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Alveolar epithelial cell (AEC) senescence is a key driver of a variety of chronic lung diseases. It remains a challenge how to alleviate AEC senescence and mitigate disease progression. Our study identified a critical role of epoxyeicosatrienoic acids (EETs), downstream metabolites of arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating AEC senescence. In vitro, we found that 14,15-EET content was significantly decreased in senescent AECs. Exogenous EETs supplementation, overexpression of CYP2J2, or inhibition of EETs degrading enzyme soluble epoxide hydrolase (sEH) to increase EETs alleviated AECs' senescence. Mechanistically, 14,15-EET promoted the expression of Trim25 to ubiquitinate and degrade Keap1 and promoted Nrf2 to enter the nucleus to exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) and alleviating AEC senescence. Furthermore, in D-galactose (D-gal)-induced premature aging mouse model, inhibiting the degradation of EETs by Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, an inhibitor of sEH) significantly inhibited the protein expression of p16, p21, and γH2AX. Meanwhile, TPPU reduced the degree of age-related pulmonary fibrosis in mice. Our study has confirmed that EETs are novel anti-senescence substances for AECs, providing new targets for the treatment of chronic lung diseases.

Research regarding the use of Nano clay to remove toxic GO (Graphene oxide) from wastewater was limited. Through a variety of characterization techniques and methods, the adsorption performance and mechanism of Nano clay for GO were systematically studied. The related effects of solution pH, temperature, adsorbent dose, and GO concentration were studied in detail. The results show that the aggregation and deposition of GO on Nano clay depends on the pH value of the solution and the type and concentration of the electrolyte, and the isotherm data fits well with the Langmuir equation. Under the best conditions (pH=3.0), the maximum removal rate is 97.8% (C0=60 mg·L-1), and the adsorption capacity is 245.8 mg.g-1 (C0=80 mg.L-1, T=303K, equilibrium time=24 h, m=10 mg). Specifically, the dissolution of Nano clay at a relatively low pH or a high pH value helps the aggregation of GO. The results of this study provide key information for predicting the fate of GO in the land-water transition zone where Nano clay exists.

Action quality assessment refers to evaluate the action quality performed by human in video,such as calculating the quality score,level and evaluating the performance of different people.It is an important direction in video understanding and computer vision research.This paper summarizes the main methods of action quality assessment,including action quality score prediction methods,level classification and ranking methods.The performance of these methods on public datasets is also analyzed.Finally,the challenge problems in future research are discussed.

This study evaluates the impact of an expanded HIV testing initiative, launched in June 2018 in Luzhou, Sichuan, China, on antiretroviral therapy (ART) initiation rates among people living with HIV (PLWH). Using an uncontrolled interrupted time-series design, we analyzed data from 11,040 PLWH between June 2016 and December 2022, extracted from 108 health facilities via the Center for Disease Control and Prevention's ART database. The primary outcome measures were ART initiation rates within 7 and 30 days of HIV diagnosis. Results showed a significant improvement in the 30-day ART initiation rate following expanded testing, increasing from 46.1% to 90.9% by the study's end. The 7-day initiation rate also improved but remained below 30%. The study found that expanded testing enhanced the role of primary health care institutions in ART initiation. However, the COVID-19 pandemic, beginning January 2020, negatively impacted ART initiation rates, with a slight effect on 30-day rates but a persistent negative impact on 7-day rates. Despite these challenges and an increased HIV burden, Luzhou's ART initiation rates surpassed the national average. This study emphasizes the effectiveness of expanded HIV testing in ensuring timely ART access, crucial for HIV epidemic control, and improved patient outcomes. It also reveals challenges in maintaining HIV services during public health crises, offering insights into health care system resilience. Future research should focus on evaluating long-term treatment outcomes and strategies to support ending the AIDS epidemic. [ABSTRACT FROM AUTHOR]

Chemical N-glycoconjugation can provide a unique way to tailor the properties of the ubiquitous amines for further expending their diverse functions and applications. Nevertheless, effective methodology for glycoconjugation of amines remains largely underdeveloped. Inspired by a biotransformation pathway of amine-containing drugs in vivo, we have developed an effective protocol that enables one-step chemical N-glycoconjugation of amines in high stereoselectivity under mild conditions. This protocol involves conversion of the amine moiety into the corresponding carbamate anion under CO2 atmosphere and a subsequent SN2 type reaction with glycosyl halides. This work provides an example of using CO2 as the coupling unit in chemical glycoconjugation reactions. A case study on the resulting N-glycoconjugates of Crizotinib, an anticancer drug, demonstrates a quick cleavage of the glucosyl carbamate linkage, testifying that this N-glyconjugation method could serve as a general approach to procure novel prodrugs. Effective methodology for glycoconjugation of amines remains underdeveloped. Here the authors report an effective protocol that enables one-step chemical N-glycoconjugation of amines in high stereoselectivity under mild conditions, inspired by a biotransformation pathway of amine-containing drugs in vivo. [ABSTRACT FROM AUTHOR]

