The SAR analysis of dietary polyphenols and their antagonistic effects on bortezomib at physiological concentrations.

Background: Bortezomib (BTZ), a primary treatment for MM, but its effectiveness can be reduced by interactions with vicinal diol moieties (VDMs) in polyphenols. Despite this, it's debated whether BTZ therapy necessitates avoiding polyphenol-rich products, given the low bioavailability of polyphenols. Additionally, it remains unclear whether the structure of polyphenols contributes to their BTZ antagonism. Therefore, our study aims to unravel the structure-activity relationship of dietary polyphenols and their BTZ antagonism at daily diet-achievable physiological concentrations. Methods: We assessed the antagonistic effects of 25 polyphenols against BTZ using cell viability assays in RPMI 8226 cells. ChemGPS-NP helped analyze the structural similarity. Additionally, long-term cytotoxicity assays evaluated these effects at physiologically relevant concentrations. Results: By cell viability assays, we found a positive correlation between the number of VDMs in gallotannins and their BTZ antagonism. Moreover, the origin and configuration of VDMs, rather than the total VDM concentration, play a pivotal role in the combined antagonistic effects against BTZ in gallotannins. Additionally, ChemGPS-NP analysis indicated that the aromaticity and C-3 hydroxyl group in flavonoids' C-rings enhance their BTZ antagonism. Finally, long-term cytotoxicity assays reveal that gallic acid (GA), epigallocatechin (EGC), and epigallocatechin gallate (EGCG), at their physiological concentrations-attainable through tea consumption-significantly and synergistically antagonize BTZ. Conclusion: Due to the potential for these polyphenols to reduce the effectiveness of BTZ, it is advisable for MM patients undergoing BTZ treatment to reduce their consumption of foods high in VDM-containing polyphenols.

Risk of mortality associated to chronic kidney disease in patients with complete left bundle branch block.

Chronic kidney disease (CKD) is associated with cardiac conduction defects and is a strong risk factor for heart failure. Complete left bundle branch block (cLBBB), a cardiac conduction abnormality, may have an unfavorable effect on ventricular mechanical synchrony and lead to the progression of heart failure. Once heart failure develops, it seems to act together with underlying CKD in a vicious circle. Therefore, this study aimed to explore the influence of CKD in patients with cLBBB by assessing the estimated glomerular filtration rate (eGFR). We examined a hospital-based sample of 416 adult patients with cLBBB from 2010 to 2013. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cox proportional hazard models were used to estimate the hazard ratio for all-cause mortality and cardiovascular mortality. A total of 416 adult patients with a mean age of 71 ± 13 years were enrolled. The median follow-up period was 3.6 years. After adjusting for clinical, electrocardiographic parameters, and medication use, cox regression analysis showed that total mortality was significantly associated with older age (Hazard Ratio (HR) = 1.03, 95% CI = 1.01-1.05, p = 0.002), presence of congestive heart failure (HR = 2.39, 95% CI = 1.63-3.49, p < 0.001), advanced CKD (HR = 2.48, 95% CI = 1.71-3.59, p < 0.001), higher HR (HR = 1.02, 95% CI = 1.01-1.03, p < 0.001) and without use of ACEI/ARB (HR = 0.59, 95% CI = 0.41-0.85, p = 0.005) were independent predictors of the total mortality. Multivariate Cox hazard regression analysis demonstrated that, in comparison to patients lacking cLBBB, the coexistence of CKD (eGFR < 60 mL/min/1.73 m2) among those with LBBB significantly heightened the risks of both total mortality (HR ratio of 5.01 vs. 2.40) and CV death (HR ratio of 61.78 vs. 14.41) even following adjustment for clinical covariates and ECG parameters. In summary, within patients exhibiting cLBBB, the presence of CKD serves as a significant risk factor for all-cause mortality.

Pre-treatment with tocilizumab reduces lipopolysaccharide-induced acute lung injury in biliary cirrhotic rats.

