[Hydrochemical Characteristics and Formation Causes of Ground Karst Water Systems in Gudui Spring Catchment].

As one of the famous karst springs in Shanxi Province, the Gudui spring is the only medium-low temperature hot spring, with a long history of development and a rich cultural accumulation. The karst groundwater in the Gudui spring catchment was taken as the research object. Through systematic sample collection and isotope analysis, hydrochemistry (Durov map, ion ratio, Gibbs map, and hydrogen and oxygen isotope) methods were comprehensively used to analyze groundwater hydrochemistry and groundwater system runoff characteristics. The87Sr/86Sr value of karst groundwater in the Gudui spring catchment was 0.709 to 0.717, and the Mg/(Mg+Ca) value was 0.27 to 0.74. By analyzing the Sr isotope composition and Mg/(Mg+Ca) and 1/Sr variation characteristics, it was concluded that the karst groundwater in the Gudui spring catchment was a mixture of deep hot water and shallow cold water. The karst water subsystem of Nanliang spring presented the characteristics of carbonate stratum runoff. The karst water subsystem of Fuling Mountain Gaoxian Haitou spring and the deep circulation subsystem of Houma Basin exhibited the runoff characteristics of carbonate rock and igneous rock strata. The karst water subsystem of Taiershan Jiuyuanshan Gudui spring presented the runoff characteristics of carbonate rock and ancient silicoaluminate strata. The δ18O value in karst groundwater of Guodui spring area ranged from -11.46‰ to -7.81‰, and the average value was -10.08‰. The range of the δD value was -83.7‰ to -60.8‰, and the average value was -73.6‰. This showed that karst groundwater in the spring area was the result of mixing of various types of water. Through comparative analysis of hydrogen and oxygen isotopes of 2014 and 2021 sampling points at the same location, it was concluded that the change in water samples at the Guduiquan resulted from the gradual accumulation of water supplied by Sanquan Reservoir. The change in Sanquan Reservoir was due to the influence of Yellow River diversion. The karst groundwater in the spring area were characterized by large calcium ion, magnesium ion, and sodium ion values; a small potassium ion value; a large sulfate value; and a small chloride value. The hydrochemical types of karst groundwater in Gudui spring catchment could be divided into SO4-Na, SO4-Ca, HCO3-Na, HCO3-Mg, HCO3-Ca, and Cl-Na. The hydrochemical types of karst groundwater showed evident hydrochemical composition zoning from HCO3-Ca·Mg→HCO3·SO4-Ca·Mg→SO4·HCO3-Na·Ca→SO4·Cl-Na·Ca. According to the comprehensive analysis of hydrochemical isotope and hydrogeological conditions, the karst water subsystem of Nanliang spring was primarily recharged by rainfall infiltration in the exposed limestone area and river infiltration, and its karst groundwater was recharged by runoff from south to north to the karst water subsystem of Fuling Mountain Gaoxian Haitou spring and the deep circulation subsystem of Houma Basin. The karst water subsystem of Taier Jiuyuan Mountain Gudui spring received rainfall infiltration supplement and upstream runoff supplement from the exposed limestone area. Its karst groundwater flowed from north to south and received the supply of Sanquan Reservoir from Yellow River water in the natural discharge area of Gudui spring.

[Hydrochemical and Isotopic Characteristics in the Surface Water of the Fenhe River Basin and Influence Factors].

The Fenhe River Basin is the mother river of Shanxi Province. Due to the over-exploitation of water resources and the impact of social and economic development, the ecological environment has deteriorated. After a series of treatment and protection measures, the water quality has since been improved. Mathematical statistics, Piper diagrams, Gibbs model, hydrogen and oxygen isotopes, and other methods were used to analyze the characteristics and sources of hydrochemistry in the surface water of the Fenhe River basin, which revealed the evolution process of surface water quality of the Fenhe River basin. The results showed that the content of the main hydrochemical components in the main stream surface water of Fenhe River basin increased gradually along the runoff path. The hydrochemical types of surface water of Fenhe River basin were mainly HCO3·SO4·Cl-Ca·Na·Mg and SO4·HCO3·Cl-Ca·Na·Mg. There were great differences in hydrochemical components of tributaries and karst water in the basin. There were also great differences in hydrochemical components of tributaries in the basin. The hydrochemical types of surface water of karst water were mainly SO4·HCO3-Ca·Mg. The hydrochemical composition of surface water in Fenhe River basin was mainly affected by rock weathering and evaporation crystallization, whereas rainfall had little effect. Na+ and K+ mainly came from the dissolution of evaporated salt rocks with Na in the surrounding loess. Ca2+, Mg2+, and HCO3- mainly came from the dissolution of carbonate rocks. SO42- may have also come from the dissolution of sulfide minerals in the loess layer around Fenhe River in addition to the dissolution of gypsum. The values of δD and δ18O of Fenhe River surface water were gradually enriched from upstream to downstream. The characteristics of hydrogen and oxygen isotopes further showed that the surface water was mainly affected by evaporation. The results of this study can provide evidence for ecological restoration and protection and ecological civilization construction in the Fenhe River basin.

