HCV genotype 6 prevalence, spontaneous clearance and diversity amongst elderly members of the Li ethnic minority in Baisha County, China

The epidemiology of hepatitis C virus varies widely across geographical regions and ethnic groups. Our previous study showed that 6 strains isolated from Baisha County, Hainan Island, China, were all new genotype 6 (gt6) subtypes which differed significantly from subtypes of other regions. In the current study, we conducted a comprehensive epidemiological survey of HCV in the Li ethnic group, native to Baisha County. Anti‐HCV antibodies were detected by 2 independent ELISAs in all participants, and positive results confirmed by the recombinant immunoblot assay (RIBA) and HCV RNA viral loads were measured. Univariate chi‐square test and multivariable logistic regression analyses were used to determine the risk factors for HCV infection and spontaneous clearance rates. Indeterminate RIBA results were excluded or included in analyses; consequently, findings were expressed as a range. Direct sequencing of partial regions within NS5B and E1 was employed for genotyping. Among 1682 participants, 117 to 153 were anti‐HCV positive (7.0%‐9.1%), with 42.7%‐52.6% confirmed to have cleared infection. Anti‐HCV positivity was associated with older age (≥60 years) (OR = 0.02, 95% CI 0.01‐0.05, P < 0.01) and surgery (OR = 2.75, 95% CI 1.36‐5.57, P < 0.01), with no significant difference found between the HCV infection group and the HCV spontaneous clearance group. The gt6 subtype distribution characteristics of Baisha County were unique, complex and diverse. The sequences did not cluster with known gt6 subtypes but formed 4 Baisha community‐specific groups. HCV infection in members of the Li minority ethnic group is characterized by high prevalence rates in the elderly, high spontaneous clearance rates and broad gt6 diversity

Inhibition of Notch1 Signaling Alleviates Endotoxin-Induced Inflammation Through Modulating Retinal Microglia Polarization

Microglial cells are resident immune cells and play an important role in various cerebral and retinal inflammatory diseases. Notch1 signaling is involved in the microglia polarization and the control of cerebral inflammatory reactions. However, its role in endotoxin-induced uveitis (EIU) remains unknown. This study aimed to investigate the role of Notch1 signaling on retinal microglia polarization and inflammation in the cultured retinal microglial cells and EIU rat model. We found that Notch1 signaling blockade with N-[N-(3, 5-difluorophenacetyl)-1-alany1-S-phenyglycine t-butyl ester (DAPT) shifted retinal microglia phenotype from pro-inflammatory M1 phenotype (COX2+ and iNOS+) to anti-inflammatory M2 phenotype (Arg-1+) and reduced the release of pro-inflammatory cytokines both in vivo and in vitro. Moreover, DAPT treatment contributed to prevent retinal ganglion cells from apoptosis, reduce the intraocular infiltrating cells, and attenuate the impairment of retinal function. Taken together, these results suggest that inhibition of Notch1 signaling could alleviate the inflammatory response in EIU rat mainly through regulating the polarization of retinal microglia. Therefore, Notch1 signaling might be a promising therapeutic target in the treatment of ocular inflammatory diseases

Analysis on Influencing Factors Decomposition and Decoupling Effect of Power Carbon Emissions in Yangtze River Economic Belt

The power industry is one of the main industries of energy consumption and carbon emissions in the Yangtze River Economic Belt, in order to accelerate the development of green and low-carbon power. This paper takes the power industry in the Yangtze River Economic Belt and the upper, middle and lower reaches from 2000 to 2020 as the research object. Based on the four absolute factors of economy, energy consumption, population and output, the generalized divisia index method (GDIM) is constructed. Combining the decoupling model with the GDIM method, a decoupling effort model is constructed based on the DPSIR framework to incorporate electricity output and economic scale into economic drivers. The main findings are as follows: The lower reaches provide the main contribution area of power carbon emissions, and the high value of carbon emissions tends to migrate eastward. Economy, output and energy consumption scale are the main factors leading to the increase in carbon emissions in the Yangtze River Economic Belt, upper, middle and lower reaches, while carbon intensity and output carbon intensity are the key factors curbing carbon emissions. Among them, economic scale is the largest positive driving factor of carbon emissions in the middle and lower reaches, and output carbon intensity is the largest negative driving factor in the upper reaches. The total decoupling effect index in the upper reaches of the Yangtze River Economic Belt increased the most and achieved decoupling of carbon emissions between 2014 and 2020. From 2016 to 2020, the total decoupling effect index of the upper, middle and lower reaches of the Yangtze River Economic Belt fluctuates within a certain range, and the total decoupling effect index of the power industry has entered a certain pressure period