Infection-related lipopolysaccharide (LPS) release causes cytokine storm and acute lung injury. Emerging data show that the interleukin 6 (IL-6) inhibitor tocilizumab can improve lung damage in patients with sepsis. This study aimed to investigate the therapeutic effect of tocilizumab on acute lung injury in cirrhotic rats. Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Tocilizumab was administered on post-operative day 21, and LPS was injected intraperitoneally on day 29. Three hours after LPS injection, hemodynamic parameters, biochemistry data, and arterial blood gas analysis were evaluated, along with measurements of IL-6 and tumor necrosis factor-α (TNF-α). Liver and lung histology was examined, and protein levels were analyzed. LPS administration reduced portal pressure, portal venous flow and cardiac index in the BDL rats. In addition, LPS administration induced acute lung injury, hypoxia and elevated TNF-α and IL-6 levels. Pre-treatment with tocilizumab did not affect hemodynamic and biochemistry data, but it ameliorated lung injury and decreased TNF-α, IL-6, and CD68-positive macrophage infiltration. Moreover, tocilizumab administration improved hypoxia and gas exchange in the BDL rats, and downregulated hepatic and pulmonary inflammatory protein expression. In conclusion, LPS administration induced acute lung injury in biliary cirrhotic rats. Pre-treatment with tocilizumab reduces lung damage and hypoxia, possibly by downregulating inflammatory proteins and reducing IL-6, TNF-α and CD68-positive macrophage recruitment in the lung.

Identification of key physicochemical properties and volatile flavor compounds for the sensory formation of roasted tilapia.

Tilapia is suitable for industrial roasting production because of its good flavor and processing adaptability. In this study, the key physicochemical properties and volatile compounds for sensory formation of roasted tilapia were identified after roasting condition optimization. The highest sensory score was obtained at 215 °C, 45 min, and 4% oil. During roasting, the a*, b*, hardness, chewiness, and oxidation of proteins and lipids significantly increased, the moisture content decreased, and the myofibrillar protein aggregation was observed by scanning electron microscope. After identification and quantification by headspace-gas chromatography-ion mobility spectrometry, 10 compounds with odor active value ≥1 were selected as characteristic flavor compounds. The correlation network indicated that the sensory formation mainly resulted from Maillard reaction, myofibrillar protein aggregation, and improvement of pleasant volatile flavor compounds induced by oxidation of proteins and lipids and water loss. This study provides an important theoretical basis and technical support for roasted tilapia production.

Depressive symptom mediates the association between the number of chronic diseases and cognitive impairment: a multi-center cross-sectional study based on community older adults.

Objective: The purpose of this study was to understand the relationship between the multiple chronic conditions (MCC), mental health and cognitive function of older adults in the community, and to propose a hypothesis that depressive symptom mediate the number of chronic diseases and cognitive impairment in older adults. Method: Participants aged 65 years and older from 35 communities in 14 cities in Guangxi, China were recruited. The residents' depressive symptom (PHQ-9) and cognitive status (AD-8) were evaluated, Chi-square test was used to explore the effects of different socio-demographic characteristics on depressive symptom and cognitive impairment. Pearson correlation analysis and the process model 4 were used to explore the relationship between the number of chronic diseases, depressive symptom and cognitive impairment. Result: A total of 11,582 older adults were included in our analysis. The rate of MCC reaching 26.53%. Hypertension combined with diabetes accounts for the highest proportion of two chronic diseases (13.2%). Among the combination of three chronic diseases, the highest incidence of coexisting hypertension combined with cervical/lumbar spondylosis, and rheumatoid arthritis (7.1%). In this study, depression symptoms accounted for 12.9% of older adults aged 65 and above, and cognitive impairment accounted for 27.4%. Female, older age, reside in urban areas, lower educational levels, no spouse, live alone, and MCC were risk factors for depressive symptom and cognitive impairment in older adults (P<0.05). Depressive symptom had a mediating effect in the number of chronic diseases and cognitive impairment, and the mediating effect (1.109) accounted for 44.13% of the total effect (0.247). Conclusion: The mental health of the older adult needs to be taken seriously, and improving depressive symptom can reduce the occurrence of cognitive impairment in older patients with MCC to a certain extent.