Identification of icaritin derivative IC2 as an SCD-1 inhibitor with anti-breast cancer properties through induction of cell apoptosis.

BACKGROUND: Breast cancer is the most common malignancy affecting women, yet effective targets and related candidate compounds for breast cancer treatment are still lacking. The lipogenic enzyme, stearoyl-CoA desaturase-1 (SCD1), has been considered a potential target for breast cancer treatment. Icaritin (ICT), a prenylflavonoid derivative from the Traditional Chinese Medicine Epimedii Herba, has been reported to exert anticancer effects in various types of cancer. The purpose of the present study was to explore the effect of the new ICT derivative, IC2, targeting SCD1 on breast cancer cells and to explore the specific mechanism. METHODS: Immunohistochemistry and semiquantitative evaluation were performed to detect the expression level of SCD1 in normal and tumor samples. Computer-aided drug design (CADD) technology was used to target SCD1 by molecular docking simulation, and several new ICT derivatives were prepared by conventional chemical synthesis. Cell viability was evaluated by an MTT assay and dead cell staining. SCD1 expression in cancer cells was determined by Western blot and qRT-PCR analyses. The enzymatic activity of SCD1 was evaluated by detecting the conversion rate of [d31] palmitic acid (PA) using Gas chromatography-mass spectrometry (GC-MS). DAPI staining, flow cytometry and Western blot were used to detect cell apoptosis. Mitochondrial membrane potential and reactive oxygen species (ROS) assays were used to determine cell mitochondrial function. Lentiviral transduction was utilized to generate SCD1-overexpressing cell lines. RESULTS: We found that SCD1 was overexpressed and correlated with poor prognosis in breast cancer patients. Among a series of ICT derivatives, in vitro data showed that IC2 potentially inhibited the viability of breast cancer cells, and the mechanistic study revealed that IC2 treatment resulted in ROS activation and cellular apoptosis. We demonstrated that IC2 inhibited SCD1 activity and expression in breast cancer cells in a dose-dependent manner. Moreover, SCD1 overexpression alleviated IC2-induced cytotoxicity and apoptosis in breast cancer cells. CONCLUSIONS: The new ICT derivative, IC2, was developed to induce breast cancer cell apoptosis by inhibiting SCD1, which provides a basis for the development of IC2 as a potential clinical compound for breast cancer treatment.

Small molecule compound M12 reduces vascular permeability in obese mice via blocking endothelial TRPV4-Nox2 interaction.

Transient receptor potential channel TRPV4 and nicotinamide adenine dinucleotide phosphate oxidase (Nox2) are involved in oxidative stress that increases endothelial permeability. It has been shown that obesity enhances the physical association of TRPV4 and Nox2, but the role of TRPV4-Nox2 association in obesity has not been clarified. In this study we investigated the function of TRPV4-Nox2 complex in reducing oxidative stress and regulating abnormal vascular permeability in obesity. Obesity was induced in mice by feeding a high-fat diet (HFD) for 14 weeks. The physical interaction between TRPV4 and Nox2 was measured using FRET, co-immunoprecipitation and GST pull-down assays. The functional interaction was measured by rhodamine phalloidin, CM-H2DCFDA in vitro, the fluorescent dye dihydroethidium (DHE) staining assay, and the Evans blue permeability assay in vivo. We demonstrated that TRPV4 physically and functionally associated with Nox2, and this physical association was enhanced in aorta of obese mice. Furthermore, we showed that interrupting TRPV4-Nox2 coupling by TRPV4 knockout, or by treatment with a specific Nox2 inhibitor Nox2 dstat or a specific TRPV4 inhibitor HC067046 significantly attenuated obesity-induced ROS overproduction in aortic endothelial cells, and reversed the abnormal endothelial cytoskeletal structure. In order to discover small molecules disrupting the over-coupling of TPRV4 and Nox2 in obesity, we performed molecular docking analysis and found that compound M12 modulated TRPV4-Nox2 association, reduced ROS production, and finally reversed disruption of the vascular barrier in obesity. Together, this study, for the first time, provides evidence for the TRPV4 physically interacting with Nox2. TRPV4-Nox2 complex is a potential drug target in improving oxidative stress and disruption of the vascular barrier in obesity. Compound M12 targeting TRPV4-Nox2 complex can improve vascular barrier function in obesity.

