Single-cell analysis reveals dysregulated inflammatory response in peripheral blood immunity in patients with acute respiratory distress syndrome

Introduction: Acute respiratory distress syndrome (ARDS) remains a major clinical challenge for patients in intensive care units. Determining the differential mechanisms underlying ARDS with different etiologies is a key goal to improve the effectiveness of ARDS therapy. Despite growing evidence that different immune cell types are involved in ARDS, the role of altered immune cell subpopulations in disease progression is unelucidated.Methods: In this study, we combined scRNA-seq and bulk-level sequencing to analyze the transcriptomes of peripheral blood mononuclear cells from healthy volunteers and patients with septic ARDS (sep-ARDS) and pneumonic ARDS (PNE-ARDS).Results: Our data revealed differential alterations at the cellular and molecular levels and within biological signaling pathways in ARDS with different etiologies. The dynamics of neutrophils, macrophages (Macs), classical dendritic cells (cDCs), myeloid-derived suppressive cells (MDSCs), and CD8+ T cells varied significantly among groups of different samples, with neutrophils and cDCs at higher, and Macs at significantly lower, amounts in the patients with sep-ARDS. Furthermore, MDSCs were highly enriched only in the sep-ARDS patients, whereas a higher abundance of CD8+ T cells was observed in patients with PNE-ARDS. In addition, these cell subpopulations were found to be significantly involved in apoptosis, inflammatory, and immune-related pathways. In particular, a significant enhancement of the oxidative stress response was observed in the neutrophil subpopulation.Conclusion: Our study shows that the composition of cells involved in the main peripheral circulation differs in patients with ARDS with different etiologies. Studying the role and mechanism of action of these cells during ARDS will provide new opportunities for the treatment of this condition

Synthesis of N-Alkylpyridin-4-ones and Thiazolo[3,2-a]pyridin-5-ones Through Pummerer-Type Reactions

N-alkylated 4-pyridones were obtained through a one-pot procedure involving either normal or interrupted Pummerer reactions between triflic anhydride activated sulfoxides and 4-fluoropyridine derivatives, followed by hydrolysis. On the other hand, triflic anhydride activated benzyl 6-fluoro-2-pyridyl sulfoxide could react with alkenes or alkynes to afford thiazolo[3,2-a]pyridin-5-ones, via the pyridinium salt intermediates

De Novo Design of a Highly Stable Ovoid TIM Barrel: Unlocking Pocket Shape towards Functional Design

The ability to finely control the structure of protein folds is an important prerequisite to functional protein design. The TIM barrel fold is an important target for these efforts as it is highly enriched for diverse functions in nature. Although a TIM barrel protein has been designed de novo, the ability to finely alter the curvature of the central beta barrel and the overall architecture of the fold remains elusive, limiting its utility for functional design. Here, we report the de novo design of a TIM barrel with ovoid (twofold) symmetry, drawing inspiration from natural beta and TIM barrels with ovoid curvature. We use an autoregressive backbone sampling strategy to implement our hypothesis for elongated barrel curvature, followed by an iterative enrichment sequence design protocol to obtain sequences which yield a high proportion of successfully folding designs. Designed sequences are highly stable and fold to the designed barrel curvature as determined by a 2.1 Å resolution crystal structure. The designs show robustness to drastic mutations, retaining high melting temperatures even when multiple charged residues are buried in the hydrophobic core or when the hydrophobic core is ablated to alanine. As a scaffold with a greater capacity for hosting diverse hydrogen bonding networks and installation of binding pockets or active sites, the ovoid TIM barrel represents a major step towards the de novo design of functional TIM barrels

Deep learning-based sea surface roughness parameterization scheme

The material related to the parameterization scheme modified in WRF and coupled model in the manuscript "Deep learning-based sea surface roughness parameterization scheme." The quality control script of the used data is also publicly available

DataSheet1_Effects of homocysteine on nonalcoholic fatty liver related disease: A mendelian randomization study.docx

Background: Since the association of homocysteine and clinical results of observational studies are controversial on non-alcoholic fatty liver related disease, we compute the two-sample Mendelian Randomization (MR) study.Objective: To evaluate whether the plasma level of homocysteine has an effect on the risk of Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and Cirrhosis after its progress, we investigated the causal relationships between plasma homocysteine and the three non-alcoholic fatty liver related diseases mentioned above.Design and methods: Summary estimates were elicited from the inverse-variance weighted (IVW) method through 12 single nucleotide polymorphisms (SNPs) which related to the plasma homocysteine, the SNPs were obtained from a large genome-wide association studies (GWAS) of 44,147 European participants. And the summary statistics for the latest and largest GWAS datasets for NAFLD (307576 in total and 1,578 cases), NASH (309055 in total and 99 cases) and Cirrhosis (306145 in total and 826 cases) were collected from Ristey FinnGen website where the association of genetic variations with blood metabolite levels was conducted using comprehensive metabolite profiling. The study was performed through two-sample MR method.Results: The result indicated that the plasma homocysteine is not significantly associated with NAFLD, and its progression, NASH and Cirrhosis.Conclusion: The evidence in this study is quite deficient to support the causal association of the individual plasma homocysteine with NAFLD, NASH and Cirrhosis, the putative of associations is not exist.</p