Wheat ESCRT-III protein TaSAL1 regulates male gametophyte transmission and controls tillering and heading date.

Charged multivesicular protein 1 (CHMP1) is a member of the endosomal sorting complex required for transport-III (ESCRT-III) complex that targets membrane localized signaling receptors to intralumenal vesicles in the multivesicular body of the endosome and eventually to the lysosome for degradation. Although CHMP1 plays roles in various plant growth and development processes, little is known about its function in wheat. In this study, we systematically analysed the members of the ESCRT-III complex in wheat (Triticum aestivum) and found that their orthologs were highly conserved in eukaryotic evolution. We identified CHMP1 homologous genes, TaSAL1s, and found that they were constitutively expressed in wheat tissues and essential for plant reproduction. Subcellular localization assays showed these proteins aggregated with and closely associated with the endoplasmic reticulum when ectopically expressed in tobacco leaves. We also found these proteins were toxic and caused leaf death. A genetic and reciprocal cross analysis revealed that TaSAL1 leads to defects in male gametophyte biogenesis. Moreover, phenotypic and metabolomic analysis showed that TaSAL1 may regulate tillering and heading date through phytohormone pathways. Overall, our results highlight the role of CHMP1 in wheat, particularly in male gametophyte biogenesis, with implications for improving plant growth and developing new strategies for plant breeding and genetic engineering.

Artemisinin and its derivatives as promising therapies for autoimmune diseases.

Artemisinin, a traditional Chinese medicine with remarkable antimalarial activity. In recent years, studies demonstrated that artemisinin and its derivatives (ARTs) showed anti-inflammatory and immunoregulatory effects. ARTs have been developed and gradually applied to treat autoimmune and inflammatory diseases. However, their role in the treament of patients with autoimmune and inflammatory diseases in particular is less well recognized. This review will briefly describe the history of ARTs use in patients with autoimmune and inflammatory diseases, the theorized mechanisms of action of the agents ARTs, their efficacy in patients with autoinmmune and inflammatory diseases. Overall, ARTs have numerous beneficial effects in patients with autoimmune and inflammatory diseases, and have a good safety profile.

Association of vitamin D with HIV infected individuals, TB infected individuals, and HIV-TB co-infected individuals: a systematic review and meta-analysis.

Background: Vitamin D deficiency (VDD) is a worldwide disease. VDD is also associated with an increased risk of HIV-related comorbidities and mortality, and patients have a tendency to develop active tuberculosis compared to those with latent tuberculosis infection. Vitamin D supplementation may modulate HIV replication, improve TB inflammation and reduce progression of HIV-TB co-infection. Methods: We meta-analyzed individual participant data from cohort studies, cross-sectional study, and RCTs of vitamin D in HIV group, TB group, and HIV-TB group. The primary outcomes were differences in vitamin D level and VDD prevalence between three groups, the secondary outcomes were CD4 count, HIV viral load, time to sputum smear conversion, time to culture conversion, relapse, morality, and TB score. Results: For vitamin D levels, the overall mean difference (MD) between HIV group and TB group was -0.21 (95% CI, -20.80-20.38; p = 0.9, I2 = 84%), HIV group and HIV-TB group was 0.87 (95% CI, -11.45-13.20; p = 0.89, I2 = 87%), and TB group and HIV-TB group was 1.17 (95% CI, -5.21-7.55; p = 0.72, I2 = 85%). For vitamin D deficiency prevalence, the overall odds ratio (OR) for HIV group versus TB group was 1.23 (95% CI, 0.46-3.31; p = 0.68; I2 = 70%), HIV group versus HIV-TB group was 1.53 (95% CI, 1.03-2.29; p = 0.04; I2 = 0%), and TB group versus HIV-TB group was 0.85 (95% CI, 0.61-1.20; p = 0.36; I2 = 22%). In HIV-TB group, the overall OR for vitamin D group versus placebo group was 0.78 (95% CI, 0.34-1.67; p = 0.52; I2 = 60%). Conclusion: Our findings indicated that there were no variations in vitamin D levels between three groups. The prevalence of vitamin D deficiency was higher in the HIV-TB group than in the HIV group. Additionally, the administration of vitamin D supplements did not have obvious impact on CD4 count and viral load. Likewise, vitamin D had no effect on time to sputum smear conversion, time to culture conversion, relapse, 12-month morality, and TB score.

Pathological proliferation: a potential mechanism for poor CD4+ T cell recovery in people living with HIV.

