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Previous studies have demonstrated that combination therapy involving radiotherapy and aspirin decreases the survival rate of cancer cells. However, the mechanism by which aspirin exerts its radiation sensitization effect at the in vivo level remains largely unclear. In this study, we employed Caenorhabditis elegans (C. elegans) as a model organism to investigate the effect of aspirin combined with radio/chemo-therapy on tumors at the individual level. Here, we illustrate that high-dose aspirin increases the expression of genes involved in core apoptosis pathways (egl-1, ced-9, ced-4 and ced-3) and induces germ cell apoptosis in C. elegans through mitochondrial outer membrane permeabilization (MOMP) and elevation of reactive oxygen species (ROS) levels. Crucially, aspirin-induces ROS upregulates the expression of genes critical for DNA damage response (hus-1, clk-2 and cep-1) and genes involved in MAPK pathways (lin-45, mek-2, mpk-1, sek-1 and pmk-1), thereby mediating the enhanced sensitivity of radio/chemo-therapy by aspirin. Notably, aspirin fails to induce germ cell apoptosis and enhance radio/chemo-therapy in C. elegans lacking the expression of each of those genes. Furthermore, in a C. elegans tumor-like symptom model, aspirin enhances radio/chemo-therapy sensitivity through ROS induction. However, low-dose aspirin can diminish the apoptotic signal of reproductive cells in C. elegans and exert anti-inflammatory effects. Our research results suggest that the tumor-suppressive and radio/chemo-therapy sensitizing effects of aspirin provide robust experimental evidence for improving the clinical efficacy of tumor radio/chemo-therapy and deepening our understanding of aspirin's mechanism of action in cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

While myofibroblasts are the key cause of abnormal extracellular matrix accumulation, the origin of which has not yet been fully elucidated. Recently, it has been found that macrophage-myofibroblast transformation (MMT) defined by the expression of both macrophage markers (F4/80 or CD68) and myofibroblast markers (α-SMA) is one of its important sources. In the process of MMT, it is unclear whether epor is involved. In this study, when BMDM was induced by tgf-β1, the number of F4/80 + α-SMA + cells increased, the cells polarized toward M2, and the expression of tgf-β1 increased. After the activation of epor, the number of F4/80 +α-SMA + cells and the polarization level of M2 were further increased. At the same time, we found that the conditioned medium from MMT cells could induce the activation of 3T3 cells with increased the expression of α-SMA and col-1. In contrast, the number of F4/80+α-SMA + cells, the polarization of M2, and the expression of Tgf-β1 decreased after epor was inhibited by siRNA. Our results demonstrate that the activation of epor in BMDMs could promote the transformation of macrophage-myofibroblast induced by TGF-β1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The synergistic management of energy-water‑carbon (EWC) nexus systems is crucial for achieving the sustainable development goals (SDGs). Therefore, a non-deterministic interval chance-constrained fractional optimization model for EWC nexus system (ICCF-EWC) management has been developed in this study. This model is capable of handling uncertain parameters represented as stochastic probability distributions and interval values, providing an effective approach to addressing dual-objective optimization problems. Meanwhile, this model is expected to investigate the effect of water scarcity/carbon abatement pressure on the overall system, and potential synergistic abatement effects. A case study of Shanxi Province shows that over the next 30 years, the cumulative installed capacity for clean and renewable energy will exceed 65 %. The dominance of coal-fired electricity will be considerably diminished, with wind power overtaking coal/gas-fired power by around 30 %. Moreover, water scarcity and carbon mitigation pressure would promote the development of electricity conversion mode to clean energy rather than the large-scale carbon capture and storage (CCS) technology upgradation of thermal power. The results can help support low-carbon transition of power systems at a province-level in China and financial incentives related policy making to advance water conservation and carbon emission mitigation. The developed model can also be adapted to other energy resource-dependent regional power systems., (Copyright © 2024. Published by Elsevier B.V.)

