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Cerebral small vessel disease (CSVD) is a leading cause of stroke and vascular cognitive impairment, but its metabolic determinants are not fully understood. Emerging evidence indicates that insulin resistance (IR) plays a crucial role in CSVD through vascular, inflammatory, and oxidative mechanisms. Higher IR levels may be associated with greater burdens of white matter hyperintensities, lacunes, cerebral microbleeds, and enlarged perivascular spaces. Mechanistic studies suggest that IR impairs endothelial nitric oxide signaling, disrupts the blood–brain barrier, promotes vascular remodeling, and alters astrocytic aquaporin-4 polarization, which together aggravate both ischemic and hemorrhagic microvascular injury. Clinically, IR represents a modifiable target, and interventions that reduce IR, including the use of pioglitazone, metformin, glucagon-like peptide-1 receptor agonists, physical activity, and dietary modification, may help slow CSVD progression. This mini review summarizes current epidemiological and mechanistic evidence linking IR to CSVD and highlights the potential of metabolic regulation as a strategy to prevent or mitigate small-vessel–related brain injury.

Background Long non-coding RNA (lncRNA) H19 is a hot spot in tumor development, progression and metastasis. This study assessed the association between H19 genetic polymorphisms and the susceptibility of lung cancer. Methods The case-control study was conducted to evaluate the association between four selected single nucleotide polymorphisms (rs217727, rs2107425, rs2735469 and rs17658052) in H19 gene and the risk of lung cancer. There were 556 female never smoking lung cancer patients and 395 cancer-free controls. Unconditional logistic regression analysis was used to analyze the associations between four SNPs and lung cancer risks by calculating the odds ratios and their 95% confidence intervals. The gene-environment interactions were assessed on both additive and multiplicative scales. Results Compared with carriers carrying homozygous CC genotype, there was a statistically significant increased risk of lung cancer for carriers of the rs2107425 TT genotype (odds ratio = 1.599, 95%CI = 1.106–2.313, P  = 0.013). In both dominant and recessive models, significant associations were found between rs2107425 and lung cancer risk, and the corresponding odds ratios were 1.346 (1.022–1.774) and 1.400 (1.011–1.937), with P values 0.035 and 0.043, respectively. There was no significant correlation between lung cancer risk and rs2735469, rs217727 and rs17658052. Interaction analysis showed that their combined effects had a greater impact on lung cancer than individual effects of polymorphism and cooking smoke exposure. However, further analysis showed that the both additive model and the multiplicative model were not statistically significant. Conclusion The polymorphism rs2107425 in H19 gene was associated with the risk of lung cancer among female who never smokes in Shenyang, China.

According to the data released by the International Agency for Research on Cancer (IARC) in 2020, lung cancer ranks second among newly diagnosed malignant tumors globally. As a special class of non-coding RNA, circRNA has become a new hotspot in the field of biomarker research. With the continuous deepening of molecular—level investigations, the underlying mechanisms of circRNA are being gradually unveiled. The more widely studied mechanism is the competitive endogenous RNA mechanism of circRNA. Studies related to circRNA expression were searched in GEO database and statistically analyzed using the “limma” package and weighted gene co-expression network analysis. The expression of circRNA, microRNA and mRNA in cells and tissues were examined via qRT-PCR. MTS assay was used to measure cell proliferation, Transwell assay was used to measure cell migration, and apoptosis assay was carried out to detect cell apoptosis. Additionally, a dual—luciferase reporter assay was further executed to explore the targeted binding relationships between circRNA-microRNA and microRNA-mRNA. It was discovered that hsa_circRNA_103809 was differentially highly expressed in non—small cell lung cancer cells, whereas miR—1270 was differentially lowly expressed. The knockdown of circ_0072088 inhibited the cell proliferation and migration, while promoting cell apoptosis. The same biological function was found with the overexpression of miR-1270. The rescue experiment further validated that circ_0072088 could regulate the biological function of cells by influencing miR-1270. Finally, the targeted binding relationship was verified by dual luciferase reporting experiment. In conclusion, circ_0072088 is differentially highly expressed in non-small cell lung cancer and can affect the progression of non-small cell lung cancer through the circ_0072088/miR-1270/TOP2A axis.