Interaction between the albumin-bilirubin score and nutritional risk index in the prediction of post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is the most common postoperative complication and the leading cause of death after hepatectomy. The albumin-bilirubin (ALBI) score and nutritional risk index (NRI) have been shown to assess end-stage liver disease and predict PHLF and patient survival. We hypothesized that the ALBI score and NRI interact in the prediction of PHLF. AIM: To analyze the interaction between the ALBI score and NRI in PHLF in patients with hepatocellular carcinoma. METHODS: This retrospective study included 186 patients who underwent hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Youjiang Medical University for Nationalities between January 2020 and July 2023. Data on patient characteristics and laboratory indices were collected from their medical records. Univariate and multivariate logistic regression were performed to determine the interaction effect between the ALBI score and NRI in PHLF. RESULTS: Of the 186 patients included in the study, PHLF occurred in 44 (23.66%). After adjusting for confounders, multivariate logistic regression identified ALBI grade 2/3 [odds ratio (OR) = 73.713, 95% confidence interval (CI): 9.175-592.199] and NRI > 97.5 (OR = 58.990, 95%CI: 7.337-474.297) as risk factors for PHLF. No multiplicative interaction was observed between the ALBI score and NRI (OR = 0.357, 95%CI: 0.022-5.889). However, the risk of PHLF in patients with ALBI grade 2/3 and NRI < 97.5 was 101 times greater than that in patients with ALBI grade 1 and NRI ≥ 97.5 (95%CI: 56.445-523.839), indicating a significant additive interaction between the ALBI score and NRI in PHLF. CONCLUSION: Both the ALBI score and NRI were risk factors for PHLF, and there was an additive interaction between the ALBI score and NRI in PHLF.

Correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 diabetic nephropathy.

Background: Diabetic nephropathy (DN) and diabetic retinopathy (DR) are common microvascular complications of diabetes. The purpose of this study was to investigate the correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 DN and to determine the capacity of retinal vascular geometric parameters in differentiating DN from non-diabetic renal disease (NDRD). Methods: The study participants were adult patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease who underwent a renal biopsy. Univariate and multivariable regression analyses were performed to evaluate associations between retinal vessel geometry parameters and pathologically diagnosed DN. Multivariate binary logistic regression analyses were performed to establish a differential diagnostic model for DN. Results: In total, 403 patients were examined in this cross-sectional study, including 152 (37.7%) with DN, 157 (39.0%) with NDRD and 94 (23.3%) with DN combined with NDRD. After univariate logistic regression, total vessel fractal dimension, arteriolar fractal dimension and venular fractal dimension were all found to be associated with DN. In multivariate analyses adjusting for age, sex, blood pressure, diabetes, DR and other factors, smaller retinal vascular fractal dimensions were significantly associated with DN (P < .05). We developed a differential diagnostic model for DN combining traditional clinical indicators and retinal vascular geometric parameters. The area under the curve of the model established by multivariate logistic regression was 0.930. Conclusions: Retinal vessel fractal dimension is of great significance for the rapid and non-invasive differentiation of DN. Incorporating retinal vessel fractal dimension into the diagnostic model for DN and NDRD can improve the diagnostic efficiency.

ADH4-a potential prognostic marker for hepatocellular carcinoma with possible immune-related implications.

OBJECTIVE: This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment. METHODS: HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues. RESULTS: ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy. CONCLUSION: This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.

Application of 11/13Fr suctioning ureteral access sheath and 8.55Fr single-use digital flexible ureteroscope in one-stage flexible ureteroscopic lithotripsy: an initial experience of 900 cases.

OBJECTIVES: To report our initial experience of one-stage flexible ureteroscopic lithotripsy(FURL) with 11/13Fr suctioning ureteral access sheath(UAS) and 8.55Fr single-use digital flexible ureteroscope(SDFU) in upper ureteral or renal calculi. MATERIALS AND METHODS: We retrospectively collected the clinical data of 900 adult patients with upper ureteral or renal calculi treated by FURL with 11/13Fr suctioning UAS and 8.55Fr SDFU from January 2022 to April 2024. Demographics, peri- and postoperative outcomes were assessed. RESULTS: In all, 40 of 940 cases(4.26%) failed to introduce UAS and required second-stage FURL because of ureterostenosis and were excluded. Mean stones size of the remaining 900 eligible cases was 1.68 ± 0.58 cm in greatest diameter. There were 228 cases of upper ureteral stone, 456 cases of renal stone and 216 cases of concomitant ureteral and renal calculi. The mean operation time was 52.20 ± 20.21 min and the postoperative hospital stay was 2.87 ± 1.37 days. The stone-free rate of 1 month postoperatively was 89.56% and only 2.44% of patients with residue underwent additional reoperation. The rate of postoperative fever, postoperative pain needing analgesic and slight ureteral mucosal injury were 5.11%, 8.22% and 7.78%, respectively. None of patient suffered from severe complications, such as sepsis or ureteral perforation. CONCLUSION: It's practical and suitable for the vast majority of adult patients to undergo FURL in single session with 11/13Fr suctioning UAS without preoperative stenting. FURL with 11/13Fr suctioning UAS and 8.55Fr SDFU is feasible, reliable, safe, and efficient in the management of renal stone and upper ureteral stone.

