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Abstract The aims of this study were to determine whether human umbilical cord mesenchymal stem cells (hucMSCs) modified by miRNA-25-3p (miR-25-3p) overexpression could promote venous endothelial cell proliferation and attenuate portal endothelial cell injury. HucMSCs and human umbilical vein endothelial cells (HUVEC) were isolated and cultured from human umbilical cord and characterized. Lentiviral vectors expressing miRNA-25-3p were transfected into hucMSCs and confirmed by PCR. We verified the effect of miR-25-3p-modified hucMSCs on HUVEC by cell co-culture and cell supernatant experiments. Subsequently, exosomes of miR-25-3p-modified hucMSCs were isolated from cell culture supernatants and characterized by WB, NTA and TEM. We verified the effects of miR-25-3p-modified exosomes derived from hucMSCs on HUVEC proliferation, migration, and angiogenesis by in vitro cellular function experiments. Meanwhile, we further examined the downstream target genes and signaling pathways potentially affected by miR-25-3p-modified hucMSC-derived exosomes in HUVEC. Finally, we established a rat portal vein venous thrombosis model by injecting CM-DiR-labeled hucMSCs intravenously into rats and examining the homing of cells in the portal vein by fluorescence microscopy. Histological and immunohistochemical experiments were used to examine the effects of miRNA-25-3p-modified hucMSCs on the proliferation and damage of portal vein endothelial cells. Primary hucMSCs and HUVECs were successfully isolated, cultured and characterized. Primary hucMSCs were modified with a lentiviral vector carrying miR-25-3p at MOI 80. Co-culture and cell supernatant intervention experiments showed that overexpression of miRNA-25-3p in hucMSCs enhanced HUVEC proliferation, migration and tube formation in vitro. We successfully isolated and characterized exosomes of miR-25-3p-modified hucMSCs, and exosome intervention experiments demonstrated that miR-25-3p-modified exosomes derived from hucMSCs similarly enhanced the proliferation, migration, and angiogenesis of HUVECs. Subsequent PCR and WB analyses indicated PTEN/KLF4/AKT/ERK1/2 as potential pathways of action. Analysis in a rat portal vein thrombosis model showed that miR-25-3p-modified hucMSCs could homing to damaged portal veins. Subsequent histological and immunohistochemical examinations demonstrated that intervention with miR-25-3p overexpression-modified hucMSCs significantly reduced damage and attenuated thrombosis in rat portal veins. The above findings indicate suggest that hucMSCs based on miR-25-3p modification may be a promising therapeutic approach for use in venous thrombotic diseases.

Abstract Toxic metals are vital risk factors affecting serum ion balance; however, the effect of their co-exposure on serum ions and the underlying mechanism remain unclear. We assessed the correlations of single metal and mixed metals with serum ion levels, and the mediating effects of mineralocorticoids by investigating toxic metal concentrations in the blood, as well as the levels of representative mineralocorticoids, such as deoxycorticosterone (DOC), and serum ions in 471 participants from the Dongdagou–Xinglong cohort. In the single-exposure model, sodium and chloride levels were positively correlated with arsenic, selenium, cadmium, and lead levels and negatively correlated with zinc levels, whereas potassium and iron levels and the anion gap were positively correlated with zinc levels and negatively correlated with selenium, cadmium and lead levels (all P

Research efforts on permanganate (Mn(VII)) combined with redox-mediator (RM), have received increasing attention due to their significant performance for bisphenol-A (BPA) removal. However, the mechanisms underpinning BPA degradation remain underexplored. Here we show the overlooked interactions between RM and BPA during permanganate oxidation by introducing an RM—N-hydroxyphthalimide (NHPI). We discovered that the concurrent generation of MnO2 and phthalimide-N-oxyl (PINO) radical significantly enhances BPA oxidation within the pH range of 5.0–6.0. The detection of radical cross-coupling products between PINO radicals and BPA or its derivatives corroborates the pivotal role of radical cross-coupling in BPA oxidation. Intriguingly, we observed the formation of an NHPI-BPA complex, which undergoes preferential oxidation by Mn(VII), marked by the emergence of an electron-rich domain in NHPI. These findings unveil the underlying mechanisms in the Mn(VII)/RM system and bridge the knowledge gap concerning BPA transformation via complexation. This research paves the way for further exploration into optimizing complexation sites and RM dosage, significantly enhancing the system's efficiency in water treatment applications.