Background: Ischemia-reperfusion injury (IRI) is an unavoidable consequence post-kidney transplantation, which inevitably leads to kidney damage. Numerous studies have demonstrated that mitophagy is implicated in human cancers. However, the function of mitophagy in kidney transplantation remains poorly understood. This study aims to develop mitophagy-related gene (MRGs) signatures to predict delayed graft function (DGF) and renal allograft loss post-kidney transplantation., Methods: Differentially expressed genes (DEGs) were identified and intersected with the MRGs to obtain mitophagy-related DEGs (MRDEGs). Functional enrichment analyses were conducted. Subsequently, random forest and SVM-RFE machine learning were employed to identify hub genes. The DGF diagnostic prediction signature was constructed using LASSO regression analysis. The renal allograft prognostic prediction signature was developed through univariate Cox and LASSO regression analysis. In addition, ROC curves, immunological characterization, correlation analysis, and survival analysis were performed., Results: Nineteen MRDEGs were obtained by intersecting 61 DEGs with 4897 MRGs. Seven hub genes were then identified through machine learning. Subsequently, a five-gene DGF diagnostic prediction signature was established, with ROC curves indicating its high diagnostic value for DGF. Immune infiltration analysis revealed that many immune cells were more abundant in the DGF group compared to the Immediate Graft Function (IGF) group. A two-gene prognostic signature was developed, which accurately predicted renal allografts prognosis., Conclusions: The mitophagy-related gene signatures demonstrated high predictive accuracy for DGF and renal allograft loss. Our study may provide new perspectives on prognosis and treatment strategies post-kidney transplantation., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024. Published by Elsevier B.V.)

Evidence concerning the impact of sand-dust storms (SDS) on asthma is limited, and little is known about the associated public health burden, especially in regions with arid climate. Therefore, this study seeks to evaluate the effect of SDS on asthma hospitalization and quantify the associated hospital and economic burden in multiple cities with typical arid climate. We collected provincial asthma hospitalization, air pollutants and meteorological data of 14 cities in Gansu province. The space-time-stratified case-crossover design combined with a conditional quasi-Poisson regression was used to estimate the association between SDS and asthma hospitalization during 2018-2022. We further explored the interactive effect of SDS and low temperature, and explored potential effect modifications of gender, age, seasons and regions by stratified analyses. Finally, we calculated the hospital and economic burden of asthma attributed to SDS. A total of 54,134 hospitalization records for asthma and 791 SDS events were recorded during the study period. Northwestern area with arid climate displayed more frequent SDS events and asthma hospitalization compared with regions with subtropical or temperate monsoon climate. The relative risk (RR) of asthma hospitalization increased with SDS, with the greatest RR at lag1, which was 1.164 with a 95% confidence interval (CI) of 1.101-1.231. We further found that low temperature had an interactive effect with SDS to trigger asthma hospitalization. Stronger associations were observed in males, school-aged children, cold season and northwestern area. The total fraction of asthma hospitalization attributable to SDS was 1.64 % (95% CI: 1.06%-2.18%), and a conservative estimate of relative healthcare costs was 4.49 (95% CI: 2.92 to 5.99) million China Yuan. Our findings suggest the necessity of controlling SDS and implementing region-specific public health policies as well as personal protective measures against SDS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Conductive hydrogels have recently gained impressive attention in flexible sensing. However, their low sensing limit and poor interface matching have raised great concern during the practical application. Therefore, incorporating excellent stretchability and adhesiveness into conductive hydrogel is highly desirable but still be a huge challenge. In this study, we synthesized composite hydrogels with desired properties by utilizing the synergistic role of hemicellulose (HC) and conductive two-dimensional material MXene. As a result, the synthesized hydrogels showed good self-adhesion (3.12 KPa on the skin), great stretchability (>1700 %), and satisfactory electrical conductivity. These multifunctional hydrogels operated as adaptable sensors, adeptly capturing the nuanced signals