Background Listeria monocytogenes can cause invasive diseases in humans and farm animals and is frequently isolated from dairy products and poultry. Listeriosis is uncommon in China but L. monocytogenes has been isolated from foods and food processing environments in China. However little is known of genetic diversity of Chinese L. monocytogenes isolates and their relationships with global isolates. Results Two hundred and twelve isolates of L. monocytogenes from food sources from 12 provinces/cities in China were analysed by serotyping, Pulsed Field Gel Electrophoresis (PFGE) and Multi-locus Sequence Typing (MLST). The predominant serotypes are 1/2a, 1/2b and 1/2c accounting for 90.1% of the isolates. PFGE divided the isolates into 61 pulse types (PTs). Twenty nine PTs were represented by more than one isolates with PT GX6A16.0004 containing the most number of isolates. MLST differentiated the isolates into 36 STs, among which 15 were novel. The 3 most common STs were ST9 (29.1%), ST8 (10.7%) and ST87 (9.2%), accounting for 49.0% of the isolates. Conclusions STs prevalent in other parts of the world are also prevalent in China including 7 STs (ST1-ST3, ST5, ST6, ST8, ST9) which caused maternal fetal infections or outbreaks, suggesting that these STs potentially can also cause severe human infections or outbreaks in China. Surveillance of these STs will provide important information for prevention of listeriosis. This study also enhances our understanding of genetic diversity of L. monocytogenes in China.

Both genetic polymorphisms and environmental risk factors play important roles in the development of human chronic diseases including lung cancer. This is the first case-control study of interaction between polymorphisms in pre-miRNA genes and cooking oil fume exposure on the risk of lung cancer. A hospital-based case-control study of 258 cases and 310 controls was conducted. Six polymorphisms in miRNAs were determined by Taqman allelic discrimination method. The gene-environment interactions were assessed on both additive and multiplicative scale. The statistical analyses were performed mostly with SPSS. The combination of the risk genotypes of five miRNA SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-608 rs4919510, miR-27a rs895819 and miR-423 rs6505162) with risk factor (cooking oil fume exposure) contributed to a significantly higher risk of lung cancer, and the corresponding ORs (95% confidence intervals) were 1.91(1.04-3.52), 1.94 (1.16-3.25), 2.06 (1.22-3.49), 1.76 (1.03-2.98) and 2.13 (1.29-3.51). The individuals with both risk genotypes of miRNA SNPs and exposure to risk factor (cooking oil fumes) were in a higher risk of lung cancer than persons with only one of the two risk factors (ORs were 1.91, 1.05 and 1.41 for miR-146a rs2910164, ORs were 1.94, 1.23 and 1.34 for miR-196a2 rs11614913, ORs were 2.06, 1.41 and 1.68 for miR-608 rs4919510, ORs were 1.76, 0.82 and 1.07 for miR-27a rs895819, and ORs were 2.13, 1.15 and 1.02 for miR-423 rs6505162, respectively). All the measures of biological interaction indicate that there were not indeed biological interactions between the six SNPs of miRNAs and exposure to cooking oil fumes on an additive scale. Logistic models suggested that the gene-environment interactions were not statistically significant on a multiplicative scale. The interactions between miRNA SNPs and cooking oil fume exposure suggested by ORs of different combination were not statistically significant.

As the central flow channel for fluid seepage through rock layers, the visible fracture system (VFS) significantly affects geoenergy extraction for petroleum, natural gas, geothermal resources, and greenhouse gas sequestration. In this work, we propose a new mode of VFS in coal seams, including hydraulic fractures, exogenetic fractures, interlayer fractures, gas-expanding fractures, and cleats. The development characteristics of VFSs in coal seams are analyzed, including containing their geometry, orientation, scale, distribution, and connection between each other. Furthermore, the implications of the VFS for fluid (gas and water) and solid (coal fines) flow through coal seams are discussed. The development of the VFS determines the effective flow conductivity, affecting the flow of gas, water, and coal fines. Additionally, as the reservoir pressure transfer channel, the VFS significantly influences depressurization with reservoir depletion, determining the extension of the methane desorption range. The exogenetic fractures and interlayer fractures dominate the expansion of the primary hydraulic fractures, and gas-expanding and cleats usually control the branch of hydraulic fractures. Furthermore, we find that the daily production rate distribution of most CBM wells presents a particular banded, L-shaped, or T-shaped pattern. It is thought that the VFS dominates the productivity of CBM in coal seams. The field production data also provide evidence that the occurrence of the VFS makes the CBM reservoir heterogeneous. This study presents a recommended framework involving the characteristics of the VFS and its influences on CBM production.

