Prospective Study of Lung Function with Prodromal, Clinical Parkinson's Disease, and Mortality.

Background: The association of lung function with the risk of developing prodromal and clinical-diagnosed Parkinson's disease (PD) and with the risk of mortality among individuals with PD remains unknown. Objective: To prospectively examine the associations of lung function with the risk of prodromal, clinical-diagnosed PD, and PD-related mortality in participants of the UK Biobank. Methods: Included were 452,518 participants free of PD at baseline. Baseline lung function, including forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and FEV1/FVC ratio, was assessed. Eight prodromal features were measured using self-reported diagnoses, hospital admission, and primary care data. Incident PD cases were identified using linkages with hospital admission, death register, and self-report. Vital status and date of death were provided by the UK National Health Service (NHS) and the NHS Central Register. We used Cox proportional hazard models to evaluate these associations. Results: Poor lung function was associated with higher risk of PD in a dose-response relationship: the adjusted hazard ratio comparing the lowest vs. the highest lung function quintile was 1.18 (95% CI, 1.02- 1.37) for FEV1, 1.14 (95% CI, 0.99- 1.29) for FVC, and 1.23 (95% CI, 1.08- 1.41) for PEF (p-trend <0.05 for all). Similar results were obtained for risk of prodromal PD and mortality among individuals with PD. Conclusions: The current study showed that individuals with poor lung function had a high future risk of prodromal and clinical PD and a higher rate of PD-related mortality.

AGBL2 promotes renal cell carcinoma cells proliferation and migration via α-tubulin detyrosination.

Background: AGBL2's role in tumorigenesis and cancer progression has been reported in several cancer studies, and it is closely associated with α-tubulin detyrosination. The roles of AGBL2 and α-tubulin detyrosination in renal cell carcinoma (RCC) pathogenesis remain unclear and require further investigation. Methods: In this study, we conducted an analysis of AGBL2 expression differences between renal clear cell carcinoma tissues and normal tissues using data from The Cancer Genome Atlas (TCGA). We performed a comprehensive prognostic analysis of AGBL2 in Kidney Renal Clear Cell Carcinoma (KIRC) using univariate and multivariate Cox regression. Based on the results of the Cox analysis, we constructed a prognostic model to assess its predictive capabilities. Receiver Operating Characteristic (ROC) analysis confirmed the diagnostic value of AGBL2 in renal cancer. We conducted further validation by analyzing cancer tissue samples and renal cancer cell lines, which confirmed the role of AGBL2 in promoting RCC cell proliferation and migration through in vitro experiments. Additionally, we verified the impact of AGBL2's detyrosination on α-tubulin using the tubulin carboxypeptidase (TCP) inhibitor parthenolide. Finally, we performed sequencing analysis on AGBL2 knockdown 786-O cells to investigate the correlation between AGBL2, immune infiltration, and AKT phosphorylation. Moreover, we experimentally demonstrated the enhancing effect of AGBL2 on AKT phosphorylation. Results: TCGA analysis revealed a significant increase in AGBL2 expression in RCC patients, which was correlated with poorer overall survival (OS), disease-specific survival (DSS), and progression-free intervals (PFI). According to the analysis results, we constructed column-line plots to predict the 1-, 3-, and 5-year survival outcomes in RCC patients. Additionally, the calibration plots assessing the model's performance exhibited favorable agreement with the predicted outcomes. And the ROC curves showed that AGBL2 showed good diagnostic performance in KIRC (AUC = 0.836)). Cell phenotyping assays revealed that AGBL2 knockdown in RCC cells significantly inhibited cell proliferation and migration. Conversely, overexpression of AGBL2 resulted in increased cell proliferation and migration in RCC cells. We observed that AGBL2 is predominantly located in the nucleus and can elevate the detyrosination level of α-tubulin in RCC cells. Moreover, the enhancement of RCC cell proliferation and migration by AGBL2 was partially inhibited after treatment with the TCP inhibitor parthenolide. Analysis of the sequencing data revealed that AGBL2 is associated with a diverse array of biological processes, encompassing signal transduction and immune infiltration. Interestingly, AGBL2 expression exhibited a negative correlation with the majority of immune cell infiltrations. Additionally, AGBL2 was found to enhance the phosphorylation of AKT in RCC cells. Conclusion: Our study suggests that AGBL2 fosters RCC cell proliferation and migration by enhancing α-tubulin detyrosination. Moreover, elevated AGBL2 expression increases phosphorylation of AKT in RCC cells.