Zn2+ chelating peptide GFLGSP: Characterization of structure/Zn2+ chelating mode and the potential mechanisms for promoting Zn2+ transport in Caco-2 cells.

This study focused on exploring the Zn2+ chelating peptide GFLGSP: the characterization of structure/Zn2+ chelating mode and the potential mechanisms for promoting Zn2+ transport in Caco-2 cells. The findings revealed the bidentate chelating between Zn2+ and carboxyl oxygen atom in Pro6 residue. Thereafter, the secondary structure of GFLGSP remained unchanged, but there was an increase in zeta potential and particle size. Notably, the GFLGSP-Zn2+ complex enhanced the Zn2+ transport rate and modulated ZIP4 and ZNT1 expression in a Caco-2 cells monolayer model. As revealed by molecular docking analysis, GFLGSP interacted with ZIP4 through intermolecular hydrogen bonds as well as Van der Waals forces. The Zn2+ transport mechanisms of the GFLGSP-Zn2+ complex encompassed ZIP4 (vital channel), endocytosis (primary pathway) and paracellular transport (supplementary pathway). Based on these results, the tilapia skin collagen-derived GFLGSP hold promise as the potential dietary Zn2+ supplement.

Dietary supplementation with mulberry leaf flavonoids and carnosic acid complex enhances the growth performance and antioxidant capacity via regulating the p38 MAPK/Nrf2 pathway.

Introduction: This study aimed to investigate the regulatory effects of mulberry leaf flavonoids and carnosic acid complex (MCC) on the growth performance, intestinal morphology, antioxidant, and p38 MAPK/Nrf2 pathway in broilers. Methods: A total of 256 healthy 8-day-old female yellow-feathered broilers were randomly divided into 4 equal groups: a control group (CON) fed a basal diet, an antibiotic group (CTC) supplemented with 50 mg/kg chlortetracycline, and two experimental groups (MCC75, MCC150) fed basal diets with 75 mg/kg and 150 mg/kg of MCC, respectively. The experiment lasted for 56 days, with days 1-28 designated as the initial phase and days 29-56 as the growth phase. Results: The results on the growth performance showed that diets supplemented with MCC and CTC decreased the feed-to-gain ratio (F/G), diarrhea rate, and death rate, while significantly increasing the average daily weight gain (ADG) (p < 0.05). Specifically, the MCC150 group enhanced intestinal health, indicated by reduced crypt depth and increased villus height-to-crypt depth ratio (V/C) as well as amylase activity in the jejunum. Both the MCC and CTC groups exhibited increased villus height and V/C ratio in the ileal (p < 0.05). Additionally, all treated groups showed elevated serum total antioxidant capacity (T-AOC), and significant increases in catalase (CAT) and glutathione peroxidase (GSH-Px) activities were observed in both the MCC150 and CTC groups. Molecular analysis revealed an upregulation of the jejunal mRNA expression levels of PGC-1α, Nrf2, and Keap1 in the MCC and CTC groups, as well as an upregulation of ileum mRNA expression levels of P38, PGC-1α, Nrf2, and Keap1 in the MCC150 group, suggesting activation of the p38-MAPK/Nrf2 pathway. Discussion: These findings indicate that dietary supplementation with MCC, particularly at a dosage of 150 mg/kg, may serve as a viable antibiotic alternative, enhancing growth performance, intestinal health, and antioxidant capacity in broilers by regulating the p38-MAPK/Nrf2 pathway.