emanating from an array of human motions. They exhibited an expansive strain tolerance, swift reactivity, and an enhanced acuity in detecting even the slightest deformations (GF = 2.1). Our research provides new insights for creating stretchable, self-adhesive, and functional hydrogels for sensing applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The avermectin derivative doramectin is widely used clinically as an antiparasitic drug and, in addition, doramectin may have a modulatory role in obesity. Adipose tissue macrophage recruitment and polarization play an important role in obesity-induced inflammation and insulin resistance. The aim of this study was to investigate the effects of doramectin on high-fat diet-induced inflammation and macrophage polarization in white adipose tissue of epididymis of obese mice. We found that compared with high-fat diet-fed obese mice, doramectin treatment resulted in a significant decrease in body weight and lipid levels, improved insulin resistance, an increase in the proportion of M2-type macrophages and a decrease in the proportion of M1-type macrophages in the epididymal white adipose tissues, as well as a decrease in the infiltration of inflammatory cells in the adipose tissues. Thus, doramectin can ameliorate high-fat diet-induced obesity and adipose inflammation by affecting macrophage polarization in white adipose tissue., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The main function of erythropoietin (EPO) is to promote hematopoiesis and improve anemia. In addition, EPO also has many non-hematopoietic effects such as anti-inflammation, anti-apoptosis and anti-oxidation. To achieve the protective effects, large doses of EPO are required, so the probability of side effects increases. Previous studies have revealed that EPO can improve pulmonary fibrosis in mice, but it has not been clarified whether the hematopoiesis of EPO contributes to amelioration of pulmonary fibrosis and whether EPO improves overall mortality. Our results show that EPO decreases hydroxyproline content, α-sma and col-1 protein levels in mice with bleomycin-induced pulmonary fibrosis. However, compared with the control group, the weight loss and mortality rate of the EPO group were not improved, while the number of red blood cells (RBCs), hemoglobin (Hb), red cell width distribution-coefficient of variation (RDW-CV) and hematocrit (HCT) were significantly higher. Furthermore, we observed massive thrombosis in the lung of EPO treated lung fibrosis mice but not in control mice. Therefore, our results show that in the condition of lung fibrosis, the hematopoietic activity of exogenous EPO is not conducive to its tissue protective effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Accumulation of senescent cells is a recognized feature in hepatocellular carcinoma (HCC), but their specific types and prognostic implications remain under investigation. This study aimed to delineate senescent cell types and their senescent patterns in HCC using publicly available bulk and single-cell mRNA sequencing data. Through gene expression and gene set enrichment analysis, we identified distinct senescent patterns within HCC samples. Notably, unconventional T cells, specifically natural killer T cells and γδT cells, were found to be the predominant senescent cell types. These cells exhibited enriched pathways related to DNA damage, senescence and the negative regulation of lymphocyte activation. Furthermore, we observed upregulation of the mTOR signaling pathway, which correlated positively with the expression of senescence-associated genes. This suggests a potential regulatory role for mTOR in the senescence of HCC. Strikingly, patients with elevated expression of senescence markers, including p16 INK4A , p21, and GLB1, demonstrated significantly reduced overall survival rates. Our findings indicate that immunosenescence in unconventional T cells may play a role in HCC progression. The potential therapeutic implications of targeting the mTOR pathway or eliminating senescent unconventional T cells warrant further exploration to improve HCC patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Chronic exposure to cold temperature is known to elevate blood pressure, leading to a condition known as cold-induced hypertension (CIH). Our previous research suggested correlations between alterations in gut microbiota, decrease in butyrate level, and the onset and progression of CIH. However, the role of butyrate in CIH and the underlying mechanisms need further investigation., Methods: We exposed Specific Pathogen Free (SPF) rats to continuous cold temperature (4 ± 1 °C) for 6 weeks to establish a CIH rat model. Rats were divided into different groups