Disturbance Estimation and Predefined-Time Control Approach to Formation of Multi-Spacecraft Systems.

Accurate sensing and control are important for high-performance formation control of spacecraft systems. This paper presents a strategy of disturbance estimation and distributed predefined-time control for the formation of multi-spacecraft systems with uncertainties based on a disturbance observer. The process begins by formulating a kinematics model for the relative motion of spacecraft, with the formation's communication topology represented by a directed graph for the formation system of the spacecraft. A disturbance observer is then developed to estimate the disturbances, and the estimation errors can be convergent in fixed time. Following this, a disturbance-estimation-based sliding mode control is proposed to guarantee the predefined-time convergence of the multi-spacecraft formation system, regardless of initial conditions. It allows each spacecraft to reach its desired position within a set time frame. The results of the analysis of the multi-spacecraft formation system are also provided. Finally, an example simulation of a five-spacecraft formation flying system is provided to demonstrate the presented formation control method.

Multitask connected U-Net: automatic lung cancer segmentation from CT images using PET knowledge guidance.

Lung cancer is a predominant cause of cancer-related mortality worldwide, necessitating precise tumor segmentation of medical images for accurate diagnosis and treatment. However, the intrinsic complexity and variability of tumor morphology pose substantial challenges to segmentation tasks. To address this issue, we propose a multitask connected U-Net model with a teacher-student framework to enhance the effectiveness of lung tumor segmentation. The proposed model and framework integrate PET knowledge into the segmentation process, leveraging complementary information from both CT and PET modalities to improve segmentation performance. Additionally, we implemented a tumor area detection method to enhance tumor segmentation performance. In extensive experiments on four datasets, the average Dice coefficient of 0.56, obtained using our model, surpassed those of existing methods such as Segformer (0.51), Transformer (0.50), and UctransNet (0.43). These findings validate the efficacy of the proposed method in lung tumor segmentation tasks.

Peptide-Functionalized Gold Nanoparticles for Boron Neutron Capture Therapy with the potential to use in Glioblastoma Treatment.

Glioblastoma is a highly aggressive glioma with limited treatment options. Boron neutron capture therapy (BNCT) offers a promising approach for refractory cancers, utilizing boron-10 (10B) and thermal neutrons to generate cytotoxic particles. Effective BNCT depends on selective targeting and retention of 10B in tumors. Current BNCT drugs face issues with rapid clearance and poor tumor accumulation. To address this, we developed gold nanoparticles (AuNPs) functionalized with cyclic arginine-glycine-aspartic acid (cRGD) peptides as a nanocarrier for Sodium Mercaptododecaborate (BSH), resulting in AuNPs-BSH&PEG-cRGD. In vitro, AuNPs-BSH&PEG-cRGD increased 10B content in GL261 glioma cells by approximately 2.5-fold compared to unmodified AuNPs-BSH&PEG, indicating enhanced targeting due to cRGD's affinity for integrin receptor αvß3. In a subcutaneous glioma mouse model, 6 hours post-intratumoral administration, the 10B concentration in tumors was 17.98 µg/g for AuNPs-BSH&PEG-cRGD, significantly higher than 0.45 µg/g for BSH. The tumor-to-blood (T/B) and tumor-to-normal tissue (T/N) ratios were also higher for AuNPs-BSH&PEG-cRGD, suggesting improved targeting and retention. This indicates that AuNPs-BSH&PEG-cRGD may enhance BNCT efficacy and minimize normal tissue toxicity. In summary, this study provides a novel strategy for BSH delivery and may broaden the design vision of BNCT nano-boron capture agents.

