Yang Zhang’s research while affiliated with Changshu Institute of Technology and other places

Zizania latifolia is the second aquatic vegetable in China. The circular valorization of its waste bracts remains ongoing concern. In this work, the cellulase‐microwave‐assisted extraction (CMAE) of polysaccharides from waste Z. latifolia bracts (PWZLBs) was explored. Seven parameters were selected via single‐factor test, of which three significant parameters were screened out using Plackett‐Burman design, followed by response surface methodology optimization. The optimal CMAE for PWZLBs were: cellulase addition of 0.5%, microwave time of 7 min, and microwave power of 425 W, resulting in a yield of 0.82 ± 0.08%. Four polysaccharide fractions (PWZLBs‐1 ~ 4) were isolated from PWZLBs, of which PWZLBs‐1 accounted for major proportion and exerted higher scavenging capacities on diphenyl picryl hydrazinyl and hydroxyl radicals. More importantly, PWZLBs‐1 elicited anticoagulation via prolonging thrombin time and prothrombin time, exhibiting potential for cardiovascular protection. Various characterizations confirmed that PWZLBs‐1 is a heteropolysaccharide containing uronic acids and sulfates, with galactose (34.3%) as the predominant monosaccharide, and has a molecular weight of 8061 kDa. This work provides clues for the circular valorization of waste Z. latifolia bracts and offers potential opportunities for the development of new cardiovascular protective drugs.

Chemotherapy-induced neuropathic pain (CINP) is a prevalent side effect of chemotherapy. Total glucosides of paeony (TGP) have been shown to be effective in pain management. This study aimed to investigate the efficacy and mechanism of TGP in alleviating CINP. Sprague–Dawley rats were treated with oxaliplatin to establish CINP models, and BV2 microglia were exposed to lipopolysaccharides (LPS) to induce pyroptosis. The impact of TGP on CINP was assessed by measuring mechanical withdrawal threshold (MWT), cold pain threshold (CPT), and thermal pain threshold (TPT), as well as inflammatory factor levels. Pyroptosis was evaluated using flow cytometry, lactate dehydrogenase (LDH) release, and pyroptosis marker levels. Quantitative real-time PCR and molecular docking were employed to identify TGP targets, while phospho-kinase arrays, western blotting, and co-immunoprecipitation were used to elucidate the mechanism. Results indicated that TGP increased MWT, CPT, and TPT and inhibited inflammatory factor release in CINP rats. Furthermore, TGP suppressed LPS-induced pyroptosis and downregulated KAT2A expression in BV2 cells; this suppression was reversed by KAT2A overexpression. Mechanistically, KAT2A overexpression activated the p38 pathway and promoted p38 succinylation at K295. KAT2A knockdown inhibited pyroptosis in LPS-induced BV2 cells, an effect that was reversed by the p38 activator metformin. Additionally, the improvements in MWT, CPT, TPT, and inflammatory factor levels observed in CINP rats treated with TGP were negated by KAT2A overexpression. In conclusion, TGP alleviated CINP by suppressing microglial pyroptosis through inhibition of the KAT2A-mediated p38 pathway activation and succinylation. This study provides insights into a potential new therapeutic approach for CINP.

