Prognostic value of depression and anxiety on colorectal cancer-related mortality: a systematic review and meta-analysis based on univariate and multivariate data.

BACKGROUND: Depression and anxiety are common mental disorders in patients with colorectal cancer (CRC); however, it remains unclear whether they are related to cancer mortality. METHOD: Based on a systematic literature search, 12 eligible studies involving 26,907 patients with CRC were included in this study. RESULTS: Univariate analysis revealed that anxiety was associated with an all-cause mortality rate of 1.42 (1.02, 1.96), whereas multivariate analysis revealed that anxiety was not associated with an all-cause mortality rate of 0.73 (0.39, 1.36). In univariate and multivariate analyses, depression was associated with all-cause mortality rates of 1.89 (1.68, 2.13) and 1.62 (1.27, 2.06), respectively, but not with the cancer-associated mortality rate of 1.16 (0.91, 1.48) in multivariate analyses. Multivariate subgroup analysis of depression and all-cause mortality showed that younger age (≤65 years), being diagnosed with depression/anxiety after a confirmed cancer diagnosis, and shorter follow-up time (<5 years) were associated with poor prognosis. CONCLUSIONS: Our study emphasizes the key roles of depression and anxiety as independent factors for predicting the survival of patients with CRC. However, owing to the significant heterogeneity among the included studies, the results should be interpreted with caution. Early detection and effective treatment of depression and anxiety in patients with CRC have public health and clinical significance.

The FBXW7-binding sites on FAM83D are potential targets for cancer therapy.

Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.

Explainable machine learning for early predicting treatment failure risk among patients with TB-diabetes comorbidity.

The present study aims to assess the treatment outcome of patients with diabetes and tuberculosis (TB-DM) at an early stage using machine learning (ML) based on electronic medical records (EMRs). A total of 429 patients were included at Chongqing Public Health Medical Center. The random-forest-based Boruta algorithm was employed to select the essential variables, and four models with a fivefold cross-validation scheme were used for modeling and model evaluation. Furthermore, we adopted SHapley additive explanations to interpret results from the tree-based model. 9 features out of 69 candidate features were chosen as predictors. Among these predictors, the type of resistance was the most important feature, followed by activated partial throm-boplastic time (APTT), thrombin time (TT), platelet distribution width (PDW), and prothrombin time (PT). All the models we established performed above an AUC 0.7 with good predictive performance. XGBoost, the optimal performing model, predicts the risk of treatment failure in the test set with an AUC 0.9281. This study suggests that machine learning approach (XGBoost) presented in this study identifies patients with TB-DM at higher risk of treatment failure at an early stage based on EMRs. The application of a convenient and economy EMRs based on machine learning provides new insight into TB-DM treatment strategies in low and middle-income countries.

Reduced production of Ethyl Carbamate in wine by regulating the accumulation of arginine in Saccharomyces cerevisiae.

Ethyl carbamate (EC), a multisite carcinogenic compound, is naturally produced from urea and ethanol in alcoholic beverages. In order to reduce the content of EC in wine, the accumulation of arginine in Saccharomyces cerevisiae was regulated by genetic modifying genes involved in arginine transport and synthesis pathways to reduce the production of urea. Knockout of genes encoding arginine permease (Can1p) and amino acid permease (Gap1p) on the cell membrane as well as argininosuccinate synthase (Arg1) respectively resulted in a maximum reduction of 66.88% (9.40 µg/L) in EC, while overexpressing the gene encoding amino acid transporter (Vba2) reduced EC by 52.94% (24.13 µg/L). Simultaneously overexpressing Vba2 and deleting Arg1 showed the lowest EC production with a decrease of 68% (7.72 µg/L). The yield of total higher alcohols of the mutants all decreased compared with that of the original strain. Comprehensive consideration of flavor compound contents and sensory evaluation results indicated that mutant YG21 obtained by deleting two allele coding Gap1p performed best in must fermentation of Cabernet Sauvignon with the EC content low to 9.40 µg/L and the contents of total higher alcohols and esters of 245.61 mg/L and 41.71 mg/L respectively. This study has provided an effective strategy for reducing the EC in wine.

