Association between negative life events through mental health and non-suicidal self-injury with young adults: evidence for sex moderate correlation.

BACKGROUND: Non-suicidal self-injury (NSSI) has exhibited an increasing trend in recent years and is now globally recognized as a major public health problem among adolescents and young adults. Negative life events (NLEs) are positively associated with NSSI. We sought to explore (1) whether sex plays a role in the risk of NLEs leading to NSSI and (2) the role played by mental health (MH). METHODS: We adopted a multi-stage cluster sampling method to select college students across four grades from May to June 2022. Generalized linear models were used to evaluate the relationships between NLEs, sex, MH and NSSI, presented as incidence-rate ratios (RRs) with 95% confidence intervals (CIs). We examined the complex relationship between these variables using the PROCESS method for moderation analysis. RESULTS: Following the exclusion of data that did not meet the study requirements, data from 3,578 students (mean age: 20.53 [± 1.65] years) were included. Poisson regression results indicate that high-level NLEs (RR = 0.110, 95%CI: 0.047-0.173) are associated with increased NSSI. Furthermore, interaction effects were observed among sex, NLEs and NSSI. MH and sex moderated the relationship between NLEs and NSSI. CONCLUSION: Identifying risk factors for NSSI is also important when exploring the interaction between NLEs and MH given the potential for NSSI to significantly increase the risk of later psychopathological symptoms and substance abuse problems. In addition, the significance of sex differences in risk factors for NSSI should be determined. This study evaluated how the impact of NLEs on NSSI can be reduced among adolescents from multiple perspectives.

Applications of magnetic solid-phase extraction in the sample preparation of natural product analysis (2020-2023).

Sample preparation, including extraction, separation, and purification, is a vital process for natural product analysis. As an attractive sample pretreatment method, magnetic solid-phase extraction (MSPE) has gained plenty of attention, mainly due to its simpler operation, less consumption of organic solvents, and shorter processing time than traditional SPE. This updated review is devoted to summarizing the applications of MSPE based on different magnetic nanomaterials in the analysis of various natural products in complex matrixes, such as biological samples, plants, and Chinese herbal preparations in the past four years (2020-2023). The preparation and fabrication of different materials are briefly introduced. Furthermore, the extraction mechanism and interaction forces between adsorbent and analytes are elaborated, and the advantages and disadvantages of different adsorbents coupled with various analytical methods for MSPE of different natural products are summarized. Moreover, the future trends and opportunities for MSPE in the natural product analysis are discussed. It is expected that this work can provide updated information for future research on the applications of MSPE in such fields.

Acrolein-triggered atherosclerosis via AMPK/SIRT1-CLOCK/BMAL1 pathway and a protection from intermittent fasting.

Circadian clock plays a vital role in the pathological progression of cardiovascular disease (CVD). Our previous studies showed that acrolein, an environmental pollutant, promoted atherosclerosis by reducing CLOCK/BMAL1 and disturbing circadian rhythm. Whereas, intermittent fasting (IF), a diet pattern, was able to ameliorate acrolein-induced atherosclerosis. In vivo, mice were fed acrolein 3 mg/kg/day via drinking water and IF for 18h (0:00-18:00). We observed that IF decreased acrolein-accelerated the formation of aortic lesion in ApoE -/- mice. Up-regulation of NF-κB, IL-1ß and TNF-α levels were found in liver and heart tissue upon acrolein exposure, while was down-regulated by IF. Interestingly, IF treatment exhibited higher AMPK, p-AMPK and SIRT1and lower MAPK expression which was caused by acrolein. Besides, circadian genes Clock/ Bmal1 expression were suppressed and disturbed treated with acrolein, while were reversed by IF. Furthermore, consistent with that in vivo, short-term starvation as a fasting cell model in vitro could improve the disorders of CLOCK/BMAL1 and raised SIRT1 via regulating AMPK, as well as ROS-MAPK induced by acrolein. In conclusion, we demonstrated that IF repressed ROS-MAPK while activated AMPK to elevate the expression of circadian clock genes to ameliorate acrolein-induced atherogenesis, which shed a novel light to prevent cardiovascular diseases.