Cyclocytidine hydrochloride (HCl) has been reported to inhibit DNA synthesis by affecting DNA polymerase. Here, we tested the antiviral effect of cyclocytidine on hepatitis B virus (HBV) DNA synthesis, which is reliant on DNA polymerase activity. Cyclocytidine HCl was treated to HBV-producing HepAD38 cells or added to an endogenous polymerase reaction, and HBV DNA was detected by Southern blot. Treatment of 20 µM cyclocytidine HCl significantly decreased the production of relaxed circular (rc) DNA in HepAD38 cells and block rcDNA synthesis in endogenous polymerase reaction (EPR), a cell free assay, possibly by inhibiting the HBV DNA polymerase activity. Cyclocytidine HCl could inhibit the synthesis of HBV rcDNA, the precursor of covalently closed circular DNA, and this result provides a case for the usage of \"old\" drugs for \"new\" applications.

Background MicroRNAs (miRNAs) have been proved to play important roles in the tumorigenesis and development of human gastric cancer (GC). Our study aims to investigate the expression and clinical significance of miR-198 in GC patients. Methods Quantitative real-time polymerase chain reaction (RT-PCR) was performed to evaluate miR-198 levels in 106 pairs of GC specimens and adjacent noncancerous tissues. Then, the associations of miR-198 expression with clinicopathological factors and patient’s survival were determined. Results The expression levels of miR-198 in GC tissues were significantly lower than those in corresponding noncancerous tissues ( p  < 0.01). Decreased miR-198 expression was significantly associated with larger tumor size, deeper invasion depth, positive lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and shorter overall survival. Moreover, multivariate regression analysis identified low miR-198 expression as an independent predictor of poor survival. Conclusions These findings suggested that miR-198 downregulation may be associated with progression of GC and that this miR may be an independent prognostic marker for GC patients.

PurposeThe role of non-coding RNA, once thought to be dark matter, is increasingly prominent in cancer. Our article explores the effect of non-coding RNA in lung adenocarcinoma and lung squamous cell carcinoma by mining TCGA public database.MethodsDownload the data by applying the official TCGA software. The data were analyzed by R data analysis packages, ‘edgeR’, ‘gplots’ and ‘survival’. We better illustrate the potential networks of lung cancer genes by constructing ceRNAs, using Cytoscape software.ResultsWe obtained genes which were differentially expressed in lung adenocarcinoma and lung squamous cell carcinoma analysis. Within these differentially expressed genes, we also conducted a survival analysis to find differentially expressed genes associated with prognosis in both lung adenocarcinoma and lung squamous cell carcinoma. Based on genes differentially expressed of both lung adenocarcinoma and lung squamous cell carcinoma, we constructed a ceRNA network to illustrate the mechanism of lung adenocarcinoma and lung squamous cell carcinoma. Our study analyzed genes which were differentially expressed in lung adenocarcinoma and lung squamous cell carcinoma using the TCGA database.ConclusionBased on this, the prognosis in both lung squamous cell carcinoma and lung adenocarcinoma was analyzed. We have also constructed a ceRNA network to provide a basis for the study of ceRNA in lung adenocarcinoma and lung squamous cell carcinoma.

Citrobacter freundii is an infrequent but established cause of diarrhea in humans. However, little is known of its genetic diversity and potential for virulence. We analyzed 26 isolates, including 12 from human diarrheal patients, 2 from human fecal samples of unknown diarrheal status, and 12 from animals, insects, and other sources. Pulsed field gel electrophoresis using XbaI allowed us to divide the 26 isolates into 20 pulse types, while multi-locus sequence typing using 7 housekeeping genes allowed us to divide the 26 isolates into 6 sequence types (STs) with the majority belonging to 4 STs. We analyzed adhesion and cytotoxicity to HEp-2 cells in these 26 strains. All were found to adhere to HEp-2 cells. One strain, CF74, which had been isolated from a goat, showed the strongest aggregative adhesion pattern. Lactate dehydrogenase (LDH) released from HEp-2 cells was evaluated as a measure of cytotoxicity, averaging 7.46%. Strain CF74 induced the highest level of LDH, 24.3%, and caused >50% cell rounding, detachment, and death. We named strain CF74 \"cytotoxic and aggregative C. freundii.\" Genome sequencing of CF74 revealed that it had acquired 7 genomic islands, including 2 fimbriae islands and a type VI secretion system island, all of which are potential virulence factors. Our results show that aggregative adherence and cytotoxicity play an important role in the pathogenesis of C. freundii.