Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) is a serious threat to public health, but its underlying mechanism remains poorly understood. In screening important genes using Gene Importance Calculator (GIC) we developed previously, ribosomal modification protein rimK-like family member A (RIMKLA) was predicted as one essential gene but its functions remained largely unknown. The current study determined the roles of RIMKLA in regulating glucose and lipid metabolism. RIMKLA expression was reduced in livers of human and mouse with NAFLD. Hepatic RIMKLA overexpression ameliorated steatosis and hyperglycemia in obese mice. Hepatocyte-specific RIMKLA knockout aggravated high-fat diet (HFD)-induced dysregulated glucose/lipid metabolism in mice. Mechanistically, RIMKLA is a new protein kinase that phosphorylates betaine-homocysteine S-methyltransferase 1 (BHMT1) at threonine 45 (Thr45) site. Upon phosphorylation at Thr45 and activation, BHMT1 eliminated homocysteine (Hcy) to inhibit the activity of transcription factor activator protein 1 (AP1) and its induction on fatty acid synthase (FASn) and cluster of differentiation 36 (CD36) gene transcriptions, concurrently repressing lipid synthesis and uptake in hepatocytes. Thr45 to alanine (T45A) mutation inactivated BHMT1 to abolish RIMKLA's repression on Hcy level, AP1 activity, FASn/CD36 expressions, and lipid deposition. BHMT1 overexpression rescued the dysregulated lipid metabolism in RIMKLA-deficient hepatocytes. In summary, RIMKLA is a novel protein kinase that phosphorylates BHMT1 at Thr45 to repress lipid synthesis and uptake. Under obese condition, inhibition of RIMKLA impairs BHMT1 activity to promote hepatic lipid deposition.

Spatiotemporal variations and priority ranking of emerging contaminants in nanwan reservoir: A case study from the agricultural region in huaihe river basin in China.

The presence of emerging contaminants (ECs) in drinking water sources is an increasing concern, yet limited data exists on their occurrence and risk in the upper Huaihe River Basin, an important agricultural region in Central China. This study investigated 70 ECs, including pesticide and antibiotics in surface water from drinking water source areas in Nanwan Reservoir along the upper reaches of the Huaihe River Basin to prioritize the ECs based on ecological risk and health risk assessment. A total of 66 ECs were detected in the surface water at least once at the selected 38 sampling sites, with concentrations ranging from 0.04 to 2508 ng/L. Ecological risk assessment using the risk quotient (RQ) method revealed high risks (RQ > 1) from 7 ECs in the dry season and 15 ECs in the wet season, with triazine pesticides as the main contributors. Non-carcinogenic risks were below negligible levels, but carcinogenic risks from neonicotinoid and carbamate pesticides and macrolide antibiotics were concerning for teenagers. Ciprofloxacin exhibited a high level of resistance risk during the wet season. A multi-indicator prioritization approach integrating occurrence, risk, and chemical property data ranked 6 pesticides and 3 antibiotics as priority pollutants. The results highlight EC contamination of drinking water sources in this agriculturally-intensive region and the need for targeted monitoring and management to protect water quality.

Global occurrence, distribution, and ecological risk assessment of psychopharmaceuticals and illicit drugs in surface water environment: A meta-analysis.

Psychopharmaceuticals and illicit drugs (PIDs) in aquatic environments can negatively impact ecosystem and human health. However, data on the sources, distribution, drivers, and risks of PIDs in global surface waters are limited. We compiled a dataset of 331 records spanning 23 PIDs in surface waters and sediments across 100 countries by conducting a systematic review and meta-analysis of 108 studies published between 2005 and 2022. Most PIDs were sewage-derived, as wastewater treatment rarely achieved complete removal. The highest total PID levels were in Ethiopia, Australia, and Armenia, with many highly contaminated samples from low- and middle-income countries with minimal prior monitoring. Socioeconomic factors (population, GDP) and environmental variables (water stress) influenced the distribution of PIDs. 3,4-Methylenedioxy amphetamine hydrochloride (MDA), Δ9-tetrahydrocannabinol (THC), and 11- Δ9­hydroxy-tetrahydrocannabinol (THCOH) posed the greatest ecological risks, especially in Oceania and North America. PIDs in surface waters present risks to aquatic organisms. Our findings elucidate the current status and future directions of PID research in surface waters and provide a scientific foundation for evaluating ecological risks and informing pollution control policies.