Research on Performance Deterioration of Internally Cured Pavement Concrete under the Coupling Effect of Salt Freeze–Thaw

This paper aims at solving the material durability problem caused by spraying deicing salt on pavement concrete in the northern winter. Super absorbent polymer (SAP) was adopted as an internal curing agent to enhance the durability of pavement concrete. Curing parameters including particle size and dosage of SAP and curing condition were optimized based on mortar tests by means of the grey target decision method. The deterioration rule of durability and mechanical properties of pavement concrete internally cured by different SAP dosages after salt freeze–thaw cycles were explored through rapid freeze–thaw test. Combined with the characteristics of pore structure, hydration and microstructure, the influence mechanism of SAP on the salt freeze–thaw resistance of pavement concrete was revealed. The experimental results showed that: (i) The reduction in mass loss rate and relative dynamic modulus was significantly improved by SAP internal curing with moderate dosage; (ii) The more freeze–thaw cycles the specimen underwent, the greater the increase in strength; (iii) After 75 cycles, the chloride ion erosion depth could be decreased by approximately 23.18%. Moreover, the addition of SAP could refine the pore size, inhibit the generation of shrinkage microcracks, and promote the degree of cement hydration in the late stage, which improved the internal density of the cement concrete structure. Therefore, the deterioration of pavement under the coupling effect of salt freeze–thaw was reduced

6-BA Delays the Senescence of Postharvest Cabbage Leaves by Inhibiting Respiratory Metabolism

6-BA, a small molecule compound of cytokinins, has been proven to delay leaf senescence in different species, including Chinese flowering cabbage; however, its specific mechanism remains relatively unknown. In this study, the application of external 6-BA delayed leaf senescence in Chinese flowering cabbage, showing that 6-BA effectively prevented the decrease in the maximum quantum yield (Fv/Fm) and overall chlorophyll content and suppressed the expression of the senescence-associated gene BrSAG12 over a 7-day period of storage. Moreover, treatment with 6-BA decreased the respiratory rate, NAD(H) content, the activities of hexose phosphate isomerase (PHI), succinate dehydrogenase (SDH), cytochrome c oxidase (CCO), and ascorbic acid oxidase (AAO) using enzyme-linked immunosorbent assay, and the transcriptional abundance of related genes by real-time quantitative polymerase chain reaction. Furthermore, 6-BA also increased the activity and expression levels of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphate gluconate dehydrogenase (6-PGDH). The group treated with 6-BA retained elevated levels of NADP (H), ATP, total ATPase, and nicotinamide adenine dinucleotide kinase (NADK) activity, as well as the expression of respiratory enzymes. Molecular docking indicated that 6-BA hinders the glycolysis pathway (EMP), tricarboxylic acid cycle (TCA), and cytochrome pathway (CCP), and sustains elevated levels of the pentose phosphate pathway (PPP) through interactions with the PHI, SDH, 6-PGDH, G6PDH, CCO, and AAO proteins, consequently delaying postharvest leaf senescence in Chinese flowering cabbage

R-spodin2 enhances canonical Wnt signaling to maintain the stemness of glioblastoma cells

