Source-oriented health risk assessment of groundwater nitrate by using EMMTE coupled with HHRA model.

Conventional concentration-oriented approaches for nitrate risk diagnosis only provide overall risk levels without identifying risk values of individual sources or sources accountable for potential health risks. Therefore, a hybrid model combining the end-member mixing model tool on Excel™ (EMMTE) with human health risk assessment (HHRA) was developed to assess the source-oriented health risks for groundwater nitrate, particularly in the Poyang Lake Plain (PLP) region. The results indicated that the EMMTE and the Bayesian stable isotope mixing model (MixSIAR) exhibited remarkable consistency in source apportionment of groundwater nitrate. The source contribution of groundwater nitrate in PLP was related to land use types, hydrogeological conditions, and soil properties. Notably, manure and sewage sources, contributing up to 53.4 %, represented the largest nitrate pollution sources, with a significant contribution of soil nitrogen and nitrogen fertilizers. The non-carcinogenic risk for four potential sources was below the acceptable threshold of 1. Given the factors including rainfall dilution and economic development, attention should be directed towards mitigating the health risks posed by manure and sewage. This study can verify the efficacy of EMMTE in source apportionment and offer valuable insights for decision-makers to regulate the largest sources of nitrate contamination and enhance groundwater management efficiency.

Determination of high-risk factors and related spatially influencing variables of heavy metals in groundwater.

Identifying high-risk factors (heavy metals (HMs) and pollution sources) by coupling receptor models and health risk assessment model (HRA) is a novel approach within the field of risk assessment. However, this coupled model ignores the contribution of spatial differentiation to high-risk factors, resulting in the assessment being subjective. Taking Dongting Plain (DTP) as an example, a coupling framework by jointly using the positive matrix factorization model (PMF), HRA, Monte Carlo simulation, and geo-detector was developed, aiming to identify high-risk factors in groundwater, and further explore key environmental variables influencing the spatial heterogeneity of high-risk factors. The results showed that at least 82.86 % of non-carcinogenic risks and 97.41 % of carcinogenic risks were unacceptable for people of all ages, especially infants and children. According to the relationships among HMs, pollution sources, and health risks, As and natural sources were defined as high-risk HMs and sources, respectively. The interactions among Holocene thickness, oxidation-reduction potential, and dissolved organic carbon emerged as the primary drivers of spatial variability in high-risk factors, with their combined explanatory power reaching up to 74%. This proposed framework provides a scientific reference for future studies and a practical reference for environmental authorities in developing effective pollution management measures.

Nutritional support therapy for liver transplantation in an adult-onset type II citrullinemia patient: a case report.

Liver transplantation is an effective measure to treat adult-onset type II citrullinemia (CTLN2). Active and effective perioperative nutrition support is a very important treatment for the prognosis of such patients. In this paper, we analyzed the process, results, and outcome of nutritional support therapy in a case of CTLN2, and concluded that the perioperative nutritional support program for CTLN2 patients should be followed prior to surgery:1.because of the prevalence of severe malnutrition in CTLN2 patients, Enteral nutrition (EN) combined with Parenteral nutrition (PN) should be the first choice for nutritional support; 2. daily energy intake should be 35 ~ 40 kcal/kg; 3. the nutritional formula should be composed of low-carbohydrates and high medium-chain triglyceride (MCT). Postoperative: initiating EN as soon as possible is recommended to restore intestinal function and adjuvant PN might be taken into consideration in the early stage. The purpose of this case was to provide experience for the development and adjustment of the perioperative nutritional support regimen for CTLN2 patients.

Enrichment of Geogenic Organoiodine Compounds in Alluvial-Lacustrine Aquifers: Molecular Constraints by Organic Matter.

