving an optimal average area under the curve (AUC) of up to 0.879 for distinguishing patients from controls. Through additional 10 public cohorts, we demonstrated the reproducibility and high specificity of these viral signatures. Our study suggests that the gut virome may play a role in PC development and could serve as a promising target for PC diagnosis and therapeutic intervention. Future studies should further explore the underlying mechanisms of gut virus-bacteria interactions and validate the diagnostic models in larger and more diverse populations.

Varied cellular abnormalities in thin vs. normal endometrium in recurrent implantation failure by single-cell transcriptomics.

BACKGROUND: Reduced endometrium thickness and receptivity are two important reasons for recurrent implantation failure (RIF). In order to elucidate differences between these two types of endometrial defects in terms of molecular signatures, cellular interactions, and structural changes, we systematically investigated the single-cell transcriptomic atlas across three distinct groups: RIF patients with thin endometrium (≤ 6 mm, TE-RIF), RIF patients with normal endometrium thickness (≥ 8 mm, NE-RIF), and fertile individuals (Control). METHODS: The late proliferative and mid-secretory phases of the endometrium were collected from three individuals in the TE-RIF group, two in the NE-RIF group, and three in the control group. The study employed a combination of advanced techniques. Single-cell RNA sequencing (scRNA-seq) was utilized to capture comprehensive transcriptomic profiles at the single-cell level, providing insights into gene expression patterns within specific cell types. Scanning and transmission electron microscopy were employed to visualize ultrastructural details of the endometrial tissue, while hematoxylin and eosin staining facilitated the examination of tissue morphology and cellular composition. Immunohistochemistry techniques were also applied to detect and localize specific protein markers relevant to endometrial receptivity and function. RESULTS: Through comparative analysis of differentially expressed genes among these groups and KEGG pathway analysis, the TE-RIF group exhibited notable dysregulations in the TNF and MAPK signaling pathways, which are pivotal in stromal cell growth and endometrial receptivity. Conversely, in the NE-RIF group, disturbances in energy metabolism emerged as a primary contributor to reduced endometrial receptivity. Additionally, using CellPhoneDB for intercellular communication analysis revealed aberrant interactions between epithelial and stromal cells, impacting endometrial receptivity specifically in the TE-RIF group. CONCLUSION: Overall, our findings provide valuable insights into the heterogeneous molecular pathways and cellular interactions associated with RIF in different endometrial conditions. These insights may pave the way for targeted therapeutic interventions aimed at improving endometrial receptivity and enhancing reproductive outcomes in patients undergoing ART. Further research is warranted to validate these findings and translate them into clinical applications for personalized fertility treatments. TRIAL REGISTRATION: Not applicable.

Metagenomic analysis of the gut virome in patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder, is recognized for its association with alterations in the gut microbiome and metabolome. This study delves into the largely unexplored domain of the gut virome in IBS patients. We conducted a comprehensive analysis of the fecal metagenomic data set from 277 IBS patients and 84 healthy controls to characterize the gut viral community. Our findings revealed a distinct gut virome in IBS patients compared to healthy individuals, marked by significant variances in between-sample diversity and altered abundances of 127 viral operational taxonomic units (vOTUs). Specifically, 111 vOTUs, predominantly belonging to crAss-like, Siphoviridae, Myoviridae, and Quimbyviridae families, were more abundant in IBS patients, whereas the healthy control group exhibited enrichment of 16 vOTUs from multiple families. We also investigated the interplay between the gut virome and bacteriome, identifying a correlation between IBS-enriched bacteria like Klebsiella pneumoniae, Fusobacterium varium, and Ruminococcus gnavus, and the IBS-associated vOTUs. Furthermore, we assessed the potential of gut viral signatures in predicting IBS, achieving a notable area under the receiver operator characteristic curve (AUC) of 0.834. These findings highlight significant shifts in the viral diversity, taxonomic distribution, and functional composition of the gut virome in IBS patients, suggesting the potential role of the gut virome in IBS pathogenesis and opening new avenues for diagnostic and therapeutic strategies targeting the gut virome in IBS management.

Pregnant patient with Xp11.2/transcription factor E3 translocation renal cell carcinoma: a case report and literature review.