by dose and duration, and the rats under cold were administered with butyrate (0.5 or 1 g/kg/day) daily. We assessed hypertension-associated phenotypes, pathological morphological changes, and endocrine-related phenotypes of brown adipose tissue (BAT). The effects of butyrate on gut microbiota and intestinal content metabolism were evaluated by 16s RNA sequencing and non-targeted metabolomics, respectively., Results: The systolic blood pressure (SBP) of rats exposed to cold after supplemented with butyrate were significantly lower than that of the Cold group. Butyrate may increase the species, abundance, and diversity of gut microbiota in rats. Specifically, butyrate intervention enriched beneficial bacterial genera, such as Lactobacillaceae, and decreased the levels of harmful bacteria genera, such as Actinobacteriota and Erysipeiotrichaceae. Cold exposure significantly increased BAT cells and the number of mitochondria. After butyrate supplementation, the levels of peroxisome proliferator-activated receptor gamma coactivator 1a and fibroblast growth factor 21 in BAT were significantly elevated (P < 0.05), and the volume and number of lipid droplets increased. The levels of ANG II and high-density lipoprotein were elevated in the Cold group but decreased after butyrate supplementation., Conclusion: Butyrate may attenuate blood pressure in CIH by promoting the growth of beneficial bacteria and the secretion of beneficial derived factors produced by BAT, thus alleviating the elevation of blood pressure induced by cold. This study demonstrates the anti-hypertensive effects of butyrate and its potential therapeutic mechanisms, offering novel insights to the prevention and treatment of CIH in populations living or working in cold environments., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

The sensitive and accurate detection of target microRNA is especially important for the diagnosis, staging, and treatment of hepatocellular carcinoma (HCC). Herein, we report a simple strand displacement and CRISPR-Cas12a amplification strategy with nanozymes as a signal reporter for the binary visual and colorimetric detection of the HCC related microRNA. Pt@Au nanozymes with excellent peroxidase enzyme activity were prepared and linked to magnetic beads via a single-stranded DNA (ssDNA) linker. The target microRNA was designed to trigger strand displacement amplification and release a DNA promoter to activate the CRISPR-Cas12a system. The activated CRISPR-Cas12a system efficiently cleaved the linker ssDNA and released Pt@Au nanozymes from magnetic beads to induce the colorimetric reaction of 3,3',5,5'-tetramethylbenzidine. The strand displacement amplification converted the single microRNA input into abundant DNA promoter output, which improved the detection sensitivity by over two orders of magnitude. Through integration of strand displacement amplification and the nanozyme-mediated CRISPR-Cas12a system, limits of detection of 0.5 pM and 10 pM for miRNA-21 were achieved with colorimetric and visual readouts, respectively. The proposed strategy can achieve accurate quantitative detection of miRNA-21 in the range from 1 pM to 500 pM. The detection results for miRNA-21 using both colorimetric and visual readouts were validated in 40 clinical serum samples. Significantly, the proposed strategy achieved visual HCC diagnosis with the naked eye and could distinguish distinct Barcelona clinical HCC stages by colorimetric detection, showing good application prospects for sensitive and facile point-of-care testing for HCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glyphosate resistance is a critically important trait for genetically modified (GM) crops. Mutation of the rice EPSPS gene results in a high level of glyphosate resistance, presenting significant potential for the development of glyphosate-tolerant crops. The resistance of rice to glyphosate is correlated with the expression levels of resistance genes. Therefore, developing a convenient, stable, and sensitive method for quantifying the OsmEPSPS protein is crucial for the development of glyphosate-resistant crops. We developed a double-antibody sandwich quantitative ELISA (DAS-ELISA) using a specific monoclonal antibody (mAb) for OsmEPSPS capture and an HRP-conjugated anti-OsmEPSPS rabbit polyclonal antibody (pAb). The method could be used to detect OsmEPSPS within a linear range of 16-256 ng/mL with robust intra- and inter-batch duplicability (%CV values: 0.17 %-7.24 %). OsmEPSPS expression in the transgenic rice lines (54.44-445.80 μg/g) was quantified using the DAS-ELISA. Furthermore, the expression of the OsmEPSPS gene was validated through Western blotting. This study demonstrated the reliability and