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Background: Although the health impacts of ambient ozone (O3) have been widely assessed, studies simultaneously investigating the acute and chronic effects of O3 on mortality from respiratory diseases (RESP) are scarce. Methods: We extracted personal information of all recorded deaths from RESP throughout 2013–2018 in six provinces in China. The daily, seasonal, and annual mean air pollutant concentrations at the township/subdistrict level were estimated by a random forest model. The acute association between the maximum daily average 8h ozone (MDA8 O3) and RESP mortality was examined by a time-stratified case-crossover study design, and the chronic association was estimated by a difference-in-differences (DID) analysis approach. We also calculated the attributable fraction (AF) of RESP mortality attributable to MDA8 O3. Results: There were 1,034,226 RESP deaths included in this study. The excess risks (ERs) of overall RESP mortality for each 10 μg/m3 increase in short-term (lag03 days) and long-term (one-year average) exposure to MDA8 O3 were 0.38 % (95%CI: 0.26 %, 0.50 %) and 4.37 % (3.91 %, 4.84 %), respectively. The AFs of overall RESP mortality ascribed to short- and long-term MDA8 O3 exposures were 3.00 % (2.03 %, 3.95 %) and 29.45 % (26.86 %, 31.95 %), respectively. The average annual number of RESP deaths attributable to short-term MDA8 O3 exposure was 30,790 and 302,254 were attributable to long-term MDA8 O3 exposure across China during 2013–2018. Conclusion: Both short- and long-term exposure to ambient MDA8 O3 were positively associated with RESP mortality, and long-term exposure to MDA8 O3 may lead to a greater RESP mortality burden than short-term exposure to MDA8 O3.

The karst groundwater flow system in the ejective folds area in the eastern Sichuan Basin shows the characteristics of a hierarchically nested structure. However, previous studies were mainly focused on hydrogeological conditions analysis, lacking qualitative evidence directly from hydrochemistry. In this study, the authors collected and sorted the chemistry data of representative karst springs and boreholes in the study area, namely, 41 shallow karst waters and 19 deep ones. The Pipper chart shows that the shallow karst water is HCO3-Ca·Mg and low Mg2+ concentration, while the deep karst water is SO4-Ca·Mg and high Mg2+ concentration. For both shallow and deep karst groundwater, the analysis of the groundwater flow system of a typical profile shows that the Mg2+ concentration value can be used to evaluate the groundwater residence time. The shallow karst groundwater system is highly controlled by geomorphology, among which the shallow incised valley springs are the discharge points of the local groundwater flow system. However, springs in deep gullies correspond to intermediate or even regional flow systems. This pattern is verified by the groundwater residence time evaluation from the Mg2+ concentration, which also reflects the movement characteristics of deep-circulation groundwater flow revealed by hot springs and boreholes.The hydrochemical characteristics can effectively indicate the pattern of groundwater flow systems. This paper provides a reference for identifying the hierarchically nested structure of groundwater flow systems in similar karst areas.

With the rapid development of new forms of Internet business, the network broadcast industry has gradually become the tuyer. The huge tax evasion event of network anchors such as Huang Wei and Lin Shanshan broke out, which caused huge social public opinion, but also reflected that there are many special difficulties in the tax work of network broadcast industry at present. However, the existing tax collection and administration system of China can not adapt to the needs of the emerging industry, which induced a series of tax evasion events. This paper will grasp the particularity of the tax work in the network live broadcast industry and analyze the realistic difficulties encountered by the tax authorities in the taxation of network broadcast industry, and put forward the countermeasures for the situation of our country based on the international advanced experience, and propose a new way to deeply integrate the tax work and high-tech.

BackgroundThe risk factors of papillary thyroid carcinoma (PTC) recurrence are meaningful for patients and clinicians. Tumor mutation burden (TMB) has been a biomarker for the effectiveness of immune checkpoint inhibitor (ICI) and prognosis in cancer. However, the role of TMB and its latent significance with immune cell infiltration in PTC are still unclear. Herein, we aimed to explore the effect of TMB on PTC prognosis.Material and MethodsRNA-seq and DNA-seq datasets of PTC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The Gene Ontology (GO) and gene set enrichment analysis (GSEA 4.0.1) were applied further to explore potential differences in PTC patients’ biological functions. The differentially expressed genes (DEGs) and immune microenvironment between the high and low TMB groups were determined.ResultsTMB had the highest AUC score than other clinical indicators in ROC analysis on recurrence-free survival, and a higher TMB score was related to a worse prognosis. Further, GSEA showed a higher level of oxidative phosphorylation (OXPHOS) in the high TMB group, and four genes correlated with recurrence-free survival rate were identified. The abundance of CD8+ T cells and M1 macrophages in the high TMB group was significantly lower than that in the low TMB group.ConclusionsOur study found that TMB was a better predictor variable at evaluating the risk of PTC recurrence. Moreover, TMB-related genes conferred dramatically correlated prognosis, which was worth exploring in guiding postoperative follow-up and predicting recurrence for PTC patients.