Background Glaucoma is a group of heterogeneous neurodegenerative diseases with abnormal energy metabolism and imbalanced neuroinflammation in the retina. Thioredoxin-interacting protein (TXNIP) is involved in glucose and lipid metabolism, and associated with oxidative stress and inflammation, however, not known whether to be involved in glaucoma neuropathy and its underlying mechanisms. Methods To establish the chronic ocular hypertension (COH) mice model. Western blot, RT-PCR, immunofluorescence and F-VEP were used to detect neuroinflammation level, glial activation and RGCs survival in retina of wild type, TXNIP knockout and MCC950 treatment COH mice. Microglia high-pressure cultured model was constructed. Western blot, RT-PCR and immunofluorescence were used to investigate the proinflammatory cytokines secretion, glucose uptake and phenotype transformation in wild type, TXNIP knockout and overexpressed microglia combined with IL-17A treatment. Finally, we explored the possible underlying mechanisms using relevant pathway inhibitor interventions. Results In this study, for the first time we reported that TXNIP expression was remarkably increased in experimental glaucomatous retina of chronic ocular hypertension (COH) mice, and it was mainly expressed in the ganglion cells layer (GCL). In addition, we found that ablation of TXNIP promoted retinal ganglion cells (RGCs) survival and alleviated visual function impairment in experimental glaucoma. Then, we explored the spatiotemporal consistency between glial activation and retinal inflammation levels in COH mice respectively with TXNIP-deficiency and under treatment of a thermo-containing protein domain 3 (NLRP3) inhibitor MCC950, and the results indicated that TXNIP probably mediated neuroinflammation in glaucomatous retina by activating microglia. Furthermore, upregulation of TXNIP was found in pressure-stimulated microglia, whereas silencing TXNIP facilitated microglial polarization trending towards M1 type and reduced glucose transporter-1 (Glut-1) expression on microglia under high pressure in vitro. Moreover, IL-17A was found to play a role in acting synergistically with TXNIP upon the regulation of microglia polarity transformation. Finally, knockout of TXNIP was revealed to promote PI3K phosphorylation, whereas inhibition of PI3K by LY294002 effectively suppressed Glut-1 expression, glucose uptake, and M1-like transformation tendency in microglia obtained from TXNIP-deficiency mice under high pressure stimulation. Conclusions TXNIP is significantly involved in the inflammation-related neuropathy of experimental glaucoma and probably facilitates M1-like microglial transformation via PI3K/Akt pathway.

Background Although alcohol consumption is considered one of the risk factors for delirium in intensive care unit (ICU) patients, quantitative research on the association between alcohol use disorder (AUD) and the development of delirium in the ICU remains relatively scarce. Methods This retrospective cohort study was conducted using the Medical Information Mart for Intensive Care-IV database, including all patients admitted to the ICU for the first time and underwent delirium assessment. Patients were divided into AUD and non-AUD groups, with the primary outcome being the occurrence of ICU delirium. Propensity score matching (PSM) was used to balance baseline characteristics between the two groups. The association between AUD and the occurrence of ICU delirium was evaluated using Cox proportional hazards and competing risk models, with sensitivity and subgroup analyses to assess the stability of the results. Results A total of 35,053 patients were included, with 3,455 (9.9%) in the AUD group. The incidence of ICU delirium and ICU mortality were significantly higher in the AUD group compared to the non-AUD group, with a longer median ICU stay. Multivariable Cox regression analysis, adjusting for all covariates, revealed a significant association between AUD and increased risk of ICU delirium (HR 1.59, 95% CI 1.50–1.69, P < 0.01). After PSM, multivariable Cox regression analysis showed consistent results (HR 1.52, 95% CI 1.41–1.65, P < 0.01), and these results remained consistent after performing competitive risk analysis. Conclusions We found a significant correlation between AUD and the incidence of delirium in the ICU, highlighting the importance of assessing and managing the risk of delirium in patients with AUD in the ICU. Clinical trial number Not applicable.

The tearing mode, a large-scale MHD instability in tokamak, typically disrupts the equilibrium magnetic surfaces, leads to the formation of magnetic islands, and reduces core electron temperature and density, thus resulting in significant energy losses and may even cause discharge termination. This process is unacceptable for ITER. Therefore, the accurate identification of a magnetic island in real time is crucial for the effective control of the tearing mode in ITER in the future. In this study, based on the characteristics induced by tearing modes, an attention-aware convolutional neural network (AM-CNN) is proposed to identify the presence of magnetic islands in tearing mode discharge utilizing the data from ECE diagnostics in the EAST tokamak. A total of 11 ECE channels covering the range of core is used in the tearing mode dataset, which includes 2.5*10^9 data collected from 68 shots from 2016 to 2021 years. We split the dataset into training, validation, and test sets (66.5%, 5.7%, and 27.8%), respectively. An attention mechanism is designed to couple with the convolutional neural networks to improve the capability of feature extraction of signals. During the model training process, we utilized adaptive learning rate adjustment and early stopping mechanisms to optimize performance of AM-CNN. The model results show that a classification accuracy of 91.96% is achieved in tearing mode identification. Compared to CNN without AM, the attention-aware convolutional neural networks demonstrate great performance across accuracy, recall metrics, and F1 score. By leveraging the deep learning model, which incorporates a physical understanding of the tearing process to identify tearing mode behaviors, the combination of physical mechanisms and deep learning is emphasized, significantly laying an important foundation for the future intelligent control of tearing mode dynamics.