Survival Benefit and Spatial Properties of Tertiary Lymphoid Structures in Esophageal Squamous Cell Carcinoma with Neoadjuvant Therapies.

Tertiary lymphoid structures (TLSs) were associated with survival in esophageal squamous cell carcinoma (ESCC) undergoing surgery alone (SA). However, their clinical relevance in neoadjuvant therapies remains less known. Here, we firstly investigated the presence, maturation and spatial distribution of TLSs in 359 ESCC patients receiving neoadjuvant chemotherapy (NCT), neoadjuvant immunotherapy (NCI), neoadjuvant chemoradiotherapy (NCRT) or SA. We found mature TLS (MTLS) was an independent prognostic factor in ESCC. NCI group had the lowest immature TLS cases. NCRT group had the lowest MTLSs. MTLSs mostly located in stromal and normal compartments; these MTLSs were positively correlated with neoadjuvant therapy outcomes. NCI group displayed the highest T cells within 150 µm proximity of TLSs among the four groups. Most T cells were dispersed up to more than 150 µm from TLSs, while B cells remained concentrated within TLSs. Innate lymphoid cells and follicular dendritic cells infiltrated and connected with survival differently in NCRT and NCI groups compared with SA group. The novel PD-L1 combined positive score, NCPS, was positively connected with MTLSs and neoadjuvant therapy efficacy. ScRNA-seq analysis revealed TLS+ tumors had increased plasma cells, B cells, Th17, Tfh and Th1, and elevated exhausted CD8+ T cells that highly expressed checkpoint molecules and granzymes. Conclusively, MTLSs favored treatment outcome in ESCC patients receiving multiple neoadjuvant therapies. The spatial distribution of MTLSs was associated with multiregional immune status modified by the neoadjuvant therapies.

Association of triglyceride-glucose index and its combination with adiposity-related indices with the incidence of myocardial infarction: a cohort study from the UK Biobank.

BACKGROUND: The triglyceride-glucose (TyG) index performs better at reflecting insulin resistance when combined with waist circumference (WC), body mass index (BMI), and waist-to-height ratio (WHtR) than when used alone. This study aimed to prospectively examine the relationships between TyG, TyG-BMI, TyG-WC, and TyG-WHtR with the incidence of myocardial infarction (MI) and its subtypes. METHODS: This cohort study included 370,390 participants from the UK Biobank. The Cox proportional hazards model and restricted cubic spline regression model were used to assess the associations of TyG, TyG-BMI, TyG-WC, and TyG-WHtR with MI, ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI). The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were employed to examine the predictive value of four indicators. RESULTS: The hazard ratios (HRs) and 95% confidence intervals (CIs) of MI in the highest quartiles for TyG, TyG-BMI, TyG-WC, and TyG-WHtR were 1.36 (1.28-1.44), 1.47 (1.39-1.56), 1.53 (1.43-1.64), and 1.58 (1.48-1.68) in the fully-adjusted model. Comparable findings were observed when the outcomes were reclassified as STEMI or NSTEMI. However, the associations of TyG-BMI, TyG-WC, and TyG-WHtR with the risk of STEMI were weaker than MI and NSTEMI. A linear dose-response association between TyG and the risk of MI and NSTEMI were demonstrated. TyG-BMI, TyG-WC, and TyG-WHtR all showed nonlinear patterns in their associations with the risk of MI, STEMI, and NSTEMI. TyG-WC was most effective in diagnosing MI (AUC: 0.648, 95% CI: 0.644-0.653), STEMI (AUC: 0.631, 95% CI: 0.622-0.639), and NSTEMI (AUC: 0.647, 95% CI: 0.641-0.654). CONCLUSION: The TyG index was linearly associated with increased risk of MI and NSTEMI, whereas TyG-BMI, TyG-WC, and TyG-WHtR were nonlinearly associated with increased risk of MI and NSTEMI. There were distinct patterns in the relationships between these indicators with STEMI. TyG-WC provided the best diagnostic effectiveness for MI, STEMI, and NSTEMI.