Polyvinyl alcohol (PVA)-based hydrogels have attracted significant attention due to their excellent biocompatibility, tunable mechanical properties, and ability to form stable three-dimensional networks. This comprehensive review explores the recent advancements in PVA-based hydrogels, focusing on their unique properties, fabrication strategies, and multifunctional applications. Firstly, it discusses various facile synthesis techniques, including freeze/thaw cycles, chemical cross-linking, and enhancement strategies, which have led to enhanced mechanical strength, elasticity, and responsiveness to external stimuli. These improvements have expanded the applicability of PVA-based hydrogels in critical areas such as biomedical, environmental treatment, flexible electronics, civil engineering, as well as other emerging applications. Additionally, the integration of smart functionalities, such as self-healing capabilities and multi-responsiveness, is also examined. Despite progress, challenges remain, including optimizing mechanical stability under varying conditions and addressing potential toxicity of chemical cross-linkers. The review concludes by outlining future perspectives, emphasizing the potential of PVA-based hydrogels in emerging fields like regenerative medicine, environmental sustainability, and advanced manufacturing. It underscores the importance of interdisciplinary collaboration in realizing the full potential of these versatile materials to address pressing societal challenges. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study. RESEARCH DESIGN AND METHODS: This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time. RESULTS: During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time. CONCLUSIONS: Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D. [ABSTRACT FROM AUTHOR]

Cold-adapted species are able to generate cryoprotective proteins and glycoproteins to prevent freezing damage. The [→4)- β -D-Man p -(1→4)- β -D-Xyl p -(1→] n xylomannan from the Alaska beetle Upis ceramboides was disclosed by Walters and co-workers in 2009 as the first glycan-based antifreeze agent, which was later reported to be found in diverse taxa. Here, we report the rapid synthesis of four types of xylomannans, including the proposed antifreeze xylomannan up to a 64-mer (Type I), the regioisomeric [→3)- β -D-Man p -(1→4)- β -D-Xyl p -(1→] n 16-mer (Type II), the diastereomeric [→4)- β -L-Man p -(1→4)- β -D-Xyl p -(1→] n 16-mer (Type III) and the block-wise [→4)- β -D-Man p -(1→] m [→4)- β -D-Xyl p -(1→] n 32-mer (Type IV), by employing a strategic iterative exponential glycan growth (IEGG) process. The nuclear magnetic resonance spectral data of the alleged natural xylomannan are in accordance only to those of the block-wise Type IV glycan and none of these synthetic xylomannans has been found to be capable of inducing thermal hysteresis. These results disprove the previous reports about the natural occurrence of antifreeze xylomannans. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B-cell lymphoma (DLBCL), which is considered to be the most common subtype of lymphoma, is an aggressive tumor. Necroptosis, a novel type of programmed cell death, plays a bidirectional role in tumors and participates in the tumor microenvironment to influence tumor development. Targeting necroptosis is an intriguing direction, whereas its role in DLBCL needs to be further discussed.Methods: We obtained 17 DLBCL-associated necroptosis-related genes by univariate cox regression screening. We clustered in GSE31312 depending on their expressions of these 17 genes and analyzed the differences in clinical characteristics between different clusters. To investigate the differences in prognosis across distinct clusters, the Kaplan-Meier method was utilized. The variations in the tumor immune microenvironment (TME) between distinct necroptosis-related clusters were investigated via “ESTIMATE”, “Cibersort” and single-sample geneset enrichment analysis (ssGSEA). Finally, we constructed a 6-gene prognostic model by lasso-cox regression and subsequently integrated clinical features to construct a prognostic nomogram.Results: Our analysis indicated stable but distinct mechanism of action of necroptosis in DLBCL. Based on necroptosis-related genes and cluster-associated genes, we identified three groups of patients with significant differences in prognosis, TME, and chemotherapy drug sensitivity. Analysis of immune infiltration in the TME showed that cluster 1, which displayed the best prognosis, was significantly infiltrated by natural killer T cells, dendritic cells, CD8+ T cells, and M1 macrophages. Cluster 3 presented M2 macrophage infiltration and the worst prognosis. Importantly, the prognostic model successfully differentiated high-risk from low-risk patients, and could forecast the survival of DLBCL patients. And the constructed nomogram demonstrated a remarkable capacity to forecast the survival time of DLBCL patients after incorporating predictive clinical characteristics.Conclusion: The different patterns of necroptosis explain its role in regulating the immune microenvironment of DLBCL and the response to R-CHOP treatment. Systematic assessment of necroptosis patterns in patients with DLBCL will help us understand the characteristics of tumor microenvironment cell infiltration and aid in the development of tailored therapy regimens.