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In this study, UPLC-Q-Exactive-MS/MS was used to rapidly analyze the chemical constituents of Meconopsis quintupli-nervia, and the anti-liver fibrosis mechanism of M. quintuplinervia was preliminarily analyzed by network pharmacology, molecular docking, and cell experiments. The chemical constituents of M. quintuplinervia were identified according to the information of MS~1 and MS~2, as well as the data in the literature and databases. SwissTargetPrediction and TargetNet were used to predict the potential targets. The targets related to liver fibrosis were collected from GeneCards and OMIM. The protein-protein interaction(PPI) network was constructed by STRING. Cytoscape 3.6.1 was used to construct and analyze thequot;constituent-target-diseasequot; network to obtain key targets and their corresponding constituents in the network. DAVID 6.8 was used for GO analysis and KEGG signaling pathway enrichment analysis. Finally, the preliminary verification was carried out by molecular docking and cell experiments. As a result, 106 chemical constituents were identified from M. quintuplinervia, including 66 flavonoids, 16 alkaloids, 18 phenolic acids, 1 anthocyanin, and 5 other constituents. Among them, 3 constituents were identified as potential new compounds, and 59 constituents were reported in M. quintuplinervia for the first time. Network pharmacology analysis showed that M. quintuplinervia presumably acted on AKT1, SRC, JUN, EGFR, STAT3, HSP90 AA1, MAPK3, and other core targets through luteolin, isorhamnetin, quercetin, apigenin, kaempferide, amurine, 2-methylflavinantine, allocryptopine, the multi and other active compounds, thereby regulating the PI3 K/AKT signaling pathway, pathways in cancer, proteoglycans in cancer, FoxO signaling pathway, and other pathways to exert anti-liver fibrosis effects. M. quintuplinervia extract(MQE) could significantly down-regulate PI3 K and AKT protein levels in the HSC-T6 cell model induced by TGF-β1, suggesting that MQE may have the ability to regulate the PI3 K/AKT signaling pathway. The findings of this study indicated that the anti-liver fibrosis effect of M. quintuplinervia had multi-constituent, multi-target, and multi-pathway characteristics, which may provide a scientific basis for the research on the pharmacodynamic materials, action mechanism, and quality markers of M. quintupli-nervia.

Organophosphate pesticides (OPs) are among the most widely used synthetic chemicals for the control of a wide variety of pests, and reactive oxygen species (ROS) caused by OPs may be involved in the toxicity of various pesticides. Previous studies have demonstrated that a reactivation of latent Epstein-Barr virus (EBV) could be induced by oxidative stress. In this study, we investigated whether OPs could reactivate EBV through ROS accumulation. The Raji cells were treated with chlorpyrifos (CPF), one of the most commonly used OPs. Oxidative stress indicators and the expression of the EBV immediate-early gene BZLF-1 were determined after CPF treatment. Our results show that CPF induces oxidative stress as evidenced by decreased malondialdehyde (MDA) level, accompanied by an increase in ROS production, DNA damage, glutathione (GSH) level, and superoxide dismutase (SOD) and catalase (CAT) activity. Moreover, CPF treatment significantly enhances the expression of BZLF-1, and the increased BZLF-1 expression was ameliorated by N-acetylcysteine (NAC) incubation. These results suggest that OPs could contribute to the reactivation of the EBV lytic cycle through ROS induction, a process that may play an important role in the development of EBV-associated diseases.

Background Hyperbaric oxygen (HBO) improves skin flap function and inhibits partial necrosis induced by ischemia–reperfusion (I/R) injury. Our study aimed to evaluate the mechanism underlying HBO regulation of the antiapoptosis factors associated with I/R injury of skin flaps. Methods The rats were divided into sham surgery, I/R, and HBO groups. Rats from the HBO group received HBO preconditioning followed by I/R surgery. Blood perfusion of the skin flaps was measured with laser Doppler flowmeters. Tissue morphology and apoptosis were subsequently assessed based on hematoxylin-eosinhe and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. Protein expression of phosphorylated apoptosis signal-regulating kinase 1 (pASK-1), phosphorylated c-Jun N-terminal kinase (pJNK), B-cell lymphoma-2 (Bcl-2), and Bcl2-associated X protein (Bax) was examined by immunodetection, and Bcl-2 messenger RNA expression was detected by quantitative polymerase chain reaction. In addition, caspase-3 activity was also measured. Results The result of microcirculation analysis showed that the survival and blood perfusion rates significantly increased in the skin flap after HBO exposure. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining revealed that cell apoptosis was significantly attenuated in the HBO group. Furthermore, HBO preconditioning increased the expression of Bcl-2 and inhibited pASK-1, pJNK, and Bax expression as determined by both immunohistochemistry and Western blot. Caspase-3 activity and the Bax/Bcl-2 ratio declined in the HBO group. Conclusions HBO preconditioning effectively ameliorates I/R injury by regulating the apoptosis signal-regulating kinase 1 and/or c-Jun N-terminal kinase pathway and anti- and proapoptosis factors.