Self-Healing Hydrogel Resulting from the Noncovalent Interaction between Ropivacaine and Low-Molecular-Weight Gelator Sodium Deoxycholate Achieves Stable and Endurable Local Analgesia in Vivo.

Regional analgesia based on the local anesthetic ropivacaine plays a crucial role in postoperative pain management and recovery; however, the short duration of analgesia limits its clinical potential. Various drug delivery systems such as microparticles and lipid carriers have been used to prolong the analgesic effect, yet most of them are prone to abrupt release from the site of administration or have poor analgesic effects of less than 48 h, which fail to meet the needs of postoperative analgesia. In this study, a low-molecular-weight gelator sodium deoxycholate-based hydrogel loaded with ropivacaine (DC-ROP gel) was designed for long-acting analgesia. The noncovalent interaction between ropivacaine and sodium deoxycholate helps to improve the stability and sustained release performance of the gel. This internal drug-binding hydrogel also avoids experiencing the burst release effect commonly seen in polymer hydrogels previously reported for the slow release of local anesthetics. DC-ROP gel exhibited the dual advantages of self-healing after compression and long-term controlled release. In mice with inflammatory pain, DC-ROP gel achieved peripheral nerve block for more than 1 week after a single injection. Histological and blood biochemical analyses confirmed that the DC-ROP gel did not produce systemic toxicity, and cytotoxicity experiments demonstrated that the DC-ROP gel resulted in low irritation. These results suggest that DC-ROP gel provides a promising strategy for local anesthetics in long-term postoperative pain management, broadening the potential of bile salt-based low-molecular-weight hydrogels for drug delivery.

Combining single-cell and bulk RNA sequencing, NK cell marker genes reveal a prognostic and immune status in pancreatic ductal adenocarcinoma.

The NK cell is an important component of the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC), also plays a significant role in PDAC development. This study aimed to explore the relationship between NK cell marker genes and prognosis, immune response of PDAC patients. By scRNA-seq data, we found the proportion of NK cells were significantly downregulated in PDAC and 373 NK cell marker genes were screened out. By TCGA database, we enrolled 7 NK cell marker genes to construct the signature for predicting prognosis in PDAC patients. Cox analysis identified the signature as an independent factor for pancreatic cancer. Subsequently, the predictive power of signature was validated by 6 GEO datasets and had an excellent evaluation. Our analysis of relationship between the signature and patients' immune status revealed that the signature has a strong correlation with immunocyte infiltration, inflammatory reaction, immune checkpoint inhibitors (ICIs) response. The NK cell marker genes are closely related to the prognosis and immune capacity of PDAC patients, and they have potential value as a therapeutic target.

Recent Advances in Revealing the Electrocatalytic Mechanism for Hydrogen Energy Conversion System.

In light of the intensifying global energy crisis and the mounting demand for environmental protection, it is of vital importance to develop advanced hydrogen energy conversion systems. Electrolysis cells for hydrogen production and fuel cell devices for hydrogen utilization are indispensable in hydrogen energy conversion. As one of the electrolysis cells, water splitting involves two electrochemical reactions, hydrogen evolution reaction and oxygen evolution reaction. And oxygen reduction reaction coupled with hydrogen oxidation reaction, represent the core electrocatalytic reactions in fuel cell devices. However, the inherent complexity and the lack of a clear understanding of the structure-performance relationship of these electrocatalytic reactions, have posed significant challenges to the advancement of research in this field. In this work, the recent development in revealing the mechanism of electrocatalytic reactions in hydrogen energy conversion systems is reviewed, including in situ characterization and theoretical calculation. First, the working principles and applications of operando measurements in unveiling the reaction mechanism are systematically introduced. Then the application of theoretical calculations in the design of catalysts and the investigation of the reaction mechanism are discussed. Furthermore, the challenges and opportunities are also summarized and discussed for paving the development of hydrogen energy conversion systems.