stability of the DAS-ELISA for OsmEPSPS detection in GM rice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background & Aims: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) placement remain unclear. This study aimed to identify the ideal moment for hemodynamic measurements and the optimal target of PPG in patients undergoing covered TIPS for variceal bleeding., Methods: Between May 2018 and December 2021, 466 consecutive patients with recurrent variceal bleeding treated with covered TIPS were prospectively included. Post-TIPS PPG was measured immediately (immediate PPG), 24-72 hours (early PPG), and again 1 month (late PPG) after TIPS placement. The agreement among PPGs measured at different time points was assessed by intra-class correlation coefficient (ICC) and Bland-Altman method. The unadjusted and confounder-adjusted effects of PPGs on clinical outcomes (portal hypertensive complications [PHCs], overt hepatic encephalopathy [OHE], further decompensation, and death) were assessed using Fine and Gray competing risk regression models., Results: The agreement between early PPG and late PPG (ICC: 0.34) was better than that between immediate PPG and late PPG (ICC: 0.23, p <0.001). Early PPG revealed an excellent predictive value for PHCs (early PPG≥ vs. <12 mmHg: adjusted hazard ratio 2.17, 95% CI 1.33-3.55, p = 0.002) and OHE (0.40, 95% CI 0.17-0.91, p = 0.030), while immediate PPG did not. Late PPG showed a predictive value for PHC risk but not OHE. By targeting the lowest risk of further decompensation, we identified an optimal hemodynamic target with early PPG ranging from 11 to 14 mmHg that was associated with a decreased risk of OHE and effective prevention of PHC., Conclusions: PPG measured 24 to 72 hours after TIPS correlates with long-term PPG and clinical outcomes, and a hemodynamic target PPG of 11-14 mmHg is associated with reduced encephalopathy but not compromised clinical efficacy., Impact and Implications: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) remain unclear. Here we show that post-TIPS PPG measured at least 24 hours but not immediately after the procedure correlated with long-term PPG and clinical events. Thus, PPG measurements taken at least 24 hours after TIPS should be used to guide decision making in order to improve clinical outcomes. Targeting a post-TIPS PPG of 11-14 mmHg or a 20%-50% relative reduction from pre-TIPS baseline measured 24-72 hours after the procedure was associated with reduced encephalopathy but not compromised clinical efficacy. Thus, these criteria could be used to guide TIPS creation and revision in patients with cirrhosis and variceal bleeding undergoing covered TIPS., Clinical Trial Registration Number: ClinicalTrials.gov, ID: NCT03590288., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Quality indicators in kidney transplants are needed to identify care gaps and improve access to transplants. We used linked administrative health care databases to examine multiple ways of defining pre-emptive living donor kidney transplants, including different patient cohorts and censoring definitions. We included adults from Ontario, Canada with advanced chronic kidney disease between January 1, 2013, to December 31, 2018. We created 4 unique incident patient cohorts, varying the eligibility by the risk of progression to kidney failure and whether individuals had a recorded contraindication to kidney transplant (eg, home oxygen use). We explored the effect of 4 censoring event definitions. Across the 4 cohorts, size varied substantially from 20 663 to 9598 patients, with the largest reduction (a 43% reduction) occurring when we excluded patients with ≥1 recorded contraindication to kidney transplantation. The incidence rate (per 100 person-years) of pre-emptive living donor kidney transplant varied across cohorts from 1.02 (95% CI: 0.91-1.14) for our most inclusive cohort to 2.21 (95% CI: 1.96-2.49) for the most restrictive cohort. Our methods can serve as a framework for developing other quality indicators in kidney transplantation and monitoring and improving access to pre-emptive living donor kidney transplants in health care systems., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Amit Garg received an investigator-initiated grant from Astellas which featured as partnership funds in CIHR-funded research. The other authors declare no conflicts of interest., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Palmitic acid (PA) is a kind of saturated high fatty acid, which is involved in physiological safety and food quality. A surface molecularly imprinted polymer (MIP) electrochemical sensor was prepared on MXene surface using dopamine (DA) as functional monomer. The electrode was modified