Organoiodine compounds (OICs) are the dominant iodine species in groundwater systems. However, molecular mechanisms underlying the geochemical formation of geogenic OICs-contaminated groundwater remain unclear. Based upon multitarget field monitoring in combination with ultrahigh-resolution molecular characterization of organic components for alluvial-lacustrine aquifers, we identified a total of 939 OICs in groundwater under reducing and circumneutral pH conditions. In comparison to those in water-soluble organic matter (WSOM) in sediments, the OICs in dissolved organic matter (DOM) in groundwater typically contain fewer polycyclic aromatics and polyphenol compounds but more highly unsaturated compounds. Consequently, there were two major sources of geogenic OICs in groundwater: the migration of the OICs from aquifer sediments and abiotic reduction of iodate coupled with DOM iodination under reducing conditions. DOM iodination occurs primarily through the incorporation of reactive iodine that is generated by iodate reduction into highly unsaturated compounds, preferably containing hydrophilic functional groups as binding sites. It leads to elevation of the concentration of the OICs up to 183 µg/L in groundwater. This research provides new insights into the constraints of DOM molecular composition on the mobilization and enrichment of OICs in alluvial-lacustrine aquifers and thus improves our understanding of the genesis of geogenic iodine-contaminated groundwater systems.

Nonextractable Polyphenols from Fu Brick Tea Alleviates Ulcerative Colitis by Controlling Colon Microbiota-Targeted Release to Inhibit Intestinal Inflammation in Mice.

This study was designed to elucidate the colon microbiota-targeted release of nonextractable bound polyphenols (NEPs) derived from Fu brick tea and to further identify the possible anti-inflammatory mechanism in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. 1.5% DSS drinking water-induced C57BL/6J mice were fed rodent chow supplemented with or without 8% NEPs or dietary fibers (DFs) for 37 days. The bound p-hydroxybenzoic acid and quercetin in NEPs were liberated up to 590.5 ± 70.6 and 470.5 ± 51.6 mg/g by in vitro human gut microbiota-simulated fermentation, and released into the colon of the mice supplemented with NEPs by 4.4- and 1.5-fold higher than that of the mice supplemented without NEPs, respectively (p < 0.05). Supplementation with NEPs also enhanced the colonic microbiota-dependent production of SCFAs in vitro and in vivo (p < 0.05). Interestingly, Ingestion of NEPs in DSS-induced mice altered the gut microbiota composition, reflected by a dramatic increase in the relative abundance of Dubosiella and Enterorhabdus and a decrease in the relative abundance of Alistipes and Romboutsia (p < 0.05). Consumption of NEPs was demonstrated to be more effective in alleviating colonic inflammation and UC symptoms than DFs alone in DSS-treated mice (p < 0.05), in which the protective effects of NEPs against UC were highly correlated with the reconstruction of the gut microbiome, formation of SCFAs, and release of bound polyphenols. These findings suggest that NEPs as macromolecular carriers exhibit targeted delivery of bound polyphenols into the mouse colon to regulate gut microbiota and alleviate inflammation.

Factors Influencing Breast Cancer Awareness in Rural Southwest China: A Cross-Sectional Study.

Background: This study aimed to explore the current knowledge level of breast cancer among rural women in Southwest China and analyze the influencing factors of breast cancer cognition. Methods: From May to November 2022, 1468 rural women were invited to participate in this study. Demographic information and the Chinese version of the Breast Cancer Awareness Measure (C-BCAM) were collected through one-on-one investigations. The data were analyzed using descriptive statistics, chi-square tests, and multiple regression analysis in SPSS 26.0. Results: The study included a total of 1468 rural women with a median age of 54.0 (IQR, 47.0, 60.0).The average score of breast cancer in the study population was 73.0 (IQR, 66.0, 82.0). Among women in Southwest China, the awareness rates of knowledge on breast cancer symptoms, barriers to seeking medical help, and risk factors were 68.8%, 98.4%, and 62.1%, respectively. The awareness rate was found to increase with higher education levels (P<0.001) and decrease with increasing age (P<0.001). Multivariate logistic regression analysis identified three variables that might influence breast cancer awareness: education level, contraceptive measures, and history of breast disease (all P<0.05). Specifically, history of breast disease (Odds ratio (OR) = 1.907, 95% CI = 1.128 ~ 3.223), middle school education (OR = 2.155, 95% CI = 1.585 ~ 2.928), and junior college education and above (OR = 5.536, 95% CI = 1.898 ~ 16.148) were positive factors for women's breast cancer awareness. Conversely, the use of intrauterine devices (OR = 0.523, 95% CI = 0.384 ~ 0.712) was found to be a negative factor for women's breast cancer awareness. Conclusion: This study highlights the insufficient awareness of breast cancer among women in rural area of Southwest China. It emphasizes the necessity of health education to improve female breast cancer awareness.

