Neobavaisoflavone Protects H9c2 Cells Against H2O2-Induced Mitochondrial Dysfunction Through ALOX15/PGC1-α Axis.

Neobavaisoflavone (NBIF) is a natural antioxidant that has a variety of pharmacological activities. To investigate the effects of NBIF on oxidative stress-induced myocardial injury, H9c2 cells were treated with H2O2. Cell counting kit-8 was used to detect cell viability. Intracellular as well as lipid radicals were detected. To measure mitochondrial function, tetramethylrhodamine ethyl ester was used to detect mitochondrial membrane potential. 12- and 15-hydroxyeicosatetraenoic acids (HETE) were measured by LC-MS/MS. ALOX15, which is the upstream protein of 12-, 15-HETE, was also measured by using western blot analysis. The results showed that H2O2 induced lipid peroxidation in cardiomyocytes and caused mitochondrial dysfunction which was relieved by NBIF treatment. Besides, H2O2 significantly increased the production of 12-HETE and 15-HETE and upregulated the expression of ALOX15 while PGC-1α was downregulated and triggered the release of cytochrome c. The treatment of NBIF decreased the expression of ALOX15 and inhibited the activation of caspase-3. NBIF protected mitochondrial membrane integrity through increasing PGC-1α and Nrf1. Our results indicated that NBIF could protect cardiomyocytes against H2O2-induced mitochondrial dysfunction via ALOX15/PGC-1α axis.

Polystyrene nanoplastics induce apoptosis, histopathological damage, and glutathione metabolism disorder in the intestine of juvenile East Asian river prawns (Macrobrachium nipponense).

Nanoplastics (NPs) are widely distributed in the aquatic environment and have become a global concern as a new type of pollutant. Many researchers have studied the physiological effects of NPs on aquatic organisms, but relatively little is known about their effects on intestinal immune function in crustaceans. Therefore, we used NPs concentrations of 0, 5, 10, 20, 40 mg/L for 28 days of stress, evaluated the effects of NPs exposure on intestinal cell apoptosis, histopathological damage, and glutathione (GSH) metabolism of juvenile East Asian river prawns (Macrobrachium nipponense). As NPs concentration increased, the contents of total GSH and oxidized glutathione decreased gradually (P < 0.05), the concentration of GSH first increased and then decreased (P < 0.05), and the activities of lysozyme, acid phosphatase, phenoloxidase, and alkaline phosphatase first increased and then decreased (P < 0.05). Additionally, intestinal tissue structure was damaged, and the apoptosis rate significantly increased (P < 0.05). The expression of intestinal autophagy genes (CTL, ALF, Crustin, ATG8, and BCL-2) increased at first and then decreased, the expression levels of TNF and Wnt4 significantly decreased, and the expression of Beclin significantly increased with increasing NPs concentration. We also found that AP-1 and PTEN were highly expressed in the hepatopancreas and were involved in intestinal immune responses. Our results showed that exposure to NPs may induce apoptosis of intestinal tissue cells, induce autophagy, and inhibit GSH metabolism, thereby reducing intestinal immune function of M. nipponense. These findings provide a reference for healthy aquaculture and ecological risk assessment of prawns.

Three-dimensional (3-D) fluoride molecular glue to improve the SnO2/perovskite interface for efficient perovskite solar cells.

Aiming at numerous defects at SnO2/perovskite interface and lattice mismatch in perovskite solar cells (PSCs), we design a kind of three-dimensional (3D) molecular glue (KBF4-TFMSA), which is derived from strong intramolecular hydrogen bonding interaction between potassium tetrafluoroborate (KBF4) and trifluoromethanesulfonamide (TFMSA). A remarkable efficiency of 25.8% with negligible hysteresis and a stabilized power output of 25.0% have been achieved, in addition, 24.57% certified efficiency of 1 cm2 device is also obtained. Further investigation reveals that this KBF4-TFMSA can interact with oxygen vacancies and under-coordinated Sn(IV) from the SnO2, in the meantime, FA+ (NH2-C=NH) and K+ cations can be well fixed by hydrogen bonding interaction between FA+  and BF4-, and electrostatic attraction between sulfonyl oxygen and K+ ions, respectively. Thereby, FAPbI3 crystal grain sizes are increased, interfacial defects are significantly reduced and carrier extraction/transport is facilitated, leading to better cell performance and excellent stabilities. Non-encapsulated devices can maintain 91% of their initial efficiency under maximum-power-point (MPP) tracking while continuous illumination (~100 mW cm-2) for 1000 h, and retain 91% of the initial efficiency after 1000 h "double 60" damp-heat stability testing (60°C and 60%RH (RH, relatively humidity)).

