Ginsenoside Rg1 ameliorates stress-exacerbated Parkinson's disease in mice by eliminating RTP801 and α-synuclein autophagic degradation obstacle.

Emerging evidence shows that psychological stress promotes the progression of Parkinson's disease (PD) and the onset of dyskinesia in non-PD individuals, highlighting a potential avenue for therapeutic intervention. We previously reported that chronic restraint-induced psychological stress precipitated the onset of parkinsonism in 10-month-old transgenic mice expressing mutant human α-synuclein (αSyn) (hαSyn A53T). We refer to these as chronic stress-genetic susceptibility (CSGS) PD model mice. In this study we investigated whether ginsenoside Rg1, a principal compound in ginseng notable for soothing the mind, could alleviate PD deterioration induced by psychological stress. Ten-month-old transgenic hαSyn A53T mice were subjected to 4 weeks' restraint stress to simulate chronic stress conditions that worsen PD, meanwhile the mice were treated with Rg1 (40 mg· kg-1 ·d-1, i.g.), and followed by functional magnetic resonance imaging (fMRI) and a variety of neurobehavioral tests. We showed that treatment with Rg1 significantly alleviated both motor and non-motor symptoms associated with PD. Functional MRI revealed that Rg1 treatment enhanced connectivity between brain regions implicated in PD, and in vivo multi-channel electrophysiological assay showed improvements in dyskinesia-related electrical activity. In addition, Rg1 treatment significantly attenuated the degeneration of dopaminergic neurons and reduced the pathological aggregation of αSyn in the striatum and SNc. We revealed that Rg1 treatment selectively reduced the level of the stress-sensitive protein RTP801 in SNc under chronic stress conditions, without impacting the acute stress response. HPLC-MS/MS analysis coupled with site-directed mutation showed that Rg1 promoted the ubiquitination and subsequent degradation of RTP801 at residues K188 and K218, a process mediated by the Parkin RING2 domain. Utilizing αSyn A53T+; RTP801-/- mice, we confirmed the critical role of RTP801 in stress-aggravated PD and its necessity for Rg1's protective effects. Moreover, Rg1 alleviated obstacles in αSyn autophagic degradation by ameliorating the RTP801-TXNIP-mediated deficiency of ATP13A2. Collectively, our results suggest that ginsenoside Rg1 holds promise as a therapeutic choice for treating PD-sensitive individuals who especially experience high levels of stress and self-imposed expectations.

A novel super-enhancer-related risk model for predicting prognosis and guiding personalized treatment in hepatocellular carcinoma.

BACKGROUND: Our research endeavored to develop a robust predictive signature grounded in super-enhancer-related genes (SERGs), with the dual objectives of forecasting survival outcomes and evaluating the tumor immune microenvironment (TiME) in hepatocellular carcinoma (HCC). METHODS: HCC RNA-sequencing data were retrieved from The Cancer Genome Atlas (TCGA), and 365 patients were randomly assigned to training or testing sets in 1:1 ratio. SERGs of HCC were downloaded from Super-Enhancer Database (SEdb). On the basis of training set, a SERGs signature was identified, and its prognostic value was confirmed by internal and external validation (GSE14520) sets. We subsequently examined the model for potential functional enrichment and the degree of tumor immune infiltration. Additionally, we carried out in vitro experiments to delve into the biological functions of CBX2 gene. RESULTS: An SE-related prognostic model including CBX2, TPX2, EFNA3, DNASE1L3 and SOCS2 was established and validated. According to this risk model, patients in the high-risk group had a significantly worse prognosis, and their immune cell infiltration was significantly different from that of low-risk group. Moreover, the high-risk group exhibited a significant enrichment of tumor-associated pathological pathways. The SERGs signature can generally be utilized to screen HCC patients who are likely to respond to immunotherapy, as there is a positive correlation between the risk score and the Tumor Immune Dysfunction and Exclusion (TIDE) score. Furthermore, the downregulation of the CBX2 gene expression was found to inhibit HCC cell viability, migration, and cell cycle progression, while simultaneously promoting apoptosis. CONCLUSIONS: We developed a novel HCC prognostic model utilizing SERGs, indicating that patients with high-risk score not only face a poorer prognosis but also may exhibit a diminished therapeutic response to immune checkpoint inhibitors (ICIs). This model is designed to tailor personalized treatment strategies to the individual needs of each patient, thereby improving the overall clinical outcomes for HCC patients. Furthermore, CBX2 is a promising candidate for therapeutic intervention in HCC.