Effect of Tacrolimus Time in Therapeutic Range on Postoperative Recurrence in Patients Undergoing Liver Transplantation for Liver Cancer.

BACKGROUND AND OBJECTIVE: Liver cancer is the second highest cause of cancer-related deaths worldwide. It is commonly treated with liver transplantation, where tacrolimus is typically used as an antirejection immunosuppressant. The purpose of this study was to evaluate the effect of tacrolimus time in therapeutic range (TTR) on liver cancer recurrence in liver transplant recipients and to compare the performance of TTRs calculated according to the target ranges recommended in published guidelines. METHODS: A total of 84 patients who underwent liver transplantation for liver cancer were retrospectively included. Tacrolimus TTR was calculated using linear interpolation from the date of transplantation until recurrence or the last follow-up according to target ranges recommended in the Chinese guideline and international expert consensus. RESULT: Twenty-four recipients developed liver cancer recurrence after liver transplantation. The CTTR (TTR calculated according to the Chinese guideline) for the recurrence group was significantly lower than that of the nonrecurrence group (26.39% vs. 50.27%, P < 0.001), whereas the ITTR (TTR calculated according to the international consensus) was not significantly different between the two groups (47.81% vs. 56.37%, P = 0.165). Multivariate survival analysis revealed that age, microvascular invasion, hepatocellular carcinoma, CTTR, and mean tacrolimus trough concentration were independent predictors of liver cancer recurrence after liver transplantation. CONCLUSIONS: TTR predicts liver cancer recurrence in liver transplant recipients. The range of tacrolimus concentrations recommended in the Chinese guideline was more beneficial than that recommended in the international consensus for Chinese patients undergoing liver transplantation for liver cancer.

Characteristics of dissolved organic matter contribute to Geogenic ammonium enrichment in coastal versus alluvial-lacustrine aquifers.

Elevated concentration levels of geogenic ammonium in groundwater arise from the mineralization of nitrogen-containing natural organic matter in various geological settings worldwide, especially in alluvial-lacustrine and coastal environments. However, the difference in enrichment mechanisms of geogenic ammonium between these two types of aquifers remains poorly understood. To address this knowledge gap, we investigated two representative aquifer systems in central Yangtze (Dongting Lake Plain, DTP) and southern China (Pearl River Delta, PRD) with contrasting geogenic ammonium contents. The use of optical and molecular characterization of DOM combined with hydrochemistry and stable carbon isotopes has revealed differences in DOM between the two types of aquifer systems and revealed contrasting controls of DOM on ammonium enrichment. The results indicated higher humification and degradation of DOM in DTP groundwater, characterized by abundant highly unsaturated compounds. The degradation of DOM and nitrogen-containing DOM was dominated by highly unsaturated compounds and CHO+N molecular formulas in highly unsaturated compounds, respectively. In contrast, the DOM in PRD groundwater was more biogenic, less degraded, and contained more aliphatic compounds in addition to highly unsaturated compounds. The degradation of DOM and nitrogen-containing DOM was dominated by aliphatic compounds and polyphenols and CHO+N molecular formulas in highly unsaturated compounds and polyphenols, respectively. As DOM degraded, the ammonium production efficiency of DOM decreased, contributing to lower ammonium concentrations in DTP groundwater. In addition, the CHO+N(SP) molecular formulas were mainly of microbial-derived and gradually accumulated with DOM degradation. In this study, we conducted the first comprehensive investigation into the patterns of groundwater ammonium enrichment based on DOM differences in various geological settings.

Associations between phthalate metabolites and cytokines in the follicular fluid of women undergoing in vitro fertilization.

Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-α when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI ≥ 23 kg/m2 (test for interaction <0.05). Our results suggest that certain phthalate metabolites or their mixtures may alter levels of inflammatory cytokines in the FF, and further research is necessary to elucidate the mechanisms underlying the relationship between phthalates exposure, ovarian dysfunction and adverse pregnancy outcomes.

Colon-Targeted Release of Turmeric Nonextractable Polyphenols and Their Anticolitis Potential via Gut Microbiota-Dependent Alleviation on Intestinal Barrier Dysfunction in Mice.

