High-Throughput Screen Reveals sRNAs Regulating crRNA Biogenesis by Targeting CRISPR Leader to Repress Rho Termination

Discovery of CRISPR-Cas systems is one of paramount importance in the field of microbiology. Currently, how CRISPR-Cas systems are finely regulated remains to be defined. Here we use small regulatory RNA (sRNA) library to screen sRNAs targeting type I-F CRISPR-Cas system through proximity ligation by T4 RNA ligase and find 34 sRNAs linking to CRISPR loci. Among 34 sRNAs for potential regulators of CRISPR, sRNA pant463 and PhrS enhance CRISPR loci transcription, while pant391 represses their transcription. We identify PhrS as a regulator of CRISPR-Cas by binding CRISPR leaders to suppress Rho-dependent transcription termination. PhrS-mediated anti-termination facilitates CRISPR locus transcription to generate CRISPR RNA (crRNA) and subsequently promotes CRISPR-Cas adaptive immunity against bacteriophage invasion. Furthermore, this also exists in type I-C/-E CRISPR-Cas, suggesting general regulatory mechanisms in bacteria kingdom. Our findings identify sRNAs as important regulators of CRISPR-Cas, extending roles of sRNAs in controlling bacterial physiology by promoting CRISPR-Cas adaptation priming

Prenatal Exposure to Lipopolysaccharide Results in Myocardial Fibrosis in Rat Offspring

The epigenetic plasticity hypothesis indicates that exposure during pregnancy may cause adult-onset disorders, including hypertension, myocardial infarction and heart failure. Moreover, myocardial fibrosis coincides with hypertension, myocardial infarction and heart failure. This study was designed to investigate the effects of prenatal exposure to lipopolysaccharide (LPS) on myocardial fibrosis. The result showed that at six and 16 weeks of age, the LPS-treated offspring exhibited increased collagen synthesis, an elevated cardiac index (CI), higher mRNA levels of TIMP-2 and TGFβ and a reduced mRNA level of MMP2. The protein levels corresponded to the mRNA levels. The offspring that were prenatally treated with pyrrolidine dithiocarbamic acid (PDTC), an inhibitor of NF-κB, displayed improvements in the CI and in collagen synthesis. Moreover, PDTC ameliorated the expression of cytokines and proteins associated with myocardial fibrosis. The results showed that maternal inflammation can induce myocardial fibrosis in offspring during aging accompanied by an imbalance of TIMP-2/MMP2 and TGFβ expression

Comprehensive Fractal Model and Pore Structural Features of Medium- and Low-Rank Coal from the Zhunnan Coalfield of Xinjiang, China

Medium and low-rank coal from the Zhunnan coalfield of Xinjiang in China was investigated for quantitatively characterizing its range of aperture structure. The pore parameters were determined by nitrogen adsorption at low temperature and mercury injection at high pressure, and the full aperture was determined. The FHH model, Menger model, Sierpinski model, and a thermodynamic model were used to calculate the comprehensive fractal dimension of the coal samples over the full range of aperture. The fractal characteristics of the pores of medium- and low-rank coal were quantitatively analyzed, which provided a reference for the overall characterization of pore structure heterogeneity in this coalfield. The results show that the FHH model and thermodynamic model more accurately calculate the fractal dimensions of less and greater than the joint pore position, respectively. The comprehensive fractal dimension of the low-rank coal pore is 2.8005–2.8811 and that of medium rank coal is 2.5710–2.6147. When compared with the medium-rank coal, pores of the low-rank coal are more developed and they exhibit a more complex structure with stronger heterogeneity. The comprehensive fractal dimension of the pores is a negative correlation with average pore size, vitrinite content, and maximum vitrinite reflectance, and positive correlation with pore volume, pore specific surface area, inertinite content, and exinite content

Systematic Review and Meta-Analysis of Factors Influencing Self-Medication in Children

To evaluate the prevalence, influencing factors, and behavior rules of self-medication in children. Articles on self-medication in children from various electronic databases (PubMed, Cochrane Library, Web of Science, the WHO website ( https://www.who.int/ ), ABI, CNKI, and Wanfang), were searched to August 2022. The single-group meta-analyses of the prevalence, influencing factors, and behavior rules of self-medication in children were performed using Revman 5.3 and Stata 16.0. The overall pooled prevalence of self-medication in children was 57% (95% CI: 0.39-0.75, I²  = 100%, P  < .00001 Z  = 6.22). The pooled prevalence for main influencing factors, in terms of caregivers, was: 73% (95% CI: 0.72-0.75, I²  = 100%, P  < .00001, Z  = 111.18) for those in rural areas; 55% (95% CI: 0.51-0.59, P  = .04, Z  = 26.92, I²  = 68%, P  < .00001) for females; 75% (95% CI: 0.74-0.76, I²  = 68%, P  < .00001, Z  = 106.66) for those whose income was less than 716 dollars; 77% (95% CI: 0.75-0.79, I²  = 99%, P  < .000001, Z  = 92.59) for the middle-aged and elderly; and 72% (95% CI: 0.58-87, I²  = 99%, P  < .00001, Z  = 9.82) for those with a degree below bachelor. In the process of self-medication for children, 19% (95% CI: 0.06-0.32, I²  = 99%, P  < .00001, Z  = 2.82) of the caregivers did not read the instructions, 28% (95% CI: −0.03-0.60, I²  = 100%, P  < .000001, Z  = 1.77) neglected adverse effects, 49% (95% CI: 0.11-0.87, I²  = 100%, P  = .01, Z  = 2.51) spontaneously increased or decreased the dosages, 49% (95% CI: 0.48-0.55, I²  = 65%, P  < .00001, Z  = 16.51) had an awareness of over-the-counter (OTC) drugs, and 41% (95% CI: 0.18-0.64, I²  = 99%, P  < .00001, Z  = 3.49) misrecognized the antibiotics. Self-medication for children was common, although the overall prevalence was not very high. The prevalence of self-medication in children was relatively higher among those caregivers who were female, rural, had low-income, were elder, or had a degree below bachelor. Common behaviors during self-medication in children included spontaneous dose increase or decrease, a lack of awareness of OTC drugs, and misconception of antibiotics. Government departments should formulate corresponding policies to provide quality health education resources for the caregivers of children

