[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.

[Distribution Characteristics and Health Risk Assessment of Metal Elements in Groundwater of Longzici Spring Area].

Longzici Spring is an important water source for industry, agriculture, and urban life in Linfen City. With the improvements in public environmental health awareness, it is particularly necessary to study the health risk of posed by metal elements in groundwater. In this study, 43 groundwater samples from Longzici Spring area were analyzed for ten metal elements (As, Cd, Hg, Al, Pb, Co, Mn, Fe, Cu, and Ni). The distribution and health risk of these metal elements in the groundwater were studied using multivariate statistical analysis and a health risk assessment model. The results show that metal elements can be ranked, from high to low, by their average concentrations in groundwater in the following order: Fe, Al, Mn, Ni, As, Cu, Co, Pb, Hg, and Cd. The concentration of Al, Mn, Fe, and As exceed the limit for class Ⅲ water, as defined in the quality standard for groundwater (GB/T 14848-2017). Different types of groundwater in the spring area showed different metal contents. The quality of karst spring water was good, reaching the standard for drinking water, while mine drainage water exceeded the standard for drinking water, with the highest metal concentration (60%) and the worst water quality. Multivariate statistical results show that Pb, Ni, Co, Cd, Mn, and Cu concentrations were mainly affected by the geochemical background, while Al, Fe, Hg, and As concentrations were closely related to human mining activities under the unique geological background of Shanxi Province. The health risk assessment showed that the different types of groundwater could be ranked by the annual total health risks, posed by metal elements to adults and children through drinking water and skin infiltration, as follows: karst well > non-karst spring > non-karst well > karst spring. The health risks mainly came from drinking water, while health risks through skin infiltration would not cause obvious harm to the human body. The metal element causing the greatest health risk in spring groundwater was As, which should therefore be controlled in the utilization of water resources, especially in children's drinking water.

[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.

Maternal oral contraceptive pill use and the risk of atopic diseases in the offspring: A systematic review and meta-analysis.

Studies of maternal oral contraceptive pill (OCP) exposure and the offspring's risk of atopic diseases are of current interest due to concerns about widespread use of OCP before or during pregnancy.We evaluated whether maternal OCP exposure is associated with an increased risk of atopic diseases by reviewing the literature and performing a meta-analysis. The PubMed and Embase databases were searched to identify potential studies for inclusion. Three common atopic outcomes were included: asthma, eczema, and rhinitis.We found 693 titles, abstracts, and citations, and 6 studies were included in this analysis. A meta-analysis revealed that maternal OCP exposure was associated with higher odds of asthma (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.02-1.19; P = .014), rhinitis (OR 1.34; 95% CI 1.07-1.68; P = .011) during childhood, whereas there was no association with eczema (OR 1.17; 95% CI 0.81-1.68; P = .383). This analysis was limited by the small number of studies included and the limited adjustments for the possible confounders in the studies.Current evidence suggests that maternal OCP exposure increases the risk for respiratory allergic diseases (asthma and rhinitis) in the offspring, but not for eczema. Given the few studies included, future larger, prospective studies that control for important confounders are needed to verify our findings.

Prediction of fatal adverse prognosis in patients with fever-related diseases based on machine learning: A retrospective study.

BACKGROUND: Fever is the most common chief complaint of emergency patients. Early identification of patients at an increasing risk of death may avert adverse outcomes. The aim of this study was to establish an early prediction model of fatal adverse prognosis of fever patients by extracting key indicators using big data technology. METHODS: A retrospective study of patients' data was conducted using the Emergency Rescue Database of Chinese People's Liberation Army General Hospital. Patients were divided into the fatal adverse prognosis group and the good prognosis group. The commonly used clinical indicators were compared. Recursive feature elimination (RFE) method was used to determine the optimal number of the included variables. In the training model, logistic regression, random forest, adaboost and bagging were selected. We also collected the emergency room data from December 2018 to December 2019 with the same inclusion and exclusion criterion. The performance of the model was evaluated by accuracy, F1-score, precision, sensitivity and the areas under receiver operator characteristic curves (ROC-AUC). RESULTS: The accuracy of logistic regression, decision tree, adaboost and bagging was 0.951, 0.928, 0.924, and 0.924, F1-scores were 0.938, 0.933, 0.930, and 0.930, the precision was 0.943, 0.938, 0.937, and 0.937, ROC-AUC were 0.808, 0.738, 0.736, and 0.885, respectively. ROC-AUC of ten-fold cross-validation in logistic and bagging models were 0.80 and 0.87, respectively. The top six coefficients and odds ratio (OR) values of the variables in the Logistic regression were cardiac troponin T (CTnT) (coefficient=0.346, OR = 1.413), temperature (T) (coefficient=0.235, OR = 1.265), respiratory rate (RR) (coefficient= -0.206,OR = 0.814), serum kalium (K) (coefficient=0.137, OR = 1.146), pulse oxygen saturation (SPO2) (coefficient= -0.101, OR = 0.904), and albumin (ALB) (coefficient= -0.043, OR = 0.958). The weights of the top six variables in the bagging model were: CTnT, RR, lactate dehydrogenase, serum amylase, heartrate, and systolic blood pressure. CONCLUSIONS: The main clinical indicators of concern included CTnT, RR, SPO2, T, ALB and K. The bagging model and logistic regression model had better diagnostic performance comprehesively. Those may be conducive to the early identification of critical patients with fever by physicians.