Clinical application of ERCP concurrent laparoscopic cholecystectomy in the treatment of cholecystolithiasis complicated with extrahepatic bile duct stones.

Objective: To compare the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP) combined with laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration and lithotomy (LCBDE) in the treatment of cholecystolithiasis combined with bile duct stones. Methods: From September 2018 to January 2022, 195 patients with cholecystolithiasis complicated with extrahepatic bile duct stones from Department of Department of General Surgery, Shanghai Jiading Central Hospital met the inclusion criteria, including 60 cases in the LC group and 86 cases in the LCBDE group. The general condition, operation success rate, complications and residual stone rate of the two groups were retrospectively analyzed. Results: In the simultaneous operation group, 58 patients successfully performed ERCP, and the indwelling rate of the abdominal drainage tube (41.7 % vs. 95.3 %) was significantly better than that in the LCBDE group. There was no significant difference in the conversion rate to open surgery, operation time, and intraoperative blood loss between the two groups. In the simultaneous surgery group, 4 patients (6.7 %) developed pancreatitis after ERCP, which was cured by conservative treatment. The pain score at 6 h after operation was significantly lower than that in the LCBDE group (3.9 ± 1.6 vs 6.5 ± 2.4). There were no significant differences in biliary leakage (1.7 % vs. 4.7 %), postoperative cholangitis (5.0 % vs. 5.8 %), incision infection (3.3 % vs. 3.5 %), and bile duct stone residue rate (5.0 % vs 3.5 %) between the two groups. There was no severe pancreatitis, second operation or death. The duration of hospital stay was shortened in the concurrent operation group (5.1 ± 2.3d vs 7.9 ± 3.7d), and the operation cost was significantly higher than that in the LCBDE group (48839.9 ± 8549.5 vs 34635.9 ± 5893.7 yuan). Conclusion: ERCP combined with LC and LCBDE are both safe and effective methods for the treatment of cholecystolithiasis combined with extrahepatic bile duct stones. The simultaneous operation group has certain advantages in patient comfort and rapid rehabilitation, which can be popularized in qualified units.

Unhealthy diets increase the likelihood of being overweight or obese among African migrant students in China, but not among African non-migrant students: a cross-sectional study.

Background: The impact of non-communicable diseases (NCDs) is disproportionately felt by immigrants from low- to medium-income countries (LMICs), partly due to their dietary habits. To thrive in their new environment, migrants either omit or consume certain food items, which could lead to nutritional deficits. As a result, most migrants experience more NCDs than their compatriots in their native countries. Therefore, we evaluated the difference in dietary habits, quality, and the influencing factors of overweight or obesity among African migrant students in Nanjing (China) and non-migrant students in Africa using cross-sectional data. Methods: The researchers used the food frequency questionnaire and the global diet quality score metrics to assess food intake and quality, respectively. Then, cross-tabulation was employed to explore the differences between the groups in meal skipping, eating habits, and diet quality. Finally, the factors associated with overweight or obesity were assessed with binary logistic regression stratified by African students in Nanjing and students in their native countries. Results: Approximately 678 responses were received, mainly between 18-25 years (46.7%) and 26-36 years (45.4 %). The majority of them (52.3%) were international students. The non-migrant African students' diets lacked citrus fruits (22.2%), deep orange fruits (15.4%), deep orange vegetables (18%), cruciferous vegetables (24.6%), and dark leafy vegetables (26.5%). While the African migrant students consumed more high-fat dairy (50.7%), processed meats (23.9%), sweets and ice creams (51.3%), sugar-sweetened beverages (40.5%), and juice (61.5%), p < 0.001. Furthermore, consuming late-night meals constantly [Exp (B) = 39.607, p = 0.049], eating twice a day [Exp (B) = 6.527, p = 0.036], consuming red meat [Exp (B) = 29.287, p = 0.001], processed meats [Exp (B) = 719.979, p = 0.0011], refined grains and baked foods [Exp (B) = 15.752, p = 0.013], and sweets and ice cream [Exp (B) = 193.633, p = 0.006] were factors inducing overweight or obesity among only African migrant students. Conclusion: Controlling the what (Western diet and nature of late-night meals) and the when of eating can drastically reduce their influence on obesogenic condition formation in African migrant students in China and elsewhere.