Recent advances in the application of [2 + 2] cycloaddition in the chemical synthesis of cyclobutane-containing natural products.

Cyclobutanes are distributed widely in a large class of natural products featuring diverse pharmaceutical activities and intricate structural frameworks. The [2 + 2] cycloaddition is unequivocally the primary and most commonly used method for synthesizing cyclobutanes. In this review, we have summarized the application of the [2 + 2] cycloaddition with different reaction mechanisms in the chemical synthesis of selected cyclobutane-containing natural products over the past decade.

PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis.

BACKGROUND: Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet ß cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed. METHODS: db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein-protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays. RESULTS: In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P < 0.01). Hepatic PANX1 overexpression ameliorated the dysregulated glucolipid metabolism in obese mice. Mice with hepatic PANX1 knockdown or global PANX1 knockout exhibited disturbed glucolipid metabolism. Restoration of hepatic PANX1 rescued the metabolic disorders of PANX1-deficient mice (P < 0.05). Mechanistically, ATP release is mediated by the PANX1-activated protein kinase B-forkhead box protein O1 (Akt-FOXO1) pathway to inhibit gluconeogenesis via P2Y receptors in hepatocytes. PANX1-mediated ATP release also activated calmodulin (CaM) (P < 0.01), which interacted with c-Jun N-terminal kinase (JNK) to inhibit its activity, thereby deactivating the transcription factor activator protein-1 (AP1) and repressing fatty acid synthase (FAS) expression and lipid synthesis (P < 0.05). FAM3A stimulated the expression of PANX1 via heat shock factor 1 (HSF1) in hepatocytes (P < 0.05). Notably, FAM3A overexpression failed to promote ATP release, inhibit the expression of gluconeogenic and lipogenic genes, and suppress gluconeogenesis and lipid deposition in PANX1-deficient hepatocytes and livers. CONCLUSIONS: PANX1-mediated release of ATP plays a crucial role in maintaining hepatic glucolipid homeostasis, and it confers FAM3A's suppressive effects on hepatic gluconeogenesis and lipogenesis.

Hepatocyte-secreted FAM3D ameliorates hepatic steatosis by activating FPR1-hnRNP U-GR-SCAD pathway to enhance lipid oxidation.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide; however, the underlying mechanisms remain poorly understood. FAM3D is a member of the FAM3 family; however, its role in hepatic glycolipid metabolism remains unknown. Serum FAM3D levels are positively correlated with fasting blood glucose levels in patients with diabetes. Hepatocytes express and secrete FAM3D, and its expression is increased in steatotic human and mouse livers. Hepatic FAM3D overexpression ameliorated hyperglycemia and steatosis in obese mice, whereas FAM3D-deficient mice exhibited exaggerated hyperglycemia and steatosis after high-fat diet (HFD)-feeding. In cultured hepatocytes, FAM3D overexpression or recombinant FAM3D protein (rFAM3D) treatment reduced gluconeogenesis and lipid deposition, which were blocked by anti-FAM3D antibodies or inhibition of its receptor, formyl peptide receptor 1 (FPR1). FPR1 overexpression suppressed gluconeogenesis and reduced lipid deposition in wild hepatocytes but not in FAM3D-deficient hepatocytes. The addition of rFAM3D restored FPR1's inhibitory effects on gluconeogenesis and lipid deposition in FAM3D-deficient hepatocytes. Hepatic FPR1 overexpression ameliorated hyperglycemia and steatosis in obese mice. RNA sequencing and DNA pull-down revealed that the FAM3D-FPR1 axis upregulated the expression of heterogeneous nuclear ribonucleoprotein U (hnRNP U), which recruits the glucocorticoid receptor (GR) to the promoter region of the short-chain acyl-CoA dehydrogenase (SCAD) gene, promoting its transcription to enhance lipid oxidation. Moreover, FAM3D-FPR1 axis also activates calmodulin-Akt pathway to suppress gluconeogenesis in hepatocytes. In conclusion, hepatocyte-secreted FAM3D activated the FPR1-hnRNP U-GR-SCAD pathway to enhance lipid oxidation in hepatocytes. Under obesity conditions, increased hepatic FAM3D expression is a compensatory mechanism against dysregulated glucose and lipid metabolism.

