csi-miR-96-5p delivered by Clonorchis sinensis extracellular vesicles promotes intrahepatic cholangiocarcinoma proliferation and migration via the ferroptosis-related PTEN/SLC7A11/GPX4 axis.

BACKGROUND: Clonorchis sinensis (CS) is classified as a group 1 carcinogen and can cause intrahepatic cholangiocarcinoma (ICC). CS extracellular vesicles (CsEVs) play important roles in mediating communication between parasitic helminths and humans. Ferroptosis is a novel cell death mechanism that is mainly induced by lipid peroxidation and iron overload. However, the role of CsEVs in the regulation of ferroptosis in ICC remains unclear. This study aimed to explore the role of CS-secreted miR-96-5p (csi-miR-96-5p) delivered by CsEVs in ICC progression and ferroptosis. METHODS: Tissue samples were collected from ICC patients with CS infection (CS-ICC) or without CS infection (NC-ICC). The levels of csi-miR-96-5p and PTEN gene were determined by quantitative polymerase chain reaction (qPCR) and western blotting, and survival analysis was performed. CsEVs were isolated and identified by ultracentrifugation and transmission electron microscopy. Lentiviruses were used to establish stable cell lines with csi-miR-96-5p mimic expression, PTEN overexpression (PTEN-EXO) and PTEN CRISPR/Cas9-based knockout (PTEN-KO) and their respective negative controls. Cell proliferation was assessed by performing Cell Counting Kit-8 assays in vitro and in a tumor xenograft model in vivo, and cell migration was assessed by performing Transwell assays. Erastin is used to induce ferroptosis. Ferroptosis levels were evaluated using biomarkers. RESULTS: High csi-miR-96-5p and low PTEN expression was observed in CS-ICC tissues and was associated with poor overall survival. csi-miR-96-5p was highly enriched in CsEVs and was taken up by ICC cells. csi-miR-96-5p mimics or PTEN-KO significantly promoted the growth and migration of ICC cells in vitro and in vivo, whereas PTEN-EXO exerted the opposite effect. Mechanistically, csi-miR-96-5p mimics or PTEN-KO inhibited erastin-induced ferroptosis, including reducing the accumulation of Fe2+, lipid reactive oxygen species, and malondialdehyde, increasing the GSH/GSSG ratio and levels of SLC7A11 and GPX4, whereas PTEN-EXOs exerted the opposite effect. CONCLUSIONS: csi-miR-96-5p delivered by CsEVs reduced ferroptosis by regulating the expression of the PTEN/SLC7A11/GPX4 axis, thereby promoting ICC proliferation and migration. For the first time to our knowledge, we found that CS miRNAs could promote tumor development through ferroptosis.

Insights into the effects of natural pyrite-activated sodium percarbonate on tetracycline removal from groundwater: Mechanism, pathways, and column studies.

In-situ chemical oxidation based on sodium percarbonate (SPC) has received much attention for remediation of groundwater contaminated with organic pollutants due to the high efficiency, stable reaction, and sustainability of SPC. Currently, metal ions and their composite materials, are mainly employed for the activation of SPC. However, due to its narrow pH range, slow Fe3+/Fe2+ circulation, and generation of refractory sludge, its application in groundwater is limited. In this study, SPC was activated with natural pyrite (FeS2) to remove tetracycline, which was selected as the target pollutant. FeS2 exhibited excellent catalytic activity and stability towards the degradation of tetracycline. The tetracycline degradation efficiency of SPC/FeS2 system reached 70 % within 10 min, and nearly half of the tetracycline was degraded in the first 5 min of the reaction. The optimum SPC dosage for the tetracycline removal was 8 mM, with FeS2 dosage of 0.5 g/L. The tetracycline removal efficiency remained above 60 % after 4 cycles, indicating its good recycling efficiency of the system. SPC/FeS2 system was not significantly affected by the initial pH or the presence of Cl-, SO42-, NO3- while, HCO3-, Ca2+, Mg2+, and humid acid suppressed the reaction. The electron paramagnetic resonance spectroscopy and quenching experiments demonstrated that OH and O2- played a dominant role in tetracycline removal by the system. S22-, as an electron donor, was able to participate in the Fe3+/Fe2+ cycle. In addition, the 13 transformation products were determined by liquid chromatography-mass spectrometry predicted that the degradation pathway of tetracycline consisted of hydroxylation, demethylation, and decarbonylation reactions. Finally, the dynamic simulation experiments of SPC/FeS2 sand column showed that FeS2 effectively activated SPC and significantly reduced the toxicity in groundwater after the packed column treatment. This study reveals that FeS2 can efficiently activate SPC and has good prospects for tetracycline-contaminated groundwater remediation applications.