High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer.

BACKGROUND: Patatin like phospholipase domain containing 8 (PNPLA8) has been shown to play a significant role in various cancer entities. Previous studies have focused on its roles as an antioxidant and in lipid peroxidation. However, the role of PNPLA8 in colorectal cancer (CRC) progression is unclear. AIM: To explore the prognostic effects of PNPLA8 expression in CRC. METHODS: A retrospective cohort containing 751 consecutive CRC patients was enrolled. PNPLA8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive scores. CRC patients were divided into high and low PNPLA8 expression groups based on the cut-off values, which were calculated by X-tile software. The prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression analysis. The overall survival (OS) rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank test. RESULTS: PNPLA8 expression was significantly associated with distant metastases in our cohort (P = 0.048). CRC patients with high PNPLA8 expression indicated poor OS (median OS = 35.3, P = 0.005). CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter OS. For patients with left-sided colon and rectal cancer, the survival curves of two PNPLA8-expression groups showed statistically significant differences. Multivariate analysis also confirmed that high PNPLA8 expression was an independent prognostic factor for overall survival (hazard ratio HR = 1.328, 95%CI: 1.016-1.734, P = 0.038). CONCLUSION: PNPLA8 is a novel independent prognostic factor for CRC. These findings suggest that PNPLA8 is a potential target in clinical CRC management.

Novel T cell exhaustion gene signature to predict prognosis and immunotherapy response in thyroid carcinoma from integrated RNA-sequencing analysis.

Exhausted CD8+ T lymphocytes and tumor-associated macrophages play critical roles in determining cancer prognosis and the efficacy of immunotherapy. Our study revealed a negative correlation between exhausted CD8+ T lymphocytes and prognosis in thyroid carcinoma (THCA). Consensus clustering divided patients into two subgroups of exhaustion with different prognoses, as defined by marker genes of exhausted CD8+ T cells. Subsequently, we constructed an eight-gene prognostic signature, and developed a risk score named the exhaustion-related gene score (ERGS) to forecast both prognosis and immunotherapy response in THCA. Bulk RNA sequencing analysis revealed a higher prevalence of M2 macrophages, indicative of an immunosuppressive tumor microenvironment (TME), in the high-ERGS group. Single-cell RNA sequencing showed that SPP1+ macrophages and CD14+ monocytes infiltrations were positively associated with higher ERGS. Functionally, it was determined that SPP1+ macrophages exert an immunosuppressive role, while CD14+ monocytes were implicated in promoting tumor progression and angiogenesis. Analysis of cell-cell interactions between SPP1+ macrophages and T cells highlighted the activation of the SPP1-CD44 and MIF-CD74 axes, both of which could foster an immunosuppressive TME. Therapeutic strategies that target SPP1+ macrophages, CD14+ monocytes, and the SPP1-CD44 and MIF-CD74 axes may potentially improve the prognosis and amplify the immunotherapy response in THCA patients.

Detection of Arsenic(V) by Fluorescence Sensing Based on Chlorin e6-Copper Ion.

The high toxicity of arsenic (As) can cause irreversible harm to the environment and human health. In this study, the chlorin e6 (Ce6), which emits fluorescence in the infrared region, was introduced as the luminescence center, and the addition of copper ion (Cu2+) and As(V) provoked a regular change in fluorescence at 652 nm, whereas that of As(III) was 665 nm, which was used to optionally detect Cu2+, arsenic (As(III), and As(V)). The limit of detection (LOD) values were 0.212 µM, 0.089 ppm, and 1.375 ppb for Cu2+, As(III), and As(V), respectively. The developed method can be used to determine Cu2+ and arsenic in water and soil with good sensitivity and selectivity. The 1:1 stoichiometry of Ce6 with Cu2+ was obtained from the Job plot that was developed from UV-visible spectra. The binding constants for Cu2+ and As(V) were established to be 1.248 × 105 M-1 and 2.35 × 1012 M-2, respectively, using B-H (Benesi-Hildebrand) plots. Fluorescence lifetimes, B-H plots, FT-IR, and 1H-NMR were used to postulate the mechanism of Cu2+ fluorescence quenching and As(V) fluorescence restoration and the interactions of the two ions with the Ce6 molecule.