MiT family translocation renal cell carcinomas (tRCCs) primarily include Xp11.2/transcription factor E3 (TFE3) gene fusion-associated renal cell carcinoma (Xp11.2 tRCC) and t(6;11)/TFEB gene fusion-associated RCC. Clinical cases of these carcinomas are rare. Fluorescence in situ hybridization can be used to identify the type, but there are no standard diagnostic and treatment methods available, and the prognosis remains controversial. Herein, we present a case of a patient with Xp11.2 tRCC at 29 weeks of gestation. The baby was successfully delivered, and radical surgery was performed for renal cancer at the same time. This is a unique and extremely rare case. We have described the case and performed a literature review to report the progress of current research on the treatment and prognosis of pregnant patients with Xp11.2/TFE3 translocation renal cell carcinoma. This study aims to contribute to improving the diagnosis and treatment of Xp11.2 tRCC in pregnant patients.

Milk Fat Globule-EGF Factor 8 (MFGE8) Mitigates Cognitive Impairment in Rats with Sepsis-Associated Encephalopathy: An fMRI Study.

BACKGROUND: Sepsis-associated encephalopathy (SAE) impairs hippocampal microglial efferocytosis, causing cognitive deficits. Previous research found that milk fat globule epidermal growth factor 8 protein (MFGE8) stimulates efferocytosis, reducing hippocampal inflammation in SAE rats. In this study, we explore MFGE8's role in alleviating cognitive impairment and its impact on neural activity using functional magnetic resonance imaging (fMRI). METHODS: Sixty male Sprague Dawley rats were divided into four groups: Sham, cecal ligation and puncture (CLP), CLP+MFGE8, and CLP+MFGE8+CGT (Cilengitide). After CLP, CLP+MFGE8 rats received intracerebroventricular MFGE8 (3.3 µg), while CLP+MFGE8+CGT rats received intraperitoneal Cilengitide (10 mg/kg). We assessed cognitive function with the Morris water maze and open field test over five days. Eight days post-surgery, rats underwent T2-weighted magnetic resonance imaging (MRI) and resting state (rs)-fMRI scans. Brain tissues were collected for western blot, hematoxylin-eosin (HE) staining, and immunofluorescence. Statistical analysis employed one-way analysis of variance (ANOVA) followed by Tukey's post-test for multiple comparisons. RESULTS: MFGE8 improved neurobehavioral performance in open field task (OFT) and morris water maze (MWM) tests. fMRI indicated a significant reduction in abnormal neural activity in the right hippocampal CA1, CA3, and dentate gyrus of SAE rats following MFGE8 treatment. Voxel-based morphometry (VBM) analysis revealed decreased high-signal areas in the hippocampus, along with reduced hippocampal volume due to alleviated neural edema. Western blot analysis demonstrated that MFGE8 enhanced ras-related C3 botulinum toxin substrate 1 (Rac1) and microtubule-associated protein 1A/1B-light chain 3 (LC3) expression in the rat hippocampus, while CGT reduced these protein levels. Behavioral experiments and fMRI results confirmed that CGT reversed the cognitive effects of MFGE8 by inhibiting microglial αVß3/αVß5 integrin receptors. CONCLUSIONS: Our findings show that MFGE8 reduced amplitude of low-frequency fluctuations (ALFF) values in the right hippocampal CA1, CA3, and the dentate gyrus, mitigating abnormal neural activity and decreasing hippocampal volume. This led to an improvement in cognitive dysfunction in SAE rats. These results suggest that MFGE8 enhances microglial efferocytosis by activating αVß3 and αVß5 integrin receptors on microglial surfaces, ultimately improving cognitive function in SAE rats.

Differential prognostic impact and potential molecular mechanisms of PCDHGA12 expression in lung adenocarcinoma and squamous cell carcinoma.

Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), subtypes of non-small cell lung cancer (NSCLC), exhibit distinct characteristics. The expression and prognostic significance of Protocadherin Gamma Subfamily A, 12 (PCDHGA12) in NSCLC remain unexplored. This study analyzed transcriptomic and genomic datasets from TCGA to investigate PCDHGA12 expression and its prognostic relevance in LUAD and LUSC. We found PCDHGA12 mRNA and protein levels were downregulated in both LUAD and LUSC tissues compared to adjacent non-cancerous tissues, with high PCDHGA12 expression correlating with lower overall survival in LUSC but not in LUAD. GSEA revealed a unique enrichment pattern associated with PCDHGA12 low expression in LUSC, especially in the DNA repair pathway. Co-expression analysis showed associations of PCDHGA12 with focal adhesion and the PI3K-AKT pathway in LUAD, and additionally with ECM-receptor interaction in LUSC. Hub gene prognosis analysis identified genes correlated with prognosis only in LUSC, reflecting PCDHGA12's influence. Mutation analysis linked with PCDHGA12 identified differential mutations in SPTA1, KEAP1, and TNR in LUAD, and a notable NAV3 mutation in LUSC. Additionally, immuno-infiltration analysis reveals a positive correlation between PCDHGA12 expression and immune cell infiltration. Specifically, lower PCDHGA12 expression in LUSC is associated with higher levels of CD8 T cells and DCs, lower levels of Tregs and M0 macrophages, and increased expression of HMGB1 and TNFRSF18. These genetic and immunological differences may account for the significant prognostic disparity of PCDHGA12 levels between LUAD and LUSC. Further experimental studies are essential to validate these associations and investigate potential targeted and immunotherapeutic strategies.

