Development and evaluation of a disulfidoptosis-related lncRNA index for prognostication in clear cell renal cell carcinoma.

Background: This study introduces a novel prognostic tool, the Disulfidoptosis-Related lncRNA Index (DRLI), integrating the molecular signatures of disulfidoptosis and long non-coding RNAs (lncRNAs) with the cellular heterogeneity of the tumor microenvironment, to predict clinical outcomes in patients with clear cell renal cell carcinoma (ccRCC). Methods: We analyzed 530 tumor and 72 normal samples from The Cancer Genome Atlas (TCGA), employing k-means clustering based on disulfidoptosis-associated gene expression to stratify ccRCC samples into prognostic groups. lncRNAs correlated with disulfidoptosis were identified and used to construct the DRLI, which was validated by Kaplan-Meier and receiver operating characteristic curves. We utilized single-cell deconvolution analysis to estimate the proportion of immune cell types within the tumor microenvironment, while the ESTIMATE and TIDE algorithms were employed to assess immune infiltration and potential response to immunotherapy. Results: The Disulfidoptosis-Related lncRNA Index (DRLI) effectively stratified ccRCC patients into high and low-risk groups, significantly impacting survival outcomes (P < 0.001). High-risk patients, marked by a unique lncRNA profile associated with disulfidoptosis, faced worse prognoses. Single-cell analysis revealed marked tumor microenvironment heterogeneity, especially in immune cell makeup, correlating with patient risk levels. In prognostic predictions, DRLI outperformed traditional clinical indicators, achieving AUC values of 0.779, 0.757, and 0.779 for 1-year, 3-year, and 5-year survival in the training set, and 0.746, 0.734, and 0.750 in the validation set. Notably, while the constructed nomogram showed exceptional predictive capability for short-term prognosis (AUC = 0.877), the DRLI displayed remarkable long-term predictive accuracy, with its AUC value reaching 0.823 for 10-year survival, closely approaching the nomogram's performance. Conclusions: The study introduces the DRLI as a groundbreaking molecular stratification tool for ccRCC, enhancing prognostic precision and potentially guiding personalized treatment strategies. This advancement is particularly significant in the context of long-term survival predictions. Our findings also elucidate the complex interplay between disulfidoptosis, lncRNAs, and the immune microenvironment in ccRCC, offering a comprehensive perspective on its pathogenesis and progression. The DRLI and the nomogram together represent significant strides in ccRCC research, highlighting the importance of molecular-based assessments in predicting patient outcomes.

Antibacterial Activities of Bacillus amyloliquefaciens DQB-1 Isolated From the Cecum of Dezhou Donkeys.

The microorganisms in the cecum of donkeys share similar functions as those in the rumen of cattle. Transformation of the cecal microenvironment by probiotics plays an important role in the health and growth of donkeys. In order to screen out excellent donkey probiotic preparations, in this study, we isolated an antibacterial strain of Bacillus amyloliquefaciens (designated as DQB-1) from the cecum of Dezhou donkey. The strain was assessed in terms of antibacterial activity, antibacterial substance analysis, and stability. The results show that, the Bacillus amyloliquefaciens DQB-1 exhibited protease production activity and can significantly inhibit the growth of bacterial and fungal pathogens. The strongest antibacterial substance would be obtained after 24 hours of growth. The most suitable storage temperature for antibacterial extracts is -20 °C. The antibacterial substance produced by Bacillus amyloliquefaciens DQB-1 isolated from donkeys has strong antibacterial activity, protease-producing activity and good stability. Therefore, it can be developed as a probiotic preparation for preventing infectious diseases in donkey farms.

PD-1 blockade inhibits lymphocyte apoptosis and restores proliferation and anti-viral immune functions of lymphocyte after CP and NCP BVDV infection in vitro.

Bovine viral diarrhea virus (BVDV) is an important virus that can cause extensive economic losses in both dairy and beef industry worldwide. Acute infection with BVDV results in peripheral blood lymphopenia, apoptosis and immunosuppression. Up-regulated programmed death-1 (PD-1) expression induces functional exhaustion of lymphocytes, inhibition of proliferation and apoptosis of lymphocytes during acute and chronic viral infections, such as HIV and HCV. However, there are no reports showing the role of PD-1 in peripheral blood lymphopenia, apoptosis and immunosuppression after acute BVDV infection. Accordingly, we measured the mRNA and protein expression of PD-1 and programmed death-ligand 1 (PD-L1) in peripheral blood mononuclear cells (PBMCs) infected with BVDV, and analyzed the effects of PD-1 blockade on immune-associated function and activity in peripheral blood lymphocytes (PBLs). The results showed that both cytopathic (CP) BVDV (strain NADL) and non-cytopathic (NCP) BVDV (strain KD) infection stimulated the mRNA and protein expression of PD-1 and PD-L1 significantly. The upregulation of PD-1/PD-L1 was accompanied by the decreased PBLs proliferation and increased apoptosis. Additionally, PD-1 blockade restored proliferation, inhibited apoptosis, increased IFN-γ production and decreased BVDV load. Remarkably, the PD-1/PD-L1 interaction has a more substantial effect on the immunoregulation of inhibiting proliferation induced by CP BVDV infection. Our findings confirm that PD-1 plays a vital role in peripheral blood lymphopenia and apoptosis caused by acute BVDV infection, and provide new insights into exploring the immunopathological mechanisms of BVDV or other members of the Flaviviridae family, and a potential therapeutic strategy to control BVDV infection.