Solid evidence has emerged supporting the role of nonextractable polyphenols (NEPs) and dietary fibers (DFs) as gut microbiota modulators. This study aims to elucidate gut microbiota-dependent release of turmeric NEPs and examine the possible anti-inflammatory mechanism in the dextran sulfate sodium-induced ulcerative colitis (UC) model. 1.5% DSS drinking water-induced C57BL/6J mice were fed a standard rodent chow supplemented with or without 8% extractable polyphenols (EPs), NEPs, or DFs for 37 days. The bound curcumin, demethoxycurcumin, and bisdemethoxycurcumin in NEPs were released up to 181.5 ± 10.6, 65.2 ± 6.0, and 69.5 ± 7.6 µg/mL by in vitro gut microbiota-simulated fermentation and released into the colon of NEP-supplemented mice by 5.7-, 11.0-, and 7.8-fold higher than pseudo germ-free mice, respectively (p < 0.05). NEPs also enhanced the colonic microbiota-dependent production of short-chain fatty acids in vitro and in vivo (p < 0.05). Interestingly, NEP feeding significantly improved the DSS-caused gut microbiota disorder, epithelial barrier damage, and inflammation of UC mice better than EPs or DFs (p < 0.05). Meanwhile, the pseudo germ-free mice supplemented with NEPs failed to ameliorate UC symptoms. These findings manifest that turmeric NEPs as macromolecular carriers exert the target delivery of polyphenols into the colon for regulating gut microbiota to restore the impaired gut barrier function for alleviation of inflammation.

Coupled effects of sedimentary iron oxides and organic matter on geogenic phosphorus mobilization in alluvial-lacustrine aquifers.

The organic matter (OM) biodegradation and reductive dissolution of iron oxides have been acknowledged as key factors in the release of geogenic phosphorus (P) to groundwater. However, the coupled effects of natural OM with iron oxides on the mobilization of geogenic P remain unclear. Groundwater with high and low P concentrations has been observed in two boreholes in the alluvial-lacustrine aquifer system of the Central Yangtze River Basin. Sediment samples from these boreholes were examined for their P and Fe species as well as their OM properties. The results show that sediments from borehole S1 with high P levels contain more bioavailable P, particularly iron oxide bound P (Fe-P) and organic P (OP) than those from borehole S2 with low P levels. Regarding borehole S2, Fe-P and OP show positive correlations with total organic carbon as well as amorphous iron oxides (FeOX1), which indicate the presence of Fe-OM-P ternary complexes, further evidenced by FTIR results. In a reducing environment, the protein-like component (C3) and terrestrial humic-like component (C2) will biodegrade. In the process of C3 biodegradation, FeOX1 will act as electron acceptors and then undergo reductive dissolution. In the process of C2 biodegradation, FeOX1 and crystalline iron oxides (FeOX2) will act as electron acceptors. FeOX2 will also act as conduits in the microbial utilization pathway. However, the formation of stable P-Fe-OM ternary complexes will inhibit the reductive dissolution of iron oxides and OM biodegradation, thus inhibiting the mobilization of P. This study provides new insights into the enrichment and mobilization of P in alluvial-lacustrine aquifer systems.

Severe wound infection by MRCNS following bilateral inguinal herniorrhaphy.

BACKGROUND: Wound infection after inguinal hernia surgery is not uncommon in the clinical setting. The common microbial aetiology of postoperative inguinal hernia wound infection is Gram-positive bacteria. Staphylococcus aureus is a common pathogen causing wound infection while Staphylococcus epidermidis and Pseudomonas are rare. Staphylococcus epidermidis as a cause of severe wound infection is rarely described in literature. We herein present a case of a 79-year-old man with a rare wound infection after bilateral inguinal herniorrhaphy caused by MRCNS (Methicillin Resistant Coagulase Negative Staphylococcus). CASE PRESENTATION: We present a case of wound infection accompanied by fever with a temperature of 38.8 °C after bilateral inguinal herniorrhaphy in a 79-year-old man. Bilateral inguinal wounds were marked by redness and swelling, with skin necrosis. In addition, an abscess of approximately 1.5 cm × 1.5 cm was seen on the left wrist. A small amount of gas under the skin in the wound area was observed after pelvic computed tomography (CT) scans. No bacteria were cultured from the inguinal wound discharge, while blood culture detected MRCNS, and Acinetobacter lwoffi was cultured from the pus in the left wrist. We chose appropriate antibiotics based on the results of the bacterial culture and the drug susceptibility results. Vacuum assisted closure (VAC) therapy was used after debridement. The patient was discharged after the wounds improved. He was followed up for ten months and showed no signs of complications. We are sharing our experience along with literature review. CONCLUSIONS: We are presenting a rare case of MRCNS wound infection following open inguinal hernia surgery. Although a rarity, clinicians performing inguinal hernia surgery must consider this entity in an infected wound and follow up the patient for complications of MRCNS.

