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Alterations to the gut microbiota have been previously suggested to be tightly linked to chronic systemic inflammation, which is a major contributing factor to complications and disease progression in chronic kidney disease (CKD). Nevertheless, the effect of gut dysbiosis on the pathogenesis and/or production of inflammatory factors in CKD has not been extensively studied to date. In the present study, we conducted 16S ribosomal DNA pyrosequencing using fecal microbiota samples and analyzed the production of serum inflammatory factors in 50 patients with CKD and 22 healthy control (HC) subjects. The results revealed that compared to the HC subjects, patients with CKD exhibited a significant reduction in the richness and structure of their fecal microbiota. At the phylum level, compared to the HC group, patients with CKD also presented reduced abundance of Actinobacteria but increased abundance of Verrucomicrobia. Moreover, the genera , and were enriched in the fecal samples of patients with CKD, while and were enriched in those of the HC subjects. The abundance of in the CKD group was significantly lower than that in the HC group (3.08 vs. 0.67%); this decrease in the abundance of , an important probiotic, in patients with CKD is a striking discovery as it has not been previously reported. Finally, we analyzed whether these changes to the fecal microbiota correlated with CKD clinical characteristics and/or the production of known inflammatory factors. Altered levels of the microbiota genera , and were shown to be correlated with CKD disease-severity indicators, including the estimated glomerular filtration rate. Most notably, was significantly negatively correlated with the production of interleukin-10. The results of the present study suggest that microbiota dysbiosis may promote chronic systemic inflammation in CKD. Furthermore, they support that modifying the gut microbiota, especially , may be a promising potential therapeutic strategy to attenuate the progression of, and/or systemic inflammation in, CKD.

High levels of salinity induce serious oxidative damage in plants. Flavonoids, as antioxidants, have important roles in reactive oxygen species (ROS) scavenging. In the present study, the tobacco R2R3 MYB type repressor, NtMYB4, was isolated and characterized. The expression of was suppressed by salinity. Overexpression of reduced the salt tolerance in transgenic tobacco plants. NtMYB4 repressed the promoter activity of and negatively regulated its expression. Rutin accumulation was significantly decreased in overexpressing transgenic plants and RNAi silenced transgenic plants. Moreover, high H O and contents were detected in both types of rutin-reduced transgenic plants under high salt stress. In addition, exogenous rutin supplementation effectively scavenged ROS (H O and ) and improved the salt tolerance of the rutin-reduced transgenic plants. In contrast, overexpressing plants had increased rutin accumulation, lower H O and contents, and higher tolerance to salinity. These results suggested that tobacco NtMYB4 acts as a salinity response repressor and negatively regulates expression, which results in the reduced flavonoid accumulation and weakened ROS-scavenging ability under salt stress.

The 1 Gt oilfield discovery solidified the Mahu oilfield as the world’s largest conglomerate oil region, underscoring the exploration potential of these reservoirs. However, optimizing and selecting the target interval for hydraulic fracturing remains challenging due to the significant heterogeneity of the structure and composition of conglomerate reservoirs. This study addresses key gaps in understanding conglomerate reservoir characteristics and their impact on hydrocarbon production, focusing on the Baikouquan (T 1 b ) Formation (Fm) on the Mahu Depression’s northern slope. It introduces a new classification to better manage these complexities. In contrast to other classification methods, the proposed approach incorporates key factors influencing hydraulic fracture (HF) propagation, including grain size, cementation, supporting forms, and gravel composition, the latter of which is introduced for the first time. Based on core and test results, the conglomerate reservoirs are categorized into two main groups—fan delta front and fan delta plain conglomerates—and further divided into eight lithofacies types. Fan delta front conglomerates are subdivided into four types: A-1 (tuff, metamorphic, and magmatic rocks-dominated gravel-supported cobble-to-boulder lithofacies), A-2 (tuff and magmatic rocks-dominated matrix-supported pebble-to-cobble lithofacies), A-3 (tuff-dominated matrix-supported granule-to-pebble lithofacies), and A-4 (tuff-dominated gravel-supported granule-to-pebble lithofacies). Fan delta plain conglomerates are further divided into four types: B-1 (tuff and magmatic rocks-dominated gravel-supported granule-to-pebble lithofacies), B-2 (tuff and sedimentary rocks-dominated gravel-supported pebble-to-cobble lithofacies), B-3 (tuff-dominated gravel-supported cobble-to-boulder lithofacies), and B-4 (tuff, magmatic, and sedimentary rocks-dominated matrix-supported pebble-to-cobble lithofacies). The novelty of this classification method lies in its integration of both geological and engineering perspectives, particularly in optimizing hydraulic fracturing strategies. The study evaluates lithofacies from geological factors such as bedding, composition, and poroperm characteristics, as well as engineering considerations like fracturing potential and flow capacity. The results reveal that certain lithofacies types correlate strongly with higher fracturing success, providing insights that can guide more efficient hydraulic fracturing practices. By addressing the challenge of heterogeneity of the structure and composition in conglomerate reservoirs, this study offers a comprehensive framework for selecting optimal target intervals for hydraulic fracturing, which can significantly enhance hydrocarbon exploration and production strategies. This approach is expected to be valuable for similar complex conglomerate reservoirs worldwide.

