Involvement of long non-coding RNAs in the progression of esophageal cancer

Esophageal cancer(EC)is one of the most common malignant tumors of the digestive system with high incidence and mortality rate worldwide.Therefore,exploring the pathogenesis of ECand searching for new targeted therapies are the current research hotspot for EC treatment.Long non-coding RNAs(lncRNAs)are endogenous RNAs with more than 200 nucleotides,but without proteincoding function.In recent years,lncRNAs have gradually become the focuses in the field of non-coding RNA.Some lncRNAs have been proved to be closely related to the pathogenesis of EC.Many lncRNAs are abnormally expressed in EC and participate in many biological processes including cell proliferation,apoptosis,and metastasis by inhibiting or promoting target gene expression.LncRNAs can also regulate the progression of EC through epithelial-mesenchymal transformation(EMT),which is closely related to the occurrence,development,and prognosis of EC.In this article,we review and discuss the involvement of lncRNAs in the progression of EC.

Structural Comparison and Drug Screening of Spike Proteins of Ten SARS-CoV-2 Variants

SARS-CoV-2(severe acute respiratory syndrome coronavirus 2)has evolved many variants with stronger infectivity and immune evasion than the original strain,including Alpha,Beta,Gamma,Delta,Epsilon,Kappa,lota,Lambda,and 21H strains.Amino acid mutations are enriched in the spike protein of SARS CoV-2.which plays a crucial role in cell infetion.However,the impact of these mutations on protein structure and function is unclear.Understanding the pathophysiology and pandemic feaures of these SARS-CoV-2 variants requires knowledge of the spike protein structures.Here,we obtained the spike protein structures of 10 main globally endemic SARS CoV-2 strains using AlphaFold2.The clustering analysis based on structural similarity revealed the unique features of the mainly pandemic SARS CoV-2 Delta variants.indicating that structural clusters can reflect the current characteristics of the epidemic more accurately than those based on the protein sequence.The analysis of the binding afinities of ACE2-RBD,antibody-NTD,and antibody-RBD complexes in the different variants revealed that the recognition of antibodies against SI NTD and RBD was decreased in the variants,especally the Delta variant compared with the original strain,which may induce the immune evasion of SARS-CoV-2 variants.Furthermore,by virtual screening the ZINC database against a high-accuracy predicted structure of Delta spike protein and experimental validation,we identified multiple compounds that target S1 NTD and RBD,which might contribute towards the development of clinical anti-SARS-CoV-2 medicines.Our findings provided a basic foundation for future in vitro and in vivo investigations that might speed up the development of potential therapies for the SARS-CoV-2 va riants.

Scrutinizing the causal relationship between schizophrenia and vitamin supplementation:a Mendelian randomization study

Objective: Observational studies have reported malnutrition and vitamin deficiency in patients with schizophrenia (SZ), which can lead to serious metabolic syndromes and decrease anti-psychiatric drug outcomes. Whereas, vitamin intake along with psychiatric medication can enhance the medication outcomes. However, it is still unknown if SZ induces vitamin deficiency. Herein, we conduct the Mendelian randomization analysis to explore the causal relationship between schizophrenia and vitamins supplementation.Methods: We retrieved the genome-wide summary statistical data for schizophrenia from recent SZ GWAS data (43,175 cases and 65,166 controls) and vitamins supplementation GWAS data from Neale’s GWAS datasets (more than 337,000 samples from the European population) and performed a two-sample Mendelian randomization analysis to determine the causal association of SZ with vitamin supplementation, in addition, we conduct the sensitivity analysis to obtain reliable results and remove confounding bias.Results: SZ have causal relationships with vitamins A, B, C, D, and E (SZ/vitamin A: β = 0.002, se= 0.001, 95% confidence interval (CI): 0.001 to 0.004,P= 1.41E-05, heterogeneityP= 0.4486;SZ/vitamin B: β= 0.004, se= 0.001, 95% CI: 0.002-0.005,P= 7.0E-05, heterogeneityP= 0.2217;SZ/vitamin C: β= 0.004, se= 0.001, 95% CI: 0.002-0.007,P= 0.001, heterogeneityP= 0.1349;SZ/vitamin D: β= 0.003, se= 0.001, 95% CI: 0.002-0.005,P= 0.001, heterogeneityP= 0.433;SZ/vitamin E: β= 0.003, se= 0.001, 95% CI: 0.002-0.005,P= 5.0E-05, heterogeneityP= 0.1382).Conclusion: Our findings suggest that vitamin levels and supplementation should be carefully controlled in patients with SZ, which in turn may enhance the therapeutic effects of antipsychotic drug treatments.