Abstract Background and Aims Oncogenesis and tumor development have been related to oxidative stress (OS). The potential diagnostic utility of OS genes in hepatocellular carcinoma (HCC), however, remains uncertain. As a result, this work aimed to create a novel OS related‐genes signature that could be used to predict the survival of HCC patients and to screen OS related‐genes drugs that might be used for HCC treatment. Methods We used The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database to acquire mRNA expression profiles and clinical data for this research and the GeneCards database to obtain OS related‐genes. Following that, biological functions from Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on differentially expressed OS‐related genes (DEOSGs). Subsequently, the prognostic risk signature was constructed based on DEOSGs from the TCGA data that were screened by using univariate cox analysis, and the Least Absolute Shrinkage and Selection Operator (LASSO) regression, and multivariate cox analysis. At the same time, we developed a prognostic nomogram of HCC patients based on risk signature and clinical‐pathological characteristics. The GEO data was used for validation. We used the receiver operating characteristic (ROC) curve, calibration curves, and Kaplan–Meier (KM) survival curves to examine the prediction value of the risk signature and nomogram. Finally, we screened the differentially expressed OS genes related drugs. Results We were able to recognize 9 OS genes linked to HCC prognosis. In addition, the KM curve revealed a statistically significant difference in overall survival (OS) between the high‐risk and low‐risk groups. The area under the curve (AUC) shows the independent prognostic value of the risk signature model. Meanwhile, the ROC curves and calibration curves show the strong prognostic power of the nomogram. The top three drugs with negative ratings were ZM‐336372, lestaurtinib, and flunisolide, all of which inversely regulate different OS gene expressions. Conclusion Our findings indicate that OS related‐genes have a favorable prognostic value for HCC, which sheds new light on the relationship between oxidative stress and HCC, and suggests potential therapeutic strategies for HCC patients.

There is a bidirectional interactive relationship between heavy metals and intestinal microorganisms. Single exposure to common heavy metals (Cd, Cr, As, Pb, etc.) may cause intestinal microecological damage and related diseases by losing the diversity and relative abundance of intestinal microorganisms. However, heavy metals in the environment are usually mixed exposure and an overall toxic effect is presented. Published studies have suggested a synergistic effect between most heavy metals, so the impact of mixed exposure on intestinal microorganisms is expected to be more significant than that of single exposure. Intestinal microorganisms are the first line of defense against heavy metals entering the body, and can reduce inflammation and oxidation caused by heavy metals via changing protein synthesis, intestinal PH, enzyme activity, etc. At the same time, the colonization of oral probiotics in the intestinal tract has a significant detoxification effect on heavy metals entering the body through synergy with intestinal microorganisms, which can promote the elimination of heavy metals, reduce the production of oxides and inflammatory mediators, reverse the changes in the relative abundance of intestinal microorganisms, and then reduce the damage of heavy metals to intestinal microecology. Therefore, probiotics may have better prospects than traditional heavy metal antidotes. In the future, more in-depth research on the mechanism of bidirectional interactive relationship between heavy metals and intestinal microorganisms is needed to provide new ideas for clinical heavy metal detoxification.

Objective. Nonalcoholic fatty liver disease (NAFLD) is becoming more prevalent in the nonobese population. The aim of this study was to investigate the combined effects of metabolism-related mixtures on NAFLD subjects in nonobese populations using four statistical models. Study Design. This was a retrospective observational study. Methods. Our study included 904 nonobese patients who had taken part in the 2017-2018 National Health and Nutrition Examination Survey (NHANES). We used logistic regression models, Bayesian kernel machine regression (BKMR), and the weighted quantile sum (WQS) regression model to estimate the association between metabolism-related indicators and NAFLD in the nonobese population. Finally, we included several indicators to create nomograms to predict the risk of NAFLD occurrence in the nonobese population. Results. Among the 904 participants, 116 (12.83%) had NAFLD. The logistic regression model found that the waist-to-hip ratio (WHR), HDL-c, triglyceride (TG), and HbA1c were positively associated with the outcomes. The WQS regression model showed that the WQS index was significantly associated with the occurrence of NAFLD in the nonobese population (OR: 5.789, 95% CI: 3.933–8.520), and WHR, TC, and TG had the largest weight. The BKMR model’s WHR and TG increased from the 25th percentile to the 75th percentile (other metabolite exposure remained fixed at the 75th percentile) and the risk of developing NAFLD increased in the nonobese people. The significant predictors mentioned above were introduced to construct the nomogram. The calibration curve, DCA, and AUROC (0.796) (95% CI: 0.743–0.843) all indicated that the model had a good potential clinical performance. Conclusions. By comparing the results of the four models together, WHR and TG were identified as important factors associated with NAFLD in the nonobese population. Further research is warranted to investigate the risk factors and pathogeny of NAFLD in nonobese populations.