FKBP10 functioned as a cancer-promoting factor mediates cell proliferation, invasion, and migration via regulating PI3K signaling pathway in stomach adenocarcinoma.

As documented, the expression, biological roles, and prognostic significance of FKBP10 in stomach adenocarcinoma (STAD) have not been investigated till now. This drives us to detect the biological roles and clinical significance of FKBP10 in STAD. The expression level of FKBP10 was measured based on the data obtained from the TCGA, ONCOMINE, and GEPIA databases, and STAD cell lines. Through in vitro experiments, cell behaviors were investigated to evaluate the effects of FKBP10 on STAD. Moreover, the PI3K-AKT signaling pathway was measured. Relying on the data of TCGA, ONCOMINE, and GEPIA databases, and cancer cell lines, FKBP10 was up-regulated in STAD when compared with normals. The patients with low expression of FKBP10 had higher survival rate than those with high FKBP10 expression. After knockdown of FKBP10 in AGS cells, cell vitality, colony formation ability, and the migratory and invasive potential were inhibited. Western blotting analysis exhibited that knockdown of FKBP10 significantly reduced the expression level of p-AKT, and p-PI3K, but it did not influence the total expression level of AKT, and PI3K. FKBP10 might serve as a crucial player in gastric cancer, and targeting FKBP10 might provide clinical utility in gastric cancer in future.

[Prediction and simulation of urban area expansion in Pearl River Delta Region under the RCPs climate scenarios].

The sizes and number of cities in China are increasing rapidly and complicated changes of urban land use system have occurred as the social economy develops rapidly. This study took the urban agglomeration of Pearl River Delta Region as the study area to explore the driving mechanism of dynamic changes of urban area in the urbanization process under the joint influence of natural environment and social economic conditions. Then the CA (cellular automata) model was used to predict and simulate the urban area changes until 2030 under the designed scenarios of planning and RCPs (representative concentration pathways). The results indicated that urbanization was mainly driven by the non-agricultural population growth and social-economic development, and the transportation had played a fundamental role in the whole process, while the areas with high elevation or steep slope restricted the urbanization. Besides, the urban area would keep an expanding trend regardless of the scenarios, however, the expanding speed would slow down with different inflection points under different scenarios. The urban expansion speed increased in the sequence of the planning scenario, MESSAGE scenario and AIM scenario, and that under the MESSAGE climate scenario was more consistent with the current urban development trend. In addition, the urban expansion would mainly concentrate in regions with the relatively high urbanization level, e.g., Guangzhou, Dongguan, Foshan, Shenzhen, Zhanjiang and Chaoshan.

[Mechanisms of grass in slope erosion control in Loess sandy soil region of Northwest China].