Discovery of a botanical compound as a broad-spectrum inhibitor against gut microbial ß-glucuronidases from the Tibetan medicine Rhodiola crenulata.

Gut microbial ß-glucuronidases (gmß-GUS) played crucial roles in regulating a variety of endogenous substances and xenobiotics on the circulating level, thus had been recognized as key modulators of drug toxicity and human diseases. Inhibition or inactivation of gmß-GUS enzymes has become a promising therapeutic strategy to alleviate drug-induced intestinal toxicity. Herein, the Rhodiola crenulata extract (RCE) was found with potent and broad-spectrum inhibition on multiple gmß-GUS enzymes. Subsequently, the anti-gmß-GUS activities of the major constituents in RCE were tested and the results showed that 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose (PGG) acted as a strong and broad-spectrum inhibitor on multiple gmß-GUS (including EcGUS, CpGUS, SaGUS, and EeGUS). Inhibition kinetic assays demonstrated that PGG effectively inhibited four gmß-GUS in a non-competitive manner, with the Ki values ranging from 0.12 µM to 1.29 µM. Docking simulations showed that PGG could tightly bound to the non-catalytic sites of various gmß-GUS, mainly via hydrogen bonding and aromatic interactions. It was also found that PGG could strongly inhibit the total gmß-GUS activity in mice feces, with the IC50 value of 1.24 µM. Collectively, our findings revealed that RCE and its constituent PGG could strongly inhibit multiple gmß-GUS enzymes, suggesting that RCE and PGG could be used for alleviating gmß-GUS associated enterotoxicity.

The protein phosphatase qGL3/OsPPKL1 self-regulates its degradation to orchestrate brassinosteroid signaling in rice.

Brassinosteroids (BRs) are a class of phytohormones that regulate plant growth and development. In previous studies, we cloned and identified PROTEIN PHOSPHATASE WITH KELCH-LIKE1 (OsPPKL1) as the causal gene for the quantitative trait locus GRAIN LENGTH3 (qGL3) in rice (Oryza sativa). We also showed that qGL3/OsPPKL1 is mainly located in the cytoplasm and nucleus and negatively regulates BR signaling and grain length. Because qGL3 is a negative regulator of BR signaling, its turnover is critical for rapid response to changes in BRs. Here, we demonstrate that qGL3 interacts with the WD40-domain-containing protein WD40-REPEAT PROTEIN48 (OsWDR48), which contains a nuclear export signal (NES). The NES signal is crucial for the cytosolic localization of OsWDR48 and also functions in the self-turnover of qGL3. We show that OsWDR48 physically interacts with and genetically acts through qGL3 to modulate BR signaling. Moreover, qGL3 may indirectly promote the phosphorylation of OsWDR48 at the Ser-379 and Ser-386 sites. Substitutions of both phosphorylation sites in OsWDR48 to non-phosphorylatable alanine enhanced the strength of the OsWDR48-qGL3 interaction. Furthermore, we found that brassinolide can promote the accumulation of non-phosphorylated OsWDR48, leading to strong interaction intensity between qGL3 and OsWDR48. Taken together, our results show that OsWDR48 facilitates qGL3 retention and induces degradation of qGL3 in the cytoplasm. These findings suggest that qGL3 self-modulates its turnover by binding to OsWDR48 to regulate its cytoplasmic localization and stability, leading to efficient orchestration of BR signal transduction in rice.

Epidemiologic changes of a longitudinal surveillance study spanning 51 years of scrub typhus in mainland China.

Scrub typhus may be one of the world's most prevalent, neglected and serious, but easily treatable, febrile diseases. It has become a significant potential threat to public health in China. In this study we used national disease surveillance data to analyze the incidence and spatial-temporal distribution of scrub typhus in mainland China during 1952-1989 and 2006-2018. Descriptive epidemiological methods and spatial-temporal epidemiological methods were used to investigate the epidemiological trends and identify high-risk regions of scrub typhus infection. Over the 51-year period, a total of 182,991 cases and 186 deaths were notified. The average annual incidence was 0.13 cases/100,000 population during 1952-1989. The incidence increased sharply from 0.09/100,000 population in 2006 to 1.93/100,000 population in 2018 and then exponentially increased after 2006. The incidence was significantly higher in females than males (χ2 = 426.32, P < 0.001). Farmers had a higher incidence of scrub typhus than non-farmers (χ2 = 684.58, P < 0.001). The majority of cases each year were reported between July and November with peak incidence occurring during October each year. The trend surface analysis showed that the incidence of scrub typhus increased gradually from north to south, and from east and west to the central area. The spatial autocorrelation analysis showed that a spatial positive correlation existed in the prevalence of scrub typhus on a national scale, which had the characteristic of aggregated distribution (I = 0.533, P < 0.05). LISA analysis showed hotspots (High-High) were primarily located in the southern and southwestern provinces of China with the geographical area expanding annually. These findings provide scientific evidence for the surveillance and control of scrub typhus which may contribute to targeted strategies and measures for the government.