[Chemical Characteristics and Causes of Groups Water in Niangziguan Spring].

Discharge in Niangziguan Spring is 7.19 m3·s-1, which is the main water supply source for Yangquan City and Pingding County. Every year, Yangquan municipal government take water from the mouth of Niangziguan Spring to supply drinking water to urban residents at a rate of approximately 1.7 m3·s-1. It is of great significance to determine the characteristics and causes of variations in spring water flow conditions for the appropriate utilization of water resources and pollution prevention. Here, sample collection and hydrochemical isotope analyses were undertaken for the Niangziguan Spring area to chemically characterize the water environment and genesis. The pH of the karst spring is 7.2-7.5 with an average of 7.36; the calcium content of the water is 112.1-135.2 mg·L-1 with a mean value of 131.4 mg·L-1; the concentration of magnesium ions is 34.8-42.3 mg·L-1 with an average of 40.8 mg·L-1; the concentration of K++Na- ions is 41.6-46.7 mg·L-1 with an average of 45.2 mg·L-1; and the sulfate ion concentration is 185.6-271.8 mg·L-1 with a mean value of 255.4 mg·L-1. The hydrochemical type of the aquifer is classified as HCO3·SO4-Ca·Mg. The spring water is characterized by high Ca2+, Mg2+, and SO42- concentrations, and low Na+, K+, and Cl- concentrations. The supply path of Chengxi Spring is shortest followed by Wulong Spring. The supply paths of the remaining five spring are much longer. The Niangziguan Spring water environment is characterized by increasing pollution from coal mine acid drainage alongside decreasing inputs from domestic sewage. Environmental isotope tracing shows that sulfate in Chengxi Spring mainly derives from precipitation and gypsum dissolution, and the concentrations of sulfate in Wulong Spring are increasing. These changes are mainly driven by the amount of coal mine acid water pollution in the area.

[Hydrochemical Characteristics and Formation Causes of Ground Karst Water Systems in the Longzici Spring Catchment].

The water of the Longzici Spring catchment is the source of industrial, agricultural, and urban domestic water in Linfen City, Shanxi Province. It is of great significance to identify the sources and influencing factors of karst water resources for their development and utilization, and the protection of the ecological environment. Taking the karst groundwater in the Longzici Spring Area as the research object, systematic sample collection and isotope analysis were carried out. Hydrochemistry methods (Durov diagram, ion ratio system, Gibbs diagram, hydrogen and oxygen isotopes, and sulfur isotopes) were used to analyze the hydrochemical characteristics of groundwater. The hydrogeochemical and environmental isotopic characteristics of Longzici Spring water are revealed. The hydrochemical field of karst groundwater in the Longzici Spring domain has obvious zonation, from the deep buried detention area to the supply area to the runoff and discharge area. The hydrochemical types of karst groundwater detention area are SO4-Ca and SO4-Ca·Mg, with total dissolved solids (TDS) of 960.5-2340 mg·L-1; the supply area is HCO3-Ca·Mg and HCO3·SO4-Ca·Mg, with TDS of 340.5-562 mg·L-1; and the runoff and discharge areas are SO4·HCO3-Ca·Mg·Na, SO4·HCO3-Ca, and SO4·HCO3-Ca·Mg, with TDS of 494.0-1168.5 mg·L-1. The karst groundwater is mainly SO4·HCO3-Ca and SO4·HCO3-Ca·Mg type water. The content range of sulfate ions is 61.6-1503 mg·L-1, with an average of 481.4 mg·L-1. A total of 70.3% of the karst groundwater SO42- samples exceed the standard. The sulfate ions in karst groundwater mainly come from the dissolution of gypsum in the Ordovician aquifer and the oxidation of pyrite in a coal aquifer. The ratio of sulfate ions in the Longzici Spring catchment that come from pyrite oxidation in water is 20.2%. According to the analysis of hydrogen, oxygen and sulfur isotopes, 70% of karst groundwater is polluted by the acid water of coal mines to different degrees. Using the software PHREEQC, it is concluded that the hydrochemical characteristics of the study area are mainly affected by dissolution and dedolomitization, rock salt, and gypsum.

