Nonaffinity of Liquid Networks and Bicontinuous Mesophases.

Amphiphiles self-assemble into a variety of bicontinuous mesophases whose equilibrium structures take the form of high-symmetry cubic networks. Here, we show that the symmetry-breaking distortions in these systems give rise to anomalously large, nonaffine collective deformations, which we argue to be a generic consequence of "mass equilibration" within deformed networks. We propose and study a minimal "liquid network" model of bicontinuous networks, in which acubic distortions are modeled by the relaxation of residually stressed mechanical networks with constant-tension bonds. We show that nonaffinity is strongly dependent on the valency of the network as well as the degree of strain-softening or strain-stiffening tension in the bonds. Taking diblock copolymer melts as a model system, liquid network theory captures quantitative features of two bicontinuous phases based on comparison with self-consistent field theory predictions and direct experimental characterization of acubic distortions, which are likely to be pronounced in soft amphiphilic systems more generally.

Evaluating three strategies of genome-wide association analysis for integrating data from multiple populations.

In livestock, genome-wide association studies (GWAS) are usually conducted in a single population (single-GWAS) with limited sample size and detection power. To enhance the detection power of GWAS, meta-analysis of GWAS (meta-GWAS) and mega-analysis of GWAS (mega-GWAS) have been proposed to integrate data from multiple populations at the level of summary statistics or individual data, respectively. However, there is a lack of comparison for these different strategies, which makes it difficult to guide the best practice of GWAS integrating data from multiple study populations. To maximize the comparison of different association analysis strategies across multiple populations, we conducted single-GWAS, meta-GWAS, and mega-GWAS for the backfat thickness of 100 kg (BFT_100) and days to 100 kg (DAYS_100) within each of the three commercial pig breeds (Duroc, Yorkshire, and Landrace). Based on controlling the genome inflation factor to one, we calculated corrected p-values (pC ). In Yorkshire, with the largest sample size, mega-GWAS, meta-GWAS and single-GWAS detected 149, 38 and 20 significant SNPs (pC < 1E-5) associated with BFT_100, as well as 26, four, and one QTL, respectively. Among them, pC of SNPs from mega-GWAS was the lowest, followed by meta-GWAS and single-GWAS. The correlation of pC among the three GWAS strategies ranged from 0.60 to 0.75 and the correlation of SNP effect values between meta-GWAS and mega-GWAS was 0.74, all showing good agreement. Collectively, even though there are differences in the integration of individual data or summary statistics, integrating data from multiple populations is an effective means of genetic argument for complex traits, especially mega-GWAS versus single-GWAS.

Integrating Multiple Database Resources to Elucidate the Gene Flow in Southeast Asian Pig Populations.

The domestic pig (Sus scrofa) and its subfamilies have experienced long-term and extensive gene flow, particularly in Southeast Asia. Here, we analyzed 236 pigs, focusing on Yunnan indigenous, European commercial, East Asian, and Southeast Asian breeds, using the Pig Genomics Reference Panel (PGRP v1) of Pig Genotype-Tissue Expression (PigGTEx) to investigate gene flow and associated complex traits by integrating multiple database resources. In this study, we discovered evidence of admixtures from European pigs into the genome of Yunnan indigenous pigs. Additionally, we hypothesized that a potential conceptual gene flow route that may have contributed to the genetic composition of the Diannan small-ear pig is a gene exchange from the Vietnamese pig. Based on the most stringent gene introgression scan using the fd statistic, we identified three specific loci on chromosome 8, ranging from 51.65 to 52.45 Mb, which exhibited strong signatures of selection and harbored the NAF1, NPY1R, and NPY5R genes. These genes are associated with complex traits, such as fat mass, immunity, and litter weight, in pigs, as supported by multiple bio-functionalization databases. We utilized multiple databases to explore the potential dynamics of genetic exchange in Southeast Asian pig populations and elucidated specific gene functionalities.

Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis.

BACKGROUND: Hepatitis B cirrhosis (HBC) is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction. Although the relationship between certain single probiotics and HBC has been explored, the impact of the complex ready-to-eat Lactobacillus paracasei N1115 (LP N1115) supplement on patients with HBC has not been determined. AIM: To compare the changes in the microbiota, inflammatory factor levels, and liver function before and after probiotic treatment in HBC patients. METHODS: This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020. Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only. Fecal samples were collected at the onset and conclusion of the 12-wk intervention period. The structure of the intestinal microbiota and the levels of serological indicators, such as liver function and inflammatory factors, were assessed. RESULTS: Following LP N1115 intervention, the intestinal microbial diversity significantly increased in the intervention group (P < 0.05), and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria. Additionally, the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors (P < 0.05). CONCLUSION: LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota, improving liver function, and reducing inflammatory factor levels.

Analysis of the value of potential biomarker S100-A8 protein in the diagnosis and pathogenesis of spinal tuberculosis.

Objectives: The objective of this study is to evaluate the value of S100-A8 protein as a diagnostic marker for spinal tuberculosis and to explore its role in the potential pathogenesis of spinal tuberculosis (STB). Methods: The peripheral blood of 100 spinal tuberculosis patients admitted to the General Hospital of Ningxia Medical University from September 2018 to June 2021 were collected as the observation group, and the peripheral blood of 30 healthy medical examiners were collected as the control group. Three samples from the observation group and three samples from the control group were selected for proteomics detection and screening of differential proteins. Kyoto Encyclopedia of Genes (KEGG) was used to enrich and analyze related signaling pathways to confirm the target protein. The serum expression levels of the target proteins were determined and compared between the two groups using enzyme-linked immunosorbent assay (ELISA). Statistical methods were used to evaluate the value of target protein as a diagnostic marker for STB. A macrophage model of Mycobacterium tuberculosis infection was constructed and S100-A8 small interfering RNA was used to investigate the molecular mechanism of the target protein. Results: S100-A8 protein has the value of diagnosing spinal tuberculosis (AUC = 0.931, p < 0.001), and the expression level in the peripheral blood of the observation group (59.04 ± 19.37 ng/mL) was significantly higher than that of the control group (43.16 ± 10.07 ng/mL) (p < 0.05). S100-A8 protein expression showed a significant positive correlation with both CRP and ESR values (p < 0.01). Its AUCs for combined bacteriological detection, T-SPOT results, diagnostic imaging, antacid staining results, and pathological results were 0.705 (p < 0.05), 0.754 (p < 0.01), 0.716 (p < 0.01), 0.656 (p < 0.05), and 0.681 (p < 0.01), respectively. Lack of S100-A8 leads to a significant decrease in the expression levels of TLR4 and IL-17A in infected macrophages. Conclusion: S100-A8 protein is differentially expressed in the peripheral blood of patients with spinal tuberculosis and healthy individuals and may be a novel candidate biomarker for the diagnosis of spinal tuberculosis. The feedback loop on the S100-A8-TLR4-IL-17A axis may play an important role in the inflammatory mechanism of spinal tuberculosis.

Structures, Biosynthesis, and Bioactivity of Oligomycins from the Marine-Derived Streptomyces sp. FXY-T5.

Oligomycins are potent antifungal and antitumor agents. Mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based metabolomic fingerprinting analysis of marine-derived actinomycetes in our in-house library provided an oligomycin-producing strain, Streptomyces sp. FXY-T5. Chemical investigation led to the discovery of five new oligomycins, 24-lumooligomycin B (1), 4-lumooligomycin B (2), 6-lumooligomycin B (3), 40-homooligomycin B (4), and 15-hydroxy-oligomycin B (5), together with seven biosynthetically related known derivatives. Their structures were assigned by MS, NMR, electronic circular dichroism (ECD), and single-crystal X-ray diffraction analyses. The biosynthesis pathway of oligomycins was first proposed based on the analysis of a type I modular polyketide synthase (PKS) system and targeted gene disruption. As expected, the isolated oligomycins showed significant antiagricultural fungal pathogen activity and antiproliferative properties from which the possible structure-activity relationships were first suggested. More importantly, oligomycins induced significant G1-phase cell cycle arrest on cancer cells and significantly attenuated their Cyclin D1 and PCNA expression through a ß-catenin signaling pathway.