Iris Cerclage To Treat Persistent Mydriasis Following Acute Angle Closure Glaucoma Improves Visual Quality.

PRCIS: We developed a modified iris cerclage technique that improves best corrected visual acuity, pupillary parameters, self-assessed photophobia, and visual function index-14 questionnaire scores in patients with acute primary angle closure and permanent mydriasis after cataract surgery. PURPOSE: To evaluate the efficacy of a modified iris cerclage technique in patients with acute primary angle closure (PAC) and permanent mydriasis after cataract surgery. PATIENTS AND METHODS: 12 eyes of 12 patients with acute PAC and permanent mydriasis at more than 3 months after phacoemulsification combined with intraocular lens (IOL) implantation underwent modified iris cerclage. Best corrected visual acuity (BCVA), intraocular pressure (IOP), pupil diameter, and visual function index-14 (VF-14) questionnaire and self-assessed photophobia scores before surgery and at 1 week, 1 month, and 3 months postoperatively were compared. Further, the postoperative pupil position and morphology and complications were evaluated. RESULTS: BCVA improved from 0.48±0.23 preoperatively to 0.28±0.15, 0.27±0.15, and 0.26±0.14 at 1 week, 1 month, and 3 months postoperatively, respectively (P=0.008). No significant difference was observed between the preoperative and postoperative IOP (P=0.974). Pupil diameter improved from 6.34±0.51 mm preoperatively to 3.59±0.33, 3.59±0.34, and 3.58±0.32 mm at 1 week, 1 month, and 3 months postoperatively, respectively (P<0.001). Self-assessed photophobia scores improved from 3.33±0.78 preoperatively to 0.83±0.72, 0.51±0.15, and 0.45±0.14 at 1 week, 1 month, and 3 months postoperatively, respectively (P<0.001). VF-14 scores improved from 47.6±6.1 points preoperatively to 67.9±6.2, 72.1±6.1, and 73.5±6.0 points at 1 week, 1 month, and 3 months postoperatively, respectively (P<0.001). Postoperatively, all pupils were centered and round. No postoperative complications, such as iris-suture slippage, iridodialysis, or exposure of the IOL's optical zone edge, were observed. CONCLUSION: Modified iris cerclage creates a centered, precisely sized, round pupil. It improves visual quality in patients with acute PAC and permanent mydriasis after cataract surgery.

Diagnostic prediction of gastrointestinal graft-versus-host disease based on a clinical- CT- signs nomogram model.

OBJECTIVE: Gastrointestinal graft-versus-host disease (GI-GVHD) is one of the complications that can easily occur after hematopoietic stem cell transplantation (HSCT). Timely diagnosis and treatment are pivotal factors that greatly influence the prognosis of patients. However, the current diagnostic method lacks adequate non-invasive diagnostic tools. METHODS: A total of 190 patients who suspected GI-GVHD were retrospectively included and divided into training set (n = 114) and testing set (n = 76) according to their discharge time. Least absolute shrinkage and selection operator (LASSO) regression was used to screen for clinically independent predictors. Based on the logistic regression results, both computed tomography (CT) signs and clinically independent predictors were integrated in order to build the nomogram, while the testing set was verified independently. The receiver operating characteristic (ROC), area under the curve (AUC), decision curve, and clinical impact curve were used to measure the accuracy of prediction, clinical net benefit, and consistency of diagnostic factors. RESULTS: Four key factors, including II-IV acute graft-versus-host disease (aGVHD), the circular target sign, multifocal intestinal inflammation, and an increased in total bilirubin, were identified. The combined model, which was constructed from CT signs and clinical factors, showed higher predictive performances. The AUC, sensitivity, and specificity of the training set were 0.867, 0.787, and 0.811, respectively. Decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) showed that the developed model exhibited a better prediction accuracy than the others. CONCLUSIONS: This combined model facilitates timely diagnosis and treatment and subsequently improves survival and overall outcomes in patients with GI-GVHD. CRITICAL RELEVANCE STATEMENT: GI-GVHD is one of the complications that can easily occur after HSCT. However, the current diagnostic approach lacks adequate non-invasive diagnostic methods. This non-invasive combined model facilitates timely treatment and subsequently improves patients with GI-GVHD survival and overall outcomes. KEY POINTS: • There is currently lacking of non-invasive diagnostic methods for GI-GVHD. • Four clinical CT signs are the independent predictors for GI-GVHD. • Association between the CT signs with clinical factors may improve the diagnostic performance of GI-GVHD.