Module-combinatorial design and screening of multifunctional polymers based on polyaspartic acid for DNA delivery.

It is crucial to develop non-viral gene vectors that can efficiently and safely transfect plasmid DNA into cells. Low transfection efficiency and high cytotoxicity of cationic polymers hinder their application as gene carriers. Modification of cationic polymers has emerged as an attractive strategy for efficient and safe nucleic acids delivery. In this study, a simple and rapid method is developed to synthesize a series of multifunctional polymers by utilizing biodegradable polyaspartic acid as the backbone and modifying it with three modules. This one-component polymer possesses capabilities for nucleic acid condensation, cellular uptake, and endosomal escape. Polymers containing imidazole, triazole, or pyridine group exhibited promising transfection activity. Substituted with dodecylamine or 2-hexyldecan-1-amine enhance cellular uptake and subsequent transfection. Furthermore, the influence of ionizable amine side chains on gene delivery is investigated. Two optimal polymers, combined with the avian encephalomyelitis virus (AEV) plasmid vaccine, induced robust specific antibody responses and cellular immune responses in mice and chickens. Through module-combination design and screening of polyaspartamide polymers, this study presents a paradigm for the development of gene delivery vectors.

De novo biosynthesis of ß-arbutin in Corynebacterium glutamicum via pathway engineering and process optimization.

BACKGROUND: ß-Arbutin, a hydroquinone glucoside found in pears, bearberry leaves, and various plants, exhibits antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. ß-Arbutin has wide applications in the pharmaceutical and cosmetic industries. However, the limited availability of high-performance strains limits the biobased production of ß-arbutin. RESULTS: This study established the ß-arbutin biosynthetic pathway in C. glutamicum ATCC13032 by introducing codon-optimized ubiC, MNX1, and AS. Additionally, the production titer of ß-arbutin was increased by further inactivation of csm and trpE to impede the competitive metabolic pathway. Further modification of the upstream metabolic pathway and supplementation of UDP-glucose resulted in the final engineered strain, C. glutamicum AR11, which achieved a ß-arbutin production titer of 7.94 g/L in the optimized fermentation medium. CONCLUSIONS: This study represents the first successful instance of de novo ß-arbutin production in C. glutamicum, offering a chassis cell for ß-arbutin biosynthesis.

Treatment of Tislelizumab-Induced Toxic Epidermal Necrolysis and Agranulocytosis: A Case Report and Literature Review.

BACKGROUND: Non-small Cell Lung Cancer (NSCLC) makes up about 85% of lung cancer cases, mainly adenocarcinoma and squamous cell carcinoma. Recently, PD-1 inhibitors have become crucial in NSCLC treatment, significantly enhancing survival for some. However, side effects, like skin reactions and hematotoxicity, limit their use, with drug-induced TEN and immunotherapy-induced agranulocytosis as severe adverse effects. CASE PRESENTATION: Herein, we have reported the case of a 75-year-old male diagnosed with metastatic Lung Squamous cell Carcinoma (LUSC) in the left lung. He received first-line treatment with one cycle of tislelizumab in combination with nab-paclitaxel and carboplatin, after which he developed Toxic Epidermal Necrolysis (TEN) and granulocytopenia. To address these two serious immune-related Adverse Events (irAEs), the patient was administered methylprednisolone in combination with gamma globulin for TEN and dexamethasone in combination with G-CSF for agranulocytosis. Antibiotics were also administered according to the patient's medication regimen. After treatment, the patient recovered and was discharged from the hospital. It was also noted that the lung tumor condition improved. CONCLUSION: Effective management of severe immune-related side effects from tislelizumab, including TEN and agranulocytosis, can be partly achieved through steroids, gamma globulin, GCSF, and antibiotics. This strategy not only alleviates these adverse effects, but also potentially improves tumor conditions, highlighting the crucial role of vigilant monitoring and management in immunotherapy.