In-Situ Anchoring of Co Single-Atom Synergistically with Cd Vacancy of Cadmium Sulfide for Boosting Asymmetric Charge Distribution and Photocatalytic Hydrogen Evolution.

In the context of reshaping the energy pattern, designing and synthesizing high-performance noble metal-free photocatalysts with ultra-high atomic utilization for hydrogen evolution reaction (HER) still remains a challenge. In a streamlined synthesis process, in-situ single atom anchoring is performed in parallel with HER by irradiating a precursory defect-state CdS/Co suspension (Co-DCdS-Ss) system under simulated sunlight and the in-situ synthesizing single-atom Co photocatalyst (Co5:DCdS) exhibits further improved catalytic performance (60.10 mmol g-1 h-1) compared with Co-DCdS-Ss (18.09 mmol g-1 h-1), reaching an apparent quantum yield of 57.6% at 500 nm and a solar-chemical energy conversion efficiency (SCC) of 6.26% at AM 1.5G. In-depth characterization tests and density functional theory (DFT) calculations prove that the anchoring of Co single atom deepens the asymmetric charge distribution of the two-coordination S atom adjacent to the cadmium vacancy (VCd). The synergy between electron delocalization VCd and Co single atom on the catalyst surface is constructed, which bifunctional sites responsible for boosting water adsorption-dissociation and hydrogen evolution. This study advances the understanding of the underlying mechanisms of synergy between surface defects and metal single atoms and opens a new horizon for the development of advanced materials in the field of photocatalysis.

Concomitant gut dysbiosis and defective gut barrier serve as the bridges between hypercortisolism and chronic systemic inflammation in Cushing disease.

OBJECTIVE: The aim of this study was to investigate the gut microbial signatures and related pathophysiological implications in patients with Cushing's disease (CD). DESIGN AND METHODS: 27 patients with CD and 45 healthy controls were enrolled. Based on obtained metagenomics data, we performed correlation, network study and genome interaction group (GIG) analysis. Fecal metabolomics and serum ELISA analysis were conducted in dichotomized CD patients. Caco-2 cells were incubated with gradient concentrations of cortisol for subsequent transepithelial electrical resistance (TEER) measurement, FITC-dextran transwell permeability assay, qPCR and western blot analysis. RESULTS: Gut microbial composition in patients with CD was notably different from that in healthy controls. Network analysis revealed that Eubacterium siraeum might serve as the core specie in the gut microbial system of CD patients. Subsequent GIG analysis identified the positive correlations between GIG9 and UFC. Further serum ELISA and fecal metabolomics uncovered that CD patients with elevated UFC levels were characterized with increased lipopolysaccharide binding protein (LBP). Moreover, remarkable positive association was found between LBP level and relative abundance of Eubacterium siraeum. TEER and FITC-Dextran transwell assays demonstrated that hypercortisolism induced increased gut permeability. Further qPCR and western blot analysis suggested that dysregulated AhR/Claudin 2 axis might be involved in the development of hypercortisolism-induced defective gut barrier function. CONCLUSIONS: Disease activity associated dysbiosis and defective gut barrier might jointly facilitate the development of systemic inflammation in patients with CD.

The Comprehensive Profiling of the Chemical Components in the Raw and Processed Roots of Scrophularia ningpoensis by Combining UPLC-Q-TOF-MS Coupled with MS/MS-Based Molecular Networking.