The gut-liver axis refers to the intimate relationship and rigorous interaction between the gut and the liver. The intestinal barrier’s integrity is critical for maintaining liver homeostasis. The liver operates as a second firewall in this interaction, limiting the movement of potentially dangerous compounds from the gut and, as a result, contributing in barrier management. An increasing amount of evidence shows that increased intestinal permeability and subsequent bacterial translocation play a role in liver damage development. The major pathogenic causes in cirrhotic individuals include poor intestinal permeability, nutrition, and intestinal flora dysbiosis. Portal hypertension promotes intestinal permeability and bacterial translocation in advanced liver disease, increasing liver damage. Bacterial dysbiosis is closely related to the development of cirrhosis and its related complications. This article describes the potential mechanisms of dysbiosis in liver cirrhosis and related complications, such as spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis, hepatic encephalopathy, and hepatocellular carcinoma, using dysbiosis of the intestinal flora as an entry point.

Abstract Increasing issues of hydrophobic membrane wetting occur in the membrane distillation (MD) process, stimulating the research on enhanced anti‐wetting methods for membrane materials. In recent years, surface structural construction (i.e., constructing reentrant‐like structures), surface chemical modification (i.e., coating organofluorides), and their combination have significantly improved the anti‐wetting properties of the hydrophobic membranes. Besides, these methods change the MD performance (i.e., increased/decreased vapor flux and increased salt rejection). This review first introduces the characterization parameters of wettability and the fundamental principles of membrane surface wetting. Then it summarizes the enhanced anti‐wetting methods, the related principles, and most importantly, the anti‐wetting properties of the resultant membranes. Next, the MD performance of hydrophobic membranes prepared by different enhanced anti‐wetting methods is discussed in desalinating different feeds. Finally, facile and reproducible strategies are aspired for the robust MD membrane in the future.

Background and aimsAdenocarcinoma is one of the most common pathological types of gastric cancer. The aims of this study were to develop and validate prognostic nomograms that could predict the probability of cancer-specific survival (CSS) for gastric adenocarcinoma (GAC) patients at 1, 3, and 5 years.MethodsIn total, 7747 patients with GAC diagnosed between 2010 and 2015, and 4591 patients diagnosed between 2004 and 2009 from the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. The 7747 patients were used as a prognostic cohort to explore GAC-related prognostic risk factors. Moreover, the 4591 patients were used for external validation. The prognostic cohort was also divided into a training and internal validation sets for construction and internal validation of the nomogram. CSS predictors were screened using least absolute shrinkage and selection operator regression analysis. A prognostic model was built using Cox hazard regression analysis and provided as static and dynamic network-based nomograms.ResultsThe primary site, tumor grade, surgery of the primary site, T stage, N stage, and M stage were determined to be independent prognostic factors for CSS and were subsequently included in construction of the nomogram. CSS was accurately estimated using the nomogram at 1, 3, and 5 years. The areas under the curve (AUCs) for the training group at 1, 3, and 5 years were 0.816, 0.853, and 0.863, respectively. Following internal validation, these values were 0.817, 0.851, and 0.861. Further, the AUC of the nomogram was much greater than that of American Joint Committee on Cancer (AJCC) or SEER staging. Moreover, the anticipated and actual CSS values were in good agreement based on decision curves and time-calibrated plots. Then, patients from the two subgroups were divided into high- and low-risk groups based on this nomogram. The survival rate of high-risk patients was considerably lower than that of low-risk patients, according to Kaplan–Meier (K-M) curves (p

Traditional mechanical bone drilling is prone to heat generation and debris accumulation which will cause tissue damage in orthopedic surgeries. Therefore, research on contactless laser bone drilling has become a mainstream trend in the development of bone surgery. This study presents a laser rapid drilling strategy for bone surgery with minimizing thermal osteonecrosis and debris based on the design of dynamic focusing and spreading droplet cooling. The laser drilled hole suffered from low temperature (Tmax = 46.2 ○C) under clinically accepted threshold of 47 ○C, presenting osteocyte-filled lacunas, visible Haversian canals and increased pullout strength when compared with that following mechanically drilling. An intact bone column without debris was extracted from a 4-mm-deep hole in vitro on a sheep tibia which provides a clean surgical method with increased drilling rate of 0.94 mm3/s. The criteria dimensionless We constant related to spreading droplets leading to effective heat transfer is determined as2.8 × 103 × Re-1/2 ≤ We ≤ 1.9 × 10-2 × Re7, yielding a high convective coefficient of 0.11 W/mm2·K for cooling. The comprehensive results of laser bone drilling proved the effectiveness of the presented technology and setup, which is significant in realizing rapid, debris-free orthopedic surgery.