Clinical Analysis and Imaging Study of Lateral Lumbar Intervertebral Fusion in the Treatment of Degenerative Lumbar Scoliosis.

OBJECTIVE: As the population ages and technology advances, lateral lumbar intervertebral fusion (LLIF) is gaining popularity for the treatment of degenerative lumbar scoliosis (DLS). This study investigated the feasibility, minimally invasive concept, and benefits of LLIF for the treatment of DLS by observing and assessing the clinical efficacy, imaging changes, and complications following the procedure. METHODS: A retrospective analysis was performed for 52 DLS patients (12 men and 40 women, aged 65.84 ± 9.873 years) who underwent LLIF from January 2019 to January 2023. The operation time, blood loss, complications, clinical efficacy indicators (visual analogue scale [VAS], Oswestry disability index [ODI], and 36-Item Short Form Survey), and imaging indicators (coronal position: Cobb angle and center sacral vertical line-C7 plumbline [CSVL-C7PL]; and sagittal position: sagittal vertical axis [SVA], lumbar lordosis [LL], pelvic incidence angle [PI], and thoracic kyphosis angle [TK] were measured). All patients were followed up. The above clinical evaluation indexes and imaging outcomes of patients postoperatively and at last follow-up were compared to their preoperative results. RESULTS: Compared to the preoperative values, the Cobb angle and LL angle were significantly improved after surgery (p < 0.001). Meanwhile, CSVL-C7PL, SVA, and TK did not change much after surgery (p > 0.05) but improved significantly at follow-up (p < 0.001). There was no significant change in PI at either the postoperative or follow-up timepoint. The operation took 283.90 ± 81.62 min and resulted in a total blood loss of 257.27 ± 213.44 mL. No significant complications occurred. Patients were followed up for to 21.7 ± 9.8 months. VAS, ODI, and SF-36 scores improved considerably at postoperative and final follow-up compared to preoperative levels (p < 0.001). After surgery, the Cobb angle and LL angle had improved significantly compared to preoperative values (p < 0.001). CSVL-C7PL, SVA, and TK were stable after surgery (p > 0.05) but considerably improved during follow-up (p < 0.001). PI showed no significant change at either the postoperative or follow-up timepoints. CONCLUSION: Lateral lumbar intervertebral fusion treatment of DLS significantly improved sagittal and coronal balance of the lumbar spine, as well as compensatory thoracic scoliosis, with good clinical and radiological findings. Furthermore, there was less blood, less trauma, and quicker recovery from surgery.

MCM8 promotes gastric cancer progression through RPS15A and predicts poor prognosis.

BACKGROUND: Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. Minichromsome maintenance proteins family member 8 (MCM8) assists DNA repair and DNA replication. MCM8 exerts tumor promotor function in multiple digestive system tumors. MCM8 is also considered as a potential cancer therapeutic target. METHODS: Bioinformatics methods were used to analyze MCM8 expression and clinicopathological significance. MCM8 expression was detected by immunohistochemistry (IHC) staining and qRT-PCR. MCM8 functions in GC cell were explored by Celigo cell counting, colony formation, wound-healing, transwell, and annexin V-APC staining assays. The target of MCM8 was determined by human gene expression profile microarray. Human phospho-kinase array kit evaluated changes in key proteins after ribosomal protein S15A (RPS15A) knockdown. MCM8 functions were reassessed in xenograft mouse model. IHC detected related proteins expression in mouse tumor sections. RESULTS: MCM8 was significantly upregulated and predicted poor prognosis in GC. High expression of MCM8 was positively correlated with lymph node positive (p < 0.001), grade (p < 0.05), AJCC Stage (p < 0.001), pathologic T (p < 0.01), and pathologic N (p < 0.001). MCM8 knockdown inhibited proliferation, migration, and invasion while promoting apoptosis. RPS15A expression decreased significantly after MCM8 knockdown. It was also the only candidate target, which ranked among the top 10 downregulated differentially expressed genes (DEGs) in sh-MCM8 group. RPS15A was identified as the target of MCM8 in GC. MCM8/RPS15A promoted phosphorylation of P38α, LYN, and p70S6K. Moreover, MCM8 knockdown inhibited tumor growth, RPS15A expression, and phosphorylation of P38α, LYN, and p70S6K in vivo. CONCLUSIONS: MCM8 is an oncogene and predicts poor prognosis in GC. MCM8/RPS15A facilitates GC progression.

