Synthesis and antiviral activities of a novel class of thioflavone and flavonoid analogues

AbstractA novel class of thioflavone and flavonoid derivatives has been prepared and their antiviral activities against enterovirus 71 (EV71) and the coxsackievirus B3 (CVB3) and B6 (CVB6) were evaluated. Compounds 7d and 9b showed potent antiviral activities against EV71 with IC50 values of 8.27 and 5.48μM, respectively. Compound 7f, which has been synthesized for the first time in this work, showed the highest level of inhibitory activity against both CVB3 and CVB6 with an IC50 value of 0.62 and 0.87μM. Compounds 4b, 7a, 9c and 9e also showed strong inhibitory activities against both the CVB3 and CVB6 at low concentrations (IC50=1.42−7.15μM), whereas compounds 4d, 7c, 7e and 7g showed strong activity against CVB6 (IC50=2.91–3.77μM) together with low levels of activity against CVB3. Compound 7d exhibited stronger inhibitory activity against CVB3 (IC50=6.44μM) than CVB6 (IC50>8.29μM). The thioflavone derivatives 7a, 7c, 7d, 7e, 7f and 7g, represent a new class of lead compounds for the development of novel antiviral agents

Activation of PAR4 Upregulates p16 through Inhibition of DNMT1 and HDAC2 Expression via MAPK Signals in Esophageal Squamous Cell Carcinoma Cells

A previous study showed that a downexpression of protease-activated receptor 4 (PAR4) is associated with the development of esophageal squamous cell carcinoma (ESCC). In this study, we explored the relationship between PAR4 activation and the expression of p16, and elucidated the underlying mechanisms in PAR4 inducing the tumor suppressor role in ESCC. ESCC cell lines (EC109 and TE-1) were treated with PAR4-activating peptide (PAR4-AP). Immunohistochemistry for DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) was performed in 26 cases of ESCC tissues. We found that DNMT1 and HDAC2 immunoreactivities in ESCC were significantly higher than those in adjacent noncancerous tissues. PAR4 activation could suppress DNMT1 and HDAC2, as well as increase p16 expressions, whereas silencing PAR4 dramatically increased HDAC2 and DNMT1, as well as reduced p16 expressions. Importantly, the chromatin immunoprecipitation-PCR (ChIP-PCR) data indicated that treatment of ESCC cells with PAR4-AP remarkably suppressed DNMT1 and HDAC2 enrichments on the p16 promoter. Furthermore, we demonstrated that activation of PAR4 resulted in an increase of p38/ERK phosphorylation and activators for p38/ERK enhanced the effect of PAR4 activation on HDAC2, DNMT1, and p16 expressions, whereas p38/ERK inhibitors reversed these effects. Moreover, we found that activation of PAR4 in ESCC cells significantly inhibited cell proliferation and induced apoptosis. These findings suggest that PAR4 plays a potential tumor suppressor role in ESCC cells and represents a potential therapeutic target of this disease

Association of low cadmium and mercury exposure with chronic kidney disease among Chinese adults aged ≥80 years: A cross-sectional study

Abstract. Background:. The heavy metals cadmium (Cd) and mercury (Hg) are known to be widespread environmental contaminants and high occupational exposure adversely affects the risk of chronic kidney disease (CKD). However, evidence from epidemiological studies linking low Cd and Hg exposure (or non-industrial) to the risk of progression to CKD are conflicting. This study aimed to explore the association of low Cd and Hg exposure with the risk of CKD in Chinese adults aged ≥80 years. Methods:. The participants were recruited for the Healthy Aging and Biomarkers Cohort Study in 2017, an ongoing perspective survey conducted in longevity areas in China initially involving 3016 older adults. We used logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals of CKD setting Cd and Hg as categorical variables. Logistic regression with restricted cubic spline was used to characterize a dose-response relationships between Cd or Hg concentrations and the risk of CKD in the study population. Results:. The ORs for the risk of CKD comparing the fourth to the first quartile of blood Cd, blood Hg, urine Cd, and urine Hg were 1.77, 1.57, 2.03, and 1.50, respectively. Restricted cubic spline models showed that blood Cd and urine Hg were significantly linearly correlated with the risk of CKD, while blood Hg and urine Cd were non-linearly correlated with the risk of CKD with a steeper slope at concentrations <2.30 μg/L and 3.30 μg/g creatinine. Conclusions:. Our findings suggest that even low Cd and Hg exposure (or non-industrial) were associated with increased risk of CKD in Chinese oldest old, although we did not find a significant multiplicative and additive interaction between Cd and Hg levels in relation to the risk of CKD

Human biomonitoring of toxic and essential metals in younger elderly, octogenarians, nonagenarians and centenarians: Analysis of the Healthy Ageing and Biomarkers Cohort Study (HABCS) in China