Background: People living with HIV (PLWH) fail to achieve normalization of CD4+ T cell counts and function, especially in immunological non-responders (INRs). The frequencies of Ki67+CD4+ T cells were inversely associated with CD4+ T cell counts in HIV infected patients. Early ART did not normalize CD4+ T cell proliferation. However, the features of the abnormal proliferation CD4+ T cell in INRs are far from known. Method: PLWH were divided into INRs (n= 16) and immunological responders (IRs, n= 53) groups. Mass cytometry was applied to peripheral blood T cells to profile the immune cells and liquid chip technique was used to measure plasma levels of cytokines and chemokines. Correlation analyses were conducted to evaluate associations between the degree of CD4+ T cell proliferation and immune function. Results: The percentage of Ki67+ CD4+ T cells were significant higher in INRs, and we defined these cells with significant higher level of Ki67, as over-proliferating cells. No significant difference of markers' expression (HLA-DR, CD38, CD57, PD-1, PD-L1, CD107a, perforin) was found between INRs and IRs. Compared with naïve CD4+ T cells in INRs, Ki67+ CD4+ T cells exhibited lower levels of CD57 and CD38. Whereas Ki67+ T cells exhibited higher levels of CD38 and CD57 and activation compared with differentiated mature central memory CD4+ T cells and effector memory CD4+ T cells. Ki67+ cells did not show higher levels of senescence and activation compared to certain Ki67- CD4+ central memory T cells in IRs. Furthermore, Ki67+ CD4+ Tcm cells exhibited positive correlations with pro-inflammatory cytokines. Conclusion: We proposed and validated the hypothesis of "pathological proliferation" in INRs: excessive proliferation of CD4+ T cells in INRs may be accompanied by aberrant activation, senescence and loss of immune function. Eventually, such over-proliferating but poor-quality cells in INRs result in incomplete recovery of both CD4+ T cell counts and function. An intervention that enhancing the proliferative capacity or functional ability or both of CD4+ T cell in INRs might therefore be beneficial.

Hydromechanical Properties and Engineering Applications of Weakly Cemented Soft Rock in Jurassic Strata.

The surrounding rock control of weakly cemented soft rock in the Jurassic strata roadway in the Northwest Mining Area has become one of the bottlenecks restricting mines' safety and efficient production. Based on the engineering background of the +170 m mining level West Wing main return-air roadway of Dananhu No. 5 Coal Mine (DNCM) in Hami Xinjiang, through field investigation and borehole peeping, the deformation and failure characteristics of the surface and depth of the roadway surrounding rock under the original support scheme were mastered. The geological composition features of the typical weakly cemented soft rock (sandy mudstone) in the study area were analyzed by X-ray fluorescence (XRF) and X-ray diffractometer (XRD) experiments. Through the water immersion disintegration resistance experiment, variable angle compression-shear experiment, and the theoretical calculation, the degradation trend of the weakly cemented soft rock hydromechanical properties was systematically revealed from the following three aspects: the water immersion disintegration resistance of sandy mudstone, the influence characteristics of water on sandy mudstone mechanical performance, and the plastic zone radius of the surrounding rock under the action of water-rock coupling. Based on that, the roadway surrounding rock control measures of "timely and active support, pay attention to the surface protection components and block the water inflow channels" were proposed. The support optimization scheme of "bolt mesh cable beam shotcrete grout" is designed pertinently, and the engineering application was executed on-site. The results demonstrated that the support optimization scheme had shown excellent application effectiveness, with an average reduction of 58.37% in the range of rock fracture compared to the original support scheme. The maximum relative displacement between the roof-to-floor and rib-to-rib is only 121 and 91 mm, respectively, which can ensure the long-term safety and stability of the roadway.

Genome wide association and haplotype analyses for the crease depth trait in bread wheat (Triticum aestivum L.).

Wheat grain has a complex structure that includes a crease on one side, and tissues within the crease region play an important role in nutrient transportation during wheat grain development. However, the genetic architecture of the crease region is still unclear. In this study, 413 global wheat accessions were resequenced and a method was developed for evaluating the phenotypic data of crease depth (CD). The CD values exhibited continuous and considerable large variation in the population, and the broad-sense heritability was 84.09%. CD was found to be positively correlated with grain-related traits and negatively with quality-related traits. Analysis of differentiation of traits between landraces and cultivars revealed that grain-related traits and CD were simultaneously improved during breeding improvement. Moreover, 2,150.8-Mb genetic segments were identified to fall within the selective sweeps between the landraces and cultivars; they contained some known functional genes for quality- and grain-related traits. Genome-wide association study (GWAS) was performed using around 10 million SNPs generated by genome resequencing and 551 significant SNPs and 18 QTLs were detected significantly associated with CD. Combined with cluster analysis of gene expression, haplotype analysis, and annotated information of candidate genes, two promising genes TraesCS3D02G197700 and TraesCS5A02G292900 were identified to potentially regulate CD. To the best of our knowledge, this is the first study to provide the genetic basis of CD, and the genetic loci identified in this study may ultimately assist in wheat breeding programs.