Longitudinal association between accelerometer-derived rest-activity rhythm and atherosclerotic cardiovascular disease.

OBJECTIVE: Rest-activity rhythm is an essential behavior for human health. However, the association between rest-activity rhythm and atherosclerotic cardiovascular disease (ASCVD) risk remains unclear. Therefore, this study aimed to elucidate the association. METHODS: This study included 87,039 participants from the UK Biobank who had 7-day accelerometry data and were free of ASCVD at baseline. Relative amplitude was calculated as the difference between the most active continuous 10-h period (M10) and the least active continuous 5-h period (L5) in 24 h, and lower relative amplitude indicated the disruption of rest-activity rhythm. Cox proportional hazard model was used to examine the association of relative amplitude with ASCVD. Further, the linear association between relative amplitude and arterial stiffness measurements, including arterial stiffness index (ASI) and carotid intima-media thickness (cIMT), was examined. RESULTS: During a mean follow-up period of 6.80 ± 1.10 years, 2798 ASCVD cases were identified. A dose-response relationship was observed between relative amplitude and ASCVD risk (P for trend<0.001). The adjusted hazard ratio, for the highest vs the lowest quintile of relative amplitude, was 1.54 (95 % confidence interval: 1.31, 1.79). Further, we found significant association of lower relative amplitude with ASI and cIMT. The onset timing of M10 at ≤06:00, 09:00, 10:00, or ≥11:00, as opposed to the reference time of 07:00, was associated with higher ASCVD risk. CONCLUSIONS: Low rest-activity rhythm amplitude was associated with a higher risk of ASCVD. Rest-activity rhythm amplitude may provide a method to identify individuals at risk of ASCVD in public health and clinical practice.

From waste to strength: Tailor-made enzyme activation design transformation of denatured soy meal into high-performance all-biomass adhesive.

Given the severe protein denaturation and self-aggregation during the high-temperature desolubilization, denatured soy meal (DSM) is limited by its low reactivity, high viscosity, and poor water solubility. Preparing low-cost and high-performance adhesives with DSM as the key feedstock is still challenging. Herein, this study reveals a double-enzyme co-activation method targeting DSM with the glycosidic bonds in protein-carbohydrate complexes and partial amide bonds in protein, increasing the protein dispersion index from 10.2 % to 75.1 % improves the reactivity of DSM. The green crosslinker transglutaminase (TGase) constructs a robust adhesive isopeptide bond network with high water-resistant bonding strength comparable to chemical crosslinkers. The adhesive has demonstrated high dry/wet shear strength (2.56 and 0.93 MPa) for plywood. After molecular recombination by enzyme strategy, the adhesive had the proper viscosity, high reactivity, and strong water resistance. This research showcases a novel perspective on developing a DSM-based adhesive and blazes new avenues for changes in protein structural function and adhesive performance.

Correlations of characteristics with tissue involvement in knee gouty arthritis: Magnetic resonance imaging analysis.