Scrophulariae Radix (SR), the dried root of Scrophularia ningpoensis Hemsl (S. ningpoensis), has been extensively used as traditional Chinese medicine for thousands of years. However, since the mid-20th century, the traditional processing technology of S. ningpoensis has been interrupted. Therefore, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technology, together with a Global Natural Product Social Molecular Networking (GNPS) method, was applied to comprehensively analyze the characteristic changes and mutual transformation of chemical constituents in the differently processed roots of S. ningpoensis, as well as to scientifically elucidate the processing mechanism of differently processed SR. As a result, a total of 149 components were identified. Notably, with the help of the GNPS data platform and MS2 fragment ions, the possible structures of four new compounds (47, 48, 50, and 73) were deduced in differently processed SR samples, in which 47, 48, and 50 are iridoid glycosides, and 73 is a phenylpropanoid glycoside. Five cyclopeptides (78, 86, 97, 99, and 104) derived from leucine (isoleucine) were identified in SR for the first time. The heatmaps analysis results indicated that leucine or isoleucine may be converted to cyclopeptides under the prolonged high-temperature conditions. Moreover, it is found that short-time steaming can effectively prevent the degradation of glycosides by inactivating enzymes. This study provides a new and efficient technical strategy for systematically identifying the chemical components, rapidly discovering the components, and preliminarily clarifying the processing mechanism of S. ningpoensis, as well as also providing a scientific basis for the improvement of the quality standards and field processing of S. ningpoensis.

Association of RIPK1 and RIPK2 Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Han Population.

Objects: Rheumatoid arthritis (RA) is a systemic autoimmune disease with an obscure pathogenesis. This study aims to identify the susceptibility conferred by specific single nucleotide polymorphisms (SNPs), namely rs17548629 within the RIPK1 gene and rs10094579 within the RIPK2 gene, in RA. Additionally, it investigates the associations between inflammatory markers and biochemical parameters at various stages of the disease. Methods: We analyzed 394 patients with RA and 258 normal controls (NCs), examining SNPs within the RIPK1 (rs17548629) and RIPK2 (rs10094579) genes using polymerase chain reaction (PCR) and sequencing techniques. Profiles of RA patients were evaluated for inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, glucose, uric acid, and creatinine. Additionally, disease-specific indicators included cyclic citrullinated peptide (CCP), rheumatoid factor (RF), antinuclear antibodies (ANA), and anti-keratin antibodies. The Disease Activity Score 28 (DAS28), based on ESR, was used to categorize RA patients into groups of high, moderate, or low disease activity. Results: We found a significant association between the RIPK1 rs17548629 genotype and RA in the additive model (p < 0.001; OR = 3.23), over-dominant model (p < 0.001; OR = 0.27), and dominant model (p < 0.001; OR = 3.94). The frequency of the C allele at rs17548629 was significantly higher in NCs than in RA patients (p < 0.001; OR = 0.322). When compared with normal controls, the RIPK1 rs17548629 genotype demonstrated significant associations with both anti-CCP-positive RA patients (p < 0.001) and anti-CCP-negative RA patients (p < 0.001). Similarly, this genotype was associated with RF-positive RA patients (p < 0.001). Furthermore, the RIPK2 rs10094579 genotype was significantly associated with CRP levels in RA patients with low disease activity in the over-dominant model (p = 0.029; OR = 0.065, adjusted for age and sex). Conclusion: The presence of the RIPK1 rs17548629 genotype is associated with RA under additive, co-dominant, and dominant models. The T allele mutation at rs17548629 increases the risk of RA in the Chinese population. The RIPK1 rs17548629 genotype was identified as being associated with RF-positive RA patients, whereas no significant association was observed in RF-negative individuals. These findings suggest that this SNP may modulate the risk of RA in an RF-dependent manner. Furthermore, the RIPK2 rs10094579 genotype correlates with CRP levels in RA patients exhibiting low disease activity. This association underscores the necessity for caution when reducing the dosage of therapy in RA patients with low disease activity who carry the CA genotype at RIPK2 rs10094579. Additional research is warranted to explore other genotypes that may influence RA susceptibility and to refine potential treatment strategies.