Highly efficient molecular film for inhibiting volatilization of hazardous nitric acid.

Nitric acid, an important basic chemical raw material, plays an important role in promoting the development of national economy. However, such liquid hazardous chemicals are easy to cause accidental leakage during production, transportation, storage and use. The high concentration and corrosive toxic gas generated from decomposition shows tremendous harm to the surrounding environment and human life safety. Therefore, how to inhibit the volatilization of nitric acid and effectively control and block the generation of the toxic gas in the first time are the key to deal with the nitric acid leakage accident. Herein, a new method of molecular film obstruction is proposed to inhibit the nitric acid volatilization. The molecular film inhibitor spontaneously spread and form an insoluble molecular film on the gas-liquid interface, changing the state of nitric acid liquid surface and inhibiting the volatilization on the molecular scale. The inhibition rate up to 96% can be achieved below 45 °C within 400 min. Cluster structure simulation and energy barrier calculation is performed to elucidate the inhibition mechanism. Theoretical analysis of energy barrier shows that the specific resistance of the inhibitor significantly increased to 460 s·cm-1 at 45 °C, and the generated energy barrier is about 17,000 kJ·mol-1, which is much higher than the maximum energy required for nitric acid volatilization of 107.97 kJ·mol-1. The molecular film obstruction strategy can effectively inhibit the volatilization of nitric acid. This strategy paves the way for preventing the volatilization of liquid hazardous chemicals in accidental leakage treatment.

Discovery of plant chemical defence mediated by a two-component system involving ß-glucosidase in Panax species.

Plants usually produce defence metabolites in non-active forms to minimize the risk of harm to themselves and spatiotemporally activate these defence metabolites upon pathogen attack. This so-called two-component system plays a decisive role in the chemical defence of various plants. Here, we discovered that Panax notoginseng, a valuable medicinal plant, has evolved a two-component chemical defence system composed of a chloroplast-localized ß-glucosidase, denominated PnGH1, and its substrates 20(S)-protopanaxadiol ginsenosides. The ß-glucosidase and its substrates are spatially separated in cells under physiological conditions, and ginsenoside hydrolysis is therefore activated only upon chloroplast disruption, which is caused by the induced exoenzymes of pathogenic fungi upon exposure to plant leaves. This activation of PnGH1-mediated hydrolysis results in the production of a series of less-polar ginsenosides by selective hydrolysis of an outer glucose at the C-3 site, with a broader spectrum and more potent antifungal activity in vitro and in vivo than the precursor molecules. Furthermore, such ß-glucosidase-mediated hydrolysis upon fungal infection was also found in the congeneric species P. quinquefolium and P. ginseng. Our findings reveal a two-component chemical defence system in Panax species and offer insights for developing botanical pesticides for disease management in Panax species.

Circ-0000953 deficiency exacerbates podocyte injury and autophagy disorder by targeting Mir665-3p-Atg4b in diabetic nephropathy.