Narrative review of magnetic resonance imaging in quantifying liver iron load.

Objective: To summarize the research progress of magnetic resonance imaging (MRI) in quantifying liver iron load. Methods: To summarize the current status and progress of MRI technology in the quantitative study of liver iron load through reviewing the relevant literature at home and abroad. Results: Different MRI sequence examination techniques have formed a series of non-invasive methods for the examination of liver iron load. These techniques have important clinical significance in the imaging diagnosis of liver iron load. So far, the main MRI methods used to assess liver iron load are: signal intensity measurement method (signal intensity, SI) [signal intensity ratio (SIR) and difference in in-phase and out-of-phase signal intensity], T2/R2 measurement (such as FerriScan technique), ultra-short echo time (UTE) imaging technique, and susceptibility weighted imaging (including conventional susceptibility weighted imaging) (SWI), quantitative susceptibility mapping (QSM), T2*/R2* measurement, Dixon and its derivative techniques. Conclusion: MRI has become the first choice for the non-invasive examination of liver iron overload, and it is helpful to improve the early detection of liver injury, liver fibrosis, liver cirrhosis and liver cancer caused by liver iron overload.

Focused ultrasound versus the loop electrosurgical excision procedure to treat women with cervical high-grade squamous intraepithelial lesions under 40: a retrospective study.

BACKGROUND: This study aimed to compare the efficacy of focused ultrasound (FUS) and the loop electrosurgical excision procedure (LEEP) for the treatment of cervical high-grade squamous intraepithelial lesions (HSILs) among women of reproductive age. METHODS: Case records of patients aged < 40 years who were treated for cervical HSILs using either FUS or LEEP from September 1, 2020 to May 31, 2022 were retrospectively reviewed. Patients were followed up for cure, recurrence, human papillomavirus (HPV) clearance, and complications within 1 year of treatment. Odds ratios and 95% confidence intervals were determined using univariate and multivariate logistic regression models to analyze the association between disease evidence or HPV clearance and treatment modalities or other covariates. RESULTS: Of the 1,054 women who underwent FUS or LEEP, 225 met our selection criteria. Among the selected women, 101 and 124 received FUS and LEEP, respectively. There was no significant difference between the FUS and LEEP groups in the cure rate during the 3-6 months of follow-up (89.11% vs. 94.35%, P = 0.085) and recurrence rate during the 6-12 months follow-up (2.22% vs. 1.71%, P = 0.790). Both groups exhibited enhanced cumulative HPV clearance rates; however, the rates were not significantly different between the FUS and LEEP groups (74.23% vs. 82.79%, P = 0.122 during the 3-6 months follow-up; 84.95% vs. 89.17%, P = 0.359 during the 6-12 months follow-up). Furthermore, the incidence of complications caused by the FUS and LEEP techniques was comparable (5.0% vs. 5.6%, P = 0.818). CONCLUSIONS: We found that FUS and LEEP have similar efficacy, safety, and reliability in treating women (aged < 40 years) with HSILs.

