Assessing the impact of circulating inflammatory cytokines and proteins as drivers and therapeutic targets in epilepsy: A Mendelian randomization study.

BACKGROUND: Previous research has demonstrated that neuroinflammation is a key element in the progress of epilepsy. Nevertheless, it is currently unidentified which inflammatory factors and proteins increase or decrease the risk of epilepsy. METHODS: We adopted Mendelian randomization techniques to explore the causal relationship between circulating inflammatory factors and proteins and various epilepsy. Our principal approach was inverse variance weighting, supplemented by several sensitivity analyses to guarantee the robustness of our findings. RESULTS: Studies have identified associations between epilepsy and specific inflammatory factors and proteins: three inflammatory factors and six proteins are linked to epilepsy in general; one inflammatory factor and four proteins are associated with focal epilepsy with no documented lesions; two inflammatory factors and three proteins are related to focal epilepsy, excluding cases with hippocampal sclerosis; two inflammatory factors and two proteins are connected to juvenile myoclonic epilepsy; two inflammatory factors and five proteins are linked to juvenile absence epilepsy; four inflammatory proteins are associated with childhood absence epilepsy; two inflammatory factors are related to focal epilepsy overall; two inflammatory factors and two proteins are connected to generalized epilepsy; and two inflammatory proteins are linked to generalized epilepsy with tonic-clonic seizures. Additionally, six inflammatory factors may play a downstream role in focal epilepsy. CONCLUSION: Our study uncovers various inflammatory factors and proteins that influence the risk of epilepsy, offering instructive insights to the diagnosis and therapy of the condition.

An empirical study on the relationship between rider recreational specialization, individual-environment fit, and heart flow experience.

The aim of the study is to create and validate a model of the relationship between specialization in leisure activities, the individual's adaptation to the environment and the heart flow experience. In order to clarify the role of the individual's adaptation to the environment in the relationship between specialization in leisure activities and the heart flow experience. The study utilized purposive sampling, cluster sampling, and random sampling. Using questionnaires and interviews to survey 525 cycling enthusiasts. Descriptive analysis, model construction and testing of the constructed path relationships were conducted using SPSS 20.0 and Amos 20.0. The results indicate that the model of the relationship between recovery specialization, individual-environment fit and heart flow experience has a good overall fit. The model shows good reliability and validity. Cyclists' recreational specialization has a statistically significant effect on individual-environment fit (ß = 0.38, P < 0.001). The fit between individual and environment has a statistically significant influence on the heart flow experience (ß = 0.39, P < 0.001). The fit between individual and environment serves as a mediating variable between recreational specialization and the heart flow experience, with the path showing statistical significance (ß = 0.15, P < 0.001). Recreational specialization has a statistically significant effect on the heart flow experience (ß = 0.30, P < 0.001). And the overall path of the effects of recreational specialization of cyclists on the fit between individual and environment is (ß = 0.45, P < 0.001), with the path showing statistical significance. Conclusion: The stronger the recreational specialization of cyclists and the greater the fit between individual and environment, the stronger their heart flow experience. The fit between individual and environment plays a partially mediating role.

The impact of internet health information usage habits on older adults' e-health literacy.

Objective: As the demand and supply sides of popular health services increasingly rely on the Internet, mastering e-health literacy should become an essential skill for older adults. The aim of this article is to analyse the effects of Internet health information usage habits on older adults' e- health literacy and to investigate the influencing mechanisms. Methods: Using a combination of random sampling and convenient sampling, data were collected through questionnaire surveys. Data from 776 older adults was analysed using correlation and hierarchical regression to analyse. Results: The mean scores for all aspects of older adults' habits of using health information on the Internet and electronic health literacy were relatively high. There was no statistically significant difference in the predictive power of the three aspects of electronic health literacy among older adults with different genders, health statuses, education levels and ages (p > 0.05). The four factors of older adults' habits of using Internet health information can increase the explanatory power of application ability, judgment ability and decision-making ability in Model 2 by 53.7%, 46.2% and 57%, respectively, with statistical significance (p < 0.001). Conclusion: The better the habits of older adults in using health information on the Internet, the higher their level of electronic health literacy. Families, communities and social groups should help older adults use online health resources to improve their e-health literacy. Older adults can use WeChat or other interpersonal information platforms to share online health information with each other.