By adopting the method of simulated precipitation and from the viewpoint of slope hydrodynamics, in combining with the analysis of soil resistance to erosion, a quantitative study was made on the mechanisms of grass in controlling the slope erosion in the cross area of wind-water erosion in Loess Plateau of Northwest China under different combinations of rainfall intensity and slope gradient, aimed to provide basis to reveal the mechanisms of vegetation in controlling soil erosion and to select appropriate vegetation for the soil and water conservation in Loess Plateau. The grass Astragalus adsurgens with the coverage about 40% could effectively control the slope erosion. This grass had an efficiency of more than 70% in reducing sediment, and the grass root had a greater effect than grass canopy. On bare slope and on the slopes with the grass plant or only the grass root playing effect, there existed a functional relation between the flow velocity on the slopes and the rainfall intensity and slope gradient (V = DJ(0.33 i 0.5), where V is flow velocity, D is the comprehensive coefficient which varies with different underlying surfaces, i is rainfall intensity, and J is slope gradient). Both the grass root and the grass canopy could markedly decrease the flow velocity on the slopes, and increase the slope resistance, but the effect of grass root in decreasing flow velocity was greater while the effect in increasing resistance was smaller than that of grass canopy. The effect of grass root in increasing slope resistance was mainly achieved by increasing the sediment grain resistance, while the effect of canopy was mainly achieved by increasing the slope form resistance and wave resistance. The evaluation of the soil resistance to erosion by using a conceptual model of sediment generation by overland flow indicated that the critical shear stress value of bare slope and of the slopes with the grass plant or only the grass root playing effect was 0.533, 1.672 and 0.925 Pa, respectively.

Contributions of TRAIL-mediated megakaryocyte apoptosis to impaired megakaryocyte and platelet production in immune thrombocytopenia.

Recent in vitro studies provide evidence for autoantibody-induced suppression of megakaryocytopoiesis and show a reduction in megakaryocyte production and maturation in the presence of immune thrombocytopenia (ITP) plasma. Here, we present CD34(+) cells from healthy umbilical cord blood mononuclear cells cultured in medium containing thrombopoietin, stem cell factor, interleukin-3, and 10% plasma from either ITP patients or healthy subjects. The quantity, quality, and apoptosis of megakaryocytes were measured. We observed that most ITP plasma boosted megakaryocyte quantity but impaired quality, resulting in significantly less polyploidy cells (N ≥ 4) and platelet release. In these megakaryocytes, we found a lower percentage of cell apoptosis, a lower expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and a higher expression of Bcl-xL. Furthermore, there was a decrease of sTRAIL in ITP plasma and in cell culture supernatants of this group compared with the control group. Our findings suggest that decreased apoptosis of megakaryocytes also contributes to in vitro dysmegakaryocytopoiesis and reduced platelet production. The abnormal expression of sTRAIL in plasma and TRAIL and Bcl-xL in megakaryocytes may play a role in the pathogenesis of impaired megakaryocyte apoptosis in ITP.

[Research progress on index system of regional ecological risk assessment].

Regional ecological risk assessment (RERA) covers the assessments of multiple risk sources, receptors, and endpoints, while the selection of assessment indices is quite complicated, being a hotspot in regional environment management research. Domestic and international researches on RERA revealed that three processes in RERA are of vital, i.e., risk probability assessment measured by risk probability index, status and value assessment of ecosystem at regional scale indicated by ecological index, and vulnerability assessment of each ecosystem in a region under risk measured by vulnerability index. The main problems in the establishment of RERA index system are the strong subjectivity and poor comparability, and thus, the index system should be set up in the three key processes under the principles of objectivity, integration, hierarchy, and comparability. Due to the fact that the status and value assessment of ecosystem is most complicated, the index system should be formulated by compulsory and optional components to increase the comparability of RERA results between regions.

[Expression and localization of hnRNP A2/B1 during differentiation of human osteosarcoma MG-63 cells induced by HMBA].

BACKGROUND & OBJECTIVE: The differentially expressed nuclear matrix proteins have great effects on canceration and regulation of cell differentiation. This study was to explore the existence and distribution of ribonucleoprotein hnRNP A2/B1 in nuclear matrix and its co-localization with Actin and Prohibitin in human osteosarcoma MG-63 cells before and after hexamethylene bisacetamide (HMBA) treatment. METHODS: The nuclear matrix of MG-63 cells before and after treatment of HMBA were selectively extracted. The expression and localization of hnRNP A2/B1 in nuclear matrix were detected by 2-D PAGE, MALDI-TOF-MS, Western blot, and immunofluorescent staining. The co-localization of hnRNP A2/B1 with Actin and Prohibitin was observed under laser scanning confocal microscope (LSCM). RESULTS: hnRNP A2/B1 was detected in the component of nuclear matrix proteins of MG-63 cells by Western blot and immunogold staining and its expression was decreased after treatment of HMBA. hnRNP A2/B1 was located in the nuclear matrix, and its expression was weakened after HMBA treatment. hnRNP A2/B1 was co-localized with Actin or Prohibitin in MG-63 cells, while the co-localization relationship was weakened during differentiation of MG-63 cells. CONCLUSIONS: hnRNP A2/B1 is a kind of nuclear matrix protein, and localizes in the nuclear matrix. The distribution and expression of hnRNP A2/B1 and its co-localization with Actin and Prohibitin play important roles during the differentiation of MG-63 cells.