Study on the Expression and Potential Function of LncRNA in Peripheral Blood of Patients with Ankylosing Spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease that has the characteristics of difficult early diagnosis and a high disability rate. OBJECTIVE: The objective of this study was to further explore the possible mechanism and potential function of lncRNA in AS. METHODS: We used lncRNA microarray technology to detect the expression of lncRNA and mRNA in patients with active AS, stable patients, and healthy controls (HC). Afterward, bioinformatics analysis was conducted on differentially expressed genes. Seven differentially expressed lncRNAs were screened out for real-time fluorescent quantitative PCR (RT-qPCR), combined with various clinical indicators for correlation analysis, and the receiver operating characteristic (ROC) curve was used to analyze the potential of lncRNA as a diagnostic marker for AS. RESULTS: The results showed that the expression levels of NR-037662 and ENST00000599316 in the AS subgroups were significantly higher than those in the HC group, while the expression levels of ENST00000577914 and ENST00000579003 were lower than those in the HC group. The expression levels of NR-003542 and ENST00000512051 in the ASA group were significantly higher than those in the ASS and HC groups, while NR-026756 was just the opposite. Spearman's correlation analysis showed that the expression level of NR-003542 was positively correlated with Bath Ankylosing Spondylitis Functional Index (BASFI), Erythrocyte Sedimentation Rate (ESR), and high sensitivity C-Reactive Protein (hsCRP). The expression level of NR-026756 was negatively correlated with the Bath Ankylosing Spine Inflammatory Disease Activity Index (BASDAI), BASFI, ESR, hsCRP, and globulin (GLOB). In addition, it was also found that the ROC curve analysis of the 4 lncRNAs between the AS group (ASA group and ASS group) and the HC group were statistically significant, and the area under the curve (AUC) of NR-037662, ENST00000599316, ENST00000577914, and ENST00000579003 was 0.804, 0.812, 0.706, and 0.698, respectively. CONCLUSION: It was found that these differentially expressed lncRNAs of AS may be involved in the occurrence and development of the disease. Among them, NR-037662, ENST00000599316, ENST00000577914, and ENST00000579003 might have the potential to become AS diagnostic molecular markers. Moreover, NR -003542, ENST00000512051, and NR-026756 might have the potential to be indicators of disease activity.

Particle-attached bacteria act as gatekeepers in the decomposition of complex phytoplankton polysaccharides.

BACKGROUND: Marine microalgae (phytoplankton) mediate almost half of the worldwide photosynthetic carbon dioxide fixation and therefore play a pivotal role in global carbon cycling, most prominently during massive phytoplankton blooms. Phytoplankton biomass consists of considerable proportions of polysaccharides, substantial parts of which are rapidly remineralized by heterotrophic bacteria. We analyzed the diversity, activity, and functional potential of such polysaccharide-degrading bacteria in different size fractions during a diverse spring phytoplankton bloom at Helgoland Roads (southern North Sea) at high temporal resolution using microscopic, physicochemical, biodiversity, metagenome, and metaproteome analyses. RESULTS: Prominent active 0.2-3 µm free-living clades comprised Aurantivirga, "Formosa", Cd. Prosiliicoccus, NS4, NS5, Amylibacter, Planktomarina, SAR11 Ia, SAR92, and SAR86, whereas BD1-7, Stappiaceae, Nitrincolaceae, Methylophagaceae, Sulfitobacter, NS9, Polaribacter, Lentimonas, CL500-3, Algibacter, and Glaciecola dominated 3-10 µm and > 10 µm particles. Particle-attached bacteria were more diverse and exhibited more dynamic adaptive shifts over time in terms of taxonomic composition and repertoires of encoded polysaccharide-targeting enzymes. In total, 305 species-level metagenome-assembled genomes were obtained, including 152 particle-attached bacteria, 100 of which were novel for the sampling site with 76 representing new species. Compared to free-living bacteria, they featured on average larger metagenome-assembled genomes with higher proportions of polysaccharide utilization loci. The latter were predicted to target a broader spectrum of polysaccharide substrates, ranging from readily soluble, simple structured storage polysaccharides (e.g., laminarin, α-glucans) to less soluble, complex structural, or secreted polysaccharides (e.g., xylans, cellulose, pectins). In particular, the potential to target poorly soluble or complex polysaccharides was more widespread among abundant and active particle-attached bacteria. CONCLUSIONS: Particle-attached bacteria represented only 1% of all bloom-associated bacteria, yet our data suggest that many abundant active clades played a pivotal gatekeeping role in the solubilization and subsequent degradation of numerous important classes of algal glycans. The high diversity of polysaccharide niches among the most active particle-attached clades therefore is a determining factor for the proportion of algal polysaccharides that can be rapidly remineralized during generally short-lived phytoplankton bloom events. Video Abstract.