The Adsorption and Aging Process of Cadmium and Chromium in Soil Micro-aggregates.

The particle size and components of soil aggregates have played important roles in the migration and transformation of heavy metals. The present study focused on the adsorption behavior and aging characteristics of cadmium (Cd) and chromium (Cr) in various granular aggregates and soil components, which were studied by analyzing the adsorption isotherm, adsorption kinetics, and heavy metal speciation distribution. The results showed that, compared with other aggregates, clay aggregates (0-0.002 mm) had the strongest adsorption effect on Cd and Cr and that there was no significant positive correlation between the adsorption amount and the particle size of aggregates for Cd and Cr. In general, the influence of three components on Cd was organic matter > amorphous iron > free iron oxide, and the influence on Cr was free iron oxide > amorphous iron > organic matter. The adsorption isotherm showed that the correlation coefficient of the Langmuir model (R2 ) was higher than that of the Freundlich model (R2 ), indicating that the adsorption of Cd and Cr by soil aggregates can be well described by the Langmuir model with monolayer adsorption behavior. Kinetic adsorption studies showed that quasi-first-order kinetics and quasi-second-order kinetics were more consistent with the actual adsorption amounts of Cd and Cr in soil aggregates, respectively. At the same time, the forms of Cd and Cr gradually transformed from unstable to stable after entering the soil. After 60 days, Cd was mainly oxidized, and residual, and Cr was mainly reduced and residual. These results provide a theoretical basis for assessing the environmental risks of Cd and Cr and providing prevention and treatment methods. Environ Toxicol Chem 2022;41:975-990. © 2022 SETAC.

Performance and Mechanisms of PropS-SH/HA Coatings in the Inhibition of Pyrite Oxidation.

Acid mine drainage (AMD) entering the environment will cause long-term environmental pollution and ecological damage, the treatment or remediation for which has become a difficult worldwide problem. To control AMD at the source, a novel composite coating, hydroxyapatite (HA) as the filler embedded in a γ-mercaptopropyltrimethoxysilane (PropS-SH) coating, was introduced in this study. The performance and mechanisms of PropS-SH/HA coatings in the inhibition of pyrite oxidation were investigated by chemical leaching testing and material structure characterization. The results of the investigations revealed that the addition of an appropriate amount of HA can enhance the passivation efficiency of the PropS-SH coating. The best coating was obtained from 3% (v/v) of PropS-SH solution with 16 wt % HA, as this coating decreased pyrite oxidation by 78.7% (based on total Fe release). The main mechanism of PropS-SH/HA for the inhibition of pyrite oxidation involved the generation of a PropS-SH network through a polycondensation reaction. The addition of HA increased the stability of the passivation film composed of PropS-SH as well as the combining capacity of PropS-SH/HA through the formation of Si-O-Si and Fe-O-Si bonds, respectively.

XPD Polymorphisms and Risk of Hepatocellular Carcinoma and Gastric Cancer: A Meta-Analysis.