with gold nanoparticles (AuNPs), ferrocene-graphene oxide-multiwalled carbon nanotubes (Fc-GO-MWCNT) composite to enhance the electroactive area and conductivity. The sensor was characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), electrochemical impedance spectroscopy (EIS) and Differential pulse voltammetry (DPV), respectively. The parameters concerning this assay and various regeneration conditions have been carefully studied. The sensor can detect PA in the range of 1 nM-1 mM (R 2  = 0.995), the limit of detection (LOD) is 0.48 nM (S/N = 3), and the limit of quantification (LOQ) is 1.61 nM. The artificial neural network (ANN) model in machine learning is further used to analyze the data collected by the sensor. The results show that the back propagation (BP) neural network in ANN is more suitable for the intelligent analysis of PA. The practicality of the sensor was confirmed by detecting PA in pork samples. This is the first MIP-based electrochemical sensor for PA, and it has great potential in practical applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Research on the association between maternal PM 2.5 exposure and hypospadias risk in male offspring, particularly in highly polluted areas, has been limited and inconsistent. This study leveraged data from China's National Population-based Birth Defects Surveillance System spanning the years 2013 to 2019, and employed sophisticated machine learning models to estimate daily PM 2.5 levels and other pollutants for mothers at a 1-km resolution and a 6-km buffer surrounding maternal residences. Multivariate logistic regression analyses were performed to evaluate the relationship between PM 2.5 exposure and hypospadias risk. For sensitivity analyses, stratification analysis was conducted, and models for one-pollutant and two-pollutants, as well as distributed lag nonlinear models, were constructed. Of the 1194,431 boys studied, 1153 cases of hypospadias were identified. A 10 μg/m 3 increase in maternal PM 2.5 exposure during preconception and the first trimester was associated with an elevated risk of isolated hypospadias, with Odds Ratios (ORs) of 1.102 (95% CI: 1.023-1.188) and 1.089 (95% CI: 1.007-1.177) at the 1-km grid, and 1.122 (95% CI: 1.034-1.218) and 1.143 (95% CI: 1.048-1.246) within the 6-km buffer. Higher quartiles of PM 2.5 exposure were associated with increased odds ratios compared to the lowest quartile. These findings highlight a significant association between PM 2.5 exposure during the critical conception period and an elevated risk of isolated hypospadias in children, emphasizing the need for targeted interventions to reduce PM 2.5 exposure among expectant mothers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Vegetation redistribution may bring unexpected climate-soil carbon cycling in terrestrial biomes. However, whether and how vegetation redistribution alters the soil carbon pool under climate change is still poorly understood on the Tibetan Plateau. Here, we applied the G-Range model to simulate the cover of herbs, shrubs and trees, net primary productivity (NPP) and soil organic carbon density (SOCD) at the depth of 60 cm on Tibetan Plateau for the individual years 2020 and 2060, using climate projection for Representative Concentration Pathways (RCP) 4.5 and RCP8.5 scenarios with the RegCM4.6 model system. Vegetation redistribution was defined as the transitions in bare ground, herbs, shrubs and trees between 2020 and 2060, with approximately 57.9 % (RCP4.5) and 59 % (RCP8.5) of the area will redistribute vegetation over the whole Tibetan Plateau. The vegetation cover will increase by about 2.4 % (RCP4.5) and 1.9 % (RCP8.5), while the NPP and SOCD will decrease by about -14.3 g C m -2  yr -1 and -907 g C m -2 (RCP4.5), and -1.8 g C m -2  yr -1 and -920 g C m -2 (RCP8.5). Shrubs and trees will expand in the east, and herbs will expand in the northwest part of the Plateau. These areas are projected to be hotspots with greater SOCD reduction in response to future climate change, and will include lower net plant carbon input due to the negative NPP. Our study indicates that the SOC pool will become a carbon source under increased air temperature and rainfall on the Tibetan Plateau by 2060, especially for the area with vegetation redistribution. These results revealed the potential risk of vegetation redistribution under climate change in alpine ecosystems, indicating the policymakers need to pay attention on the vegetation redistribution to mitigate the soil carbon emission and achieve the goal of carbon neutrality on the Tibetan Plateau., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Society for Cryobiology. Published by Elsevier Inc. All rights reserved.)