Amino acids are the basic structural units of life, and their intake levels affect disease and health. In the case of renal disease, alterations in amino acid metabolism can be used not only as a clinical indicator of renal disease but also as a therapeutic strategy. However, the biological roles and molecular mechanisms of natural chiral amino acids in human proximal tubular epithelial cells (HK-2) remain unclear. In this study, cell viability assays revealed that chiral acidic amino acids (Glu and Asp) and aromatic amino acids (Trp and Phe) inhibited cell growth. The molecular mechanisms indicated that cell growth was closely related to ROS levels. Specifically, chiral Glu, Asp, Trp, and Phe induced oxidative stress and mitochondria-dependent apoptosis in HK-2 cells. This was manifested by elevated levels of intracellular ROS, 8-OHdG, and MDA, increased activities of antioxidant enzymes CAT, SOD, and GPx, decreased mitochondrial membrane potential, increased cytoplasmic Ca2+ concentration, and cell acidification. The expression levels of apoptosis-related molecules Caspase-9, Caspase-3, Cyt-C, and Bax were increased, and the expression level of anti-apoptotic molecule Bcl-2 was decreased. Moreover, L-Glu, D-Asp, L-Trp, and D-Phe exhibited a more pronounced inhibition of cell growth and elicited more substantial alterations in gene expression compared to the other configurations.

Endometrial collagen I undergoes dynamic degradation and remodelling in response to endometrial stromal cell (ESC) decidualization and embryo implantation. However, excessive collagen I deposition in the endometrium during the implantation window may impair decidualization, causing embryo implantation failure in patients with endometriosis (EMS). We found that endometrial collagen I expression during the mid-secretory phase was increased in the EMS group of patients. Collagen I stimulation resulted in decreased expression of the decidualization markers prolactin and insulin-like growth factor binding protein-1 in ESCs, impeding ESC transformation to a decidual morphology and decreasing the blastocyst-like spheroid expansion area in vitro. Treatment with extracellular vesicles (EVs) derived from the ectopic ESCs of EMS patients (EMS-EVs) increased collagen I expression in vivo and in vitro and decreased the blastocyst-like spheroid expansion area. Furthermore, EV microRNA (miRNA) sequencing revealed that there were 40 upregulated and 77 downregulated miRNAs in EMS-EVs when compared to the EVs derived from ESCs in the endometrium of control patients (CTL-EVs), including increased expression of miR-25-3p that targets phosphatase and tensin homolog (PTEN). We also found that PTEN expression was decreased and p-Akt expression was increased in the endometrium of EMS patients and EMS-EV-treated ESCs. miR-25-3p transfected ESCs exhibited increased collagen I, decreased PTEN, and increased p-Akt. Additionally, an EV uptake study further showed that EMS-EVs were preferentially taken up by ESCs rather than by endometrial epithelial cells. These results suggest that EMS-EVs encapsulating miR-25-3p might be preferentially taken up by eutopic ESCs where they may induce endometrial collagen I deposition to impair ESC decidualization in EMS.

Plain Language Summary For global greenhouse gas monitoring, passive remote sensing technology has consistently struggled to balance the reliability and usability of monitoring data in cloudy regions. The AEMS employs 1,572 nm IPDA lidar technology for active remote sensing of global XCO2, enabling effective processing and utilization of cloud echo data. In this study, we focused on the concentrations of CO2 columns using cloud top echoes and performed a preliminary comparison of cloud top XCO2 results with related data products from the passive satellite OCO‐2 and CarbonTracker. By quantifying the difference in CO2 concentration between two altitude layers above the sea surface, we assessed ocean carbon absorption capacity, and the results demonstrated high reliability. This work highlights the significant advantages of spaceborne IPDA lidar in global CO2 measurement, cloud echo data processing, and ocean carbon flux assessment, providing valuable data support for climate change research.