BACKGROUND: Cancer is associated with genetic variants of DNA repair genes that alter DNA repair capacity. The aim of this meta-analysis was to evaluate the relations between the rs13181 and rs1799793 XPD gene polymorphisms and risk for hepatocellular carcinoma (HCC) and gastric cancer. METHODS: Relevant publications were systematically sought from Web of Science, Pubmed, and China Academic Journals Full-text Database. The selection of eligible studies was performed by 2 independent authors. A total of 32 case-control studies were included. Meta-analyses were undertaken in all study participants and each ethnic group. RESULTS: The risk of HCC was significantly increased with the XPD rs13181 G allele (P = 0.028, pooled odds ratio (OR) = 1.36, 95% confidence interval (CI) = 1.03-1.80) in all study participants. A subgroup analysis by ethnicity showed that the association was significant in Chinese (P = 0.009, pooled OR = 1.49, 95% CI = 1.11-2.02), but not in Caucasians (P = 0.619, pooled OR = 1.17, 95% CI = 0.64-2.13). Meta-analysis of the XPD rs1799793 polymorphism and HCC showed an association between its variant T allele and increased HCC risk in all study participants (P = 0.017, pooled OR = 1.23, 95% CI = 1.04-1.46, all Chinese). Our results showed no associations between the XPD rs13181 G allele and rs1799793 T allele and gastric cancer risk (rs13181: P = 0.298, pooled OR = 1.10, 95% CI = 0.92-1.31; rs1799793: P = 0.068, pooled OR = 1.31, 95% CI = 0.98-1.74). CONCLUSIONS: This meta-analysis demonstrated that the XPD rs13181 G allele and rs1799793 T allele have significant associations with HCC and may be risk factors for HCC in the Chinese population. Current evidence indicated that they are not related to gastric cancer risk.

The clinical profiles, management, and prognostic factors of biliary mixed neuroendocrine nonneuroendocrine neoplasms: A systematic review of the literature.

BACKGROUND: Mixed neuroendocrine nonneuroendocrine neoplasms (MiNENs) originating from the biliary system (gallbladder, biliary tract, or ampulla of Vater) are extremely rare and have not been discussed in detail or systematically. We aimed to present the demographics, clinicopathological characteristics, management, and prognostic factors of biliary MiNENs. METHODS: A systematic search of electronic biomedical databases (Web of Science, PUBMED, and Embase) was performed to identify eligible studies. Survival was analyzed with the Kaplan-Meier method. Log-rank tests were used to evaluate the differences between groups, and the effects of various clinical and histopathological features on prognosis were analyzed by univariate and multivariate Cox regression. RESULTS: Fifty-three publications (patients, n = 67) were included. The median overall survival time was 21.0 months. Fifty-one patients (76.1%) underwent radical surgery and median survival for 41 months (P < .001). Twenty-two patients who received adjuvant radiochemotherapy treatment after radical surgery had a median survival for 43 months (P = .076). Radical resection (P < .001), Ki-67 index (P = .011), tumor stage (P < .001), neuroendocrine (NEC) grade (P = .011), and non-NEC grade (P = .017) were independent statistically significant prognostic factors according to univariate analysis; radical resection (P = .010) and small morphological subtype (P = .036) were independent statistically significant prognostic factors associated with higher overall survival according to multivariate analysis, and radical resection (P = .005) and age < 65 years (P = .026) were associated with higher recurrence free survival time. CONCLUSION: Radical resection is essential for long-term survival. Aggressive multimodality therapy with adjuvant radiochemotherapy and biotherapy may improve survival of biliary MiNENs. Further randomized controlled trials are needed to determine the standard treatment.

Efficacy and Safety of Digital Single-Operator Cholangioscopy in the Diagnosis of Indeterminate Biliary Strictures by Targeted Biopsies: A Systematic Review and Meta-Analysis.

BACKGROUND: Biliary strictures are frequently encountered in clinical practice. The determination of their nature is often difficult. This study aims to systematically evaluate the efficacy and safety of the second generation of digital single-operator cholangioscopy (SpyGlass DS, DSOC) in indeterminate biliary strictures (IBDS) through biopsies. METHODS: All relative studies published in Medline, the Cochrane Library, Web of Science, and EMBASE were included. The diagnostic tests for IBDS were compared to the surgical histology, autopsy, or long-term clinical follow-up. The methodological quality of the included studies was evaluated by the Quality Assessment of Studies of Diagnostic Accuracy Included in Systematic Reviews (QUADAS-2). RESULTS: A total of 11 studies, which involved 356 patients diagnosed through biopsies, were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.74 (95% CI: 0.67-0.80), 0.98 (95% CI: 0.95-1.00), 10.52 (95% CI: 5.45-20.32), 0.31 (95% CI: 0.23-0.41), and 65.18 (95% CI: 26.79-158.61), respectively. The area under the curve (AUC) was 0.9479, and the pooled adverse event rate was 7%. The sensitivity and specificity in the heterogeneity analysis were I2 = 48.1% and I2 = 25.4%, respectively. CONCLUSION: SpyGlass DS is a safe and effective technique for IBDS. However, future randomized trials are needed to determine optimal number of biopsies.