[Occurrence Distribution and Risk Assessment of Organophosphate Esters in A Typical Area of the Estuary in the Yellow River Basin].

As a type of emerging pollutant, organophosphate esters (OPEs) have the characteristics of toxicity, persistence, and bioaccumulation. Due to their wide use in production and life, OPEs pose potential risks to ecosystems when they enter the environment. In this study, the concentrations of 14 species of OPEs in surface water were determined using UPLC-MS/MS, and the spatial distribution of the OPEs in the surface water of the estuary of the Yellow River basin was further analyzed. The pollution sources were analyzed using correlation analysis and principal component analysis, and the ecological risk was evaluated. The results indicated that the concentration of Σ14OPEs in surface water ranged from 183.81 to 1674.52 ng·L-1, with an average concentration of 638.25 ng·L-1. Tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propanyl) phosphate (TCPP) were the main OPEs. The Xiaoqing River flowing through the urban area differed from the main stream of the Yellow River and other branches in terms of OPEs composition characteristics, which showed a greater impact from human activities. The distribution of Σ14OPEs showed an obvious regional pattern, with a trend of increasing and then decreasing along the direction of the Yellow River inlet. The results of source analysis revealed that human activities such as industrial wastewater discharge from different industries, transportation, and atmospheric deposition were the sources of OPEs in surface water. The ecological risk assessment results indicated that TCEP posed a high risk to aquatic organisms in the main stream of the Yellow River, Xiaoqing River, and Zhimai River, and tri-n-butyl phosphate (TnBP) and triphenyl phosphate (TPhP) posed a low risk at some sites.

FAM3A maintains metabolic homeostasis by interacting with F1-ATP synthase to regulate the activity and assembly of ATP synthase.

Reduced mitochondrial ATP synthase (ATPS) capacity plays crucial roles in the pathogenesis of metabolic disorders. However, there is currently no effective strategy for synchronously stimulating the expressions of ATPS key subunits to restore its assembly. This study determined the roles of mitochondrial protein FAM3A in regulating the activity and assembly of ATPS in hepatocytes. FAM3A is localized in mitochondrial matrix, where it interacts with F1-ATPS to initially activate ATP synthesis and release, and released ATP further activates P2 receptor-Akt-CREB pathway to induce FOXD3 expression. FOXD3 synchronously stimulates the transcriptions of ATPS key subunits and assembly genes to increase its assembly and capacity, augmenting ATP synthesis and inhibiting ROS production. FAM3A, FOXD3 and ATPS expressions were reduced in livers of diabetic mice and NAFLD patients. FOXD3 expression, ATPS capacity and ATP content were reduced in various tissues of FAM3A-deficient mice with dysregulated glucose and lipid metabolism. Hepatic FOXD3 activation increased ATPS assembly to ameliorate dysregulated glucose and lipid metabolism in obese mice. Hepatic FOXD3 inhibition or knockout reduced ATPS capacity to aggravate HFD-induced hyperglycemia and steatosis. In conclusion, FAM3A is an active ATPS component, and regulates its activity and assembly by activating FOXD3. Activating FAM3A-FOXD3 axis represents a viable strategy for restoring ATPS assembly to treat metabolic disorders.

Imipramine activates FAM3A-FOXA2-CPT2 pathway to ameliorate hepatic steatosis.