[Localization of prohibitin in nuclear matrix and its expressive alteration during the differentiation of human osteosarcoma MG-63 cells induced by HMBA].

To explore the existence,distribution of prohibitin in nuclear matrix and the co-localization relationship between prohibitin and the products of some interrelated genes in the human osteosarcoma MG-63 cells before and after HMBA treatment, the nuclear matrix of MG-63 cells and the cells induced by HMBA were selectively extracted. It was confirmed by Western blot that prohibitin existed in the component of nuclear matrix protein of MG-63 cells and its expression was decreased by HMBA treatment. The immunofluorescence observation revealed that prohibitin located in the nuclear matrix, and its distribution regions and expression level had altered after HMBA treatment. The co-localization and its alternation of distributive area in the cells treated by HMBA were observed between prohibitin and the products of oncogenes or tumor repression genes including c-fos, c-myc, p53 and Rb by using laser scanning confocal microscopy. The results of this study demonstrated that prohibitin was a kind of nuclear matrix protein, and locacted in the nuclear matrix,and the distribution and expression of prohibitin and its relationship with associated genes play an important role during the differentiation of MG-63 cell.

[Advances of research on abnormality of cell immunity in idiopathic thrombocytopenic purpura: review].

It was long believed that platelets are prematurely destroyed in the reticuloendothelial system by platelet autoantibodies in idiopathic thrombocytopenic purpura. However, humoral mechanisms cannot account for all observations made in this disorder, and it is increasingly evident that cellular mechanisms contribute to platelet destruction. In this review the tolerance of T cell, abnormality of T cell apoptosis, abnormal activation of T cells, T cell subtype and its function changes, and T cell-mediated cytotoxicity were summarized.

[Changes of nuclear matrix proteins during differentiation of human osteosarcoma MG-63 cells induced by HMBA].

Human osteosarcoma MG-63 cells were induced into differentiation by hexamethylene bisacetamide (HMBA). Its nuclear matrix proteins were selectively extracted, and subjected to two dimensional gel electrophoresis analysis. The resulted protein patterns were analyzed by Melanie software. There were 12 spots changed remarkably during the differentiation induced by HMBA, nine of which were identified. The up-regulated proteins were identified as MHC class II antigen, interferon-stimulated gene factor 3d, hypothetical protein DKFZp434M2221.1,8-hydroxy-guanine glycosylase homolog ogg1, and vimentin. The down-regulated ones were hnRNP A2/B1 and actin; and two newly expressed proteins under induction were 60S ribosomal protein L21 and ST2 protein. This study suggests that the induced differentiation of carcinoma cells is accompanied with changes of nuclear matrix proteins, and confirms the presence of some specific nuclear matrix proteins associated with carcinoma cell growth and differentiation. The changed nuclear matrix proteins are potential markers for cancer diagnosis or targets for cancer therapy.

[Ultraviolet transmission spectra of BC(x)N thin films].

BCN, BC2N and BC3N thin films with transmission increasing properties in the ultraviolet region were deposited by RF magnetron sputtering with different sputtering power (80-130 W). Fourier transform infrared absorption and X-ray photoelectron spectroscopy results suggested that the films were atomnic-level hybrids composed of B, 'C and N atoms. The compositions and transmission increasing properties of samples in the ultraviolet region were strongly influenced by sputtering power, which determined the transmission increasing properties in the ultraviolet region by changing compositions. And the lower the atomic number of C in the thin films, the better the transmission increasing properties in the ultraviolet region. The BCN thin films deposited at the sputtering power of 110 W possessed the lowest atonic number of C and the best transmission increasing properties in the ultraviolet region. And the increase in average transmissivity from 200 to 350 nm was about 40% compared with glass.

Changes of nuclear matrix proteins following the differentiation of human osteosarcoma MG-63 cells.