ARL8B promotes hepatocellular carcinoma progression and inhibits antitumor activity of lenvatinib via MAPK/ERK signaling by interacting with RAB2A.

Tumor recurrence and metastasis are important factors affecting postoperative survival in hepatocellular carcinoma (HCC) patients. ADP Ribosylation factor-like GTPase 8B (ARL8B) plays a crucial role in many biological processes, including lysosomal function, immune response, and cellular communication, all of which are related to the occurrence and development of tumors. However, its role in HCC remains unclear. Herein, we revealed that ARL8B is consistently elevated in HCC tissues compared to normal liver tissues, suggesting an unfavorable outcome in HCC patients. Increased ARL8B levels promoted the malignant phenotype of HCC in vitro and in vivo. Notably, ARL8B also induced epithelial-to-mesenchymal transition (EMT) in HCC cells. Mechanistically, the results of bioinformatics analysis combined with mass spectrometry revealed the potential downstream target molecule RAB2A of ARL8B. ARL8B directly interacted with RAB2A and increased the levels of GTP-bound RAB2A, thereby contributing to the activation of the extracellular signal-regulated kinase (ERK) signaling pathway. Interestingly, knockout of ARL8B in Hep3B cells enhanced the antitumor activity of lenvatinib in vitro and in vivo. Furthermore, AAV-shARL8B enhanced the inhibition of HCC growth through lenvatinib, providing new insights into its mechanism of action in lenvatinib-insensitive patients. In conclusion, ARL8B promotes the malignant phenotype of HCC and EMT via RAB2A mediated activation of the MAPK/ERK signaling pathway and is expected to be a valuable prognostic indicator and therapeutic target for HCC patients.

Luteinizing hormone is independently associated with high-sensitive cardiac troponin T elevation in postmenopausal T2DM patients: A cross-sectional study.

BACKGROUND: It is known that the risk of ischemic heart disease increases in patients with type 2 diabetes mellitus (T2DM). For female patients, the incidence of heart disease can be even greater after menopause, accompanied by dramatic changes in sex hormones. We investigated the correlations between sex hormones and markers of ischemic heart diseases in postmenopausal females with T2DM patients. METHODS: This cross-sectional study collected data from 324 hospitalized postmenopausal females with T2DM. Multiple linear regression analyses were conducted to determine the correlations between sex hormones and cardiac markers including high-sensitive cardiac troponin T (hs-cTnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels. RESULTS: Multiple linear regression analyses revealed that luteinizing hormone (LH) was positively and independently associated with hs-cTnT concentrations in postmenopausal females with T2DM (ß = 0.189, p = 0.002). Postmenopausal females with T2DM and subclinical myocardial injury had higher LH levels than those without subclinical myocardial injury (29.67 vs. 25.08 mIU/mL, p < 0.001). A multivariate logistic regression analysis confirmed an independent and significant association between elevated LH and subclinical myocardial injury in postmenopausal females with T2DM (adjusted odds ratio [OR] = 1.077, 95% confidence interval [CI], 1.033-1.124; p < 0.001). As another gonadotropin, the follicle-stimulating hormone did not show independent correlations with hs-cTnT or NT-proBNP (p > 0.05). Neither estrogen nor testosterone was correlated with cardiac markers. CONCLUSIONS: Elevated LH levels were positively and independently associated with increased hs-cTnT levels in postmenopausal women with T2DM. Our findings suggest that LH could serve as a potential marker for assessing the risk of subclinical myocardial injury in postmenopausal females with T2DM.

Synthesis and Anti-Liver Fibrosis Research of Aspartic Acid Derivatives.