Expanded newborn screening facilitates early identification and intervention of patients with inborn errors of metabolism (IEMs), There is a lack of disease spectrum data for many areas in China. To determine the disease spectrum and genetic characteristics of IEMs in Xi'an city of Shaanxi province in northwest China, 146152 newborns were screening by MSMS from January 2014 to December 2019 and 61 patients were referred to genetic analysis by next generation sequencing (NGS) and validated by Sanger sequencing. Seventy-five newborns and two mothers were diagnosed with IEMs, with an overall incidence of 1:1898 (1:1949 without mothers). There were 35 newborns with amino acidemias (45.45%, 1:4176), 28 newborns with organic acidurias (36.36%, 1:5220), and 12 newborns and two mothers with FAO disorders (18.18%; 1:10439 or 1:12179 without mothers). Phenylketonuria and methylmalonic acidemia were the two most common disorders, accounting for 65.33% (49/75) of all confirmed newborn. Some hotspot mutations were observed for several IEMs, including PAH gene c.728G>A for phenylketonuria; MMACHC gene c.609G>A and c.567dupT, MMUT gene c.323G>A for methylmalonic acidemia and SLC25A13 gene c.852_855del for citrin deficiency. Our study provides effective clinical guidance for the popularization and application of expanded newborn screening, genetic screening, and genetic counseling of IEMs in this region.

BackgroundChronic liver fibrosis is an inevitable stage for the development of patients with chronic hepatitis B (CHB). However, anti-fibrotic therapies have been unsuccessful so far. The biological functions and molecular mechanisms of long non-coding RNAs (lncRNAs) in the host immune system during chronic hepatitis B virus (HBV) infection, especially in fibrosis, are still largely unknown.MethodThe total RNA of peripheral blood mononuclear cells (PBMCs) from asymptomatic carriers (ASCs) or CHB receiving at least 8 years of anti-viral treatments was analyzed using Arraystar microarray and validated via quantitative real-time PCR (qRT-PCR). Correlation analysis was conducted based on correlation coefficients, Clusterprofile, and RNA Interactome Database (RAID). The functions of lncRNA in monocytes were determined via loss-of-function RNAi or gain-of-function lentivirus assays. The expression levels of mRNAs or proteins were evaluated using qRT-PCR, western blotting assay, or enzyme linked immunosorbent assays (ELISA).ResultsA total of 1,042 mRNA transcripts (630 up-regulated and 412 down-regulated) were identified being differentially expressed between ASC and CHB patients. Through enrichment analysis we focused on the transforming growth factor beta (TGF- β ) signaling pathway and validated their expression in a larger cohort. Moreover, we found that lncRNA ENST00000519726 (lncRNA-HEIM) was highly expressed in monocytes and further up-regulated upon HBV infection. LncRNA-HEIM played an important role in CHB patients with long-term antiviral treatments, and its elevated expression was remarkably correlated with the TGF- β signaling pathway, especially with the two members namely TGF- β and SMAD4. Furthermore, altering the endogenous lncRNA-HEIM level in monocytes significantly affected the production of TGF- β , as well as the fibrosis of hepatic stellate cells by affecting the expression of collagen I and α -smooth muscle actin ( α -SMA).ConclusionThese findings not only added knowledge to the understanding of the roles of which lncRNA-HEIM played in the activation of HSCs in CHB patients with long-term medication, but also provided a promising therapeutic target in the future treatment for liver fibrosis.

MicroRNAs (MiRNAs), which regulate the gene expression leading to translational inhibition or mRNA degradation, are involved in carcinogenesis and tumor progression. Previous studies have demonstrated that miR-221 was one of the most consistent overexpressed miRNAs in several types of cancer. However, the role of miR-221 in human liver cancer progression is not yet fully elucidated. Levels of miR-221 and plant homeodomain finger 2 (PHF2) expressions in human hepatocellular carcinoma (HCC) tissues and cell lines were detected using western blotting and quantitative real-time PCR (qRT-PCR). Cell migration was studied using the transwell assays. A dual-luciferase reporter system was used to validate the target gene of miR-221. The results indicated that miR-221 promoted HCC cell migration. By performing subsequent systematic bioinformatic analyses, we found PHF2 was the target gene of miR-221 and the direct binding relationship was further validated by dual-luciferase reporter assay. In addition, lower expression of PHF2 promoted HCC cell migration and linked to worse overall survival in HCC patients. Finally, the negative correlation between miR-221 and PHF2 expression levels in HCC specimens was further confirmed. Taken together, our findings implied that miR-221 could be a potential candidate for the therapeutics of HCC metastasis.