Objective: This study investigates the MRI features of knee gouty arthritis (KGA), examines its relationship with the extent of tissue involvement, and assesses whether risk factors can predict KGA. Materials and methods: Patients diagnosed with KGA underwent MRI examinations, and two independent observers retrospectively analyzed data from 44 patients (49 knees). These patients were divided into mild and severe groups based on tissue involvement observed during arthroscopy. MRI features were summarized, and the intraclass correlation coefficient evaluated interobserver reproducibility. Single-factor analysis compared clinical indicators and MRI features between groups, while Cramer's V coefficient assessed correlations. Multivariate logistic regression identified predictors of tissue involvement extent, and a ROC curve evaluated diagnostic performance. Results: Among 49 knees, 18 had mild and 31 had severe tissue involvement. Key MRI features included ligament sketch-like changes, meniscal urate deposition, irregularly serrated cartilage changes, low-signal signs within joint effusion, synovial proliferation, Hoffa's fat pad synovitis, gouty tophi, bone erosion, and bone marrow edema. The interobserver reliability of the MRI features was good. Significant differences (P < 0.05) were observed between the groups for anterior cruciate ligament (ACL) sketch-like changes, Hoffa's fat pad synovitis, and gouty tophi. ACL sketch-like changes (r = 0.309), Hoffa's fat pad synovitis (r = 0.309), and gouty tophi (r = 0.408) were positively correlated with the extent of tissue involvement (P < 0.05). ACL sketch-like changes (OR = 9.019, 95 % CI: 1.364-61.880), Hoffa's fat pad synovitis (OR = 6.472, 95 % CI: 1.041-40.229), and gouty tophi (OR = 5.972, 95 % CI: 1.218-29.276) were identified as independent predictors of tissue involvement extent (P < 0.05). The area under the ROC curve was 0.862, with a sensitivity of 67.70 %, specificity of 94.40 %, and accuracy of 79.14 %. Conclusion: This comprehensive analysis of MRI features identifies ligament sketch-like changes, meniscal urate deposition, and low-signal signs within joint effusion as characteristic MRI manifestations of KGA. Irregular cartilage changes are valuable for differential diagnosis in young and middle-aged patients. ACL sketch-like changes, Hoffa's fat pad synovitis, and gouty tophi correlate with tissue involvement severity and are critical in predicting and assessing the extent of tissue involvement in KGA.

The switch triggering the invasion process: Lipid metabolism in the metastasis of hepatocellular carcinoma.

ABSTRACT: In humans, the liver is a central metabolic organ with a complex and unique histological microenvironment. Hepatocellular carcinoma (HCC), which is a highly aggressive disease with a poor prognosis, accounts for most cases of primary liver cancer. As an emerging hallmark of cancers, metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs, including the liver. Specifically, rewiring of the liver metabolic microenvironment, including lipid metabolism, is driven by HCC cells, propelling the phenotypes of HCC cells, including dissemination, invasion, and even metastasis in return. The resulting formation of this vicious loop facilitates various malignant behaviors of HCC further. However, few articles have comprehensively summarized lipid reprogramming in HCC metastasis. Here, we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver, and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying mechanisms. In addition, we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy, aiming to offer new perspectives for targeted therapy.

Dynamic release of siloxanes in the form of biogas from simulated municipal-solid-waste landfill and the corresponding driving mechanism.

Simulated landfill bioreactors were established and operated for 635 days to investigate the dynamic release of seven siloxanes in landfill biogas (denoted by octamethyltrisiloxane (L3), decamethyltetrasiloxane (L4), dodecamethylpentasiloxane (L5), hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6)). In total, 259.45, 252.73, 233.30, 80.40, 4.35, 1.67 and 1.10 mg of D5, D3, D4, D6, L4, L5 and L3 were discharged from 57 kg of municipal solid waste (MSW). More than 70 % of the siloxanes were released before day 119, indicating that the peak period of siloxane discharge occurred during the hydrolysis and acid production stage. The cyclosiloxanes (D3, D4, D5 and D6) were the dominant siloxane species in the biogas. The mass load of discharged cyclosiloxanes was more than 98 % of that of the total siloxanes. In addition to the variation in the concentration distribution profiles of the different siloxane species in the MSW, transformations among species may have an important effect on the release of siloxanes. The main transformation products were D3 and D4 with high release rates (>20 %) and high measured contents of trimethylsilanol (TMSOH) and functional microorganisms (Pseudomonas) were observed during landfilling. These results suggested that MSW degradation and transformation of siloxanes both drive the dynamic release of siloxanes during long-term landfilling.