Genetic Variability and Evolutionary Dynamics of Papaya Ringspot Virus and Papaya Leaf Distortion Mosaic Virus Infecting Feral Papaya in Hainan Island.

The commercialized genetically modified (GM) papaya cultivars have protected papaya from the devastating disease caused by papaya ringspot virus (PRSV). However, papaya leaf distortion mosaic virus (PLDMV), which causes similar infection symptoms but is serologically distinct from PRSV, was found as a competitive threat to the papaya industry. Our study surveyed the occurrence of PRSV and PLDMV as well as the transgenic markers of the 35S promoter from cauliflower mosaic virus (CaMV 35S) and the neomycin phosphotransferase II (NPT II) gene in feral papaya plants, which were found frequently growing outside of cultivated papaya fields on Hainan Island. In total, 123 feral papayas, comprising 62 (50.4%) GM plants and 61 (49.6%) non-GM ones, were sampled. Among them, 23 (18.7%) were positive for PRSV, 49 (39.8%) were positive for PLDMV, including 5 plants co-infected by PRSV and PLDMV, and 56 (45.5%) plants were free of either virus. In traditional papaya growing regions, we detected fewer PRSV-infected plants (2 in 33, 6%) than in other regions (21 in 90, 23%). But overall, whether transgenic or not made no significance in PRSV incidence (P=0.230), with 9 PRSV-infected plants among 62 GM papayas and 14 among 61 non-GM papayas. Phylogenetic and genetic differentiation analysis showed a clear correlation between PRSV and PLDMV populations and their geographical origins. Negative selection was estimated for the selected gene regions of both viruses. Notably, PLDMV has deviated from neutral evolution and experienced population expansion, exhibiting increased genetic diversity and is becoming the predominant threat to papaya in Hainan.

Immune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function.

Histone H3-mutant gliomas are deadly brain tumors characterized by a dysregulated epigenome and stalled differentiation. In contrast to the extensive datasets available on tumor cells, limited information exists on their tumor microenvironment (TME), particularly the immune infiltrate. Here, we characterize the immune TME of H3.3K27M and G34R/V-mutant gliomas, and multiple H3.3K27M mouse models, using transcriptomic, proteomic and spatial single-cell approaches. Resolution of immune lineages indicates high infiltration of H3-mutant gliomas with diverse myeloid populations, high-level expression of immune checkpoint markers, and scarce lymphoid cells, findings uniformly reproduced in all H3.3K27M mouse models tested. We show these myeloid populations communicate with H3-mutant cells, mediating immunosuppression and sustaining tumor formation and maintenance. Dual inhibition of myeloid cells and immune checkpoint pathways show significant therapeutic benefits in pre-clinical syngeneic mouse models. Our findings provide a valuable characterization of the TME of oncohistone-mutant gliomas, and insight into the means for modulating the myeloid infiltrate for the benefit of patients.

Integrated Carbon Layer and CoNiP Cocatalyst on SnWO4 Film for Enhanced Photoelectrochemical Water Splitting.

α-SnWO4 is a promising semiconductor for solar water splitting, however, its performance is limited by weak water oxidation and poor charge transfer. In this study, we employ a vapor deposition method to uniformly implement a carbon layer onto the surface of SnWO4 coupled with a CoNiP cocatalyst, successfully constructing the integrated CoNiP/C/SnWO4 film photoanode and alleviating the oxidation of Sn2+ when loading electrocatalyst. Incorporating the carbon layer enhances the interface charge conduction behavior between the SnWO4 substrate and the CoNiP cocatalyst, thereby mitigating charge recombination. The synergistic interplay between the carbon layer and CoNiP leads to a remarkable achievement, as evidenced by the photocurrent of 1.72 mA cm-2 (1.23 V vs. RHE) observed for SnWO4 film measured in 0.2 M potassium phosphate buffer solution. In this work, we demonstrate the viability of tailoring SnWO4 photoanode and provide valuable insights for prospective advancements in modifying SnWO4 photoanode.