Long Non-Coding RNA B3GALT5-AS1 Suppresses Keloid Progression by Regulating the ß-Trcp1-Mediated Ubiquitination of HuR.

Background: lncRNA ß­1,3­galactosyltransferase 5­AS1 (B3GALT5-AS1) plays a vital regulatory role in colon and gastric cancers. However, the biological functions and regulatory mechanisms of B3GALT5-AS1 in keloid progression remain unknown. This study aims to investigate the molecular mechanisms in the B3GALT5-AS1-regulated keloid proliferation and invasion. Methods: Secondary mining of the lncRNA sequencing data from GSE158395 was conducted to screen differentially expressed lncRNAs between keloid and normal tissues. MTT, cell migration and invasion assays were performed to detect the effects of B3GALT5-AS1 on keloid fibroblasts (KFs) proliferation and metastasis. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were also determined to evaluate glycolysis in KFs. RNA pull-down and RNA-protein immunoprecipitation assays were used to confirm the interaction between B3GALT5-AS1 and Hu-Antigen R (HuR). Further ubiquitination and rescue experiments were performed to elucidate the regulatory relationship between B3GALT5-AS1 and HuR. Results: B3GALT5-AS1 was significantly down-regulated in keloid tissues and fibroblasts. B3GALT5-AS1 overexpression significantly inhibited KFs proliferation, glycolysis, invasion, and migration and promoted cell apoptosis, whereas silencing B3GALT5-AS1 inhibited these effects. Moreover, B3GALT5-AS1 binds to HuRand reduces its stability through ß-Transducin repeats-containing protein 1 (ß-Trcp1)-mediated ubiquitination. Overexpression of HuR reversed the inhibition of B3GALT5-AS1 on cell proliferation, migration, and invasion in KFs, where glycolysis pathway was involved. Conclusion: Our findings illustrate that B3GALT5-AS1 has great effect on inhibition of keloid formation, which provides a potential target for keloid therapy.

Aldehyde dehydrogenase 2 rs671 a/A Genotype is Associated with an Increased Risk of Early Onset Coronary Artery Stenosis.

Background: The role of aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases has been gradually studied. However, it is unclear whether ALDH2 polymorphism is associated with the risk of early onset (onset age ≤55 years old in men and ≤65 years old in women) coronary artery stenosis (CAS). The association between ALDH2 single nucleotide polymorphism (SNP) rs671 and risk in patients with early onset CAS was investigated in this study. Methods: The study included 213 early onset CAS patients and 352 individuals without CAS were set as controls. The ALDH2 rs671 polymorphism was genotyped by polymerase chain reaction (PCR) - microarray. Differences in ALDH2 rs671 genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for gender, body mass index (BMI), smoking history, drinking history, and diabetes mellitus to assess the relationship between ALDH2 rs671 genotypes and early onset CAS risk. Results: The frequency of the ALDH2 rs671 G/G genotype was lower in the early onset CAS patients (43.7% vs 55.3%, p=0.007) than that in the controls. The frequency of the ALDH2 rs671 A allele was higher (32.9% vs 25.0%) than that in the controls (p=0.005). After adjusting for other confounding factors, multivariate logistic regression showed that ALDH2 rs671 A/A genotype (A/A vs G/G: odds ratio (OR) 2.508, 95% confidence interval (CI): 1.130-5.569, p=0.024), overweight (BMI≥24.0 vs 18.5-23.9: OR 5.047, 95% CI: 3.275-7.777, p<0.001), history of smoking (yes vs no: OR 2.813, 95% CI: 1.595-4.961, p<0.001), and diabetes mellitus (yes vs no: OR 2.191, 95% CI: 1.397-3.437, p=0.001) were the independent risk factors of early onset CAS. Conclusion: In men ≤55 years old and women ≤65 years old, individuals with ALDH2 rs671 A/A genotype, overweight (BMI ≥24.0 kg/m2), smoking history, and diabetes mellitus increased risk of developing CAS.

Boosting Up Electrosynthesis of Urea with Nitrate and Carbon Dioxide via Synergistic Effect of Metallic Iron Cluster and Single-Atom.