Integrated single-cell and bulk RNA sequencing analysis identifies a cancer-associated fibroblast-related gene signature for predicting survival and therapy in gastric cancer.

As the dominant component of the tumor microenvironment, cancer-associated fibroblasts (CAFs), play a vital role in tumor progression. An increasing number of studies have confirmed that CAFs are involved in almost every aspect of tumors including tumorigenesis, metabolism, invasion, metastasis and drug resistance, and CAFs provide an attractive therapeutic target. This study aimed to explore the feature genes of CAFs for potential therapeutic targets and reliable prediction of prognosis in patients with gastric cancer (GC). Bioinformatic analysis was utilized to identify the feature genes of CAFs in GC by performing an integrated analysis of single-cell and transcriptome RNA sequencing using R software. Based on these feature genes, a CAF-related gene signature was constructed for prognostic prediction by LASSO. Simultaneously, survival analysis and nomogram were performed to validate the prognostic predictive value of this gene signature, and qRT-PCR and immunohistochemical staining verified the expression of the feature genes of CAFs. In addition, small molecular drugs for gene therapy of CAF-related gene signatures in GC patients were identified using the connectivity map (CMAP) database. A combination of nine CAF-related genes was constructed to characterize the prognosis of GC, and the prognostic potential and differential expression of the gene signature were initially validated. Additionally, three small molecular drugs were deduced to have anticancer properties on GC progression. By integrating single-cell and bulk RNA sequencing analyses, a novel gene signature of CAFs was constructed. The results provide a positive impact on future research and clinical studies involving CAFs for GC.

Link between sterile inflammation and cardiovascular diseases: Focus on cGAS-STING pathway in the pathogenesis and therapeutic prospect.

Sterile inflammation characterized by unresolved chronic inflammation is well established to promote the progression of multiple autoimmune diseases, metabolic disorders, neurodegenerative diseases, and cardiovascular diseases, collectively termed as sterile inflammatory diseases. In recent years, substantial evidence has revealed that the inflammatory response is closely related to cardiovascular diseases. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway which is activated by cytoplasmic DNA promotes the activation of interferon regulatory factor 3 (IRF3) or nuclear factor-κB (NF-κB), thus leading to upregulation of the levels of inflammatory factors and interferons (IFNs). Therefore, studying the role of inflammation caused by cGAS-STING pathway in cardiovascular diseases could provide a new therapeutic target for cardiovascular diseases. This review focuses on that cGAS-STING-mediated inflammatory response in the progression of cardiovascular diseases and the prospects of cGAS or STING inhibitors for treatment of cardiovascular diseases.

Gene expression and methylation profiles show the involvement of POMC in primary hyperparathyroidsm.

Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma, which produces excess parathyroid hormones. Its pathogenic mechanisms have not yet been fully understood. To investigate the mechanism in the pathogenesis of PHPT, the transcriptome and genome-wide DNA methylation profiles of parathyroid adenoma were analyzed. The candidate genes that may be involved in the PHPT were verified via qRT-PCR, immunohistochemistry, western blot, and methylation-specific PCR. A total of 1650 differentially expressed genes and 2373 differentially methylated regions were identified. After the integration of its transcriptome and DNA methylation data, IL6, SYP, GNA01, and pro-opiomelanocortin (POMC) were the candidate genes that demonstrated a similar pattern between their mRNA expression and DNA methylation status. Of the 4 candidate genes, POMC, a pro-peptide which is processed to a range of bioactive peptide products like ACTH, was further confirmed to be expressed at low levels at both the mRNA and protein levels, which may be due to POMC promoter hypermethylation. Hypermethylation of the POMC promoter may contribute to its low expression, which may be involved in the pathogenesis of PHPT.

