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Summary Vacuolar (H+)‐PPases (VPs), are key regulators of active proton (H+) transport across membranes using the energy generated from PPi hydrolysis. The VPs also play vital roles in plant responses to various abiotic stresses. Their functions in plant responses to pathogen infections are unknown. Here, we show that TaVP, a VP of wheat (Triticum aestivum) is important for wheat resistance to Chinese wheat mosaic virus (CWMV) infection. Furthermore, overexpression of TaVP in plants induces the activity of PPi hydrolysis, leading to plants cell death. A virus‐derived small interfering RNA (vsiRNA‐20) generated from CWMV RNA1 can regulate the mRNA accumulation of TaVP in wheat. The accumulation of vsiRNA‐20 can suppress cell death induced by TaVP in a dosage‐dependent manner. Moreover, we show that the accumulation of vsiRNA‐20 can affect PPi hydrolysis and the concentration of H+ in CWMV‐infected wheat cells to create a more favorable cellular environment for CWMV replication. We propose that vsiRNA‐20 regulates TaVP expression to prevent cell death and to maintain a weak alkaline environment in cytoplasm to enhance CWMV infection in wheat. This finding may be used as a novel strategy to minimize virus pathogenicity and to develop new antiviral stratagems.

The aim of this study was to evaluate the expression and role of Grhl2 in gastric cancer. Immunohistochemistry was performed to explore the expression of Grhl2 in gastric cancer and surrounding non-tumor tissues. Moreover, the mRNA and protein expression level of Grhl2 in human immortalized gastric epithelial cell line GES-1 and four gastric cancer cell lines (MGC803, SGC7901, MKN45, HGC27) were detected by qRT-PCR and Western blotting, respectively. To further investigate the role of Grhl2 in gastric cancer as well as the potential mechanisms, SGC7901 cells were transfected with lentiviral constructs expressing Grhl2 or empty vector, and then proliferation and apoptosis of SGC7901 cells were evaluated by MTT assay and flow cytometry, respectively. Finally, the protein expression level of c-Myc and Bcl-2 was detected by Western blotting. Both mRNA and protein expression level of Grhl2 were significantly downregulated in gastric cancer. Exogenous Grhl2 transduced into SGC7901 cells significantly inhibited the proliferation and promoted apoptosis. Meanwhile, over-expression of Grhl2 decreased c-Myc and Bcl-2 protein expression level. Taken together, our results demonstrated that Grhl2 downregulated in gastric cancer and may function as a tumor suppressor and play an important role in the development and progression of gastric cancer. These results may provide a new clue for treatment for gastric cancer.

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In this comprehensive article, we present an overview of some most common autoimmune antibodies believed to be potentially pathogenic for autoimmune epilepsies and elaborate their pathogenic mode of action in molecular levels based on the existing knowledge. Findings of the studies of immunemodulatory treatments for epilepsy are also discussed, and guidelines for immunotherapy are sorted out. We aim to summarize the emerging understanding of different pathogenic mechanisms of autoantibodies and clinical immunotherapy regimens to open up therapeutic possibilities for future optimum therapy. We conclude that early diagnosis of autoimmune epilepsy is of great significance, as early immune treatments have useful disease-modifying effects on some epilepsies and can facilitate the recovery.

The geometric, optical, and magnetic properties of the M@Sn(12) clusters (M=Ti, V, Cr, Mn, Fe, Co, Ni) are studied using the relativistic density-functional method. The geometric optimization shows that the ground states of these clusters are probably very close to the I(h) structure. Our calculations demonstrate that the optical gaps of the M@Sn(12) can be tuned from infrared to green, and the magnetic moments of them vary from 2 mu(B) to 5 mu(B) by doping d transition metal atoms into Sn(12) cage, suggesting that M@Sn(12) could be a new class of potential nanomaterials with tunable magnetic and optical properties.

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OBJECTIVE Type 1 diabetes mellitus (T1DM) is a rare, irreversible immune-related adverse event reported in patients receiving treatment with immune checkpoint inhibitors (ICI). However, clinical risk factors for ICI-induced T1DM (ICI-T1DM) and its impact on survival in patients remain unknown. RESEARCH DESIGN AND METHODS We used Optum’s Clinformatics Data Mart database for assessment of the incidence and characteristics of T1DM in a large de-identified cohort of patients treated with ICI between 2017 and 2020. We applied Fine-Gray and cause-specific hazard models to study associations between patient/treatment characteristics and ICI-T1DM and applied the Cox model with ICI-T1DM as a time-varying covariate to assess the impact of ICI-T1DM on survival. RESULTS ICI-T1DM was observed in 261 of 30,337 (0.86%) patients. Dual use of antibodies to cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) was associated with increasing risk of ICI-T1DM (hazard ratio [HR] 1.62; 95% CI 1.15–2.26) vs. anti–PD-L1 or anti–PD-1 alone. Younger age (HR 1.19 for every 5-year decrease; 95% CI 1.13–1.25) and preexisting non-T1DM diabetes (HR 4.48; 95% CI 3.45–5.83) were also associated with higher risk of ICI-T1DM. Conversely, prior use of immunosuppressive medications (HR 0.57; 95% CI 0.34–0.95) was associated with lower incidence of ICI-T1DM, but part of its protective effect may be due to the increased mortality rate. Development of ICI-T1DM does not seem to significantly impact patient survival. CONCLUSIONS The risk of ICI-T1DM is associated with the type of ICI therapy, patient age, and preexisting non-T1DM diabetes. These data may help guide risk assessment and screening practices for patients during ICI therapy.