Electrocatalytic conversion of nitrates and carbon dioxide to urea under ambient conditions shows promise as a potential substitute for traditional urea synthesis processes characterized by high consumption and pollution. In this study, a straightforward one-pot method is employed to prepare a highly efficient FeNC-Fe1N4 electrocatalyst, consisting of atomically dispersed Fe1N4 sites and metallic Fe clusters (FeNC) with particle size of 4-7 nm. The FeNC-Fe1N4 catalyst exhibits remarkable electrocatalytic activity for urea synthesis from nitrate anion (NO3 -) and carbon dioxide (CO2), achieving a urea production rate of 38.2 mmol gcat -1 h-1 at -0.9 V (vs RHE) and a Faradaic efficiency of 66.5% at -0.6 V (vs RHE). Both experimental and theoretical results conclusively demonstrate that metallic Fe clusters and Fe1N4 species provide active sites for the adsorption and activation of NO3 - and CO2, respectively, and the synergistic effect between Fe1N4 and metallic Fe clusters significantly enhances the electrochemical efficiency of urea synthesis. In all, this work contributes to the rational design and comprehensive synthesis of a dual-active site iron-based electrocatalyst, facilitating efficient and sustainable urea synthesis.

Synchronous papillary and follicular thyroid carcinomas: the first retrospective cohort study and literature review.

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

Platelet-derived major histocompatibility complex class I coating on Treponema pallidum attenuates natural killer cell lethality.

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

Activity and resistance to KRASG12C inhibitors in non-small cell lung cancer and colorectal cancer.

Non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) are associated with a high mortality rate. Mutations in the V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) proto-oncogene GTPase (KRAS) are frequently observed in these cancers. Owing to its structural attributes, KRAS has traditionally been regarded as an "undruggable" target. However, recent advances have identified a novel mutational regulatory site, KRASG12C switch II, leading to the development of two KRASG12C inhibitors (adagrasib and sotorasib) that are FDA-approved. This groundbreaking discovery has revolutionized our understanding of the KRAS locus and offers treatment options for patients with NSCLC harboring KRAS mutations. Due to the presence of alternative resistance pathways, the use of KRASG12C inhibitors as a standalone treatment for patients with CRC is not considered optimal. However, the combination of KRASG12C inhibitors with other targeted drugs has demonstrated greater efficacy in CRC patients harboring KRAS mutations. Furthermore, NSCLC and CRC patients harboring KRASG12C mutations inevitably develop primary or acquired resistance to drug therapy. By gaining a comprehensive understanding of resistance mechanisms, such as secondary mutations of KRAS, mutations of downstream intermediates, co-mutations with KRAS, receptor tyrosine kinase (RTK) activation, Epithelial-Mesenchymal Transitions (EMTs), and tumor remodeling, the implementation of KRASG12C inhibitor-based combination therapy holds promise as a viable solution. Furthermore, the emergence of protein hydrolysis-targeted chimeras and molecular glue technologies has been facilitated by collaborative efforts in structural science and pharmacology. This paper aims to provide a comprehensive review of the recent advancements in various aspects related to the KRAS gene, including the KRAS signaling pathway, tumor immunity, and immune microenvironment crosstalk, as well as the latest developments in KRASG12C inhibitors and mechanisms of resistance. In addition, this study discusses the strategies used to address drug resistance in light of the crosstalk between these factors. In the coming years, there will likely be advancements in the development of more efficacious pharmaceuticals and targeted therapeutic approaches for treating NSCLC and CRC. Consequently, individuals with KRAS-mutant NSCLC may experience a prolonged response duration and improved treatment outcomes.

Mechanical properties of municipal solid waste under different stress paths: Effects of plastic content and particle gradation.