Abstract Background As newly identified Wnt enhancer, R-spondin gene family members have been linked to various cancers; however, their role in isocitrate dehydrogenase-wildtype subtype of human glioblastoma (GBM) cells remains unknown. Methods Human U87 and U251 cell lines were used to perform the experiments. GBM stem-like cells were enriched in stem cell growth media and induced to differentiate using retinoid acid or growth factor deprivation. Wnthigh and Wntlow subpopulations were isolated and evaluated by MTS, sphere formation, transwell migration and xenograft formation assays. Results R-spondin 2 but not R-spondin 3 potentiates Wnt/β-catenin signaling in GBM cell lines. While R-spondin 2 does not affect cell growth, it induces the expression of pluripotent stem cell markers in combination with Wnt3A. GBM stem-like cells are endowed with intrinsic high activity of β-catenin signaling, which can be further intensified by R-spondin 2. In addition, R-spondin2 promotes stem cell self-renewal and suppresses retinoid acid- or growth factor deprivation-induced differentiation, indicating R-spondin 2 maintains stem cell traits in GBM. On the other hand, we identify subpopulations of GBM cells that show distinctive responsiveness to Wnt/β-catenin signaling. Interestingly, Wnthigh and Wntlow cells display distinctive biologic properties. Moreover, Wnthigh cell-inoculated xenografts exhibit enhanced tumorigenicity and increased expression levels of R-spondin 2 compared to Wntlow cell-inoculated xenografts. Conclusion Our study reveals a novel regulatory mechanisms underlying the over-activation of β-catenin-mediated signaling in the pathogenesis of GBM

Influences of Impurity Gases in Air on Room-Temperature Hydrogen-Sensitive Pt–SnO₂ Composite Nanoceramics: A Case Study of H₂S

The slight but cumulative influence of impurity gases in air poses a great threat to the long-term stability of room-temperature gas sensors. Room-temperature hydrogen-sensitive Pt–SnO2 composite nanoceramics of 5 wt% Pt were prepared through pressing and sintering. The response of a sample was over 10,000 after being exposed to 500 ppm H2S–20% O2–N2 at room temperature, and the room-temperature hydrogen sensing capacity was seriously degraded even for samples that had aged dozens of days since H2S exposure. Mild heat treatments such as 160 °C for 10 min were found able to fully activate those H2S-exposed samples. As the peak of S 2p electron was clearly detected in H2S-exposed samples, it was proposed that for room-temperature hydrogen-sensitive Pt–SnO2 composite nanoceramics, H2S exposure induced degradation results from the poisoning of Pt by H2S deposited on it, which can be removed through a mild heat treatment. Periodic mild heat treatment should be a convenient and effective measure for room-temperature metal oxide gas sensors to achieve long-term stability through preventing the accumulation of impurity gases in air deposited on them

Virtual screening combined with experimental verification reveals the potential mechanism of Fuzitang decoction against Gouty Arthritis

Background: and Purpose: Fuzitang decoction (FZT), a classic prescription of traditional Chinese medicine (TCM), has excellent efficacy in treating gouty arthritis (GA). However, the underlying molecular mechanism remains obscure. In the present study, we aimed to explore the underlying mechanisms of FZT in treating GA by virtual screening combined with experimental verification. Methods: In this study, the active components of FZT and their corresponding targets were screened from the TCMSP database and TargetNet database. Then, the potential targets of FZT against GA were retrieved from multiple databases to generate a network. Protein-protein interaction, herbal-component-target, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were applied to identify potential targets and related signaling pathways. Furthermore, molecular docking simulation was applied to identify the interactions between the drug and targets. Finally, in vitro experiments were conducted to validate the potential targets and signaling pathways. Results: In the present study, several crucial components, including kaempferol, luteolin, catechin, deoxyandrographolide, and perlolyrine in FZT, were obtained through network pharmacology, and several potential targets to treat GA were developed, such as PPARG, CYP3A4, PTGS2 (known as COX2), VEGFA, and CYP1A1. Experimental validation suggested that deoxyandrographolide significantly suppressed the expression of IL-1β, COX2, NLRP3 and IL-6 in inflammatory monocyte cells. Conclusions: Our results identified a novel anti-inflammatory compound, deoxyandrographolide, which helps to explain the potential mechanism of FZT in treating GA and provides evidence to support FZT's clinical use