Targeting C21orf58 is a Novel Treatment Strategy of Hepatocellular Carcinoma by Disrupting the Formation of JAK2/C21orf58/STAT3 Complex.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Functionally uncharacterized genes are an attractive repository to explore candidate oncogenes. It is demonstrated that C21orf58 displays an oncogenic role in promoting cell growth, tumorigenesis and sorafenib resistance of HCC cells by abnormal activation of STAT3 signaling. Mechanistically, a novel manner to regulate STAT3 signaling that adaptor C21orf58 forms a ternary complex is reveal with N-terminal domain of STAT3 and SH2 domain of JAK2, by which C21orf58 overactivates wild-type STAT3 by facilitating its phosphorylation mediated by JAK2, and hyper-activates of constitutively mutated STAT3 due to preferred binding with C21orf58 and JAK2. Moreover, it is validated that inhibition of C21orf58 with drug alminoprofen, selected by virtual screening, could effectively repress the viability and tumorigenesis of HCC cells. Therefore, it is identified that C21orf58 functions as an oncogenic adaptor, reveal a novel regulatory mechanism of JAK2/STAT3 signaling, explain the cause of abnormal activity of activated mutants of STAT3, and explore the attractive therapeutic potential by targeting C21orf58 in HCC.

Optimal timing for awake prone positioning in Covid-19 patients: Insights from an observational study from two centers.

BACKGROUND: The widespread application and interest in awake prone positioning stems from its ease and availability and its ability to enhance patients' oxygenation. Nevertheless, due to the absence of consensus over the regimen of awake prone positioning, the efficacy of awake prone positioning remains uncertain. OBJECTIVE: To explore the optimal regimen for awake prone positioning, including the timing of initiation, ideal daily duration, and strategies for improving patient comfort and encouraging adherence. DESIGN: Retrospective observational study. SETTING(S): Two university-affiliated hospitals in Shanghai. PARTICIPANTS: Between December 2022 and February 2023, a total of 475 patients with COVID-19-related pneumonia who received awake prone positioning were observed. METHODS: The data were collected from the hospital's electronic medical record system. The differentiation efficiency of peripheral blood oxygen saturation [SpO2]:fractional oxygen concentration in inspired air [FiO2] ratio at first awake prone positioning for different outcomes was tested by the area under the receiver operating characteristic curve. The Cox proportional hazard regression model was used to analyze the relationship between time to occurrence of 28-day outcomes and collected variables. Kaplan-Meier curves were plotted with the percentage of 28-day outcomes according to the SpO2:FiO2 ratio at first awake prone positioning after controlling covariates through Cox regression. RESULTS: The best efficiency in predicting patient outcomes was achieved when the cutoff SpO2:FiO2 ratio at first awake prone positioning was 200. Patients with a reduced SpO2:FiO2 ratio (≤200) experienced more adverse respiratory outcomes (RR = 5.42, 95%CI [3.35, 8.76], p < 0·001) and higher mortality (RR = 16.64, 95%CI [5.53, 50.13], p < 0.001). Patients with a SpO2:FiO2 ratio of ≥200 at first awake prone positioning, longer duration between first awake prone positioning and admission, more awake prone positioning days, and better awake prone positioning completion were significantly protected from 28-day adverse respiratory outcomes and mortality. CONCLUSIONS: Initiating awake prone positioning with a SpO2:FiO2 ratio exceeding 200, increasing the number of awake prone positioning days, prolonging the time between first awake prone positioning and admission, and achieving better completion of awake prone positioning were found to be significantly associated with reduced adverse respiratory outcomes and mortality. REGISTRATION: ClinicalTrials.gov; No.: NCT05795751; URL: www. CLINICALTRIALS: gov.