Risk Factors for Non-Alcoholic Fatty Liver Disease in Patients with Bipolar Disorder: A Cross-Sectional Retrospective Study.

Purpose: The co-morbidity of non-alcoholic fatty liver disease (NAFLD) in patients with bipolar disorder (BD) has a negative impact on patient treatment and prognosis. This study aimed to identify the prevalence of NAFLD in patients with BD and investigate the risk factors of NAFLD. Patients and Methods: A total of 678 patients with BD were included in the study. Clinical data were obtained from the hospital's electronic health record system. Data included fasting blood glucose, alanine aminotransferase, triglycerides, aspartate aminotransferase, high-density lipoprotein cholesterol (HDL), alkaline phosphatase, total cholesterol, glutamine transpeptidase, uric acid, apolipoprotein A1, apolipoprotein B, and liver ultrasound findings. Results: The prevalence of NAFLD was 43.66% in patients with BD. Significant differences in body mass index (BMI), mean age, diabetes prevalence, course of BD, fasting blood glucose, alanine aminotransferase, HDL, alkaline phosphatase, triglycerides, aspartate aminotransferase, uric acid, glutamine transpeptidase, apolipoprotein B, total cholesterol, and apolipoprotein A1 were seen between the groups (all P<0.01). Male sex, age, BMI, course of BD, alanine aminotransferase, fasting blood glucose, aspartate aminotransferase, diabetes, glutamine transpeptidase, total cholesterol, alkaline phosphatase, triglycerides, uric acid, apolipoprotein B, HDL, and apolipoprotein A1 levels were correlated with NAFLD (all P<0.05). In patients with BD, diabetes (OR=6.412, 95% CI=1.049-39.21), BMI (OR=1.398, 95% CI=1.306-1.497), triglycerides (OR=1.456, 95% CI=1.036-2.045), and apolipoprotein A1 (OR=0.272, 95% CI=0.110-0.672) were risk factors for NAFLD (all P<0.05). Conclusion: Risk factors for NAFLD in patients with BD include diabetes, BMI, course of BD, and a low level of apolipoprotein A1. A proactive approach to disease management, such as appropriate physical activity and adoption of a healthy diet, and regular monitoring of changes in patient markers should be adopted to reduce the prevalence of NAFLD.

Readiness and challenges of carbon capture technologies based on the shipping industry.

In the context of carbon emission reduction in the shipping industry, CCUS technology can modify ships to reduce carbon emissions, providing a new direction for the green development of the shipping industry. Based on this, this paper investigates the technology related to carbon capture on ships, firstly puts forward the applicable requirements of carbon capture technology; and analyses the adaptability of the existing carbon capture solutions to the shipping industry; and discusses the development prospect of carbon capture on ships through the three challenges of space utilisation, safety, and economy; and finally analyses the related policies. After analysis and discussion, this paper concludes that the alcohol-amine method is the most suitable carbon capture solution for ships, but there are challenges in economics and space utilisation. The future research direction lies in optimising the performance of the absorber, improving the energy efficiency of the system and solving the CO2 storage problem.

TRIM27 promotes the Warburg effect and glioblastoma progression via inhibiting the LKB1/AMPK/mTOR axis.

Altered protein ubiquitination is associated with cancer. The novel tripartite motif (TRIM) family of E3 ubiquitin ligases have been reported to play crucial roles in the development, growth, and metastasis of various tumors. The TRIM family member TRIM27 acts as a potential promoter of tumor development in a wide range of cancers. However, little is known regarding the biological features and clinical relevance of TRIM27 in glioblastoma (GBM). Here, we report findings of elevated TRIM27 expression in GBM tissues and GBM cell lines. Further functional analysis showed that TRIM27 deletion inhibited GBM cell growth both in vitro and in vivo. Furthermore, we found that TRIM27 promoted the growth of GBM cells by enhancing the Warburg effect. Additionally, the inactivation of the LKB1/AMPK/mTOR pathway was critical for the oncogenic effects of TRIM27 in GBM. Mechanistically, TRIM27 could directly bind to LKB1 and promote the ubiquitination and degradation of LKB1, which in turn enhanced the Warburg effect and GBM progression. Collectively, these data suggest that TRIM27 contributes to GNM pathogenesis by inhibiting the LKB1/AMPK/mTOR axis and may be a promising candidate as a potential diagnostic and therapeutic marker for patients with GBM.