Liver fibrosis plays an important role in the progression of liver disease, but there is a severe shortage of direct and efficacious pharmaceutical clinical interventions. Literature research indicates that aspartic acid exhibits hepatoprotective properties. In this paper, 32 target compounds were designed and synthesized utilizing aspartic acid as the lead compound, of which 22 were new compounds not reported in the literature. These compounds were screened for their inhibitory effects on the COL1A1 promoter to assess in vitro anti-liver fibrosis activity and summarized structure-activity relationships. Four compounds exhibited superior potency with inhibition rates ranging from 66.72% to 97.44%, substantially higher than EGCG (36.46 ± 4.64%) and L-Asp (11.33 ± 0.35%). In an LPS-induced inflammation model of LX-2 cells, both 41 and 8a could inhibit the activation of LX-2 cells, reducing the expression of COL1A1, fibronectin, and α-SMA. Upon further investigation, 41 and 8a ameliorated liver fibrosis by inhibiting the IKKß-NF-κB signaling pathway to alleviate inflammatory response. Overall, the study evaluated the anti-liver fibrosis effects of aspartic acid derivatives, identified the potency of 41, and conducted a preliminary exploration of mechanisms, laying the foundation for the discovery of novel anti-liver fibrosis agents.

Characterization and degradation mechanism of a newly isolated hydrolyzed polyacrylamide-degrading bacterium Alcaligenes faecalis EPDB-5 from the oilfield sludge.

Hydrolyzed polyacrylamide (HPAM) is posing serious threats to ecosystems. However, biodegradation is an effective method to remove HPAM owing to its low cost and environmental friendliness. In this study, Alcaligenes faecalis EPDB-5 was isolated as a highly efficient HPAM degrading strain from sludge contaminated with polymerized produced water from Daqing oilfield. Under the optimal conditions, the strain EPDB-5 demonstrated an impressive HPAM degradation rate of 86.05%, the total nitrogen (TN) removal of 71.96% and chemical oxygen demand (COD) removal of 67.98%. Meanwhile, it can maintain a stable degradation rate higher than 75% under different pH and temperature conditions. 27 genes that play a key role in HPAM degradation were annotated by metagenomics sequencing. The key genes were involved in multiple KEGG pathways, including biofilm formation, biosynthesis secondary metabolites, and metabolic pathways. SEM, GPC, and FTIR analyses revealed that the structure of HPAM after biodegradation showed pores, a significant decrease in molecular weight, -NH2 detachment, and carbon chain breakage. Particularly, we propose a possible mechanism of biofilm formation - HPAM degradation - biofilm disappearance and reorganization. Moreover, the degradation rate of strain EPDB-5 on real wastewater containing HPAM was 29.97% in only three days. This work expands our knowledge boundary about the HPAM degradation mechanism at the functional gene level, and supports the potential of strain EPDB-5 as a novel auxiliary microbial resource for the practical application of HPAM.

Efficacy and safety of perioperative immunotherapy combinations for resectable non-small cell lung cancer: a systematic review and network meta-analysis.

INTRODUCTION: Several trials of perioperative immunotherapy for resectable non-small cell lung cancer (NSCLC) reported positive results. They were designed to adjuvant, neoadjuvant and sandwich (neoadjuvant plus adjuvant) immunotherapy with immune checkpoint inhibitors and chemotherapy (CT). The differences between neoadjuvant and sandwich modalities were unclear. METHOD: We performed a systematic review and Bayesian network meta-analysis by retrieving relevant literature from PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, WHO ICTRP and major international conferences. RESULTS: We analyzed 8 studies involving 3429 patients, including 6 neoadjuvant plus adjuvant (Neo-Adj) and 2 neoadjuvant (Neo) trials. Neo-Adj had better event-free survival (EFS) (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.45-0.71) than CT. There existed no difference between Neo-Adj and Neo in EFS (HR = 0.87, 95% CI: 0.53-1.46) and overall survival (OS) (HR = 1.04, 95% CI: 0.38-2.57). Neo might have lower incidence of treatment-related adverse events (TRAEs) (relative risk [RR] = 0.96, 95% CI: 0.87-1.12) than Neo-Adj. Subgroup analysis of PD-L1 ≥ 50% suggested that EFS of Neo-Adj (HR = 0.46, 95% CI: 0.27-0.76) and Neo (HR = 0.24, 95% CI: 0.06-0.89) was better than CT, and Neo-Adj potentially caused shorter EFS than Neo (HR = 1.92, 95% CI: 0.46-7.84). CONCLUSIONS: Our results suggest that Neo-Adj and Neo have similar EFS for patients with PD-L1 < 1% or 1-49%. However, patients with PD-L1 ≥ 50% may obtain more EFS benefit from Neo than Neo-Adj. Neo might present a more favorable assessment than Neo-Adj when evaluating OS. Moreover, adding adjuvant immunotherapy may increase toxicity.