Circular RNAs (circRNAs) are special non-coding RNA (ncRNA) molecules that play a significant role in many diseases. However, the biogenesis and regulation of circRNAs in diabetic nephropathy (DN) are largely unknown. Here, we investigated the expression profile of circRNAs in kidney of DN mice through circular RNA sequencing (circRNA-seq). The renal biopsy samples of patients with DN had low circ -0,000,953 expression, which was significantly associated with renal function. Furthermore, loss-of-function and gain-of-function experiments were carried out to prove the role of circ -0,000,953 in DN. Podocyte conditional knockin (cKI) or systemic overexpression of circ -0,000,953 alleviated albuminuria and restored macroautophagy/autophagy in kidney of diabetic mice. However, circ -0,000,953 knockdown exacerbated albuminuria and podocyte injury. Mechanistically, we found circ -0,000,953 directly binds to Mir665-3p-Atg4b to perform its function. Silencing of Mir665-3p or overexpression of Atg4b recovered podocyte autophagy both in vitro and in vivo. To examine the cause of circ -0,000,953 downregulation in DN, bioinformatics prediction found that circ -0,000,953 sequence has a high possibility of containing an m6A methylation site. Additionally, METTL3 was proved to regulate the expression and methylation level of circ -0,000,953 through YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). In conclusion, this study revealed that circ -0,000,953 regulates podocyte autophagy by targeting Mir665-3p-Atg4b in DN. Therefore, circ -0,000,953 is a potential biomarker for prevention and cure of DN.Abbreviation: CCL2/MCP-1: C-C motif chemokine ligand 2; ceRNA: competing endogenous RNA; circRNA: circular RNA; cKI: conditional knockin; cKO: conditional knockout; CRE: creatinine; DM: diabetes mellitus; DN: diabetic nephropathy; ESRD: end-stage renal disease; HG: high glucose; IF: immunofluorescence; MAP1LC3/LC3B: microtubule-associated protein 1 light chain 3 beta; MPC5: mouse podocyte clone 5; MTECs: mouse tubular epithelial cells; MTOR: mechanistic target of rapamycin kinase; NC: normal control; ncRNA: non-coding RNA; NPHS1: nephrosis 1, nephrin; NPHS2: nephrosis 2, podocin; PAS: periodic acid-Schiff; RELA/p65: v-rel reticuloendotheliosis viral oncogene homolog A (avian); SDs: slit diaphragm proteins; Seq: sequencing; STZ: streptozotocin; SV40: SV40-MES13-cells, mouse mesangial cell line; T1D: type 1 diabetes mellitus; T2D: type 2 diabetes mellitus; TEM: transmission electron microscopy; TNF/TNF-α: tumor necrosis factor; VECs: vascular endothelial cells; WT1: WT1 transcription factor; YTHDF2: YTH N6-methyladenosine RNA binding protein 2.

[Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis
and Lung Adenocarcinoma].

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer. METHODS: Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases. RESULTS: A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts. CONCLUSIONS: This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.

Network pharmacology and molecular docking-based study on exploring the potential mechanism of Lycium barbarum L: In the treatment of atherosclerosis.

BACKGROUND: Goji berries (Lycium barbarum L) are herbal medicine that have a long history of use and multiple pharmacological activities. In this study, we investigated the potential therapeutic effects of Goji berries on atherosclerosis (AS) using network pharmacology and molecular docking. METHODS: The active compounds of Goji berries were identified using the Traditional Chinese Medicine Systems Pharmacology platform, as well as the literature and the targets of each active compound were obtained using the Swiss Target Prediction database. The AS-related targets were collected from the GeneCards and OMIM databases to obtain the common targets of Goji berries and AS. The drug-compound-target-disease network and protein-protein interaction network were constructed using the Cytoscape software to obtain the core target proteins of Goji berries related to AS. Gene ontology analysis of the core targets and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed by Metascape. The target-chemical correlations were verified using AutoDock molecular docking. RESULTS: After analysis, 44 active compounds within Goji berries were obtained that exhibit associations with AS. Among these, the proteins exhibiting the highest degrees of interaction within the compound-targeted protein protein-protein interaction network were AKT1, SRC, MAPK3, MAPK1, RELA, and STAT3. The gene ontology-biology process analysis showed that compound-targeted proteins were mainly involved in regulating small molecule metabolic process, cellular response to chemical stress, reactive oxygen species metabolic process, and regulation of inflammatory response. Kyoto encyclopedia of genes and genomes pathway mainly included lipid and AS in which AKT1, SRC, MAPK3, and MAPK1 were involved. Advanced glycation end-product-receptor for advanced glycation end-product signaling pathway in diabetic complications, Chagas disease, and pancreatic disease. Molecular docking assessment showed that fucosterol is bound to AKT1, MAPK3, and SRC. CONCLUSION: This study demonstrates that network pharmacology and molecular docking analyses contribute to a better understanding of Goji berries active compounds and targets as potential therapeutic drugs for treating AS.

Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway.

The aim of this study was to analyze the role of Ezrin in esophageal squamous cell carcinoma (ESCC) and investigate potential therapeutic targets for ESCC by interfering with Ezrin expression. Bioinformatics analysis revealed that Ezrin expression differed significantly among patients with different clinical stage ESCC. Moreover, there was a significant correlation between Ezrin and yes-associated protein/connective tissue growth factor (YAP1/CTGF) levels in esophageal cancer. Sixty paraffin-embedded ESCC tissue samples were examined and Ezrin and YAP1/CTGF levels were determined using immunohistochemistry. The positive expression rates of Ezrin and YAP1/CTGF were significantly lower in adjacent tissues than in ESCC tissues. Furthermore, knockdown of Ezrin expression inhibited colony formation and reduced cell migration and invasion. Compared with control ESCC cells, protein expression levels of YAP1 and CTGF were significantly downregulated in cells with Ezrin knocked down. We conclude that Ezrin may be involved in ESCC progression through the Hippo signaling pathway.

Pediatric population (aged 3-11 years) received primary inactivated SARS-CoV-2 vaccination prior to infection exhibiting robust humoral immune response following infected with Omicron variant: a study conducted in Beijing.

Objective: Analysis of SARS-CoV-2 IgG antibody and neutralizing antibody levels following SARS-CoV-2 infection in children aged 3-11 years, comparing those who had received the inactivated SARS-CoV-2 vaccine to those who were unvaccinated prior to infection, provides evidence for public health centers in formulating vaccination strategies and control policies. Methods: A study was conducted on children who visited the Children's Hospital, Capital Institute of Pediatrics from January 10, 2023 to March 31, 2023 (Beijing, China). Participants or their guardians completed a survey questionnaire providing information about their SARS-CoV-2 infection history and vaccination status. Serum samples were collected for testing of SARS-CoV-2 immunoglobulin G (IgG) and neutralizing antibodies (Nabs), which were performed using chemiluminescence immunoassay. Results: The study included 1,504 children aged 3-11 years with previous SARS-CoV-2 infection history. Among the 333 unvaccinated children, the serum SARS-CoV-2 IgG antibody level was median 2.30 (IQR, 1.27-3.99). However, children received one dose (78 cases) and two doses (1093 cases) of the inactivated vaccine prior to infection showed significantly higher SARS-CoV-2 IgG antibody levels, with values of median 10.11 (IQR, 8.66-10.93) and median 10.58 (IQR, 9.79-11.07), respectively. As to the unvaccinated children, 70.3% (234/333) were negative for SARS-CoV-2 Nabs, which were less than 6.00AU/ml. The remaining 29.7% (99/333) showed relatively low levels of Nabs, ranging from 6.00 to 50.00AU/ml. In contrast, for children who had received two doses of vaccine prior to infection, an overwhelming 99.3% (1086/1093) exhibited high levels of Nas in the range of 100.00-120.00 AU/ml. Remarkably, these elevated Nab levels persisted for at least a period of 3 months post-infection in children who had received two doses of inactivated SARS-CoV-2 vaccine prior to infection, regardless of age or sex and vaccine manufacturer. Conclusion: The administration of two doses of inactivated SARS-CoV-2 vaccine prior to infection has been shown to significantly enhance humoral immunity following SARS-CoV-2 infection in pediatric populations, producing adequate Nabs that persist at elevated levels for up to 3 months post-infection. For unvaccinated children who displayed weak humoral immunity following a primary natural infection, timely vaccination is recommended to bolster their immunization protection. The findings underscore the importance of vaccination in strengthening immune responses and protecting pediatric populations against SARS-CoV-2 infection.

A retrospective study of dynamic navigation system-assisted implant placement.