Development and interpretation of a pathomics-driven ensemble model for predicting the response to immunotherapy in gastric cancer.

BACKGROUND: Only a subset of patients with gastric cancer experience long-term benefits from immune checkpoint inhibitors (ICIs). Currently, there is a deficiency in precise predictive biomarkers for ICI efficacy. The aim of this study was to develop and validate a pathomics-driven ensemble model for predicting the response to ICIs in gastric cancer, using H&E-stained whole slide images (WSI). METHODS: This multicenter study retrospectively collected and analyzed H&E-stained WSIs and clinical data from 584 patients with gastric cancer. An ensemble model, integrating four classifiers: least absolute shrinkage and selection operator, k-nearest neighbors, decision trees, and random forests, was developed and validated using pathomics features, with the objective of predicting the therapeutic efficacy of immune checkpoint inhibition. Model performance was evaluated using metrics including the area under the curve (AUC), sensitivity, and specificity. Additionally, SHAP (SHapley Additive exPlanations) analysis was used to explain the model's predicted values as the sum of the attribution values for each input feature. Pathogenomics analysis was employed to explain the molecular mechanisms underlying the model's predictions. RESULTS: Our pathomics-driven ensemble model effectively stratified the response to ICIs in training cohort (AUC 0.985 (95% CI 0.971 to 0.999)), which was further validated in internal validation cohort (AUC 0.921 (95% CI 0.839 to 0.999)), as well as in external validation cohort 1 (AUC 0.914 (95% CI 0.837 to 0.990)), and external validation cohort 2 (0.927 (95% CI 0.802 to 0.999)). The univariate Cox regression analysis revealed that the prediction signature of pathomics-driven ensemble model was a prognostic factor for progression-free survival in patients with gastric cancer who underwent immunotherapy (p<0.001, HR 0.35 (95% CI 0.24 to 0.50)), and remained an independent predictor after multivariable Cox regression adjusted for clinicopathological variables, (including sex, age, carcinoembryonic antigen, carbohydrate antigen 19-9, therapy regime, line of therapy, differentiation, location and programmed death ligand 1 (PD-L1) expression in all patients (p<0.001, HR 0.34 (95% CI 0.24 to 0.50)). Pathogenomics analysis suggested that the ensemble model is driven by molecular-level immune, cancer, metabolism-related pathways, and was correlated with the immune-related characteristics, including immune score, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data score, and tumor purity. CONCLUSIONS: Our pathomics-driven ensemble model exhibited high accuracy and robustness in predicting the response to ICIs using WSIs. Therefore, it could serve as a novel and valuable tool to facilitate precision immunotherapy.

Ameliorative effect of total ginsenosides from heat-treated fresh ginseng against cyclophosphamide-induced liver injury in mice.

This study evaluated the effect of heat treatment on the conversion of ginsenoside and the ameliorative effect of heat-treated total ginsenoside (HG) from fresh ginseng on cyclophosphamide (CTX)-induced liver injury. LC-MS analysis revealed that the content of rare ginsenosides increased markedly after heat treatment. HG significantly attenuated CTX-induced hepatic histopathological injury in mice. Western blotting analysis showed that untreated total ginsenoside (UG) and HG regulated the Nrf2/HO-1 and TLR4/MAPK pathways. Importantly, these results may be relevant to the modulation of the intestinal flora. UG and HG significantly increased the short-chain fatty acids (SCFAs)-producing bacteria Lactobacillus and reduced the LPS-producing bacteria Bacteroides and Parabacteroides. These changes in intestinal flora affected the levels of TNF-α, LPS and SCFAs. In short, UG and HG alleviated CTX-induced liver injury by regulating the intestinal flora and the LPS-TLR4-MAPK pathway, and HG was more effective. HG has the potential to be a functional food that can alleviate chemical liver injury.