Characterization and prediction of OATP1B activity in prostate cancer patients on abiraterone acetate using endogenous biomarker coproporphyrin I.

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are important hepatic transporters. We previously identified OATP1B3 being critically implicated in the disposition of abiraterone. We aimed to further investigate the effects of abiraterone on the activities of OATP1B1 and OATP1B3 utilizing a validated endogenous biomarker coproporphyrin I (CP-I). We utilized OATP1B-transfected cells to characterize the inhibitory potential of abiraterone against OATP1B-mediated uptake of CP-I. Inhibition constant (Ki) was incorporated into our physiologically based pharmacokinetic (PBPK) modeling to simulate the systemic exposures of CP-I among cancer populations receiving either our model-informed 500 mg or clinically approved 1000 mg abiraterone acetate (AA) dosage. Simulated data were compared with clinical CP-I concentrations determined among our 9 metastatic prostate cancer patients receiving 500 mg AA treatment. Abiraterone inhibited OATP1B3- but not OATP1B1-mediated uptake of CP-I in vitro, with an estimated Ki of 3.93 µM. Baseline CP-I concentrations were simulated to be 0.81 {plus minus} 0.26 ng/mL, and determined to be 0.72 {plus minus} 0.16 ng/mL among metastatic prostate cancer patients, both of which were higher than those observed for healthy subjects. PBPK simulations revealed an absence of OATP1B3-mediated interaction between abiraterone and CP-I. Our clinical observations confirmed that CP-I concentrations remained comparable to baseline levels up to 12 weeks post 500 mg AA treatment. Using CP-I as an endogenous biomarker, we identified the inhibition of abiraterone on OATP1B3 but not OATP1B1 in vitro, which was predicted and observed to be clinically insignificant. We concluded that the interaction risk between AA and substrates of OATP1Bs is low. Significance Statement We utilized the endogenous biomarker coproporphyrin I (CP-I) and identified abiraterone as a moderate inhibitor of organic anion transporting polypeptide (OATP) 1B3 in vitro. Subsequent physiologically based pharmacokinetic (PBPK) simulations and clinical observations suggested an absence of OATP1B-mediated interaction between abiraterone and CP-I among prostate cancer patients. This multi-pronged study concluded that the interaction risk between abiraterone acetate and substrates of OATP1Bs is low, demonstrating the application of PBPK-CP-I modelling in predicting OATP1B-mediated interaction implicating abiraterone.

Revolutionizing Tetracycline Hydrochloride Remediation: 3D Motile Light-Driven MOFs Based Micromotors in Harsh Saline Environments.

Traditional light-driven metal-organic-frameworks (MOFs)-based micromotors (MOFtors) are typically constrained to two-dimensional (2D) motion under ultraviolet or near-infrared light and often demonstrate instability and susceptibility to ions in high-saline environments. This limitation is particularly relevant to employing micromotors in water purification, as real wastewater is frequently coupled with high salinity. In response to these challenges, ultrastable MOFtors capable of three-dimensional (3D) motion under a broad spectrum of light through thermophoresis and electrophoresis are successfully synthesized. The MOFtors integrated photocatalytic porphyrin MOFs (PCN-224) with a photothermal component made of polypyrrole (PPy) by three distinct methodologies, resulting in micromotors with different motion behavior and catalytic performance. Impressively, the optimized MOFtors display exceptional maximum velocity of 1305 ± 327 µm s-1 under blue light and 2357 ± 453 µm s-1 under UV light. In harsh saline environments, these MOFtors are not only maintain high motility but also exhibit superior tetracycline hydrochloride (TCH) removal efficiency of 3578 ± 510 mg g-1, coupling with sulfate radical-based advanced oxidation processes and peroxymonosulfate. This research underscores the significant potential of highly efficient MOFtors with robust photocatalytic activity in effectively removing TCH in challenging saline conditions, representing a substantial advancement in applying MOFtors within real-world water treatment technologies.