Plastics within municipal solid waste (MSW) are non-degradable. As MSW continues to degrade, the relative content of plastics rises, and particle gradation may also change. Moreover, throughout the landfilling process, MSW is subjected to various stress conditions, potentially influencing its mechanical properties. This study explored the effects of varying plastic contents, different particle gradations, and distinct stress paths on the mechanical properties of MSW, and consolidated drained triaxial tests of 42 groups of reconstituted MSW specimens were conducted. The results showed that there was an optimal plastic content of 6-9 % for MSW, where the shear strength of MSW was higher than that of MSW with other plastic contents. When the stress path changed from TC45 to TC72, the optimal plastic content of MSW changed from 6 % to 9 %. As the plastic content increased, both the cohesion and internal friction angle of the MSW initially increased, then subsequently decreased. The impact of plastic content on cohesion was more pronounced than on the internal friction angle, especially at larger strains. Under various stress paths, MSW with distinct particle size distributions demonstrated diverse stress-strain behaviors. Traditional criteria for evaluating well-graded conditions in soils are not suitable for MSW. The effect of gradation on the cohesion of MSW is essentially due to the predominant role of fiber content; the relationship between gradation and the internal friction angle in MSW is complex and correlates closely with the content of both coarse and fine particles, as well as fibers. This study serves as an essential reference for predicting deformations in landfills and analyzing the stability of landfill slopes.

Dual­regulated oncolytic adenovirus carrying ERCC1­siRNA gene possesses potent antitumor effect on ovarian cancer cells.

Ovarian cancer is a multifactorial and deadly disease. Despite significant advancements in ovarian cancer therapy, its incidence is on the rise and the molecular mechanisms underlying ovarian cancer invasiveness, metastasis and drug resistance remain largely elusive, resulting in poor prognosis. Oncolytic viruses armed with therapeutic transgenes of interest offer an attractive alternative to chemical drugs, which often face innate and acquired drug resistance. The present study constructed a novel oncolytic adenovirus carrying ERCC1 short interfering (si)RNA, regulated by hTERT and HIF promoters, termed Ad­siERCC1. The findings demonstrated that this oncolytic adenovirus effectively inhibits the proliferation, migration and invasion of ovarian cancer cells. Furthermore, the downregulation of ERCC1 expression by siRNA ameliorates drug resistance to cisplatin (DDP) chemotherapy. It was found that Ad­siERCC1 blocks the cell cycle in the G1 phase and enhances apoptosis through the PI3K/AKT­caspase­3 signaling pathways in SKOV3 cells. The results of the present study highlighted the critical effect of oncolytic virus Ad­siERCC1 in inhibiting the survival of ovarian cancer cells and increasing chemotherapy sensitivity to DDP. These findings underscore the potent antitumor effect of Ad­siERCC1 on ovarian cancers in vivo.

Genetic prediction of micronutrient levels and the risk of colorectal polyps: A mendelian randomization study.

OBJECTIVE: Previous epidemiological and experimental studies have yielded conflicting results regarding the influence of human micronutrient levels on the risk of colorectal polyps (CP). In our study, we conducted a two-sample Mendelian randomization (MR) investigation to probe the link between 13 human micronutrients (calcium, selenium, magnesium, phosphorus, folate, vitamins B-6, B-12, C, D, beta-carotene, iron, zinc, and copper) and the genetic susceptibility to CP. METHODS: Summary statistics for CP (n = 463,010) were obtained from pan-European genome-wide association studies, and instrumental variables for 13 micronutrients were screened from published genome-wide association studies (GWAS). After selecting suitable instrumental variables, we performed a two-sample MR study, deploying sensitivity analyses to judge heterogeneity and pleiotropy, using inverse variance weighted methods as our primary estimation tool. RESULTS: Our study identified that a genetic predisposition to elevated toenail and circulating selenium or serum ß-carotene concentrations lowers the risk of CP occurrence. However, no statistically significant association was observed between the other 11 micronutrients and the risk of CP. CONCLUSION: The study findings provide evidence that the micronutrient selenium and ß-carotene may confer protective effects against the development of CP.

Ammonium sulfate denatures transport medium less dependent on guanidinium isothiocyanate and enables SARS-CoV-2 RNA and antigen detection compatibility.