BACKGROUND: To evaluate the accuracy of implant placement assisted by a dynamic navigation system, as well as its influencing factors and learning curve. METHODS: At Macao We Care Dental Center, 55 cases of implant placement using dynamic navigation were retrospectively evaluated. To evaluate their accuracy, the apex, tip, and angle deviations of preoperatively planned and postoperatively placed implants were measured. The effects of the upper and lower jaws, different sites or lateral locations of dental implants, and the length and diameter of the implants on accuracy were analyzed, as well as the variation in accuracy with the increase in the number of surgical procedures performed by dentists. RESULTS: The implant had an apex deviation of 1.60 ± 0.94 mm, a tip deviation of 1.83 ± 1.03 mm, and an angle deviation of 3.80 ± 2.09 mm. Statistical differences were observed in the tip deviation of implants at different positions based on three factors: jaw position, lateral location, and tooth position (P < 0.05). The tip deviation of the anterior teeth area was significantly greater than those of the premolar and molar areas. There were no statistically significant differences in apex deviation, tip deviation, or angle deviation between the implants of different diameters and lengths (P > 0.05). There were significant differences in the angle deviation between the final 27 implants and the first 28 implants. Learning curve analysis revealed that angle deviation was negatively correlated with the number of surgical procedures, whereas the regression of apex deviation and tip deviation did not differ statistically. CONCLUSIONS: The accuracy of dynamic navigation-assisted dental implants meets the clinical needs and is higher than that of traditional implants. Different jaw positions, lateral locations, and implant diameters and lengths had no effect on the accuracy of the dental implants guided by the dynamic navigation system. The anterior teeth area had a larger tip deviation than the posterior teeth area did. As the number of dynamic implantation procedures performed by the same implant doctor increased, the angle deviation gradually decreased.

Calculated plasma volume status is associated with poor outcomes in acute ischemic stroke treated with endovascular treatment.

Background and purpose: The impact of calculated plasma volume status (PVS) on the prognosis of acute ischemic stroke treated with endovascular treatment (EVT) remains undetermined. This study aimed to investigate the association between PVS and 90 days functional outcomes after EVT. Methods: We enrolled patients treated with EVT in the anterior circulation from a prospective registry. The endpoint was a modified Rankin scale score of ≥3 points at 90 days after EVT. We used multivariable logistic regression models to investigate the association between PVS and poor outcomes. We used the restricted cubic spline to present the linearity between PVS and poor outcomes. Results: Among the 187 enrolled patients (median age, 65 years; 35.8% women), a total of 81 patients (43.3%) experienced poor outcomes at 90 days. In multivariable analyses, PVS was associated with poor outcomes despite increasing confounding factors (odds ratio, 3.157; 95% confidence interval, 1.942-5.534; P < 0.001). The restricted cubic spline revealed a positive correlation between PVS and the risk of poor outcomes after EVT (P for nonlinearity = 0.021). Conclusion: Our study found that an elevated PVS value was associated with poor outcomes after EVT. Further prospective cohorts were warranted to evaluate the utility of PVS in AIS treated with EVT.

Association of tumor necrosis factor-α-308G/A polymorphism with the risk of obstructive sleep apnea: A meta-analysis of 14 case-control studies.

Although numerous studies have suggested the association between TNF-α-308G/A polymorphism and susceptibility to obstructive sleep apnea (OSA), the results remained controversial and ambiguous. We performed the present meta-analysis to derive a more precise estimation.The PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wanfang databases, and Weipu databases (until January 8, 2022) were accessed to retrieve relevant articles. Pooled odds ratios (ORs) with 95% confidence interval (95% CI) were calculated using the STATA statistical software.Totally, fourteen studies involving 2595 cases and 2579 controls were enrolled in this meta-analysis. Pooled results demonstrated significant association between TNF-α-308G/A polymorphism and OSA risk for the overall population(allele model:OR = 1.87 [1.47, 2.38] (n = 14), dominant model: OR = 1.88[1.48, 2.39] (n = 14), recessive model:OR = 2.83 [2.00, 4.00] (n = 11), homozygous model:OR = 3.30 [2.32, 4.68] (n = 11), and heterozygous model:OR = 1.67 [1.36, 2.06] (n = 14); P<0.001, respectively).Subgroup analysis showed that in both Caucasians and Asians, the A allele conferred increased risk to OSA compared to the G allele (Caucasians: OR = 1.40[1.03, 1.90] (n = 5), P = 0.033, Asians: OR = 2.30 [1.62, 3.26] (n = 9), P< 0.001). In subgroup analysis restricted to hospital-based individuals, significant association between TNF-α-308G/A polymorphism and OSA risk was identified under each genetic model. Whereas, in population-based individuals, increased risk of OSA were only found in homozygous model (OR = 2.19[1.23, 3.90] (n = 3), P = 0.008) and recessive model (OR = 1.77 [1.00, 3.13] (n = 3), P = 0.048). There was a substantial between-study heterogeneity (I2 = 69.10%) across studies which was explained by source of control participants (P = 0.036) by meta-regression. The results of leave-one-out meta-analysis and publication bias suggested the reliability and stability of our results.This meta-analysis suggested that TNF-α-308A allele may be a risk factor for the development of OSA. However, large scale,multi-center and well-designed case-control studies are needed in the future.