The identification of arsenic species produced in the dissolution of crystalline orpiment under anoxic conditions: XAS evidence.

The orpiment (As2S3) is an important secondary mineral in the geochemical process of arsenic (As) in the environment. The dissolution of orpiment has a close relationship with the migration and transformation of As. The dissolved species of As2S3 is closely related to sulfide (S-II) in the anoxic and sulfidic environment. This paper focuses on the various As species formed when As2S3 dissolved in the presence and absence of excess S-II under anoxic conditions with simulation tests via X-ray absorption spectroscopy (XAS), liquid chromatography with (hydride generation) atomic fluorescence spectrophotometry, and Raman spectroscopy. The results showed that the As produced when As2S3 dissolved in the excess S-II contained a mixture of arsenite and thioarsenite (ThioAsIII). Based on the linear combination fitting, ThioAsIII is the dominant As species (88.2 %) with arsenite as the leftover component. However, the percentage of ThioAsIII decreased to 43.7 % if As2S3 dissolved in the absence of excess S-II, indicting ThioAsIII favored under sulfidic conditions. The findings may give further insights about the role and formation mechanism of ThioAsIII in the dissolution process of As2S3. ENVIRONMENTAL IMPLICATION: The dissolution of crystallization orpiment has a close relationship with the transport of As in the environment. Qualitatively and quantitatively identification of the dissolved species of As2S3 in the presence and absence of excess S-II may be helpful for a better understanding and predicting the fate of As. The formed trithioarsenite was the dominant dissolved species compared to arsenite in the sulfidic system. It has higher mobility than AsV and AsIII, and has been found in many As-related adsorption/desorption and redox reactions. Therefore, great cautions should be given when choosing technologies to remediate the As contaminated soils and waters.

Therapeutic effect of Corbrin (Bailing) capsule on patients with renal insufficiency: A meta-analysis.

Objective: At present, there remains controversy regarding the clinical efficacy of Corbrin (Bailing) capsules in the treatment of renal insufficiency (RI). A meta-analytic approach was adopted in this study to assess the clinical efficacy of Corbrin capsules for treating RI, aiming to provide a certain level of clinical evidence to guide the selection of RI therapeutic interventions. Methods: The meta-analysis was conducted on databases containing PubMed, CNKI, Weipu Database, Cochrane Library and Wanfang until January 2023. The search for relevant studies was conducted without language restrictions. The study encompassed a randomized controlled trial that examined the efficacy of Corbrin capsules in treating RI. Blood urea nitrogen (BUN), serum creatinine (Scr), 24-h urine protein quantity (24 h UPQ), and estimated creatinine clearance (ECC) were amalgamated using standardized mean difference (SMD) and its corresponding 95 % confidence interval (CI). Meanwhile, the treatment effect (TE) outcome was aggregated using odds ratio (OR) and its corresponding 95 % CI. To evaluate heterogeneity, the Q test and I2 statistics were employed within a random-effects model framework. Results: A total of 11 eligible articles were included, involving 1100 patients (594 in the Corbrin capsule group and 516 in the control group). Compared with control subjects, the SMD was-1.3532 for Ser (95 % CI: 2.0617 to -0.6448), -1.7868 for UPQ (95 % CI: 2.8901 to -0.6836), -1.3302 for BUN (95 % CI: 2.2428 to -0.4176), and 1.7842 for ECC (95 % CI: 0.6774-2.8910). TE had an OR of 1.9786 (95 % CI: 0.7153-5.4734), and publications were not found to be biased (t = 0.5627, P = 0.6738). Conclusion: In RI patients, Corbrin capsule has a relatively good therapeutic effect.

Pregnant outcomes of patients with positive anticentromere antibodies receiving in vitro fertilization-embryo transfer. / æŠ—ç€ä¸ç‚¹æŠ—ä½“é˜³æ€§æ‚£è€ ä½“å¤–å—ç²¾ç»“å±€åˆ†æž.