Feammox in alluvial-lacustrine aquifer system: Nitrogen/iron isotopic and biogeochemical evidences.

Groundwater nitrogen contamination is becoming increasingly serious worldwide, and natural nitrogen attenuation processes such as anaerobic ammonium oxidation coupled to iron reduction ("Feammox") play an important role in mitigating contamination. Although there has been intensive study of Feammox in soils and sediments, still lacks research on this process in groundwater. This study makes effort to demonstrate the occurrence of Feammox in groundwater by combining information from Fe/N isotope composition, the quantitative polymerase chain reaction (qPCR) assay, and 16S rRNA gene sequencing. Poyang Lake Plain of Yangtze River in central China was selected as the case study area. The critical evidences that indicate Feammox in groundwater include favorable hydrogeochemical conditions of the alluvia-lacustrine aquifer systems, the simultaneous enrichment of 15N in ammonium and 56Fe, the relative high abundance of Acidimicrobiaceae bacterium A6, and the joint elevation of the abundance of the Feammox bacteria and the concentration of Fe(III). Redundancy analysis (RDA) indicated that Geothrix and Rhodobacter may participate directly or cooperatively in the Feammox process. Ammonium-oxidizing archaea (AOA) involved in ammonium-oxidizing or Feammox process may be stimulated by Fe(III) under a low oxygen concentration and weakly acidic condition. Anammox may be indirectly enhanced by products of the nitrogen transformation processes involving Feammox bacteria and AOA. Fe(III) concentration is an important environmental factor affecting the abundance of functional microorganisms related to nitrogen cycling and the composition of ammonium-oxidizing and iron-reducing microbes. Specific geological background (such as the widespread red soils) and anthropogenic input of ammonium, iron, and acidic substances may jointly promote Feammox in groundwater.

Identification of a Novel Glycosyltransferase Prognostic Signature in Hepatocellular Carcinoma Based on LASSO Algorithm.

Although many prognostic models have been developed to help determine personalized prognoses and treatments, the predictive efficiency of these prognostic models in hepatocellular carcinoma (HCC), which is a highly heterogeneous malignancy, is less than ideal. Recently, aberrant glycosylation has been demonstrated to universally participate in tumour initiation and progression, suggesting that dysregulation of glycosyltransferases can serve as novel cancer biomarkers. In this study, a total of 568 RNA-sequencing datasets of HCC from the TCGA database and ICGC database were analysed and integrated via bioinformatic methods. LASSO regression analysis was applied to construct a prognostic signature. Kaplan-Meier survival, ROC curve, nomogram, and univariate and multivariate Cox regression analyses were performed to assess the predictive efficiency of the prognostic signature. GSEA and the "CIBERSORT" R package were utilized to further discover the potential biological mechanism of the prognostic signature. Meanwhile, the differential expression of the prognostic signature was verified by western blot, qRT-PCR and immunohistochemical staining derived from the HPA. Ultimately, we constructed a prognostic signature in HCC based on a combination of six glycosyltransferases, whose prognostic value was evaluated and validated successfully in the testing cohort and the validation cohort. The prognostic signature was identified as an independent unfavourable prognostic factor for OS, and a nomogram including the risk score was established and showed the good performance in predicting OS. Further analysis of the underlying mechanism revealed that the prognostic signature may be potentially associated with metabolic disorders and tumour-infiltrating immune cells.

Unraveling the impact of iron oxides-organic matter complexes on iodine mobilization in alluvial-lacustrine aquifers from central Yangtze River Basin.