Background: Metals can be either toxic or essential to health, as they play different role in oxidative stress and metabolic homeostasis during the ageing process. Population-based biomonitoring have documented levels and ranges in concentrations among general population of 0–79 years of age. In people aged 80 and above, toxic metals and essential metals may have different risk profiles, and thus need to be better studied. Objective: Our aim is to investigate concentrations of toxic metals (arsenic, cadmium, lead and mercury) and essential metals (chromium, cobalt, molybdenum, manganese, nickel and selenium) and their role in diseases, nutritional status among younger elderly, octogenarians, nonagenarians and centenarians. Methods: A total of 932 younger elderly, 643 octogenarians, 540 nonagenarians, 386 centenarians were included from the cross-sectional Healthy Aging and Biomarkers Cohort Study in 2017–2018. Blood or urine biological substrates were collected from each participant to determine the concentrations of toxic metals and essential metals by inductively coupled plasma mass spectrometry. Random forest was constructed to rank the importance of toxic metals and essential metals in longevity. LASSO penalized regressions were performed to select the most significant metals associated with diseases and nutritional status, of which simultaneously included all metals and adjusted for the confounding factors. Results: Compared to women, we found higher biomarker concentrations in men for toxic metals (41.2 µg/L vs 34.4 µg/L for blood lead, 1.56 µg/L vs 1.19 µg/L for blood mercury) and lower concentration of essential metals (0.48 µg/L vs 0.58 µg/L for blood molybdenum, 10.0 µg/L vs 11.1 µg/L for blood manganese). These factors may contribute to gender difference observed in longevity, that women live longer than men. Blood lead and urine cadmium tended to increase with age (P <0.001); blood cobalt, molybdenum, manganese increased with age, blood selenium decreased with age while the prevalence of selenium deficiency was extremely low in centenarians. Among toxic metals and essential metals, LASSO penalized regression identified the most significant metals associated with chronic kidney disease was cadmium and arsenic; and it was manganese, cobalt, and selenium for diabetes; it was selenium, molybdenum, lead for anemia; it was mercury for underweight. In random forest model, the top four important metals in longevity were selenium, arsenic, lead and manganese both in men and women. Conclusions: Generally, toxic metals levels were significantly higher while essential metals were relatively sufficient in Chinese centenarians. Toxic metals and essential metals played different role in diseases, nutritional status and longevity in the process of aging. Our research provided real world evidence of biomonitoring reference values to be used for the ongoing population health surveillance in longevity

Green-Solvent-Processable Low-Cost Fluorinated Hole Contacts with Optimized Buried Interface for Highly Efficient Perovskite Solar Cells

Solution-processed hole contact materials, as an indispensable component in perovskite solar cells (PSCs), have been widely studied with consistent progress achieved. One bottleneck for the commercialization of PSCs is the lack of hole contact materials with high performance, cost-effective preparation, and green-solvent processability. Therefore, the development of versatile hole contact materials is of great significance. Herein, we report two novel donor–acceptor (D–A)-type hole contact molecules (FMPA–BT-CA and 2FMPA–BT-CA) with low cost and alcohol-based processability by utilizing a fluorination strategy. We showed that the fluorine atoms lead to the lowered highest occupied molecular orbital (HOMO) energy levels and larger dipole moments for FMPA–BT-CA and 2FMPA–BT-CA. Moreover, fluorination also improves the buried interfacial interaction between hole contacts and perovskite. As a result, a remarkable power conversion efficiency (PCE) of 22.37% along with good light stability could be achieved for green-solvent-processed FMPA–BT-CA-based inverted PSC devices, demonstrating the great potential of environmentally compatible hole contacts for highly efficient PSCs

Between Copper, Silver and Gold: Japanese Banks of Issue in Taiwan, Northeast China and Korea, 1879–1937

This article provides the first comparative overview in English of Japanese colonial banks before World War II with an emphasis on their roles as banks of issue in Taiwan, Korea and Northeast China. It discusses at length similarities and differences in these banks’ note circulation patterns, in their note-reserve requirements and their actual application, and in their geographical spread and respective colonial mandates. There was some variation in Japanese bank note issuance in the colonial setting of Korea and Taiwan, in ‘Manchukuo’ and in those parts of China that remained nominally sovereign. But all Japanese colonial banks seem, in one way or another, to have astutely adjusted the spread of their note issue in order to control for flagging demand due to nationalist boycotts, or to conversely cash in on demand spurts for notes resulting from crises in the indigenous financial sector. The banks of issue under review here were theoretically subject to a 100 per cent reserve requirement, but the make-up of their metallic bullion reserve and the degree of their notes’ convertibility were very dissimi¬lar, reflecting varying local conditions. Both in terms of reserve ratios, and note denominations—the banks prudently followed charter obligations that were devised by the Japanese Treasury but, at the same time, were reminiscent of the obligations that British overseas banks also had to abide by. Thus, the findings discussed here shed light on the inception and adaptability of Japanese colonial policy in the lead-up to the Pacific War