Incidence of kidney cancer after liver transplantation: a meta-analysis.

The purpose of this systematic review and meta-analysis was to investigate the relationship between liver transplantation and kidney cancer. Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines were followed. PubMed, the Web of Science, and the Cochrane databases were searched for peer-reviewed cohort studies in which standardized incidence of kidney cancer post-transplant was compared to the general population by means of standardized incidence ratio (SIR) with 95% confidence interval (CI). No limits were placed on language or year of publication. A fixed-effects model was used for pooling the data. Of the 937 citations identified from the electronic databases, we included nine cohort studies with 53913 liver transplant patients, a male percentage of 56.8% and a minimum follow-up of 12.4 months and more. The meta-analysis revealed that liver transplant recipients faced a significantly higher risk of developing kidney cancer than the general population with the pooled SIR of 2.02 (95% CI, 1.64-2.50; P < 0.001). No significant between-study heterogeneity was observed (I = 0, Phet = 0.553). On sensitivity analysis after removing the study by Engles et al. with the largest sample size (37 888 liver transplant recipients), the SIR remained stable (SIR 2.75; 95% CI, 1.85-4.10; P < 0.001). Overall, our synthesis of the literature indicates that an increased risk of kidney cancer exists after liver transplantation. Future studies should evaluate the potential risk factors associated with kidney cancer.

Long non-coding RNA LINC00160 functions as a decoy of microRNA-132 to mediate autophagy and drug resistance in hepatocellular carcinoma via inhibition of PIK3R3.

The introduction of long non-coding RNAs (lncRNAs) has revolutionized the treatment of hepatocellular carcinoma (HCC). Thus, in the present study, we aimed to evaluate the effect of a newly found lncRNA, LINC00160, on autophagy and drug resistance of HCC. Interaction among LINC00160, miR-132 and PIK3R3 was verified by dual luciferase reporter gene assay. Loss- and gain-of function experiments were conducted in HCC cells to explore the roles of LINC00160, miR-132 and PIK3R3 in HCC by determining cell viability, autophagy and apoptosis. Finally, tumorigenicity in nude mice was established to confirm the in vitro findings. LINC00160 and PIK3R3 were up-regulated but miR-132 was down-regulated in HCC tissues and cells. LINC00160 may regulate miR-132 and PIK3R3 was the target gene of miR-132. LINC00160 increased the expression of LC3I/LC3II and Atg5 but decreased the p62 expression, while silencing of LINC00160 or over-expression of miR-132 suppressed HCC cell viability, autophagy, drug-resistance and tumorigenicity in nude mice but promoted HCC cell apoptosis by inhibiting the PIK3R3 expression. Taken together, silencing of LINC00160 suppresses autophagy and drug resistance in HCC by regulating miR-132-targeted PIK3R3.

Utility of multiple endoscopic techniques in differential diagnosis of gallbladder adenomyomatosis from gallbladder malignancy with bile duct invasion: A case report.