STING/ACSL4 axis-dependent ferroptosis and inflammation promote hypertension-associated chronic kidney disease.

Hypertension is a primary modifiable risk factor for cardiovascular diseases, which often induces renal end-organ damage and complicates chronic kidney disease (CKD). In the present study, histological analysis of human kidney samples revealed that hypertension induced mtDNA leakage and promoted the expression of stimulator of interferon genes (STING) in renal epithelial cells. We used angiotensin II (AngII)- and 2K1C-treated mouse kidneys to elucidate the underlying mechanisms. Abnormal renal mtDNA packing caused by AngII promoted STING-dependent production of inflammatory cytokines, macrophage infiltration, and a fibrogenic response. STING knockout significantly decreased nuclear factor-κB activation and immune cell infiltration, attenuating tubule atrophy and extracellular matrix accumulation in vivo and in vitro. These effects delayed CKD progression. Immunoprecipitation assays and liquid chromatography-tandem mass spectrometry showed that STING and ACSL4 were directly combined at the D53 and K412 amino acids of ACSL4. Furthermore, STING induced renal inflammatory response and fibrosis through ACSL4-dependent ferroptosis. Last, inhibition of ACSL4 using small interfering RNA, rosiglitazone, or Fer-1 downregulated AngII-induced mtDNA-STING-dependent renal inflammation. These results suggest that targeting the STING/ACSL4 axis might represent a potential strategy for treating hypertension-associated CKD.

Characteristics of injury mechanisms in children and differences between urban and rural areas in central China.

BACKGROUND: Some studies lack detailed analyses of the differences and characteristics of pediatric injury mechanisms between urban and rural areas. OBJECTIVE: We aim to understand the characteristics, trends, and mortality rates of injury mechanisms in children in urban and rural areas in central China. RESULTS: In a study involving 15,807 pediatric trauma patients, it was observed that boys constituted the majority (65.4%) and those aged ≤ 3 years were the most prevalent (28.62%). Falls (39.8%), burns (23.2%), and traffic accidents (21.1%) were identified as the top three injury mechanisms. The head (29.0%) and limbs (35.7%) were found to be the most susceptible to injury. Additionally, children between the ages of 1-3 years exhibited a higher likelihood of sustaining burn injuries compared to other age groups. The main causes of burn injury were hydrothermal burns (90.3%), flame burns (4.9%), chemical burns (3.5%), and electronic burns (1.3%). In urban areas, the major injury mechanisms were falls (40.9%), traffic accidents (22.4%), burns (20.9%), and poison (7.1%), whereas, in rural areas, they were falls (39.5%), burns (23.8%), traffic accidents (20.8%), and penetration (7.0%). Over the past decade, the overall incidences of pediatric trauma have been decreasing. In the past year, the number of injured children was the highest in July, and the overall mortality rate due to trauma was 0.8%. CONCLUSION: Our findings revealed that in different age groups, the injury mechanisms are different in urban and rural areas. Burns are the second leading cause of trauma in children. A decrease in pediatric trauma over the past 10 years indicates targeted measures and preventive intervention may effectively prevent pediatric trauma.

Novel discovery of schisandrin A regulating the interplay of autophagy and apoptosis in oligoasthenospermia by targeting SCF/c-kit and TRPV1 via biosensors.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10-15 g/L, and the quantitative limit reached 1.0 × 10-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.