Solanum torvum induces ferroptosis to suppress hepatocellular carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum torvum Sw. (ST) is used to clear heat toxins, promote blood circulation, and alleviate blood stasis. Therefore, this plant has traditionally been used as an ethnomedicine for common cold, chronic gastritis, and tumors. AIM OF THE STUDY: This study aimed to elucidate the mechanism by which ST induces ferroptosis in hepatocellular carcinoma (HCC), the combination effect with lenvatinib, and the impact on lenvatinib-resistant cells. MATERIALS AND METHODS: Cell viability assays were performed using different hepatoma cell lines treated with ST. Lipid peroxidation and iron assays were performed using flow cytometry. Molecules involved in the ferroptosis pathway were detected by Western blotting. Finally, a lenvatinib-resistant cell line was established to evaluate the antiproliferative effects of ST. RESULTS: ST ethanol extract inhibited the growth of various hepatoma cell lines. A significant reduction in glutathione peroxidase 4 (GPX4) expression was observed following ST treatment, which was accompanied by increased lipid peroxidation and Fe2+ accumulation. ST induced ferroptosis mainly through heme oxygenase-1 (HO-1) expression. HO-1 knockdown reduced ST-induced lipid peroxidation and reversed GPX4 suppression. Acyl-CoA synthetase long-chain family member 4 (ACSL4) also participated in ST-induced ferroptosis. ST and lenvatinib combination showed an additive effect, and ST retained its potential anti-HCC efficacy in a lenvatinib-resistant cell line. CONCLUSION: This study demonstrated that the ethanol extract of ST inhibits hepatoma cell growth by inducing ferroptosis. ST displayed an additive effect with lenvatinib in Hep 3B cells and showed remarkable anti-HCC activity in lenvatinib-resistant Hep 3B cells. Collectively, the study shows that ST might have the potential to reduce lenvatinib use in clinical practice and salvage cases of lenvatinib resistance.

Thiadiazol ligand-based laccase-like nanozymes with a high Cu+ ratio for efficient removal of tetracyclines through polymerization.

A promising water treatment technology involves inducing the polymerization of organic pollutants to form corresponding polymers, enabling rapid, efficient, and low CO2 emission removal of these pollutants. However, there is currently limited research on utilizing polymerization treatment technology for removing tetracyclines from water. In this study, we synthesized a laccase-mimic nanozyme (Cu-ATZ) with a high Cu+ ratio using 2-amino-1,3,4-thiadiazole as a ligand inspired by natural laccase. The Cu-ATZ exhibited enhanced resistance to more severe application conditions and improved stability compared to natural laccase, thereby demonstrating a broader range of potential applications. The excellent catalytic properties of Cu-ATZ enabled the nanozyme to be used in the polymerization process to remove tetracyclines from water. In order to simulate actual antibiotic pollution of water bodies, tetracyclines were added to the water from sewage treatment plants. Following Cu-ATZ treatment of the water sample, the chemical oxygen demand (COD) content was found to have decreased by over 80 %. In conclusion, this study presented a novel approach for tetracycline elimination from water.

Utility of Chimeric Mice with Humanized Livers for Predicting Hepatic Organic Anion - Transporting Polypeptide 1B (OATP1B) - Mediated Clinical Drug-Drug Interactions.

The influence of transporters on the pharmacokinetics of drugs is being increasingly recognized, and drug-drug interactions (DDIs) via modulation of transporters could lead to clinical adverse events. Organic anion-transporting polypeptide 1B (OATP1B) are liver specific uptake transporters in humans that can transport a broad range of substrates, including statins. It is a challenge to predict OATP1B-mediated DDIs using preclinical animal models because of species differences in substrate specificity and abundance levels of transporters. PXB-mice are chimeric mice with humanized livers that are highly repopulated with human hepatocytes and have been widely used for drug metabolism and pharmacokinetics studies in drug discovery. In the present study, we measured the exposure increases (blood AUC and Cmax) of ten OATP1B substrates in PXB-mice upon co-administration with rifampin, a potent OATP1B specific inhibitor. These data in PXB-mice were then compared with the observed DDIs between OATP1B substrates and single-dose rifampin in humans. Our findings suggest that the DDIs between OATP1B substrates and rifampin in PXB-mouse are comparable with the observed DDIs in the clinic. Since most OATP1B substrates are metabolized by CYPs and/or are substrates of P-glycoprotein (P-gp), we further validated the utility of PXB-mice to predict complex DDIs involving inhibition of OATP1B, CYPs and P-gp using CsA and gemfibrozil as perpetrators. Overall, the data support that the chimeric mice with humanized livers could be a useful tool for the prediction of hepatic OATP1B-mediated DDIs in humans. Significance Statement The ability of PXB-mouse with humanized liver to predict OATP1B-mediated drug-drug interactions (DDIs) in humans was evaluated. The plasma exposure increases of ten OATP1B substrates with rifampin, an OATP1B inhibitor, in PXB-mice have a good correlation with those observed in humans. More importantly, PXB-mice can predict complex DDIs including inhibition of OATP1B, CYPs and P-gp in humans. PXB-mice are a promising useful tool to assess OATP1B-mediated clinical DDIs.