Guidelines for permanent iodine-125 seed interstitial brachytherapy for pancreatic cancer (2023 edition): The Chinese expert consensus workshop report.

ABSTRACT: The incidence of pancreatic cancer is increasing worldwide. Approximately, 60% of patients with pancreatic cancer have distant metastases at the time of diagnosis, of which only 10% can be removed using standard resection. Further, patients derive limited benefits from chemotherapy or radiotherapy. As such, alternative methods to achieve local control have emerged, including permanent iodine-125 seed interstitial brachytherapy. In 2023, the Chinese College of Interventionalists, affiliated with the Chinese Medical Doctor Association, organized a group of multi-disciplinary experts to compose guidelines for this treatment modality. The aim of this conference was to standardize the procedure for permanent iodine-125 seed interstitial brachytherapy, including indications, contraindications, pre-procedural preparation, procedural operations, complications, efficacy evaluation, and follow-up.

Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer invasiveness by activation of target of rapamycin kinase/autophagy signaling.

BACKGROUND: Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers. AIM: To investigate the role of MOB3B in colorectal cancer (CRC). METHODS: This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results. RESULTS: MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts. CONCLUSION: Loss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.

A Bio-Inspired Multifunctional Hydrogel Network with Toughly Interfacial Chemistry for Highly Reversible Flexible Zinc Batteries.

Flexible and high-performance aqueous Zn-ion batteries (ZIBs), coupled with low cost and safe, are considered as one of the most promising energy storage candidates for wearable electronics. However, most of hydrogel electrolytes suffer from poor mechanical properties and interfacial chemistry, which limits them to suppressed performance levels in flexible ZIBs, especially under harsh mechanical strains. Herein, a bio-inspired multifunctional hydrogel electrolyte network (polyacrylamide (PAM)/trehalose) with improved mechanical and adhesive properties was developed via a simple trehalose network-repairing strategy to stabilize the interfacial chemistry for highly reversible flexible ZIBs. As a result, the trehalose-modified PAM hydrogel exhibits a superior strength and stretchability up to 100 kPa and 5338%, respectively, as well as strong adhesive properties to various substrates. Also, the PAM/trehalose hydrogel electrolyte provides superior anti-corrosion capability for Zn anode and regulates Zn nucleation/growth, resulting in achieving a high Coulombic efficiency of 98.8%, and long-term stability over 2400 h. Importantly, the flexible Zn//MnO2 pouch cell exhibits excellent cycling performance under different bending conditions, which offers a great potential in flexible energy-related applications and beyond.

Thoracoscopic pulmonary resection combined with real-time image-guided percutaneous ablation for multiple pulmonary nodules: a novel surgical approach and literature review.