Liver indicators affecting the relationship between BMI and hypertension in type 2 diabetes: a mediation analysis.

BACKGROUND: Body mass index (BMI) is an important risk factor for hypertension in diabetic patients. However, the underlying mechanisms remain poorly understood. Although liver-derived biological intermediates may play irreplaceable roles in the pathophysiology of diabetes, few studies have explored them in the association between BMI and hypertension in diabetes. OBJECTIVE: To investigate the role of liver enzymes in mediating the relationship between BIM exposure and hypertension in type 2 diabetes mellitus (T2DM). METHODS: We included a total of 1765 participants from the China National Diabetic Chronic Complications Study Cohort. Associations between liver enzymes and hypertension were estimated using multivariable regression models. The function of liver indicators in the relationship between BMI and hypertension was assessed using mediation analysis. Mediation analysis was conducted, taking into account age, diabetes duration, current smoking, fasting plasma glucose level, glycated hemoglobin, anti-diabetic therapy, and family history of diseases, including diabetes, hypertension, obesity, and hyperlipidemia. RESULTS: For men, the association of BMI with hypertension was partially mediated by alanine aminotransferase (ALT), with a proportion of mediation was 68.67%, by aspartate aminotransferase (AST) was 27.02%, and by γ-glutamyltransferase (GGT) was 38.58%, by AST/ALT was 63.35%; for women, the proportion mediated by ALT was 36.93%, and by AST was 37.47%, and GGT was 44.60%, and AST/ALT was 43.73% for BMI (all P < 0.05). CONCLUSION: The effect of BMI on hypertension is partly mediated by liver indicators (ALT, AST, GGT, and AST/ALT) in diabetic patients. Our results may provide opportunities to identify new targets for hypertension interventions.

Cross-reaction mediated by distinct key amino acid combinations in the complementary-determining region (CDR) of a monoclonal antibody.

In immunology, cross-reaction between antigens and antibodies are commonly observed. Prior research has shown that various monoclonal antibodies (mAbs) can recognize a broad spectrum of epitopes related to influenza viruses. However, existing theories on cross-reactions fall short in explaining the phenomena observed. This study explored the interaction characteristics of H1-74 mAb with three peptides: two natural peptides, LVLWGIHHP and LPFQNI, derived from the hemagglutinin (HA) antigen of the H1N1 influenza virus, and one synthetic peptide, WPFQNY. Our findings indicate that the complementarity-determining region (CDR) of H1-74 mAb comprised five antigen-binding sites, containing eight key amino acid residues from the light chain variable region and 16 from the heavy chain variable region. These critical residues formed distinct hydrophobic or hydrophilic clusters and functional groups within the binding sites, facilitating interaction with antigen epitopes through hydrogen bonding, salt bridge formation, and π-π stacking. The study revealed that the formation of the antibody molecule led to the creation of binding groups and small units in the CDR, allowing the antibody to attach to a variety of antigen epitopes through diverse combinations of these small units and functional groups. This unique ability of the antibody to bind with antigen epitopes provides a new molecular basis for explaining the phenomenon of antibody cross-reaction.

Two new sesquiterpene glycosides from the stems of Dendrobium henanense and their anti-inflammatory activity.

Two new sesquiterpene glycosides, 8α,12,15ß-trihydroxycopacamphan-15-O-ß-D-glucopyranoside (1) and dendrobiumane C-11-O-ß-D-glucopyranoside (2), along with three known terpenoids (3-5) were isolated from the aerial stems of Dendrobium henanense. Their structures were elucidated based on NMR-spectroscopic and HR-MS analyses. All compounds could reduce the levels of NO, TNF-α and IL-1ß in LPS-induced RAW264.7 cells with IC50 values ranging from 10.37 to 34.55 µΜ.