Introduction: Rapid identification of infected individuals through viral RNA or antigen detection followed by effective personal isolation is usually the most effective way to prevent the spread of a newly emerging virus. Large-scale detection involves mass specimen collection and transportation. For biosafety reasons, denaturing viral transport medium has been extensively used during the SARS-CoV-2 pandemic. However, the high concentrations of guanidinium isothiocyanate (GITC) in such media have raised issues around sufficient GITC supply and laboratory safety. Moreover, there is a lack of denaturing transport media compatible with SARS-CoV-2 RNA and antigen detection. Methods: Here, we tested whether supplementing media containing low concentrations of GITC with ammonium sulfate (AS) would affect the throat-swab detection of SARS-CoV-2 or a viral inactivation assay targeting coronavirus and other enveloped and non-enveloped viruses. The effect of adding AS to the media on RNA stability and its compatibility with SARS-CoV-2 antigen detection were also tested. Results and discussion: We found that adding AS to the denaturing transport media reduced the need for high levels of GITC, improved SARS-COV-2 RNA detection without compromising virus inactivation, and enabled the denaturing transport media compatible with SARS-CoV-2 antigen detection.

Synthesis of selenophene-containing flavonols and 2-styrylchromones: Evaluation of their activities compared with selenophene-containing chalcones as potential anticancer agents.

Previously, we documented the synthesis and assessed the biological effects of chalcones containing selenium against HT-29 human colorectal adenocarcinoma cells, demonstrating their significant potential. As research on selenium-containing flavonoids remains limited, this article outlines our design and synthesis of three selenium-based flavonols and three 2-styrylchromones. We conducted evaluations of these compounds to determine their impact on human lung cancer cells (A549, H1975, CL1-0, and CL1-5) and their influence on normal lung fibroblast MRC5 cells. Additionally, we included selenium-based chalcones in our testing for comparative purposes. Our findings highlight that the simplest compound, designated as compound 1, exhibited the most promising performance among the tested molecules.

The discovery of a novel single-function intermolecular Diels-Alder enzyme for the biosynthesis of hetero-dimer lithocarpins.

The deep-sea fungus Phomopsis lithocarpus FS508 produces tenellone-macrolide conjugated hetero-dimer lithocarpins A-G with anti-tumor activities. The deficiency of new intermolecular Diels-Alder (DA) enzymes hindered the development of new bioactive hetero-dimers. A novel single-function intermolecular DA enzyme, g7882, was initially discovered in this study. The deletion of g7882 led to the disappearance of lithocarpin A and an increase in precursor level . the overexpression of g7882 significantly improved lithocarpin A yield. The in vitro function of g7882DA was also confirmed by biochemical reaction using tenellone B as a substrate. Additionally, the knockout of KS modules of PKS in cluster 41 and cluster 81 (lit cluster) eliminated the production of lithocarpins, which firstly explains the biosynthetic process of hetero-dimer lithocarpins mediated by DA enzyme in FS508. Furthermore, the removal of a novel acetyltransferase GPAT in cluster 41 and the oxidoreductase, prenyltransferase in cluster81 resulted in the reduction of lithocarpin A in P. lithocarpus. The overexpression of gpat in P. lithocarpus FS508 improved the yield of lithocarpin A significantly and produced a new tenellone derivative lithocarol G. This study offers a new DA enzyme tool for the biosynthesis of novel hetero-dimer and biochemical clues for the biosynthetic logic elucidation of lithocarpins.

CCL20 and CD8A as potential diagnostic biomarkers for HBV-induced liver fibrosis in chronic hepatitis B.