Chiral Metal Self-assemblies of Zirconium-Tetrahedra and Their Second Harmonic Generation Activity.

The chirality of metal-organic cages holds enormous potential for novel applications in diverse fields, while it is relatively rare to employ such asymmetric units for the construction of noncentrosymmetric materials. Herein, by self-assembling the 4,4',4''-nitrilotribenzoic acid (H3NBA) with bis(cyclopentadienyl)-zirconium dichloride (Cp2ZrCl2, Cp = η5-C5H5) in different solvent conditions, we have obtained three hierarchical packing modes of metallo-tetrahedra with distinct spatial symmetry groups (designated as Zr-α, Zr-ß, and Zr-γ). Among them, Zr-α employs a simple cubic arrangement and is a common centrosymmetric superstructure, which consists of a pair of equimolar metallo-tetrahedra enantiomers in its unit cell. While Zr-ß results in conglomerates with spontaneous resolution without using any resolving agents, giving rise to two enantiopure entities separately (Zr-ß-P, Zr-ß-M). More importantly, Zr-γ breaks the inversion center of symmetry and crystallizes into a racemic yet non-centrosymmetric superstructure with face-centered cubic packing mode. Based on the non-centrosymmetric nature, the hierarchical superstructure Zr-γ displayed good second harmonic generation activities. This work presents a successful instance wherein the reaction solvent induces the modulation of intermolecular packing mode to afford non-centrosymmetric solid materials, which can greatly promote the development of noncentrosymmetric solid (NCS) materials.

GPR158 in pyramidal neurons mediates social novelty behavior via modulating synaptic transmission in male mice.

Impairment in social communication skills is a hallmark feature of autism spectrum disorder (ASD). The role of G-protein-coupled receptor 158 (GPR158) in ASD remains largely unexplored. In this study, we observed that both constitutive and cell-/tissue-specific knockouts of Gpr158 in pyramidal neurons or the medial prefrontal cortex (mPFC) result in impaired novelty preference, while sociability remains unaffected in male mice. Notably, the loss of GPR158 leads to a significant decline in excitatory synaptic transmission, characterized by a reduction in glutamate vesicles, as well as the expression and phosphorylation of GluN2B in the mPFC. We successfully rescue the phenotype of social novelty deficits either by reintroducing GPR158 in the mPFC of Gpr158 deficient mice or by chemogenetic activation of pyramidal neurons where Gpr158 is specifically ablated. Our findings indicate that GPR158 in pyramidal neurons plays a specific role in modulating social novelty and may represent a potential target for treating social disorders.

In vitro and in vivo performance of amorphous solid dispersions of ursolic acid as a function of polymer type and excipient addition.

OBJECTIVES: The objective of this research was to enhance the bioavailability of ursolic acid (UA) by preparing multielement amorphous solid dispersion (ASD) systems comprising excipients. METHODS: The ASDs were prepared via the solvent evaporation method, characterized by a range of techniques, and investigated with respect to permeability of human colorectal adenocarcinoma cell line (Caco-2) cells monolayers and pharmacokinetics, with comparisons made to the physical mixture and the pure drug. KEY FINDINGS: The (UA-choline)-Polyethylcaprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer (Soluplus)-Vitamin E polyethylene glycol succinate (TPGS) ASD demonstrated superior dissolution properties compared to the corresponding binary solid dispersions and ternary solid dispersions (P < .05). The permeability studies of Caco-2 cell monolayers revealed that the ASD exhibited moderate permeability, with an efflux rate that was significantly lower than that of the UA raw material (P < .05). Pharmacokinetic studies in rats demonstrated that the oral bioavailability of the ASD was 19.0 times higher than that of UA (P < .01). CONCLUSIONS: The research indicated that the multielement ASD could be employed as an efficacious drug delivery system for UA. Furthermore, the Soluplus/TPGS/choline combination represents a promising candidate for the fabrication of ASDs that can load weakly acidic and poorly soluble drugs.