The biodegradation of organic matter triggers the reductive dissolution of iron oxides with the transformation among iodine species has been mostly accepted as the key iodine mobilization process in groundwater system. However, molecular characteristics of natural organic matter (NOM) and their interaction with iron oxides on geogenic iodine enrichment remain unclear. We used Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to characterize the molecular composition of both dissolved organic matter (DOM) in groundwater and water-soluble organic matter (WSOM) in aquifer sediments being depth-matched with groundwater from monitoring wells in typical iodine-affected aquifers within the central Yangtze River Basin. The results show that WSOM in high-iodine sediments contains more high molecular weight (HMW) organic compounds with higher aromaticity and nominal oxidation state of carbon (NOSC), including polycyclic aromatics, polyphenols and highly unsaturated compounds. These compounds are mostly positively associated with amorphous iron oxides (Feox1) in aquifer sediments. The association between iodine and WSOM is highly consistent with that between amorphous Feox1 and WSOM, but is contrary to that between crystalline iron oxides (Feox2) and WSOM. DOM in groundwater with higher iodine concentration contains more aliphatic compounds and less polyphenols. The complexation of HMW organic compounds of WSOM to iodine-bearing amorphous Feox1 plays an important role in iodine mobilization, which could inhibit the amorphous Feox1 transformation to crystalline Feox2. These observations indicate the biodegradation of HMW organic matter (polycyclic aromatics, polyphenols and highly unsaturated compounds) in WSOM fueling the reductive dissolution of amorphous Feox1 predominantly promotes the release of iodine from aquifer sediments into groundwater. This research provides new insights into the mobilization mechanisms of iodine in alluvial-lacustrine groundwater system controlled by the Fe-OM complexation at the molecular level.

Synthesis and bioevaluation of diaryl urea derivatives as potential antitumor agents for the treatment of human colorectal cancer.

The development of inhibitors targeting the PI3K-Akt-mTOR signaling pathway has been greatly hindered by the on-target AEs, such as hyperglycemia and hepatotoxicities. In this study, a series of diaryl urea derivatives has been designed and synthesized based on clinical candidate gedatolisib (6aa), and most of the newly synthesized derivatives showed kinase inhibitory and antiproliferative activities within nanomolar and submicromolar level, respectively. The terminal l-prolineamide substituted derivative 6 ab showed 8.6-fold more potent PI3Kα inhibitory activity (0.7 nM) and 4.6-fold more potent antiproliferative effect against HCT116 cell lines (0.11 µM) compared with control 6aa. The potential antitumor mechanism and efficacy of 6 ab in HCT116 xenograft models have also been evaluated, and found 6 ab showed comparable in vivo antitumor activity with 6aa. The safety investigations revealed that compound 6 ab exhibited more safer profiles in the selectivity of liver cells (selectivity index: >6.6 vs 1.85) and blood glucose regulation than 6aa. In addition, the in vitro stability assays also indicated our developed compound 6 ab possessed good metabolic stabilities.

Distribution, bioavailability, and human health risk assessment of arsenic in groundwater-soil-rice system in the Jianghan Plain, Central China.

Many studies have reported high arsenic concentrations in the groundwater and soil of the Jianghan Plain (JHP), an important rice production base in China. However, no comprehensive study on the occurrence and risk of As in groundwater-soil-rice systems in this region has been conducted. In this study, As concentrations in groundwater, soil, rice straw, and rice grain samples were analyzed. Arsenic concentrations were found to range from BDL to 42.88 µg/L (median 0.34 µg/L) in phreatic water, BDL to 41.77 µg/L (median 8.64 µg/L) in soil pore water, 10.20 to 21.90 mg/kg (mean 16.52 mg/kg) in soil, 0.204 to 2.860 mg/kg (mean 0.847 mg/kg) in rice straw, and 0.131 to 0.951 mg/kg (mean 0.449 mg/kg) in rice grain. Arsenic uptake by rice from soils was evaluated according to bioavailable As defined by chemical extraction and diffusive gradients in thin films. The results indicated that owing to the low content of highly mobile As fractions, the less mobile As fraction (mainly bound with amorphous Fe/Al (hydr)oxides) also contributed to bioavailable As, suggesting that amorphous Fe/Al bound As should be considered in analyzing bioavailable As. In terms of the geoaccumulation index and the Chinese paddy soil standard (GB15618-2018) limit (25 mg/kg), As pollution in water and soils in the study area is at a low level and can be considered relatively safe. However, the target hazard quotients and cancer risk assessment indicated that As pollution is at a dangerous level with potential human health risk. According to the bioconcentration factor, the bioavailability of soil is higher in JHP compared with other rice-growing areas owing to the unique hydrogeological conditions and irrigation using groundwater with high As content. Rice planting areas in JHP should be set as far away from large rivers as possible, and groundwater with high As concentrations must be pre-treated prior to irrigation.