Background: The main cause of the liver fibrosis (LF) remains hepatitis B virus (HBV) infection, especially in China. Histologically, liver fibrosis still occurs progressively in chronic hepatitis B (CHB) patients, even if HBV-DNA is negative or undetectable. The diagnosis of LF is beneficial to control the development of it, also it may promote the reversal of LF. Although liver biopsy is the gold standard of diagnosis in LF at present, it isa traumatic diagnosis. There are no diagnostic biomarkers as yet for the condition. It is badly in need of biomarkers clinically, which is simple to test, minimally invasive, highly specific, and sensitive. Early detection of HBV-LF development is crucial in the prevention, treatment, and prognosis prediction of HBV-LF. Cytokines are closely associated with both immune regulation and inflammation in the progression of hepatitis B virus associated-liver fibrosis (HBV-LF). In this bioinformatic study, we not only analyzed the relationship between HBV-LF and immune infiltration, but also identified key genes to uncover new therapeutic targets. Objectives: To find potential biomarkers for liver fibrosis in the development of chronic hepatic B patients. Materials and methods: We obtained two sets of data including CHB/healthy control and CHB/HBV-LF from the Integrated Gene Expression (GEO) database to select for differential expression analysis. Protein-protein interaction (PPI) network was also generated, while key genes and important gene modules involved in the occurrence and development of HBV-LF were identified. These key genes were analyzed by functional enrichment analysis, module analysis, and survival analysis. Furthermore, the relationship between these two diseases and immune infiltration was explored. Results: Among the identified genes, 150 were individually associated with CHB and healthy control in the differential gene expression (DGE) analysis. While 14 with CHB and HBV-LF. It was also analyzed in the Robust rank aggregation (RRA) analysis, 34 differential genes were further identified by Cytohubba. Among 34 differential genes, two core genes were determined: CCL20 and CD8A. CCL20 was able to predict CHB positivity (area under the receiver operating characteristic curve [AUC-ROC] = 0.883, 95% confidence interval [CI] 0.786-0.963), while HBV-LF positivity ([AUC-ROC] = 0.687, 95% confidence interval [CI] 0.592-0.779). And CD8A was able to predict CHB positivity ([AUC-ROC] = 0.960, 95% confidence interval [CI] 0.915-0.992), while HBV-LF positivity ([AUC-ROC] = 0.773, 95% confidence interval [CI] 0.680-0.856). Relationship between CCL20 gene expression and LF grades was P < 0.05, as well as CD8A. Conclusion: CCL20 and CD8A were found to be potential biomarkers and therapeutic targets for HBV-LF. It is instructive for research on the progression of LF in HBV patients, suppression of chronic inflammation, and development of molecularly targeted-therapy for HBV-LF.

Detection of chromosomal instability using ultrasensitive chromosomal aneuploidy detection in the diagnosis of precancerous lesions of gastric cancer.

Background: The diagnosis of Precancerous Lesions of Gastric Cancer (PLGC) is challenging in clinical practice. We conducted a clinical study by analyzing the information of relevant chromosome copy number variations (CNV) in the TCGA database followed by the UCAD technique to evaluate the value of Chromosomal Instability (CIN) assay in the diagnosis of PLGC. Methods: Based on the screening of gastric cancer related data in TCGA database, CNV analysis was performed to explore the information of chromosome CNV related to gastric cancer. Based on the gastroscopic pathology results, 12 specimens of patients with severe atrophy were screened to analyze the paraffin specimens of gastric mucosa by UCAD technology, and to explore the influence of related factors on them. Results: The results of CNV in TCGA database suggested that chromosome 7, 8, and 17 amplification was obvious in patients with gastric cancer. UCAD results confirmed that in 12 patients with pathologic diagnosis of severe atrophy, five of them had positive results of CIN, with a positive detection rate of 41.7%, which was mainly manifested in chromosome seven and chromosome eight segments amplification. We also found that intestinalization and HP infection were less associated with CIN. And the sensitivity of CIN measurement results was significantly better than that of tumor indicators. Conclusion: The findings suggest that the diagnosis of PLGC can be aided by UCAD detection of CIN, of which Chr7 and 8 may be closely related to PLGC.

First Report of Kiwifruit Root Rot Caused by Globisporangium spinosum in China.