Mitochondrial FAM3A has been revealed to be a viable target for treating diabetes and nonalcoholic fatty liver disease (NAFLD). However, its distinct mechanism in ameliorating hepatic steatosis remained unrevealed. High-throughput RNA sequencing revealed that carnitine palmityl transferase 2 (CPT2), one of the key enzymes for lipid oxidation, is the downstream molecule of FAM3A signaling pathway in hepatocytes. Intensive study demonstrated that FAM3A-induced ATP release activated P2 receptor to promote the translocation of calmodulin (CaM) from cytoplasm into nucleus, where it functioned as a co-activator of forkhead box protein A2 (FOXA2) to promote the transcription of CPT2, increasing free fatty acid oxidation and reducing lipid deposition in hepatocytes. Furthermore, antidepressant imipramine activated FAM3A-ATP-P2 receptor-CaM-FOXA2-CPT2 pathway to reduce lipid deposition in hepatocytes. In FAM3A-deficient hepatocytes, imipramine failed to activate CaM-FOXA2-CPT2 axis to increase lipid oxidation. Imipramine administration significantly ameliorated hepatic steatosis, hyperglycemia and obesity of obese mice mainly by activating FAM3A-ATP-CaM-FOXA2-CPT2 pathway in liver and thermogenesis in brown adipose tissue (BAT). In FAM3A-deficient mice fed on high-fat-diet, imipramine treatment failed to correct the dysregulated lipid and glucose metabolism, and activate thermogenesis in BAT. In conclusion, imipramine activates FAM3A-ATP-CaM-FOXA2-CPT2 pathway to ameliorate steatosis. For depressive patients complicated with metabolic disorders, imipramine may be recommended in priority as antidepressive drug.

Factors determining household-level food insecurity during COVID-19 epidemic: a case of Wuhan, China.

BACKGROUND: In coping with the coronavirus disease 2019 (COVID-19) epidemic, cities adopted social isolation and lockdown measures; however, little is known about the impacts of these restrictions on household food security. OBJECTIVE: This study provides a timely assessment of household food insecurity (HFI) in the Chinese city of Wuhan during the COVID-19 epidemic period and also investigates its determinant factors. DESIGN: We collected valid data on food insecurity from 653 households in Wuhan via an online questionnaire in March 2020. The Household Food Insecurity Access Scale Score (HFIASS) was used to measure HFI, and a multiple linear regression model was used to determine the HFIASS. RESULTS: The mean HFIASS in Wuhan was 9.42 (standard deviation: 5.82), with more than 50% of the households had an HFIASS < 9. Compared with normal conditions, lockdown measures had a huge negative impact on household food security. The results revealed that socio-demographic characteristics remained the underlying determinants of HFIASS during the epidemic. Households in Wuhan with local Hukou (city household registration) and self-owned property had a lower risk of food insecurity. DISCUSSION AND CONCLUSION: After the restriction of conventional food access channels, intermediary food purchase methods such as group purchasing, shopping with the help of neighborhood committees, property management agents, and volunteers became the most important or the only channel for residents to access food. There were similarities in the use of these intermediary channels. Based on the probability that the epidemic will continue and the probability of similar public health-related outbreaks in the future, the study calls for a more resilient and responsive sustainable food supply system by harnessing the capacity of communities, e-commerce and rapid logistics.

Aqueous chlorination of ephedrine: Kinetic, reaction mechanism and toxicity assessment.

Ephedrine (EPH) is widely detected in the water environment, because it is the major ingredient in drugs treating influenza, asthma or hypotension, and is also a highly sought-after chemical precursor in the illicit manufacture of methamphetamine. In this study, transformation of EPH during the chlorination process was investigated for the first time, and the impact of water parameters including pH, different cations and anions on EPH transformation was evaluated as well. The degradation of EPH in the presence of NaClO fit the second order reaction kinetics, with a rate constant of 7.43 × 102 ((mol·L-1)-1·min-1). Increasing the dosage of NaClO increased the observed pseudo first order rate constant for EPH degradation (kobs). Degradation rate of EPH decreased with the increasing pH from 2.0 to 10.0, due to the formation of a chlorammonium intermediate that reacted with NaClO. Low concentration of Br- and I- did not exert significant influence on the degradation of EPH, while at high concentrations a promotive effect was observed. Other ions including Fe3+, Cu2+, NO3-, SO42-, Mg2+ and Ca2+ exerted negative effects even at relatively low concentrations. Based on the degradation products/intermediates identified by UPLC-MS/MS, the EPH degradation pathways were proposed. The reaction mechanism involved in the EPH degradation included dehydration, hydroxylation, deamination and demethylation. Toxicity assays by V. qinghaiensis sp. nov proved that the EPH transformation products were much more toxic than the parent compound. Results indicated that chlorination is an effective approach for the elimination of EPH in the aquatic environment, however, attention should be paid to its toxicity involvement during the chlorination process.

Health Risk Assessment and Source Apportionment for Heavy Metals in a Southern Chinese Reservoir Impacted by Stone Mining Activities.