Summary Introduction Many pathways have been reported involving the effect of hydrogen-rich saline on protecting skin flap partial necrosis induced by the inflammation of ischemia/reperfusion injury. This study focused on the influence of hydrogen-rich saline treatment on apoptosis pathway of ASK-1/JNK and Bcl-2/Bax radio in I/R injury of skin flaps. Methods Adult male Sprague–Dawley rats were divided into three groups. Group 1 was sham surgery group, Group 2 and 3 were ischemia/reperfusion surgery treated with physiological saline and hydrogen-rich saline respectively. Blood perfusion of flap was measured by Laser doppler flowmeters. Hematoxylin and eosin staining was used to observe morphological changes. Early apoptosis in skin flap was observed through TUNEL staining and presented as the percentage of TUNEL-positive cells of total cells. pASK-1, pJNK, Bcl-2 and Bax were examined by immunodetection. In addition Bcl-2, Bax and caspase-3 were detected by qPCR. Caspase-3 activity was also measured. Results Compared to the Group 2, tissues from the group 3 were observed with a high expression of Bcl-2 and a low expression of pASK-1, pJNK, and Bax, a larger survival area and a high level of blood perfusion. Hydrogen-rich saline ameliorated inflammatory infiltration and decreased cell apoptosis. Conclusion The results indicate that hydrogen-rich saline could ameliorate ischemia/reperfusion injury and improve flap survival rate by inhibiting the apoptosis factor and, at the same time, promoting the expression of anti-apoptosis factor.

To estimate prevalence of HIV/AIDS among children and the transmission routes in a highly endemic villages of AIDS.Totally 208 high-risk women of child bearing age and 159 of their children aged 0 - 14 years were investigated. Their medical histories of blood donation or transfusion were collected, blood samples were taken and sera were separated for HIV test. Enzyme-linked immunosorbent assay (ELISA) and Western blot assay were performed for HIV antibody. The Nested-polymerase chain reaction (PCR) assay amplifying gag gene p17 was performed on samples of children aged less than 18 months.Thirty-seven HIV infected cases were found among 159 children aged 0 - 14 years of whom 33 were infected by mother-to-child transmission (89.2%, 33/37), 3 by blood transfusion (8.1%, 3/37) and one by iatrogenic route (2.7%, 1/37). Sixty seven mothers who were seropositive for HIV and their 86 children who were born after 1992 were investigated, 33 cases of them were infected with HIV. The rate of vertical transmission was 38.4% (33/86). The HIV vertical transmission rate among mothers with AIDS (68.8%, 22/32) was significantly greater than that among mothers with asymptomatic HIV infection (20.4%, 11/54, P0.05). The number of children infected with HIV through vertical transmission increased from 1993 to 2001. Among 37 children infected with HIV, 12 cases developed AIDS and 4 of them died, of whom 2 cases died from tuberculosis. The morbidity of AIDS was 27.3% (9/33). Ninety three point nine percent (31/33) of infected mothers didn't know their HIV seropositive status before pregnancy and delivery. Of 8 pregnant women infected with HIV, one had aggravation of AIDS, 2 miscarried, 2 terminated their pregnancy and 3 continued their pregnancy.Mother-to-child transmission of HIV was the major route of HIV/AIDS transmission to the children. The main reason leading to HIV infection in children was the lack of prenatal HIV counseling and testing for the high-risk women of childbearing age and lake of interventions. The countermeasures must be taken to control the further transmission of AIDS in order to protect the health of women and children in the highly endemic areas of AIDS.

[1] Natural rains are generally considered as weakly acidic. Long-term measurement in the Tibetan capital city, Lhasa, reveals that alkaline rain is also natural. For the last 3 years the volume-weighted mean pH of rainwater is 7.5. Earlier observation shows even higher average pH values, such as 8.36 in the 1987–1988 period. The major cause of alkaline rain is the alkaline and soil-borne continental dusts in this semiarid area. Bicarbonate is the dominant anion in the water samples. The analysis also shows that the rainwater in this city contains few pollutants, compared with other places in the world. Measurements carried out in two additional industrial cities on the northern and northeastern Tibetan Plateau, Xining and Germu, demonstrate how fast human activities such as industrial development may increase rainwater acidity. In a period of 13 years the rainfall pH value of Germu has dropped from 8.03 to 6.8, representing a manyfold increase of the H+ concentration. Such an increase was caused by rising contents of NO−3 and SO−24 in the atmosphere. On the basis of the measurements on the Tibetan Plateau, evidence from other places around the world, and the experiments and calculation, the authors believe that the original pH of natural rainwater in arid and semiarid areas on this planet should be weakly alkaline because of the influence of alkaline dusts.

A temporal variation and spatial distribution of the snow-covered area (SCA) over the Tibetan Plateau (TP) are analyzed using moderate-resolution imaging spectrometer (MODIS)/Terra 8-day snow cover products (MOD10A2) from 2001 to 2013 and the SCA is compared with in situ snow cover days (SCD) from the meteorological network in the TP. Results show that at monthly levels the minimum SCA occurs in July, followed by August, and the SCA increases rapidly from September, reaching the maximum in March; on average, 2002, 2005, and 2008 are snowy years, whereas 2001, 2003, 2007, and 2010 are less-snow years. Apart from strong seasonal variations, the general trend of interannual snow cover variations from 2001 to 2013 is not obvious, remaining at a relatively stable status. The snow cover over the TP is characterized by uneven geographic distribution. In general, snow is abundant with a long duration in the high mountains while it is less abundant and with a short duration in the vast interior of the TP. The interannual variations of snow cover over the TP from ground-based meteorological stations using SCD are very consistent with MODIS SCA, with a correlation coefficient of 0.80 (P

Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75mg/kg body weight (1/20 LD50) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity.