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During the thermite welding of in-service oil pipelines, empirical values are often used for the dosage of aluminum powder welding flux, and the uncertainty of temperature and residual stress generated during the welding poses a serious threat to the construction of pipeline and its safe operation. In response to this problem, the thermite welding process of pipelines in different wall thickness and with different dosages of welding flux was analyzed with the numerical simulation software ANSYS.Specifically, a finite element model of thermite welding was established, and thus the change law of the temperature field and residual stress field with different dosages of aluminum powder welding flux and different pipeline wall thicknesses was obtained,which was also verified by test. As indicated by the results, the maximum temperature in the welding area of pipelines with same wall thickness rises with the increasing dosage of welding flux. The maximum temperature in the welding area decreases with the increasing of pipeline wall thickness in the case that equivalent welding flux is used. Besides, with the increasing of pipeline wall thickness, the maximum residue stress at the weld is up to 150 MPa, lower than the yield limit of material, so that no burn-through and crack will occur during thermite welding, and the simulation results are consistent with the test results. Moreover, it is safe and reliable to conduct thermite welding in 6 mm to 8 mm pipeline in service with 10 g to 20 g of aluminum powder. Generally, the numerical simulation method could provide reference for the safe operation of thermite welding of in-service pipelines, thus reducing the construction risks of pipelines in service.

Objective To explore whether inhibiting autophagy can enhance the sensitivity of photothermal treatment under mild photothermal conditions. Methods CQ@PLGA@PDA NPs were prepared by an improved double emulsification method and a PDA-based surface modification method. After basic characterization, CCK-8 method was used to detect the cytotoxicity of nanoparticles; the near-infrared laser irradiation nanoparticle solution was used to detect the heating effect; CCK-8 method and live-dead cell staining were used to detect the killing effect of tumor cells; Western blot was used to detect the expression of autophagy-related proteins. Results The CQ@PLGA@PDA NPs were successfully prepared, with a particle size of 253.10±2.39 nm, a zeta potential of -22.57±0.80 mV, uniform particle size and good dispersion. The temperature of nanoparticle solution increased to 45℃ after the near-infrared laser irradiation for 10 min. CQ@PLGA@PDA NPs had no obvious toxicity to cells. The survival rates of breast cancer cell MDA-MB-231 and mouse embryonic fibroblast NIH-3T3 cell were above 95%. The inhibition of autophagy under mild photothermal conditions could improve the sensitivity of photothermal therapy. Conclusion The prepared CQ@PLGA@PDA NPs have good photothermal performance and high biological safety; by inhibiting autophagy, they can effectively kill tumor cells under mild photothermal conditions(< 50℃).

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in the AsA population remain unclear. Here, we utilized available gene expression data and genotype data based on all non-HLA SNP associations in EA and AsA SLE patients detected using the Immunochip genotyping array. We identified 2778 ancestry-specific and 327 trans-ancestry SLE-risk polymorphisms. Genetic associations were examined using connectivity mapping and gene signatures based on predicted biological pathways and were used to interrogate gene expression datasets. SLE-associated pathways in AsA patients included elevated oxidative stress, altered metabolism and mitochondrial dysfunction, whereas SLE-associated pathways in EA patients included a robust interferon response (type I and II) related to enhanced cytosolic nucleic acid sensing and signaling. An independent dataset derived from summary genome-wide association data in an AsA cohort was interrogated and identified similar molecular pathways. Finally, gene expression data from AsA SLE patients corroborated the molecular pathways predicted by SNP associations. Identifying ancestry-related molecular pathways predicted by genetic SLE risk may help to disentangle the population differences in clinical severity that impact AsA and EA individuals with SLE.

IntroductionMushroom-forming fungi comprise diverse species that develop complex multicellular structures. In cultivated species, both ecological adaptation and artificial selection have driven genome evolution. However, little is known about the connections among genotype, phenotype and adaptation in mushroom-forming fungi.ObjectivesThis study aimed to (1) uncover the population structure and demographic history of Lentinula edodes, (2) dissect the genetic basis of adaptive evolution in L. edodes, and (3) determine if genes related to fruiting body development are involved in adaptive evolution.MethodsWe analyzed genomes and fruiting body-related traits (FBRTs) in 133 L. edodes strains and conducted RNA-seq analysis of fruiting body development in the YS69 strain. Combined methods of genomic scan for divergence, genome-wide association studies (GWAS), and RNA-seq were used to dissect the genetic basis of adaptive evolution.ResultsWe detected three distinct subgroups of L. edodes via single nucleotide polymorphisms, which showed robust phenotypic and temperature response differentiation and correlation with geographical distribution. Demographic history inference suggests that the subgroups diverged 36,871 generations ago. Moreover, L. edodes cultivars in China may have originated from the vicinity of Northeast China. A total of 942 genes were found to be related to genetic divergence by genomic scan, and 719 genes were identified to be candidates underlying FBRTs by GWAS. Integrating results of genomic scan and GWAS, 80 genes were detected to be related to phenotypic differentiation. A total of 364 genes related to fruiting body development were involved in genetic divergence and phenotypic differentiation.ConclusionAdaptation to the local environment, especially temperature, triggered genetic divergence and phenotypic differentiation of L. edodes. A general model for genetic divergence and phenotypic differentiation during adaptive evolution in L. edodes, which involves in signal perception and transduction, transcriptional regulation, and fruiting body morphogenesis, was also integrated here.

Abstract Background Leukocyte infiltration plays an important role in the pathogenesis and progression of myositis, and is highly associated with disease severity. Currently, there is a lack of: efficacious therapies for myositis; understanding of the molecular features important for disease pathogenesis; and potential molecular biomarkers for characterizing inflammatory myopathies to aid in clinical development. Methods In this study, we developed a simple model and predicted that 1) leukocyte-specific transcripts (including both protein-coding transcripts and microRNAs) should be coherently overexpressed in myositis muscle and 2) the level of over-expression of these transcripts should be correlated with leukocyte infiltration. We applied this model to assess immune cell infiltration in myositis by examining mRNA and microRNA (miRNA) expression profiles in muscle biopsies from 31 myositis patients and 5 normal controls. Results Several gene signatures, including a leukocyte index, type 1 interferon (IFN), MHC class I, and immunoglobulin signature, were developed to characterize myositis patients at the molecular level. The leukocyte index, consisting of genes predominantly associated with immune function, displayed strong concordance with pathological assessment of immune cell infiltration. This leukocyte index was subsequently utilized to differentiate transcriptional changes due to leukocyte infiltration from other alterations in myositis muscle. Results from this differentiation revealed biologically relevant differences in the relationship between the type 1 IFN pathway, miR-146a, and leukocyte infiltration within various myositis subtypes. Conclusions Results indicate that a likely interaction between miR-146a expression and the type 1 IFN pathway is confounded by the level of leukocyte infiltration into muscle tissue. Although the role of miR-146a in myositis remains uncertain, our results highlight the potential benefit of deconvoluting the source of transcriptional changes in myositis muscle or other heterogeneous tissue samples. Taken together, the leukocyte index and other gene signatures developed in this study may be potential molecular biomarkers to help to further characterize inflammatory myopathies and aid in clinical development. These hypotheses need to be confirmed in separate and sufficiently powered clinical trials.

Abstract Background The σB protein of Muscovy duck reovirus (DRV), one of the major structural proteins, is able to induce neutralizing antibody in ducks, but the monoclonal antibody (MAb) against σB protein has never been characterized. Results Four hybridoma cell lines secreting anti-DRV σB MAbs were obtained, designated 1E5, 2F7, 4E3 and 5D8. Immunoglobulin subclass tests differentiated them as IgG2b (1E5 and 4E3) and IgM (2F7 and 5D8). Dot blot and western blotting assays showed that MAbs reacted with His-σB protein in a conformation-independent manner. Competitive binding assay indicated that the MAbs delineated two epitopes, A and B of σB. Immunofluorescence assay indicated that the four MAbs could specifically bind to Vero cells infected with DRV and σB was distributed diffusely in the cytoplasma of infected cells. MAbs had universal reactivity to all DRVs tested in an antigen-capture enzyme-linked immunosorbent assay. Conclusion Results of this research provide important information about the four monoclonal antibodies and therefore the MAbs may be useful candidate for the development of a MAb capture ELISA for rapid detection of DRVs. In addition, it showed that the σB protein was located in the cytoplasma of infected cells by immunofluorescence assay with MAbs. Virus isolation and RT-PCR are reliable way for detection of DRV infection, but these procedures are laborious, time consuming, and requiring instruments. These obvious diagnosis problems highlight the ongoing demand of rapid, reproducible, and automatic methods for the sensitive detection of DRV.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type I interferon signature. Here we report a missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47phox subunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant that drives a strong SLE-associated signal detected by the Immunochip in the GTF2IRD1-GTF2I region at 7q11.23 with a complex genomic structure. We show that the p.Arg90His substitution, which is reported to cause reduced reactive oxygen species (ROS) production, predisposes to SLE (odds ratio (OR) = 3.47 in Asians (Pmeta = 3.1 × 10-104), OR = 2.61 in European Americans, OR = 2.02 in African Americans) and other autoimmune diseases, including primary Sjögren's syndrome (OR = 2.45 in Chinese, OR = 2.35 in European Americans) and rheumatoid arthritis (OR = 1.65 in Koreans). Additionally, decreased and increased copy numbers of NCF1 predispose to and protect against SLE, respectively. Our data highlight the pathogenic role of reduced NOX2-derived ROS levels in autoimmune diseases.

As a technology for water landscape performance that considers landscape, ecological, and social effects, nature-based solutions play a crucial role in enhancing the functionality of integrated ecosystem services on the micro-scale. This study conducted a systematic investigation into the landscape performance of the "Clear as a Drain" composite sponge facility at Handan Garden Expo Park. The following conclusions were drawn: (1) In terms of ecological restoration support services, the "Clear as a Drain" artificial wetland exhibited diverse habitat types, a rich variety of plant species specific to the site's region, and high plant diversity indices for shrubs (1.776) and herbaceous aquatic plants (3.352). Reclaimed water reused in the artificial terraced wetland promoted plant growth and diversity while contributing to site self-rehabilitation; plants also significantly contributed to carbon fixation, oxygen release, and carbon emission reduction. (2) Regarding ecological restoration regulation services, the artificial wetland effectively purified reclaimed water with substantial improvements observed in incoming water quality during spring, summer, and autumn—particularly notable purification effects were observed during the summer months. Pollutant reduction rates for COD, BOD5 ammonia nitrogen, TP, and TN reached 75.8%, 72.1%, 93.8%, 96.7%, and 90.3%, respectively; different independent subsystems within the wetland demonstrated distinct advantages in pollutant removal; park plants displayed strong air purification capabilities; annual energy savings from park plants could fully cover daily energy consumption for nearby residents. This case could serve as guidance for scientific management and design parameter optimization of other composite sponge facilities. [ABSTRACT FROM AUTHOR]