Thyroid carcinoma (TC) is the most common endocrine malignancy. The incidence rate of thyroid cancer has increased rapidly in recent years. The occurrence and development of thyroid cancers are highly related to the massive genetic and epigenetic changes. Therefore, it is essential to explore the mechanism of thyroid cancer pathogenesis. Genome-Wide Association Studies (GWAS) have been widely used in various diseases. Researchers have found multiple single nucleotide polymorphisms (SNPs) are significantly related to TC. However, the biological mechanism of these SNPs is still unknown. In this paper, we used one GWAS dataset and two eQTL datasets, and integrated GWAS with expression quantitative trait loci (eQTL) in both thyroid and blood to explore the mechanism of mutations and causal genes of thyroid cancer. Finally, we found rs1912998 regulates the expression of IGFALS (P = 1.70E-06) and HAGH (P = 5.08E-07) in thyroid, which is significantly related to thyroid cancer. In addition, KEGG shows that these genes participate in multiple thyroid cancer-related pathways.

Abstract Gene‐editing technology has become a transformative tool for the precise manipulation of biological genomes and holds great significance in the field of animal disease‐resistant breeding. Mastitis, a prevalent disease in animal husbandry, imposes a substantial economic burden on the global dairy industry. In this study, a regulatory sequence gene editing breeding strategy for the successful creation of a gene‐edited dairy (GED) goats with enhanced mastitis resistance using the ISDra2‐TnpB system and dairy goats as the model animal is proposed. This included the targeted integration of an innate inflammatory regulatory sequence (IRS) into the promoter region of the lysozyme (LYZ) gene. Upon Escherichia Coli (E. coli) mammary gland infection, GED goats exhibited increased LYZ expression, showing robust anti‐mastitis capabilities, mitigating PANoptosis activation, and alleviating blood‐milk‐barrier (BMB) damage. Notably, LYZ is highly expressed only in E. coli infection. This study marks the advent of anti‐mastitis gene‐edited animals with exogenous‐free gene expression and demonstrates the feasibility of the gene‐editing strategy proposed in this study. In addition, it provides a novel gene‐editing blueprint for developing disease‐resistant strains, focusing on disease specificity and biosafety while providing a research basis for the widespread application of the ISDra2‐TnpB system.

Prime editor, an editing tool based on the CRISPR/Cas9 system, allows for all 12 types of nucleotide exchanges and arbitrary indels in genomic sequences without the need for inducing DNA double-strand breaks. Despite its flexibility and precision, prime editing efficiency is still low and hindered by various factors such as target sites, editing types, and the length of the primer binding site. In this study, we developed a prime editing system by incorporating an RNA motif at the 3′ terminal of the pegRNA and integrating all twin prime editor factors into a single plasmid. These two strategies enhanced prime editing efficiency at target sites by up to 3.58-fold and 2.19-fold, respectively. Subsequently, enhanced prime editor was employed in goat cells and embryos to efficiently insert a 38 bp attB sequence into the Gt(ROSA)26Sor (Rosa26) and C-C motif chemokine receptor 5 (CCR5) loci. The enhanced prime editor can mediate 11.9% and 6.8% editing efficiency in parthenogenetic activation of embryos through embryo microinjection. In summary, our study introduces a modified prime editing system with improved editing and transfection efficiency, making it more suitable for inserting foreign sequences into primary cells and embryos. These results broaden the potential applications of prime editing technologies in the production of transgenic animals.

Studies reveal that there exists much interaction and communication between bacterial cells, with parts of these social behaviors depending on cell-cell contacts. The cell-cell contact has proved to be crucial for determining various biochemical processes. However, for cell culture with relatively low cell concentration, it is difficult to precisely control and retain the contact of a small group of cells. Particularly, the retaining of cell-cell contact is difficult when flows occur in the medium. Here, we report an optofluidic method for realization and retaining of Escherichia coli cell-cell contact in a microfluidic channel using an abrupt tapered optical fibre. The contact process is based on launching a 980-nm wavelength laser into the fibre, E. coli cells were trapped onto the fibre tip one after another, retaining cell-cell contact and forming a highly organized cell chain. The formed chains further show the ability as bio-optical waveguides. [ABSTRACT FROM AUTHOR]

In the context of the active digitalization of the economic space, a fundamental transformation of thinking, methodological approaches to the development and implementation of public policy and its tools for building effective integration interaction to achieve strategic advantages in a strategic perspective is taking place. It is these circumstances that determine the relevance of the research topic. The purpose of the publication is to study the features of the integration interaction between Russia and China in the context of the digital transformation of the economy. The study is based on the modern methodology of economic analysis, performed using the deductive and inductive approaches, using the methods of comparative, structural-logical, statistical analysis. As a result of the study, it was proved that the development of long-term relations between Russia and China is based on the virtual exchange of resources in the context of the digital transformation of the economy.