A quantitative model using multi-parameters in dual-energy CT to preoperatively predict serosal invasion in locally advanced gastric cancer.

OBJECTIVES: To develop and validate a quantitative model for predicting serosal invasion based on multi-parameters in preoperative dual-energy CT (DECT). MATERIALS AND METHODS: A total of 342 LAGC patients who underwent gastrectomy and DECT from six centers were divided into one training cohort (TC), and two validation cohorts (VCs). Dual-phase enhanced DECT-derived iodine concentration (IC), water concentration, and monochromatic attenuation of lesions, along with clinical information, were measured and collected. The independent predictors among these characteristics for serosal invasion were screened with Spearman correlation analysis and logistic regression (LR) analysis. A quantitative model was developed based on LR classifier with fivefold cross-validation for predicting the serosal invasion in LAGC. We comprehensively tested the model and investigated its value in survival analysis. RESULTS: A quantitative model was established using IC, 70 keV, 100 keV monochromatic attenuations in the venous phase, and CT-reported T4a, which were independent predictors of serosal invasion. The proposed model had the area-under-the-curve (AUC) values of 0.889 for TC and 0.860 and 0.837 for VCs. Subgroup analysis showed that the model could well discriminate T3 from T4a groups, and T2 from T4a groups in all cohorts (all p < 0.001). Besides, disease-free survival (DFS) (TC, p = 0.015; and VC1, p = 0.043) could be stratified using this quantitative model. CONCLUSION: The proposed quantitative model using multi-parameters in DECT accurately predicts serosal invasion for LAGC and showed a significant correlation with the DFS of patients. CRITICAL RELEVANCE STATEMENT: This quantitative model from dual-energy CT is a useful tool for predicting the serosal invasion of locally advanced gastric cancer. KEY POINTS: Serosal invasion is a poor prognostic factor in locally advanced gastric cancer that may be predicted by DECT. DECT quantitative model for predicting serosal invasion was significantly and positively correlated with pathologic T stages. This quantitative model was associated with patient postoperative disease-free survival.

In Situ Encapsulation of Atomically Precise Nanoclusters in Reticular Frameworks via Mechanochemical Synthesis.

The combination of atomically precise nanoclusters (APNCs) and reticular frameworks is promising for generating component-specific nanocomposites with emergent properties. However, traditional liquid-phase synthesis often hampers this potential by damaging APNCs and limiting combination diversity. Here, mechanochemical synthesis to explore the encapsulation of diverse oil- and water-soluble APNCs within various reticular frameworks is employed, establishing a database of 21 unique APNC-framework combinations, including metal-organic frameworks (MOFs), covalent-organic frameworks (COFs), hydrogen-bonded organic frameworks (HOFs), and multivariate MOFs. These framework coatings not only spatially immobilize APNCs but also secure their structures, preventing aggregation and degradation while enhancing stability and activity. Encapsulating Au25 in HOFs resulted in a remarkable 315-fold increase in catalytic activity compared to Au25 homogeneous catalyst, highlighting the framework's crucial role in catalytic enhancement. The mechanochemical synthesis strategy facilitates tailored support screening, catering to specific needs, and shows promise for developing multifunctional systems, including enzyme-APNC@frameworks material for cascade reactions.

Protein O-GlcNAcylation coupled to Hippo signaling drives vascular dysfunction in diabetic retinopathy.