The formation of complex fracture networks through the fracturing technology is a crucial operation used to improve the production capacity of tight gas/oil. In this study, physical simulation experiments of hydraulic fracturing were conducted with a true triaxial test system on cubic shale oil samples from the Yanchang Formation, China. The fractures were scanned by CT both before and after the experiments and then reconstructed in 3D. The complexity of fracture networks was investigated quantitatively by the fractal theory with topology. Finally, the effect of the horizontal stress ratio, fluid viscosity, and natural fractures on the complexity of the fracture networks was discussed. The results indicate that the method based on fractal theory and topology can effectively characterize the complexity of the fracture network. The change rates of the fractal dimension (K) are 0.45–3.64%, and the fractal dimensions (DNH) of the 3D fracture network after fracturing are 1.9522–2.1837, the number of connections per branch after fracturing (CB) are 1.57–2.0. The change rate of the fractal dimension and the horizontal stress ratio are negatively correlated. However, the change rate of the fractal dimension first increases and then decreases under increasing fluid viscosities, and a transition occurs at a fluid viscosity of 5.0 mPa·s. Whether under different horizontal stress ratios or fluid viscosities, the complexity of the fracture networks after fracturing can be divided into four levels according to DNH and CB. Complex fracture networks are more easily formed under a lower horizontal stress ratio and a relatively low fluid viscosity. A fracturing fluid viscosity that is too low or too high limits the formation of a fracture network.

Background Congenital pulmonary airway malformation (CPAM) is the most frequent pulmonary developmental malformation and the pathophysiology remains poorly understood. This study aimed to identify the characteristic gene expression patterns and the marker genes essential to CPAM. Methods Tissues from the cystic area displaying CPAM and the area of normal appearance were obtained during surgery. Bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) were performed for integrating analysis. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify specifically expressed genes to CPAM. Results In total, 2074 genes were significantly differentially expressed between the CPAM and control areas. Of these differentially expressed genes (DEGs), 1675 genes were up-regulated and 399 genes were down-regulated. Gene ontology analysis revealed these DEGs were specifically enriched in ciliated epithelium and involved in immune response. We also identified several CPAM-related modules by iWGCNA, among them, P15_I4_M3 module was the most influential module for distinguishing CPAMs from controls. By combining the analysis of the expression dataset from RNA-seq and scRNA-seq, SPOCK2, STX11 , and ZNF331 were highlighted in CPAM. Conclusions Through our analysis of expression datasets from both scRNA-seq and bulk RNA-seq of tissues obtained from patients with CPAM, we identified the characteristic gene expression patterns associated with the condition. Our findings suggest that SPOCK2 could be a potential biomarker gene for the diagnosis and therapeutic target in the development of CPAM, whereas STX11 and ZNF331 might serve as prognostic markers for this condition. Further investigations with larger samples and function studies are necessary to confirm the involvement of these genes in CPAM.

Insulin-like growth factor-1 (IGF-1) function declines with age and is associated with brain ageing and the progression of age-related neurological conditions. The reversible binding of IGF-1 to IGF binding protein (IGFBP)-3 regulates the amount of bioavailable, functional IGF-1 in circulation. Cyclic glycine-proline (cGP), a metabolite from the binding site of IGF-1, retains its affinity for IGFBP-3 and competes against IGF-1 for IGFBP-3 binding. Thus, cGP and IGFBP-3 collectively regulate the bioavailability of IGF-1. The molar ratio of cGP/IGF-1 represents the amount of bioavailable and functional IGF-1 in circulation. The cGP/IGF-1 molar ratio is low in patients with age-related conditions, including hypertension, stroke, and neurological disorders with cognitive impairment. Stroke patients with a higher cGP/IGF-1 molar ratio have more favourable clinical outcomes. The elderly with more cGP have better memory retention. An increase in the cGP/IGF-1 molar ratio with age is associated with normal cognition, whereas a decrease in this ratio with age is associated with dementia in Parkinson disease. In addition, cGP administration reduces systolic blood pressure, improves memory, and aids in stroke recovery. These clinical and experimental observations demonstrate the role of cGP in regulating IGF-1 function and its potential clinical applications in age-related brain diseases as a plasma biomarker for—and an intervention to improve—IGF-1 function.

Sparganium longifolium was reported as a hybrid between S. emersum and S. gramineum based on its intermediate type or the common characteristics of its parent species. Its hybrid origin needs to be confirmed using molecular technology. We investigated the origin of S. longifolium based on 10 populations of S. emersum , S. gramineum and S. longifolium from five lakes in European Russia, using sequences of six nuclear loci and one chloroplast DNA fragment. Haplotype network, principal coordinate analysis and genetic clustering based on data of nuclear loci confirmed that S. longifolium is the hybrid between S. emersum and S. gramineum . We found that the natural hybridization between S. emersum and S. gramineum is bidirectional but asymmetrical, and the latter mainly acts as maternal species. We also found that all samples of S. longifolium were F1 generations, and thus hypothesized that S. emersum and S. gramineum could likely maintain their species boundary through the post-zygote reproductive isolation mechanism of F1 generation sterility.