Rationale and design of ProUrokinase in Mild IsChemic strokE (PUMICE): a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial.

BACKGROUND AND PURPOSE: Recombinant human prourokinase (rhPro-UK) is a new generation of specific plasminogen activator, that is non-inferior to alteplase in acute ischemic stroke. We aimed to investigate the efficacy and safety of rhPro-UK compared with standard medical treatment in acute mild ischemic stroke within 4.5 hours of symptom onset. METHODS AND DESIGN: Prourokinase in mild ischemic stroke is a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial. Patients who had an acute ischemic stroke within 4.5 hours from symptom onset and with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 will be recruited. Patients will be randomly assigned (1:1) to receive intravenous rhPro-UK (35 mg) or standard medical treatment. The follow-up duration will be 90 days. The calculated sample size is 1446. STUDY OUTCOMES: Primary efficacy outcome is an excellent functional outcome, defined as a modified Rankin Scale (mRS) score ≤ 1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, mRS score ≤ 2 at 90 days, early neurological improvement at 24 hours (a decrease of NIHSS score ≥ 4 points compared with baseline or NIHSS score ≤ 1 point), Barthel index of 75-100 points at 90 days, quality of life at 90 days, and activities of daily living at 90 days. Safety outcomes are symptomatic intracranial haemorrhage within 36 hours, mortality at 90 days, moderate and severe systematic bleeding at 90 days, and adverse events/serious adverse events within 90 days. DISCUSSION: This large phase III randomised clinical trial will answer the question of whether thrombolysis is beneficial for acute mild ischemic stroke, and may provide evidence for rhPro-UK in patients had an acute mild ischemic stroke within 4.5 hours of symptom onset. TRIAL REGISTRATION NUMBER: NCT05507645.

Assessment of Perfusion Volumes by a New Automated Software for Computed Tomography Perfusion.

INTRODUCTION: To compare the perfusion volumes assessed by a new automated CT perfusion (CTP) software iStroke with the circular singular value decomposition software RAPID and determine its predictive value for functional outcome in patients with acute ischaemic stroke (AIS) who underwent endovascular treatment (EVT). METHODS: Data on patients with AIS were collected from four hospitals in China. All patients received CTP followed by EVT with complete recanalisation within 24 hours of symptom onset. We evaluated the agreement of CTP measures between the two softwares by Spearman's rank correlation tests and kappa tests. Bland-Altman plots were used to evaluate the agreement of infarct core volume (ICV) on CTP and ground truth on diffusion-weighted imaging (DWI). Logistic regression models were used to test the association between ICV on these two softwares and functional outcomes. RESULTS: Among 326 patients, 228 had DWI examinations and 40 of them had infarct volume >70 mL. In all patients, the infarct core and hypoperfusion volumes on iStroke had a strong correlation with those on RAPID (ρ=0.68 and 0.66, respectively). The agreement of large infarct core (volume >70 mL) was substantial (kappa=0.73, p<0.001) between these two softwares. The ICV measured by iStroke and RAPID was significantly correlated with independent functional outcome at 90 days (p=0.009 and p<0.001, respectively). In patients with DWI examinations and those with an ICV >70 mL, the ICV of iStroke and RAPID was comparable on individual agreement with ground truth. CONCLUSION: The automatic CTP software iStroke is a reliable tool for assessing infarct core and mismatch volumes, making it clinically useful for selecting patients with AIS for acute reperfusion therapy in the extended time window.