TRAF6-Mediated Inflammatory Cytokines Secretion in LPS-induced Colorectal Cancer Cells Is Regulated by miR-140

BACKGROUND/AIM:Colorectal cancer (CRC) cells secrete inflammatory cytokines that affect CRC progression. The aim of the present study was to determine if micro-RNA-140(miR-140) regulates inflammatory cytokine secretion induced by lipopolysaccharide (LPS) in colorectal cancer cells by targeting tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6). MATERIALS AND METHODS:Fifty fresh colon-cancer specimens and normal colorectal tissues were collected from patients with CRC and tested for the expression miR-140. Human CRC cell lines SW480 and HCT116 were treated with various concentrations and times with LPS. miR-140 and mRNA expression of potentially related genes were analyzed by qPCR. Protein expression was analyzed using western blot or ELISA. Overexpression plasmids with pcDNA3.1-TRAF6, pGL4.10-wtTRAF6 and pGL4.10-mutTRAF6 were constructed. miRNA target gene prediction and a dual luciferase assay were used to analyze miR-140-targeted TRAF6. RESULTS:miR-140 expression was up-regulated in CRC tissues. In CRC cells, LPS could increase miR-140 expression in a time- and concentration-dependent manner. LPS increased inflammatory cytokine mRNA expression levels in SW480 and HCT116 human colon-cancer cells. miRNA-140 suppressed TRAF6 expression via targeting the 3'UTR. TRAF6 affected miR-140-mediated inflammatory cytokine expression of SW480 and HCT116 cells under LPS treatment. CONCLUSION:miR-140 regulates inflammatory cytokine secretion of LPS-induced colorectal cancer cells by targeting TRAF6

Structural and Acidic Characteristics of Multiple Zr Defect Sites in UiO-66 Metal–Organic Frameworks

Although defects are prevalent in metal–organic frameworks (MOFs) and usually play a crucial role in modulating their performance in various applications, detailed structural characterizations of various defects remain a challenging task mainly due to their disordered, heterogeneous, and local nature. In this work, by using solid-state nuclear magnetic resonance spectroscopy (SSNMR) techniques in conjunction with density functional theory (DFT) calculations, it is clearly elucidated that the trimethylphosphine (TMP)-assisted 31P NMR strategy is capable of greatly facilitating the qualitative and quantitative description of the detailed structural and acidic characteristics as well as the evolution process of various Zr defects with subtle distinctions in UiO-66 upon moderate thermal treatment, hence surpassing most conventional analytical techniques. These results offer a fundamental understanding of the defect chemistry in MOFs

Protective effect of total aralosides of Aralia elata (Miq) Seem (TASAES) against diabetic cardiomyopathy in rats during the early stage, and possible mechanisms

Total aralosides of Aralia elata (Miq) Seem (TASAES) from Chinese traditional herb Longya Aralia chinensis L was found to improve cardiac function. The present study was to determine the protective effects of TASAES on diabetic cardiomyopathy, and the possible mechanisms. Therefore, a single dose of streptozotocin was used to induce diabetes in Wister rats. Diabetic rats were immediately treated with low, medium and high doses of TASAES at 4.9, 9.8 mg/kg and 19.6 mg/kg body weight by gavage, respectively, for eight weeks. Cardiac function was evaluated by in situ hemodynamic measurements, and patch clamp for the L-type Ca2+ channel current (ICa2+-L) and transient outward K+ channel current (Ito). Histopathological changes were observed under light and electron microscope. The expression of pro-fibrotic factor, connective tissue growth factor (CTGF) was monitored using immunohistochemistry staining. Compared with diabetic group, medium and high doses, but not low dose, of TASAES showed a significant protection against diabetes-induced cardiac dysfunction, shown by increased absolute value of left ventricular systolic pressure (LVSP) and maximum rates of pressure development (±dp/dtmax), and enhanced amplitude of ICa2+-L (P < 0.05). Histological staining indicated a significant inhibition of diabetes-caused pathological changes and up-regulation of CTGF expression (P < 0.05). The results suggest that TASAES prevents diabetes-induced cardiac dysfunction and pathological damage through up-regulating ICa2+-L in cardiac cells and decreasing CTGF expression