Metabolic disorder significantly contributes to diabetic vascular complications, including diabetic retinopathy, the leading cause of blindness in the working-age population. However, the molecular mechanisms by which disturbed metabolic homeostasis causes vascular dysfunction in diabetic retinopathy remain unclear. O-GlcNAcylation modification acts as a nutrient sensor particularly sensitive to ambient glucose. Here, we observe pronounced O-GlcNAc elevation in retina endothelial cells of diabetic retinopathy patients and mouse models. Endothelial-specific depletion or pharmacological inhibition of O-GlcNAc transferase effectively mitigates vascular dysfunction. Mechanistically, we find that Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), key effectors of the Hippo pathway, are O-GlcNAcylated in diabetic retinopathy. We identify threonine 383 as an O-GlcNAc site on YAP, which inhibits its phosphorylation at serine 397, leading to its stabilization and activation, thereby promoting vascular dysfunction by inducing a pro-angiogenic and glucose metabolic transcriptional program. This work emphasizes the critical role of the O-GlcNAc-Hippo axis in the pathogenesis of diabetic retinopathy and suggests its potential as a therapeutic target.

Effect of Pouring Techniques and Funnel Structures on Crucible Metallurgy: Physical and Numerical Simulations.

In the planar flow casting process of amorphous strips, the flow behavior of molten metal and the inclusion content in the crucible are crucial to the morphology and magnetic properties of the material. This study conducts a comparative analysis of the effects of non-immersed and immersed funnels, as well as various funnel structures, on the fluid flow and inclusion removal efficiency in the crucible by integrating numerical and physical models. The findings reveal that for the same pouring flow rate, the diameter of the liquid column in non-immersed pouring conditions is smaller than that of the funnel outlet, leading to a faster injection flow velocity. As a result, the melt in the crucible is subjected to severe impacts, accompanied by an increased possibility of slag entrapment. Conversely, immersed pouring substantially reduces the velocity of the molten metal at the funnel outlet, thereby extending the residence time in the crucible and diminishing the volume of the dead zone. Additionally, the molten metal backflows due to the negative pressure formed in the inner chamber of the funnel. The design of a trumpet-shaped funnel increases the effective volume while reducing the height of the backflow fluid, consequently reducing the velocity of the molten metal at the funnel outlet and prolonging the residence time. Compared to the conventional pouring process with the non-immersed funnel, the outlet velocity is reduced from 1.1 m/s to 0.12 m/s by adopting the immersed funnel with an inverted trapezoidal trumpet structure. This reduction results in a stable flow state, a 9.69% reduction in the dead zone volume fraction, and a 22.96% increase in average inclusion removal efficiency. These improvements demonstrate that a crucible funnel with a well-designed structure and the implementation of an immersion process can significantly improve the metallurgical effects in the planar flow casting process.

Preparation of pectin/carboxymethyl cellulose composite films via high-pressure processing and enhancement of antimicrobial packaging.

This study investigated the impact of high-pressure processing (HPP) treatment on the structure and physicochemical properties of pectin (PEC)/carboxymethyl cellulose (CMC) composite films, along with the development of new active films incorporating emodin as an antibacterial agent. The results showed that 500 MPa/20 min HPP treatment significantly improved the tensile strength (from 45.91 ± 4.63 MPa to 52.24 ± 4.87 MPa) and elongation at the break (from 5.00 ± 1.44 % to 11.72 ± 2.97 %) of the films. It also improved the film's thermal stability and had no significant effect on its thermal degradability. Moreover, emodin was incorporated into the PEC/CMC film-forming solution and subjected to 500 MPa/20 min HPP treatment to investigate the structure, functional properties, optical properties, and antibacterial activity of the film. The emodin caused the film structural alteration, but significantly improved the water vapor barrier properties. It also reduced the film brightness and light transmission. The antibacterial assessment demonstrated that the film's antibacterial activity was correlated positively with increasing emodin content, and the number of viable cells of Staphylococcus aureus decreased by 1.29 log10 CFU/mL, 1.70 log10 CFU/mL, and 1.80 log10 CFU/mL with different levels of EM antimicrobial films after 12 h.