Translocation of PKG1α acts on TRPV4-C1 heteromeric channels to inhibit endothelial Ca(2+) entry.

AIM: TRPV4-C1 heteromeric channels contribute to store-operated Ca(2+) entry in vascular endothelial cells. However, the negative regulation of these channels is not fully understood. This study was conducted to investigate the inhibitory effect of PKG1α on TRPV4-C1 heteromeric channels. METHODS: Immuno-fluorescence resonance energy transfer (FRET) was used to explore the spatial proximity of PKG1α and TRPC1. Phosphorylation of endogenous TRPC1 was tested by phosphorylation assay. [Ca(2+)]i transients and cation current in MAECs were assessed with Fura-2 fluorescence and whole-cell recording, respectively. In addition, rat mesenteric arteries segments were prepared, and vascular relaxation was examined with wire myography. RESULTS: In immuno-FRET experiments, after exposure of these cells to 8-Br-cGMP, more PKG1α was observed in the plasma membrane, and PKG1α and TRPC1 were observed to be in closer proximity. TAT-TRPC1(S172) and TAT-TRPC1(T313) peptide fragments, which contain the PKG targeted residues Ser172 and Thr313, respectively, were introduced into isolated endothelial cells to abrogate the translocation of PKG1α. Furthermore, a phosphorylation assay demonstrated that PKG directly phosphorylates TRPC1 at Ser172 and Thr313 in endothelial cells. In addition, PKG activator 8-Br-cGMP markedly reduced the magnitude of the 4αPDD-induced and 11,12-EET-induced [Ca(2+)]i transients, the cation current and vascular relaxation. CONCLUSION: This study uncovers a novel mechanism by which PKG negatively regulates endothelial heteromeric TRPV4-C1 channels through increasing the spatial proximity of TRPV4-C1 to PKG1α via translocation and through phosphorylating Ser172 and Thr313 of TRPC1.

Synthesis and biological evaluation of a series of 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-2-substituted tetrahydroisoquinoline derivatives.

Multidrug resistance in cancer is a major cause of failure in cancer chemotherapy. In search of new compounds with strong reversal activity and simple molecular structure, we have synthesized a series of compounds in which different substituents were linked to the 2-position of the 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)- tetrahydroisoquinoline system. Compounds were analyzed for their cytotoxicity by MTT in K562 cell line in vitro, all of the derivatives exhibited little cytotoxic activity. In the meantime, these compounds were evaluated by MTT in K562/A02 cell line in vitro, 6e, 6h and 7c exhibited similar or more potent activities than verapamil with the IC50 values at 0.66, 0.65 and 0.96µM, and with the ratio factor of 24.13, 24.50 and 16.59, respectively.

dbHCCvar: a comprehensive database of human genetic variations in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common cancer with a high mortality rate. The complete pathogenesis of HCC is not completely understood, and highly efficient therapy is still unavailable. In the past several decades, various genetic variations such as mutations and polymorphisms have been reported to be associated with HCC risk, progression, survival, and recurrence. However, to our knowledge, these genetic variations have not been comprehensively and systematically compiled. In this study we constructed dbHCCvar, a free online database of human genetic variations in HCC. Eligible publications were collected from PubMed, and detailed information and major research data from each eligible study were then extracted and recorded in our database. As a result, dbHCCvar contains almost all human genetic variations reported to be associated or not associated with HCC risk, clinical pathology, drug reaction, survival, or recurrence to date. It is expected that dbHCCvar will function as a useful tool for researchers to facilitate the search and identification of new genetic markers for HCC. dbHCCvar is free for all visitors at http://GenetMed.fudan.edu.cn/dbHCCvar.

Ethyl 1-cyclo-propyl-6,7-difluoro-8-meth-oxy-4-oxo-1,4-dihydro-quinoline-3-carboxyl-ate.

In the title compound, C(16)H(15)F(2)NO(4), the dihedral angle between the three-membered ring and the quinoline ring system is 64.3 (3)°. In the crystal structure, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules, forming a column running along [101].