OBJECTIVES: To analyze the pregnant outcomes in patients with positive anti-centromere antibody (ACA) receiving in vitro fertilization (IVF) -embryo transfer (ET) and natural conception. METHODS: A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received in vitro fertilization-embryo transfer therapy and had the results of antinuclear antibody (ANA) spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023. Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching. Embryo outcomes of IVF were compared between the two groups, and the impact of different fertilization methods and the use of immunosuppressants on pregnant outcomes were analyzed using self-matching analysis. The natural conception and disease progress were followed up for ACA-positive patients after IVF failure. RESULTS: The ACA-positive patients accounted for 0.86% of all IVF patients (34/3955) and 2.51% of total ANA-positive IVF patients. Regardless of whether patients received conventional IVF (c-IVF) or intracytoplasmic sperm injection (ICSI), the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group (both P<0.01). Moreover, the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos (both P<0.05). In 5 cases of ACA-positive patients who underwent ICSI cycles, the double pronuclei rate did not increase compared to c-IVF cycles (P>0.05), and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos (both P<0.05). After 1-2 months of immunosuppressant treatment, 12 ACA-positive patients underwent c-IVF/ICSI again, and there were no changes in egg retrieval and fertilization before and after medication (both P>0.05), but there was an improvement in the 2PN embryo cleavage rate (P<0.05). The number of embryos transferred was similar between the ACA-positive and negative groups, but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group (both P<0.05), with no significant difference in miscarriage rate between the two groups (P>0.05). Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure, resulting in a total of 7 cases of clinical pregnancy. CONCLUSIONS: Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes, with no improvement observed with ICSI and immunosuppressant use. However, ACA-positive patients may still achieve natural pregnancy.

Production and Functional Analysis of Collagen Hexapeptide Repeat Sequences in Pichia pastoris.

In the development of biomaterials with specific structural domains associated with various cellular activities, the limited integrin specificity of commonly used adhesion sequences, such as the RGD tripeptide, has resulted in an inability to precisely control cellular responses. To overcome this limitation, we conducted multiple replications of the integrin α2ß1-specific ligand, the collagen hexapeptide Gly-Phe-Pro-Gly-Glu-Arg (GFPGER) in Pichia pastoris. This enabled the development of recombinant collagen with high biological activity, which was subsequently expressed, isolated, and purified for structural and functional analysis. The proteins carrying the multiple replications GFPGER sequence demonstrated significant bioactivity in cells, leading to enhanced cell adhesion, osteoblast differentiation, and mineralization when compared to control groups. Importantly, these effects were mediated by integrin α2ß1. The new collagen constructed in this study is expected to be a biomaterial for regulating specific cell functions and fates.

Landscape of gut mucosal immune cells showed gap of follicular or memory B cells into plasma cells in immunological non-responders.

BACKGROUND: The gut is an important site for human immunodeficiency virus (HIV) infection and immune responses. The role of gut mucosal immune cells in immune restoration in patients infected with HIV undergoing antiretroviral therapy remains unclear. METHODS: Ileocytes, including 54 475 immune cells, were obtained from colonoscopic biopsies of five HIV-negative controls, nine immunological responders (IRs), and three immunological non-responders (INRs) and were analyzed using single-cell RNA sequencing. Immunohistochemical assays were performed for validation. The 16S rRNA gene was amplified using PCR in faecal samples to analyze faecal microbiota. Flow cytometry was used to analyze CD4+ T-cell counts and the activation of T cells. RESULTS: This study presents a global transcriptomic profile of the gut mucosal immune cells in patients infected with HIV. Compared with the IRs, the INRs exhibited a lower proportion of gut plasma cells, especially the IGKC+IgA+ plasma cell subpopulation. IGKC+IgA+ plasma cells were negatively associated with enriched f. Prevotellaceae the INRs and negatively correlated with the overactivation of T cells, but they were positively correlated with CD4+ T-cell counts. The INRs exhibited a higher proportion of B cells than the IRs. Follicular and memory B cells were significantly higher in the INRs. Reduced potential was observed in the differentiation of follicular or memory B cells into gut plasma cells in INRs. In addition, the receptor-ligand pairs CD74_MIF and CD74_COPA of memory B/ follicular helper T cells were significantly reduced in the INRs, which may hinder the differentiation of memory and follicular B cells into plasma cells. CONCLUSIONS: Our study shows that plasma cells are dysregulated in INRs and provides an extensive resource for deciphering the immune pathogenesis of HIV in INRs. KEY POINTS: An investigation was carried out at the single-cell-level to analyze gut mucosal immune cells alterations in PLWH after ART. B cells were significantly increased and plasma cells were significantly decreased in the INRs compared to the IRs and NCs. There are gaps in the transition from gut follicular or memory B cellsinto plasma cells in INRs.