BACKGROUND: Gallbladder adenomyomatosis (GAM) is a benign lesion, characterized by thickening of the gallbladder wall and a focal mass, which overlap with the features of gallbladder malignancy. Consequently, differential diagnosis of GAM from gallbladder cancer is difficult and approximately 20% of suspected malignant biliary strictures are postoperatively confirmed as benign lesions. Herein, we report a case in which a preoperative diagnosis of GAM was made by a combination of endoscopic and imaging techniques. CASE SUMMARY: A 40-year-old man was referred to our hospital chiefly for a fever and right upper abdominal pain with dark urine. Enhanced computed tomography showed thickening of the gallbladder wall and a mass in the gallbladder neck with involvement of the hepatic bile ducts, which was suspected to be malignant. Gallbladder malignancy with bile duct invasion was ruled out by subsequent endoscopic examinations, including endoscopic retrograde cholangio-pancreatography, intraductal ultrasound, and SpyGlass. Endoscopic examinations showed a homogeneous hyperechoic lesion with smooth margins of benign bile duct stricture suggestive of inflammatory stenosis of the bile duct. The patient underwent laparoscopic cholecystectomy. GAM was postoperatively diagnosed and confirmed based on the histopathology results, which are consistent with the preoperative diagnosis. Notably, no malignant event occurred in the patient during a 12-mo follow-up period. CONCLUSION: A combination of endoscopic techniques may help in the differential diagnosis of GAM from gallbladder cancer.

Relationship of ALDH2 rs671 and CYP2E1 rs2031920 with hepatocellular carcinoma susceptibility in East Asians: a meta-analysis.

BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2) and cytochrome p450 2E1 (CYP2E1) are important alcohol-metabolizing enzymes. The aim of this meta-analysis was to evaluate the association of ALDH2 rs671 and CYP2E1 rs2031920 polymorphisms with hepatocellular carcinoma (HCC) susceptibility in East Asians. METHODS: A systematic search strategy was implemented in MEDLINE, PubMed, Scopus, Embase, and China Academic Journals databases. Nineteen case-control studies were selected for inclusion. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated through random-effects or fixed-effects models. Subgroup analysis, meta-regression, sensitivity analysis, cumulative meta-analysis, and evaluation of publication bias were performed. RESULTS: The overall meta-analysis did not find a significant association of ALDH2 rs671 and CYP2E1 rs2031920 genotypes with HCC susceptibility in East Asians. In addition, stratified analysis by country, Hardy-Weinberg equilibrium status, and source of controls also did not identify any association. CONCLUSION: The ALDH2 rs671 and CYP2E1 rs2031920 polymorphisms are not associated with HCC susceptibility in East Asians.

How vegetation influence the macrobenthos distribution in different saltmarsh zones along coastal topographic gradients.

Macrobenthos are a key constituent of coastal salt marsh ecosystems and have often been used as sensitive indicators of the environment quality. In this study, field investigations in vegetated regions and adjacent bare patches of low, middle and high marshes were conducted to explore whether and how vegetation influence the macrobenthos distribution in different saltmarsh zones along coastal topographic gradients. Results showed that vegetation positively or negatively influenced macrobenthos mainly by changing their environment in different saltmarsh zones, as there were different degrees of physical stresses and food supply for the macrobenthos from the low to the high marsh. In the low marsh, no major differences in macrobenthos indices between the bare and vegetated sediments were found, yet density and biomass of the molluscs were higher in the bare patches. In the middle marsh, vegetation promoted the biomass and diversity indices but not the density and species richness of the macrobenthos, and vegetation was beneficial for some types of crustaceans but was detrimental for some types of polychaetes. In the high marsh, vegetation promoted the biomass, density, and species richness of the macrobenthos compared to those of adjacent bare patches. Coastal topographic gradients also had effects on macrobenthos distribution consistently with different habitat preferences and ecological niches, and the low marsh had the highest species richness, Shannon diversity, Pielou evenness and Margalef richness. This study also provided scientific implications for the management and restoration of the ecosystems in different intertidal saltmarsh zones.

LncRNA SNHG15 promotes hepatocellular carcinoma progression by sponging miR-141-3p.