Achieving Enhanced Dielectric and Energy Storage Performance in Poly(vinyl chloride-glycidyl methacrylate) through Tuning Interchain Interactions.

Glassy polymer dielectrics exhibit significant advantages in energy storage density and discharge efficiency; however, their potential application in thin-film capacitors is limited by the complexity of the production process, rising costs, and processing challenges arising from the brittleness of the material. In this study, a small amount of the polar monomer glycidyl methacrylate (GMA) was copolymerized with vinyl chloride (VC) using a highly integrated and precisely controlled process. This effectively facilitated the bulk synthesis of P(VC-GMA) copolymers, aimed at enhancing the dielectric properties and energy storage capabilities of the copolymer. Moreover, the incorporation of GMA into PVC induces significant alterations in the structural sequence of the copolymer, resulting in an enhancement of interchain interactions that ultimately contribute to an increase in the modulus and improved breakdown strength. With a GMA content of 2.4 mol %, P(VC-GMA) exhibits a significant enhancement in discharge energy density, surpassing that of a pure PVC copolymer, while maintaining high discharge efficiency and stability. The finding of this study paves the way for future advancements in high-energy-storage polymer dielectrics, thereby expanding the scope of advanced dielectric materials.

CO2 Valorization in Deep Eutectic Solvents.

The deep eutectic solvent (DES) has emerged in recent years as a valuable medium for converting CO2 into valuable chemicals because of its easy availability, stability, and safety, and its capability to dissolve carbon dioxide. CO2 valorization in DES has evolved rapidly over the past 20 years. As well as being used as solvents for acid/base-promoted CO2 conversion for the production of cyclic carbonates and carbamates, DESs can be used as reaction media for electrochemical CO2 reduction for formic acid and CO. Among these products, cyclic carbonates can be used as solvents and electrolytes, carbamate derivatives include the core structure of many herbicides and pesticides, and formic acid and carbon monoxide, the C1 electrochemical products, are essential raw materials in the chemical industries. An overview of the application of DESs for CO2 valorization in recent years is presented in this review, followed by a compilation and comparison of product types and reaction mechanisms within the different types of DESs, and an outlook on how CO2 valorization will be developed in the future.

PROS1 is a crucial gene in the macrophage efferocytosis of diabetic foot ulcers: a concerted analytical approach through the prisms of computer analysis.

BACKGROUND: Diabetic foot ulcers (DFUs) pose a serious long-term threat because of elevated mortality and disability risks. Research on its biomarkers is still, however, very limited. In this paper, we have effectively identified biomarkers linked with macrophage excretion in diabetic foot ulcers through the application of bioinformatics and machine learning methodologies. These findings were subsequently validated using external datasets and animal experiments. Such discoveries are anticipated to offer novel insights and approaches for the early diagnosis and treatment of DFU. METHODS: In this work, we used the Gene Expression Omnibus (GEO) database's datasets GSE68183 and GSE80178 as the training dataset to build a gene model using machine learning methods. After that, we used the training and validation sets to validate the model (GSE134431). On the model genes, we performed enrichment analysis using both gene set variant analysis (GSVA) and gene set enrichment analysis (GSEA). Additionally, the model genes were subjected to immunological association and immune function analyses. RESULTS: In this study, PROS1 was identified as a potential key target associated with macrophage efflux in DFU by machine learning and bioinformatics approaches. Subsequently, the key biomarker status of PROS1 in DFU was also confirmed by external datasets. In addition, PROS1 also plays a key role in macrophage exudation in DFU. This gene may be associated with macrophage M1, CD4 memory T cells, naïve B cells, and macrophage M2, and affects IL-17, Rap1, hedgehog, and JAK-STAT signaling pathways. CONCLUSIONS: PROS1 was identified and validated as a biomarker for DFU. This finding has the potential to provide a target for macrophage clearance of DFU.