Kiwifruit is widely cultivated for its high vitamin C content and nutritional value. In January 2022, root rot symptoms were found in about 30% of Actinidia chinensis cv. Jinyan plants grafted on A. deliciosa rootstocks in an orchard located in Sanming (26.32°N, 117.23°E), Fujian Province of China. The affected plants appeared stunted, with brown and decaying roots, some of which were covered with white hyphae. To isolate the pathogen, the surfaces of typical symptomatic roots were sterilized for 30 s using 75% ethanol, followed by four rinses in sterile water, placing on potato dextrose agar (PDA), and incubating away from light at 25°C for 7 days. 16 Globisporangium-like isolates were obtained through hyphal tip isolation, displaying a milky-white appearance with irregular protuberances on the surface, and yellow-white backs with radial fold lines. The isolates were then cultured on corn meal agar for 5 days at 25°C in dark for morphological characteristics. Under microscope, the hyphae appeared as long strips without septa and 4.1 to 8.2 µm wide (average 6.7 µm), containing irregularly sized spherical droplets. Both terminal and intercalary hyphae swellings were observed; these appeared either spherical or subspherical, with some having projections. Their dimensions were 12.3 to 27.6 µm (average 17.3 µm). The oospores were mostly spherical, either plerotic or aplerotic, 11.8 to 22.3 µm wide (average 18.9 µm), with occasional projections. The antheridia were rod-shaped and curved, with one end attached to the oogonia. Amplification of the sequences of internal transcribed spacer (ITS) regions and cytochrome c oxidase subunit I (COI) were conducted using the primers ITS1/ITS4 (White et al. 1990) and OomCoxI-Levlo/OomCoxI-Levup (Robideau et al. 2011), respectively. The sequencing results revealed identical ITS and COI sequences in all 16 isolates. BLASTn analysis of the 969-bp ITS sequence ON202808 showed 99.38-99.59% similarity (965/971bp, 967/971bp) with the KJ162353 and AY598701 sequences from Globisporangium spinosum isolates, while the 700-bp COI sequence ON075783 showed 100% and 99.41% identity (680/680bp, 676/680bp) with the GenBank sequences HQ708835 and HQ708832, respectively, from G. spinosum. Phylogenetic analysis also showed that the obtained isolate (termed MA16) clustered with isolates from G. spinosum on the same evolutionary branch. For pathogenicity testing, four-month-old healthy Jinyan (A. chinensis) plants grown in sterilized media were transferred to sterile petri dishes covered with wet filter paper, and their roots were inoculated with a 5-mm-wide disk of MA16 when cultivated on PDA medium for 5 days. Miliang-1 (A. deliciosa) and Hongyang (A. chinensis) plants were treated similarly. The control groups each included three plants that were inoculated with non-colonized PDA. The plants were kept at 25 °C with a 12-/12-h light/dark cycle for 10 days when the inoculated plants exhibited root rot symptoms similar to those seen in the field, together with rotting and browning of the leaves. The control plants appeared healthy with no symptoms. After re-isolated from infected tissues, the pathogen was verified to be G. spinosum according to its ITS sequence, thus fulfilling the Koch's postulates. Recently, Pythium spinosum has been classified as G. spinosum according to whole-genome sequencing and phylogenomic analysis (Nguyen et al. 2022). Based on the morphological features and pathogenicity results, MA16 was identified as G. spinosum (van der Plaats-Niterink 1981; Huo et al. 2023). This report appears to be the first description of kiwifruit root rots caused by G. spinosum in China, and its identification will assist the development of strategies to counteract the disease.

Cytosolic DNA initiates a vicious circle of aging-related endothelial inflammation and mitochondrial dysfunction via STING: the inhibitory effect of Cilostazol.

Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Sting deficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases. A proposed model illustrates the central role of STING in mediating a vicious circle of cfDNA-STING-SASP-cfDNA to aggravate age-related endothelial inflammation and mitochondrial damage.

Integration of adsorption, reduction, and filtration in PANI/PVDF nanofiber composite membrane for removal of Cr(VI).

Here, polyaniline/polyvinylidene fluoride (PANI/PVDF) nanofiber composite membrane was fabricated using electrostatic spinning technology to remove hexavalent chromium Cr(VI). The employment of PANI not only extremely enhanced the hydrophilic property of the nanofiber membrane, but also facilitated the transfer of Cr2O72- from water to the membrane. The PANI/PVDF membrane had an extremely excellent performance in getting rid of Cr(VI) and a quite large flux (250 L/m2 h). The maximum adsorption quantity of the membrane could reach 334.5 mg/g in which adsorption played 52.12% part and reduction played 47.87% part. The removal rate could reach nearly 100% immediately in the permeate solution under filtration while it needed 240 min to reach 100% only by static adsorption. Therefore, the interception of the membrane and the adsorption reduction of PANI had synergistic effect on removal of Cr(VI). Furthermore, the removal rate of Cr(VI) could still reach 95.97% after reused 8 times. The membrane showed a very good reusability and application prospect.