Risk Factors and Clinical Features of Peripartum Cardiomyopathy in a Chinese Population.

Purpose: We investigated the risk factors and characteristic clinical features of peripartum cardiomyopathy (PPCM) to lay the groundwork for early identification, screening, diagnosis, and intervention in high-risk pregnant women. Patients and methods: A retrospective case-control study was conducted to analyze data from 44 patients with PPCM and 226 normal pregnant women from a Chinese population. Results: Significant differences were found between the groups in terms of various factors such as age, body mass index (BMI), heart rate, and medical history. Logistic regression models identified abnormal electrocardiography (OR=18.852), upper respiratory tract infection (OR=41.822), gestational hypertension (OR=18.188), and cesarean section (OR=8.394) as risk factors for PPCM. Common clinical features observed in patients with PPCM included cough, wheezing, and chest tightness (68.18%), left heart enlargement (56.82%) and valvular insufficiency (81.82%). Additionally, cardiotropic virus was detected in a subset of patients (43.18%) and NT-proBNP was elevated ≥ 400 pg/mL (81.82%). Conclusion: In the Chinese population, the presence of abnormal electrocardiograms during pregnancy, history of upper respiratory tract infection, gestational hypertension, and maternal choice of cesarean section suggest the possibility of PPCM development. Factors such as advanced age, family history of cardiovascular disease, gestational diabetes mellitus, eclampsia, anemia, and hypoproteinemia should be considered. Clinically, patients present with cough, wheezing, chest tightness, enlarged left heart, valvular insufficiency and NT-proBNP elevated ≥ 400 pg/mL. This study could serve as a valuable reference for medical practitioners for the early identification and screening of patients with PPCM.

Effect of long snake moxibustion on gut microbiota of patients with ankylosing spondylitis.

OBJECTIVE: To study the effect of long snake moxibustion intervention on gut microbiota of patients with ankylosing spondylitis (AS) by 16S rDNA sequencing technology. METHODS: 30 AS patients and 30 healthy volunteers were recruited and treated with long snake moxibustion once a week for 12 weeks. AS patients were divided into pre-treatment and post-treatment groups. VAS, BASDAI and BASFI scores of AS patients before and after treatment were collected. 16S rDNA high-throughput sequencing technology was used to analyze the characteristics and differences of gut microbiota in AS patients before and after treatment and in healthy volunteers. RESULTS: VAS, BASDAI and BASFI scores of AS patients after long snake moxibustion treatment were lower than those of pre-treatment group (P<0.05). The results of gut microbiota Alpha diversity showed that ace and chao1 index of the post-treatment group were higher than those of the healthy group (P<0.05), but there was no statistical significance in ace and chao1 index between the pre-treatment group and the post-treatment group (P>0.05). Beta diversity analysis showed that mild classification aggregation occurred between the healthy group and the pre-treatment group , but did not reach a significant level, and there was no significant difference between the the pre-treatment group and the post-treatment group. The results of species abundance showed that, at the phylum level, compared with the healthy group, the relative abundance of Firmicutes and Proteobacteria decreased in the pre-treatment group, while the relative abundance of Bacteroidetes and Actinobacteria increased. Compared with the pre-treatment group, the relative abundance of Firmicutes increased and the relative abundance of Actinobacteria decreased in the post-treatment group, but there were no statistically significant differences in the above changes (P>0.05). At the genus level, compared with the healthy group, the relative abundances of Subdoligranulum in the pre-treatment group were increased (P<0.05), while the relative abundances of Bifidobacterium and Streptococcus were decreased (P<0.05). Compared with the pre-treatment group, the relative abundance of Romboutsia in the post-treatment group was increased (P<0.05). CONCLUSION: Long snake moxibustion can obviously improve the clinical symptoms of AS patients. The possible mechanism of action is related to regulating the abundance of gut microbiota, increasing beneficial bacteria and restoring the homeostasis of gut microorganisms.