Background: Due to the widespread use of computed tomography (CT) screening and advances in diagnostic techniques, an increasing number of patients with multiple pulmonary nodules are being detected and pathologically diagnosed as synchronous multiple primary lung cancers (sMPLC). It has become a new challenge to treat multiple pulmonary nodules and obtain a favorable prognosis while minimizing the perioperative risk for patients. The purpose of this study was to summarize the preliminary experience with a hybrid surgery combining pulmonary resection and ablation for the treatment of sMPLC and to discuss the feasibility of this novel procedure with a literature review. Methods: This is a retrospective non-randomized controlled study. From January 1, 2022 to July 1, 2023, four patients underwent hybrid surgery combining thoracoscopic pulmonary resection and percutaneous pulmonary ablation for multiple pulmonary nodules. Patients were followed up at 3, 6 and 12 months postoperatively and the last follow-up was on November 30, 2023. Clinical characteristics, perioperative outcomes, pulmonary function recovery and oncologic prognosis were recorded. Meanwhile we did a literature review of studies on hybridized pulmonary surgery for the treatment of multiple pulmonary nodules. Results: All the four patients were female, aged 52 to 70 years, and had no severe cardiopulmonary dysfunction on preoperative examination. Hybrid surgery of simultaneous pulmonary resection and ablation were performed in these patients to treat 2 to 4 pulmonary nodules, assisted by intraoperative real-time guide of C-arm X-ray machine. The operation time was from 155 to 240 minutes, and intraoperative blood loss was from 50 to 200 mL. Postoperative hospital stay was 2 to 7 days, thoracic drainage duration was 2 to 6 days, and pleural drainage volume was 300-1,770 mL. One patient presented with a bronchopleural fistula due to pulmonary ablation; the fistula was identified and sutured during thoracoscopic surgery and the patient recovered well. No postoperative 90-day complications occurred. After 3 months postoperatively, performance status scores for these patients recovered to 80 to 100. No tumor recurrence or metastasis was detected during the follow-up period. Conclusions: Hybrid procedures combining minimally invasive pulmonary resection with ablation are particularly suitable for the simultaneous treatment of sMPLC. Patients had less loss of pulmonary function, fewer perioperative complications, and favorable oncologic prognosis. Hybrid surgery is expected to be a better treatment option for patients with sMPLC.

Safety and short-term outcomes of esophagectomy after neoadjuvant immunotherapy combined with chemotherapy or chemoradiotherapy for locally advanced esophageal squamous cell cancer: analysis of two phase-II clinical trials.

Background: Preoperative chemotherapy (CT) or chemoradiotherapy (CRT) show survival benefits in patients with locally advanced esophageal squamous cell carcinoma (ESCC); however, ESCC patients still have a dismal prognosis. We conducted two phase-II, single-armed clinical trials to assess the potential benefits, efficacy, feasibility, and safety of esophagectomy after combining preoperative CT or CRT and neoadjuvant programmed cell death protein 1 (PD-1) inhibitors in the treatment of ESCC. Methods: Patients were included with histologically confirmed ESCC (clinical stage II-IVA according to the American Joint Committee on Cancer 8th staging system) from two phase-II, single-arm trials (NCT04506138 and NCT03940001). Patients underwent two doses of intravenous PD-1 inhibitor (either camrelizumab or sintilimab) every 3 weeks, combined with two cycles of either CT or CRT. The primary endpoint of the study was the safety and short-term outcomes of esophagectomy as measured by the risk of developing complications within 30 days, after the combination of preoperative PD-1 inhibitor and CT or CRT Secondary endpoint was to evaluate the pCR rates (pT0N0), primary tumor pCR rates (pT0), operation time, postoperative stay, and 30-day mortality rate between both groups. Results between both groups were compared using a multivariable log-binomial regression model to obtain the adjusted relative risk ratios (RRs). Results: Between May 2019 and June 2022, 55 patients were included. All patients completed neoadjuvant therapy. Age, sex, performance status, clinical stage, histologic subtype, procedure type, operative time, and blood loss volume were similar between the two groups. The primary tumor pCR rates were 52.9% in the nICRT group and 21.6% in the nICT group (P=0.03), while the postoperative pCR rates were 41.2% in the nICRT group and 21.6% in the nICT group (P=0.19). The minimally invasive surgery rates were 89.2% (33/37) in the nICT group and 94.1% (16/17) in the nICRT group. The risk of developing pulmonary, anastomotic, or other complications were similar between the two groups. Conclusions: Esophagectomy was safe after the addition of the PD-1 inhibitor to preoperative CT or CRT in ESCC neoadjuvant therapies. Follow-up and the exploratory endpoints, including biomarkers analyses, are ongoing.

Development of a machine learning-based model to predict major adverse events after surgery for type A aortic dissection complicated by malnutrition.