Metal contaminants in drinking water pose a potential threat to human health. Metal elements (Fe, Mn, Cu, Cr, Cd, As, and Pb) in Shanzi Reservoir, China, a drinking water source for nearby cities, were measured in 2013 and 2014. The distribution characteristics of metal elements in water were identified and a health risk assessment model was used to evaluate potential harm. Principal component analysis and cluster analysis were used to determine the main sources of metal pollutants. The results showed that Pb and As exceeded the standard at some sampling sites, whereas other metal elements met the drinking water standards. The spatial distribution of metal elements was extremely uneven and might be affected by either the geochemical environment or human activities in the study region. The total risk value of metals (5 × 10-5 a-1 ) was below the recommended value of the United States Environmental Protection Agency (USEPA), the total cancer risk was higher than the total noncancer risk, and both risks were higher for children than for adults. Arsenic was the priority control pollutant, and the priority control site was located upstream of the reservoir. Source analysis showed that Fe, Mn, and Cu were mainly from soil formation and stone mining and processing industries; Pb and As were mainly from agricultural activities, free dumping and burning of domestic garbage, and atmospheric deposition from transportation emissions; Cd was mainly from agricultural application of fertilizers and pesticides; and Cr was from the stone mining and processing industry and from the electroplating and metal manufacturing industries. Integr Environ Assess Manag 2020;16:342-352. © 2019 SETAC.

Occurrence and Risk Assessment of Antibiotics in Manure, Soil, Wastewater, Groundwater from Livestock and Poultry Farms in Xuzhou, China.

Antibiotics in manure, soil, wastewater, and groundwater samples from the livestock and poultry farms in Xuzhou City were investigated in the present study. The concentrations of antibiotics in all matrices varied greatly among farms. Total concentrations of fluoroquinolones and macrolides were much higher than those of sulfonamides in manures and soil samples. Total concentrations of antibiotics in wastewater of livestock farms were higher than those of poultry farm. Josamycin (JM) and tilmicosin (TIL) accounted for more than 74% of the nine macrolides in all groundwater samples. Sulfamethizole (SMT), fleroxacin (FLE), cinoxacin (CIN) and JM were the main antibiotics detected in manure and soil samples, while sulfamethoxypyridazine (SMP), sulfameter (SME), SMT, FLE, JM and TIL accounted for a large proportion of antibiotics in surface and groundwater. The risk assessment of target antibiotics revealed that JM in wastewater showed relatively high RQs for aquatic organisms.

In-situ fabrication of Ag/P-g-C3N4 composites with enhanced photocatalytic activity for sulfamethoxazole degradation.

A series of Ag/P-g-C3N4 composites with different Ag content were synthesized for the first time by thermal polymerization combined with photo-deposition method. The composites were characterized by X-ray powder diffraction, field emission scanning electron microscope coupled with energy-dispersive X-ray spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, ultraviolet-visible diffuse reflectance spectra, N2 absorption-desorption and X-ray photoelectron spectroscopy. Ag was successfully dispersed on the surface of P-g-C3N4. The photocatalytic performance of P-g-C3N4 and Ag/P-g-C3N4 was evaluated by degrading sulfamethoxazole (SMX) under visible light irradiation. In the presence of 5% Ag/P-g-C3N4, 100% of SMX was degraded within 20 min. The enhanced photocatalytic activity of Ag/P-g-C3N4 was attributed to the surface plasmon resonance effect of metallic Ag and Schottky barrier formed on the interface between Ag and P-g-C3N4, which could speed up the generation rate of electrons and holes and inhibit the recombination of photogenerated electron-hole pairs. The radical quenching tests indicated that holes and superoxide radicals were the dominant active species involved in SMX degradation. The synthesized materials maintained high catalytic activity after five cycle runs. The concentration and the intermediates during the degradation process were determined by LC-MS/MS, and the tentative degradation pathways of SMX in photocatalytic system were proposed.

Spatiotemporal profile of tetracycline and sulfonamide and their resistance on a catchment scale.