Human osteosarcoma MG-63 cells were induced into differentiation by 5 mmol/L hexamethylene bisacetamide (HMBA). Their nuclear matrix proteins (NMPs) were selectively extracted and subjected to two-dimensional gel electrophoresis analysis. The results of protein patterns were analyzed by Melanie software. The spots of differentially expressed NMPs were excised and subjected to in situ digestion with trypsin. The maps of peptide mass fingerprinting were obtained by MALDI-TOF-MS analysis, and were submitted for NCBI database searches by Mascot tool. There were twelve spots changed remarkably during the differentiation induced by HMBA, nine of which were identified. The roles of the regulated proteins during the MG-63 differentiation were analyzed. This study suggests that the induced differentiation of cancer cells is accompanied by the changes of NMPs, and confirms the presence of some specific NMPs related to the cancer cell proliferation and differentiation. The changed NMPs are potential markers for cancer diagnosis or targets for cancer therapy.

Computational studies and drug design for HIV-1 reverse transcriptase inhibitors of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs.

Molecular docking and molecular dynamics simulation were applied to study the binding mode of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs anti-HIV inhibitors with HIV-1 RT. The results suggest that there is a strong hydrogen bond between DCK O16 and NH of Lys101, and that DCK analogues might act similarly as other types of HIV-1 RT inhibitors. The investigation about drug resistance for DCK shows no remarkable influence on the most frequently observed mutation K103N of HIV-1 RT. Based on the proposed mechanism, some new structures were designed and predicted by a SVM model. All compounds exhibited potent inhibitory activities against HIV replication in H9 lymphocytes with EC50 values lower than 1.95 microM. The rationality of the method was validated by experimental results.

Molecular modeling, design, synthesis, and biological evaluation of novel 3',4'-dicamphanoyl-(+)-cis-khellactone (DCK) analogs as potent anti-HIV agents.

Our current studies aimed at developing new potential anti-AIDS drug candidates have focused on the design and synthesis of new DCK analogs with improved molecular water solubility. Based on the structures and biodata of previous DCK analogs, 3D-QSAR studies have been performed which resulted in two reliable computational models, CoMFA and CoMSIA, with r(2) values of 0.995 and 0.987, and q(2) values of 0.662 and 0.657, respectively. In accord with these 3D-QSAR models, 15 new DCK analogs with polar functional groups at the 3-position were subsequently designed, synthesized, and evaluated against HIV-1 replication in H9 and MT4 cell lines. New DCK analogs 3b, 3c, 4b, 4c, 6a, 7c, and 9a showed promising potency with EC(50) values ranging from 0.09 to 0.0002 microM in both assays. Meanwhile, these promising compounds also showed a wide range of predicted logP values from 0.90 to 5.19, which increased the probability of identifying anti-HIV drug candidates from this class of compounds for clinical trials. Furthermore, both experimental and predicted values matched well, corroborating the reliability of the established 3D-QSAR models.

Altered profiles of nuclear matrix proteins during the differentiation of human gastric mucous adenocarcinoma MGc80-3 cells.

AIM: To find and identify specific nuclear matrix proteins associated with proliferation and differentiation of carcinoma cells, which will be potential markers for cancer diagnosis and targets in cancer therapy. METHODS: Nuclear matrix proteins were selectively extracted from MGc80-3 cells treated with or without hexamethylamine bisacetamide (HMBA), and subjected to 2-D gel electrophoresis. The resulted protein patterns were analyzed by Melanie software. Spots of nuclear matrix proteins differentially expressed were excised and subjected to in situ digestion with trypsin. Peptide masses were obtained by matrix-assisted laser-desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) analysis and submitted for database searching using Mascot tool. RESULTS: The MGc80-3 cells were induced into differentiation by HMBA. There were 22 protein spots which changed remarkably in the nuclear matrix, from differentiation of MGc80-3 cells compared to control. Eleven of which were identified. Seven proteins--actin, prohibitin, porin 31HL, heterogeneous nuclear ribonucleoprotein A2/B1, vimentin, ATP synthase, and heat shock protein 60 were downregulated, whereas three proteins--heat shock protein gp96, heat shock protein 90-beta, and valosin-containing protein were upregulated, and the oxygen-regulated protein was only found in the differentiated MGc80-3 cells. CONCLUSION: The induced differentiation of carcinoma cells is accompanied by the changes of nuclear matrix proteins. Further characterization of those proteins will show the mechanism of cellular proliferation and differentiation, as well as cancer differentiation.