Objective: This study aims to develop a predictive model for the risk of major adverse events (MAEs) in type A aortic dissection (AAAD) patients with malnutrition after surgery, utilizing machine learning (ML) algorithms. Methods: We retrospectively collected clinical data from AAAD patients with malnutrition who underwent surgical treatment at our center. Through least absolute shrinkage and selection operator (LASSO) regression analysis, we screened for preoperative and intraoperative characteristic variables. Based on the random forest (RF) algorithm, we constructed a ML predictive model, and further evaluated and interpreted this model. Results: Through LASSO regression analysis and univariate analysis, we ultimately selected seven feature variables for modeling. After comparing six different ML models, we confirmed that the RF model demonstrated the best predictive performance in this dataset. Subsequently, we constructed a model using the RF algorithm to predict the risk of postoperative MAEs in AAAD patients with malnutrition. The test set results indicated that this model has excellent predictive efficacy and clinical applicability. Finally, we employed the Shapley additive explanations (SHAP) method to further interpret the predictions of this model. Conclusion: We have successfully constructed a risk prediction model for postoperative MAEs in AAAD patients with malnutrition using the RF algorithm, and we have interpreted the model through the SHAP method. This model aids clinicians in early identification of high-risk patients for MAEs, thereby potentially mitigating adverse clinical outcomes associated with malnutrition.

Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

A large-aperture, high-power ultrawideband radiation system with beam broadening capacity.

Due to the limited maximum output power of the pulsers based on avalanche transistors, high-power ultrawideband (UWB) radiation systems usually synthesize plenty of modules simultaneously to achieve a high peak effective potential (rEp). However, this would lead to an increased aperture size as well as a narrower beam, which would limit their applications in intentional electromagnetic interference fields. In this paper, a high-power UWB radiation system with beam broadening capacity is developed. To achieve beam broadening in the time domain, a power-law time delay distribution method is proposed and studied by simulation, and then the relative excitation time delays of the modules are optimized to achieve higher rEp and avoid beam splitting in the beam broadening mode. In order to avoid false triggering of the pulser elements when implementing the beam broadening, the mutual coupling effect in the system is analyzed and suppressed by employing onboard high-pass filters, since the mutual coupling effect is much more severe in the low-frequency range. Finally, a radiation system with 36 modules is developed. Measuring results indicate that in the high-rEp mode, the developed system could achieve a maximum effective potential rEp of 313.6 kV and a maximum pulse-repetition-rate of 20 kHz. In the beam broadening mode, its half-peak-power beam width in the H-plane is broadened from the original value of 3.9° to 7.9°, with a maximum rEp of 272.9 kV. The polarization direction of the system could be flexibly adjusted by a built-in motor.

Floral Response to Heat: A Study of Color and Biochemical Adaptations in Purple Chrysanthemums.

Chrysanthemums are among the world's most popular cut flowers, with their color being a key ornamental feature. The formation of these colors can be influenced by high temperatures. However, the regulatory mechanisms that control the fading of chrysanthemum flower color under high-temperature stress remain unclear. This study investigates the impact of high temperatures on the color and biochemical responses of purple chrysanthemums. Four purple chrysanthemum varieties were exposed to both normal and elevated temperature conditions. High-temperature stress elicited distinct responses among the purple chrysanthemum varieties. 'Zi Feng Che' and 'Chrystal Regal' maintained color stability, whereas 'Zi Hong Tuo Gui' and 'Zi lian' exhibited significant color fading, particularly during early bloom stages. This fading was associated with decreased enzymatic activities, specifically of chalcone isomerase (CHI), dihydroflavonol 4-reductase (DFR), and anthocyanidin synthase (ANS), indicating a critical period of color development under heat stress. Additionally, the color fading of 'Zi Lian' was closely related to the increased activity of the peroxidase (POD) and polyphenol oxidase (PPO). Conversely, a reduction in ß-glucosidase (ßG) activity may contribute significantly to the color steadfastness of 'Zi Feng Che'. The genes Cse_sc027584.1_g010.1 (PPO) and Cse_sc031727.1_g010.1 (POD) might contribute to the degradation of anthocyanins in the petals of 'Zi Hong Tuo Gui' and 'Zi Lian' under high-temperature conditions, while simultaneously maintaining the stability of anthocyanins in 'Zi Feng Che' and 'Chrystal Regal' at the early bloom floral stage. The findings of this research provide new insights into the physiological and biochemical mechanisms by which chrysanthemum flower color responds to high-temperature stress.