Tetracyclines and sulfonamides are the two classes of antibiotics commonly used in the medical, industrial and agricultural activities. Their extensive usage has caused the proliferation and propagation of resistant bacteria (ARB) and resistance genes (ARGs) in the environment. In this study, the occurrence and distribution of tetracyclines (TC, OTC and CTC) and sulfonamides (SMX, SCX and TMP), their associated ARB and ARGs were quantified in water and sediments collected from the mainstream of Liaohe River, northeast China. The average concentration of tetracyclines was higher in May, while the concentration of sulfonamides was slightly higher in October. The highest concentrations of the total tetracyclines and sulfonamides in sediments were 2.7×103 ng/g and 2.1×102 ng/g respectively detected in May. All detected ARGs were found generally with high abundance. The tetA, tetB and tetE genes were dominant (4.4×10-2 to 9.8×10-1 copies of tet genes/copies of 16S rRNA genes) in total communities, and the average abundance of sul genes was expressed above 10-1 in the water samples in May and October. Redundance analysis (RDA) and principle component analysis (PCA) indicated that the antibiotic residue was the most important contributor to the level of tetracycline and sulfonamide resistance genes, and some hydrogeological conditions (e.g. flow rate, intersection settlement) influenced the distribution of resistance genes. Results from this study could help understand the proliferation and propagation of antibiotic resistance on a river catchment scale and mitigate the potential risks to public health.

Predicting trace metal bioavailability to chironomids in sediments by diffusive gradients in thin films.

The technique of diffusive gradients in thin films (DGT) has been developed as a promising tool to assess metal bioavailability in sediment. However, it has yet to be determined whether the DGT-labile metal in sediment is representative of bioavailable fraction for benthic organisms. In this study, the performance of DGT for predicting metal bioavailability was evaluated by exposing DGT and chironomids Chironomus tentans to a series of metal-contaminated natural sediments in the laboratory. Conventional methods, including acid-volatile sulfides and simultaneously extracted metals method, and total recoverable and dilute-acid extractable metal concentrations were also used to assess the availability of Zn, Cu and Pb to chironomids. The bioassay results showed that >70% of the larvae (73 ±â€¯1.7%-98 ±â€¯0.5%) survived in all sediment samples, however, an enhanced uptake of Zn, Cu and Pb by C. tentans in contaminated sediments was observed compared to control sediments. The correlation analyses indicated that the total recoverable metal concentrations and DGT-metal fluxes in the surficial sediment (-1 cm) were all significantly associated with metal bioaccumulation in C. tentans (p < 0.01). Given the advantages of DGT devices for in situ and time-averaged measurement of the potentially bioavailable fraction, DGT-metal fluxes were proved to be a better surrogate to predict C. tentans response to metal contamination. The results further supported the applicability of the DGT technique as an alternative method to assess the bioavailability of metals in sediment to benthic invertebrates.

Development and application of the diffusive gradients in thin films technique for simultaneous measurement of methcathinone and ephedrine in surface river water.

In this study, a passive sampling technique, diffusive gradients in thin films (DGT) was developed to simultaneously measure two drugs, methcathinone (MC) and ephedrine (EPH) in surface water. Four types of binding gels and four types of filter membranes were tested for the optimal configuration. XAD18 agarose binding gel and agarose diffusive gel, together with polyethersulfone filter membrane were used for measuring MC and EPH in the DGT device. 5% NH3 in acetonitrile was used as the elution solvent, with the elution efficiency for MC and EPH higher than 71%. At 25°C, the diffusion coefficients of MC and EPH in the diffusive gel were 7.60×10-6cm2s-1 and 6.62×10-6cm2s-1, respectively. The DGT was effective in a wide range of pH (4-11) and ionic strength (NaCl: 0.001-0.5M). The DGT device was deployed in Beijing urban surface water for successive 7days to measure the time-weighted concentrations of MC and EPH. Results showed that EPH was detected in all samples, while MC was below its detection limit. DGT concentrations were comparable to the concentrations determined by SPE. This study demonstrated that the developed DGT method was effective to monitor the two drugs in surface water in situ.

MiR-92a promotes stem cell-like properties by activating Wnt/ß-catenin signaling in colorectal cancer.