Small nucleolar RNA host gene 15 (SNHG15) is a long noncoding RNA (lncRNA), which promotes progression of multiple cancers. Its specific function in hepatocellular carcinoma (HCC), however, is uncertain. The aims of our study were, therefore, to explore the role of SNHG15 in HCC. SNHG15 and miR-141-3p expression were assessed via quantitative real-time PCR (qRT-PCR) in 58 paired HCC samples and adjacent matched adjacent normal tissues. CCK-8 assay, flow cytometric examination, and wound healing/invasion assays were used to respectively assess how SNHG15 influences cell proliferation, the cell cycle, and the migratory and invasive potential of HCC cells. MicroRNA (miRNAs) that targeted SNHG15 was screened by Starbase2.0 and identified by RNA immunoprecipitation and luciferase reporter assays. SNHG15 expression was markedly increased, whereas miR-141-3p expression was substantially reduced in HCC cells and tissue samples relative to normal controls. When SNHG15 was knocked down, this resulted in a significant disruption to the proliferation, as well as the invasive and migratory ability of these HCC cells. miR-141-3p was also found to be an SNHG15 target in HCC cells. Furthermore, miR-141-3p inhibitor partially reversed the observed SNHG15 depletion-mediated reduction in HCC proliferation, migration, and invasion. By repressing miR-141-3p, SNHG15 could modulate zinc finger E-box binding homeobox 2 (ZEB2) and E2F transcription factor 3 (E2F3) expression, both of which are miR-141-3p targets. These finding suggested that SNHG15 promoted HCC progression via negative regulation of miR-141-3p, thus identifying a potential novel HCC treatment pathway.

Machine Learning Model Analysis of Breeding Habitats for the Black-necked Crane in Central Asian Uplands under Anthropogenic Pressures.

The black-necked crane (Grus nigricollis) is the only alpine crane species and is endemic to the Tibetan Plateau. The breeding habitats of this species are poorly understood, which greatly hampers practical research and conservation work. Using machine learning methods and the best-available data from our 7,000-kilometer mega-transect survey and open access data, we built the first species distribution model (SDM) to analyze the black-necked crane's breeding habitats. Our model showed that current conservation gaps account for 26.7% of its predicted breeding habitats. Specifically, the northern parts of the Hengduan Mountains and the southeastern Tibet Valley, the northern side of the middle Kunlun Mountains, parts of the Pamir Plateau, the northern Pakistan Highlands and the western Hindu Kush should be considered as its main potential breeding areas. Additionally, our model suggested that the crane prefers to breed in alpine meadows at an elevation over 2,800 m, a maximum temperature of the warmest month below 20.5 °C, and a temperature seasonality above 7,800 units. The identified conservation gaps and potential breeding areas can aid in clearly prioritizing future conservation and research, but more attention and study should be directed to the unassessed Western Development of China to secure this endangered crane lineage and other wildlife on the Tibetan Plateau.

Why choose Random Forest to predict rare species distribution with few samples in large undersampled areas? Three Asian crane species models provide supporting evidence.

Species distribution models (SDMs) have become an essential tool in ecology, biogeography, evolution and, more recently, in conservation biology. How to generalize species distributions in large undersampled areas, especially with few samples, is a fundamental issue of SDMs. In order to explore this issue, we used the best available presence records for the Hooded Crane (Grus monacha, n = 33), White-naped Crane (Grus vipio, n = 40), and Black-necked Crane (Grus nigricollis, n = 75) in China as three case studies, employing four powerful and commonly used machine learning algorithms to map the breeding distributions of the three species: TreeNet (Stochastic Gradient Boosting, Boosted Regression Tree Model), Random Forest, CART (Classification and Regression Tree) and Maxent (Maximum Entropy Models). In addition, we developed an ensemble forecast by averaging predicted probability of the above four models results. Commonly used model performance metrics (Area under ROC (AUC) and true skill statistic (TSS)) were employed to evaluate model accuracy. The latest satellite tracking data and compiled literature data were used as two independent testing datasets to confront model predictions. We found Random Forest demonstrated the best performance for the most assessment method, provided a better model fit to the testing data, and achieved better species range maps for each crane species in undersampled areas. Random Forest has been generally available for more than 20 years and has been known to perform extremely well in ecological predictions. However, while increasingly on the rise, its potential is still widely underused in conservation, (spatial) ecological applications and for inference. Our results show that it informs ecological and biogeographical theories as well as being suitable for conservation applications, specifically when the study area is undersampled. This method helps to save model-selection time and effort, and allows robust and rapid assessments and decisions for efficient conservation.