Unraveling the relationship between gut microbiota and site-specific endometriosis: a Mendelian randomization analysis.

Background: Although numerous studies have illustrated the connection between gut microbiota and endometriosis, a conspicuous gap exists in research focusing on the pathogenesis of endometriosis at various sites and its linkage with infertility. Methods: In this study, we used a two-sample Mendelian randomization analysis to investigate the effect of gut microbiota on the development of endometriosis in different regions, including the uterus, ovary, fallopian tube, pelvic peritoneum, vagina, and rectovaginal septum, as well as the intestine. Additionally, we explored the correlation between gut microbiota and endometriosis-induced infertility. Genetic associations with gut microbes were obtained from genome-wide association study (GWAS) datasets provided by the MiBioGen consortium, whereas endometriosis-related GWAS data were sourced from the FinnGen dataset. In our analysis, single-nucleotide polymorphisms were used as instrumental variables, with the primary estimation of the causal effect performed via the inverse variance weighting method. Our sensitivity analyses incorporated heterogeneity tests, pleiotropy tests, and the leave-one-out method. Results: We identified associations at the genus level between four bacterial communities and endometriosis. Subsequently, several associations between the gut microbiota and various subtypes of endometriosis at different anatomical sites were recognized. Specifically, three genera were linked with ovarian endometriosis, six genera were associated with tubal endometriosis, four genera showed links with pelvic peritoneum endometriosis, five genera were connected with vaginal and rectovaginal septum endometriosis, and seven genera demonstrated linkages with intestinal endometriosis. Additionally, one genus was associated with adenomyosis, and three genera exhibited associations with endometriosis-induced infertility. Conclusion: Our study elucidates associations between gut microbiota and site-specific endometriosis, thereby augmenting our understanding of the pathophysiology of endometriosis. Moreover, our findings pave the way for potential therapeutic strategies targeting gut microbiota for individuals grappling with endometriosis-related infertility.

Modified Metal-Organic Framework (MOF-818) inspired by natural enzymes for intelligent detection of total antioxidants and bisphenol A in infant beverages.

BACKGROUND: Accurate and quick judgement of the food quality can protect the legitimate rights of consumers. Currently, nanozymes are widely employed in the rapid detection of food due to their stability and economy. The contents of bisphenol A and antioxidant can be used to measure the quality of beverages. However, due to the complexity of the actual samples, it is still challenging to achieve the sensitive detection of both at the same time. The development of nanozyme with high enzyme activity is essential for sensitive detection of targets in complex foods. RESULTS: In this work, a novel nanomaterial (ZrTGA) was synthesized based on thioglycolic acid-modified Metal-Organic Framework (MOF-818). The interaction between Cu-S bonds and increase in the proportion of Cu1+ resulted in ZrTGA exhibiting higher peroxidase-like and polyphenol oxidase-like activities. These enzyme activities were 317 % and 200 % of the original values, respectively. With high enzyme activity can sensitively detect two important indicators of bisphenol A and antioxidants in beverages. The increased enzyme activity of ZrTGA enabled the content of both substances to be detected by smartphone extraction of RGB. Finally, through the output of the ''0″ and ''1″ signals of the logic gates, it is possible to quickly determine the level of the two substances and thus directly assess the quality of the beverages. SIGNIFICANCE: The modification of nanozyme enables the detection of substances at low concentrations based on enhancing dual-enzyme activity. The combination of mobile phone photography and logic gate technology enables the continuous detection of two important indicators in beverages, overcoming the limitations of traditional large-scale instruments. It also provides an alternative strategy for food quality detection.