We previously reported the oncogenic function of miR-92a in colorectal cancer. This study identified that miR-92a was upregulated in chemoresistant colorectal cancer cells and tissues. Ectopic expression of miR-92a conferred resistance to 5-fluorouracil-induced apoptosis in vitro, while antagomiR-92a significantly enhanced chemosensitivity in vivo. Moreover, Overexpression of miR-92a promoted the tumor sphere formation and the expression of stem cell markers. MiR-92a overexpression also displayed higher tumourigenesis in vivo. Furthermore, we demonstrated that miR-92a upregulates the Wnt/ß-catenin signaling activity via directly targeting KLF4, GSK3ß and DKK3, which are multiple level negative regulators of the Wnt/ß-catenin signaling cascade. In addition, our results indicate IL-6/STAT3 pathway increases miR-92a expression by directly targeting its promoter, resulting in Wnt/ß-catenin signaling activation and consequent promotion of stem-like phenotypes of colorectal cancer cells. Our present results suggest the essential role of IL-6/STAT3/miR-92a/Wnt/ß-catenin pathway in regulating the stem cell-like traits of colorectal cancer cells and provide a potential target for colorectal cancer therapy.

[Effect of Acupuncture at Thirteen Evil Acupoints on Liver Function, and the Contents of Blood Ammonia and ß-endorphin in Patients with Hepatic Encephalopathy].

OBJECTIVE: To observe the therapeutic effect of acupuncture at thirteen evil acupoints in patients with hepatic encephalopathy, and to explore its possible mechanism. METHODS: Patients with hepatic encephalopathy were randomly divided into acupuncture group (n=38) and western medicine group (n=36). Patients in the western medicine group were treated by intravenous injection of aspartate ornithine and branched chain amino acids, and those in the acupuncture group were treated with acupuncture at thirteen evil acupoints on the basis of the western medicine. All the patients were treated for 1 week. The liver function and blood ammonia were measured by automatic biochemical analyzer. The changes of plasma ß-endorphin were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Following the treatment, of the 36 and 38 hepatic encep-halopathy patients in the western medicine and acupuncture groups, 12 and 18 experienced a marked improvement in their symptoms, 13 and 16 were effective, and 11 and 4 invalid, with the effective rates being 69.4% and 89.5%, respectively. Compared with pre-treatment, the levels of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, and plasma ß-endo-rphin and blood ammonia were significantly lower in both western medicine and acupuncture groups(P<0.01), and the therapeutic effects of the acupuncture group were obviously superior to those of the western medicine group in the above mentioned indexes (P<0.05, P<0.01). CONCLUSIONS: Treatment of acupuncture at thirteen evil acupoints combined with western medicine can enhance the curative effect of hepatic encephalopathy, improve patients' liver function and decrease the levels of plasma ammonia and ß-endorphin.

Investigation and Application of a New Passive Sampling Technique for in Situ Monitoring of Illicit Drugs in Waste Waters and Rivers.

Illicit drugs constitute a class of emerging contaminants that has been drawing significant concern due to its potent pharmacological and biological activities. In this study, an in situ passive sampling approach that uses diffusive gradients in thin films (DGT) was successfully tested for measuring ketamine (KET), methamphetamine (METH), and amphetamine (AMP) in water. The diffusion coefficients of KET, METH, and AMP in diffusive gel were (8.13 ± 0.12) × 10-6, (8.55 ± 0.14) × 10-6, and (7.72 ± 0.18) × 10-6 cm2 s-1 at 22 °C, respectively. The capacities of an XAD binding gel for KET, METH, and AMP were 92, 57, and 45 µg per binding gel disc, which were suitable for long-term environmental monitoring. The DGT measurement of these drugs was not influenced by the pH (4 to 9) and the ionic strength (0.001 M - 0.1 M) and unaffected by the water flow, demonstrating the effectiveness of the XAD-based DGT for the in situ monitoring of illicit drugs. DGT samplers were deployed in a WWTP influent and natural rivers in Beijing, China. The ng L-1 levels of the drugs were high in the wastewater influent and low in river waters, with an insignificant fluctuation during the seven-day monitoring. The DGT-measured concentrations were comparable to the average concentrations determined by SPE method, which suggested that the average data measured by DGT could be substituted for high-frequency grab sampling. This study has demonstrated systematically for the first time that DGT is effective and accurate for monitoring illicit drugs in wastewater and surface waters, and provides a powerful tool to investigating the presence, transport, and environmental behaviors of these drugs in the aquatic ecosystem.