Polyphenol-protein complexes delivery systems are gaining attention for their potential health benefits and food industry development. However, creating an ideal delivery system requires extensive wet-lab experimentation. To address this, we collected 525 ligand-protein interaction data pairs and established an interaction prediction model using Bilinear Attention Networks. We utilized 10-fold cross validation to address potential overfitting issues in the model, resulting in showed higher average AUROC (0.8443), AUPRC (0.7872), and F1 (0.8164). The optimal threshold (0.3739) was selected for the model to be used for subsequent analysis. Based on the model prediction results and optimal threshold, by verifying experimental analysis, the interaction of paeonol with the following proteins was obtained, including bovine serum albumin (lgK a  = 6.2759), bovine β-lactoglobulin (lgK a  = 6.7479), egg ovalbumin (lgK a  = 5.1806), zein (lgK a  = 6.0122), bovine α-lactalbumin (lgK a  = 3.9170), bovine lactoferrin (lgK a  = 4.5380), the first four proteins are consistent with the predicted results of the model, with lgK a >5. The established model can accurately and rapidly predict the interaction of polyphenol-protein complexes. This study is the first to combine open ligand-protein interaction experiments with Deep Learning algorithms in the food industry, greatly improving research efficiency and providing a novel perspective for future complex delivery system construction., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Plasma amyloid-β (Aβ), phosphorylated tau-181 (p-tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) potentially aid in the diagnosis of neurodegenerative dementias. We aim to conduct a comprehensive comparison between different biomarkers and their combination, which is lacking, in a multicenter Chinese dementia cohort consisting of Alzheimer's disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP)., Methods: We enrolled 92 demented patients [64 AD, 16 FTD, and 12 PSP with dementia] and 20 healthy controls (HC). Their plasma Αβ, p-tau181, NfL, and GFAP were detected by highly sensitive-single molecule immunoassays. Αβ pathology in patients was measured by cerebrospinal fluid or/and amyloid positron emission tomography., Results: All plasma biomarkers tested were significantly altered in dementia patients compared with HC, especially Aβ42/Aβ40 and NfL showed significant performance in distinguishing AD from HC. A combination of plasma Aβ42/Aβ40, p-tau181, NfL, and GFAP could discriminate FTD or PSP well from HC and was able to distinguish AD and non-AD (FTD/PSP)., Conclusions: Our results confirmed the diagnostic performance of individual plasma biomarkers Aβ42/Aβ40, p-tau181, NfL, and GFAP in Chinese dementia patients and noted that a combination of these biomarkers may be more accurate in identifying FTD/PSP patients and distinguishing AD from non-AD dementia., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Seed vigor is an essential quality evaluation index for seed selection. However, accurately detecting the vigor of a single corn seed is challenging. In this study, we constructed a single-fiber spatially resolved detection device using visible/near-infrared spectroscopy to investigate the patterns and correlations between spatially resolved spectroscopy (SRS) at 500-1000 nm and seed vigor. The device collected spectral data at a light source-detector distance of 5-6.6 mm on the embryo side (S1) and endosperm side (S2) of the corn seeds. The proposed spectral ratio method based on SRS and spectral combination analysis achieved an improvement in the detection accuracy of different corn seed vigor. Modeling by SG-CARS-PLSDA using the ratio method showed further improvement in the prediction ability. The highest accuracy for both S1 and S2 in the Zhengdan 958 variety was 91.67 %, while those of S1 and S2 for the Shaandan 650 variety were 86.67 % and 88.33 %, respectively. In addition, SRS was found to be more advantageous in S2 acquisition, verifying the potential of SRS in the non-destructive testing of seed vigor. This provides a favorable reference for the comprehensive evaluation of other internal quality indices of seeds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Food packaging is an essential part of food transportation, storage and preservation. Biodegradable biopolymers are a significant direction for the future development of food packaging materials. As a natural biological polysaccharide, chitosan has been widely concerned by researchers in the field of food packaging due to its excellent film-forming property, good antibacterial property and designability. Thus, the application research of chitosan-based food packaging films, coatings and aerogels has been greatly developed. In this review, recent advances on chitosan-based food packaging materials are summarized. Firstly, the development background of chitosan-based packaging materials was described, and then chitosan itself was introduced. In addition, the design, preparation and applications of films, coatings and aerogels in chitosan-based packaging for food preservation were discussed, and the advantages and disadvantages of each research in the development of chitosan-based packaging materials were analyzed. Finally, the application prospects, challenges and suggestions for solving the problems of chitosan-based packaging are summarized and prospected., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The inflammation of chronic wounds plays a key hindering role in the wound healing process. Slowing down the inflammatory response is significant for the repair of chronic wounds. Studies have revealed that succinate can inactivate gastrin D (GSDMD) and prevent cell pyroptosis. Chitosan has anti-inflammatory properties and is commonly used as wound healing material. Therefore, we used succinic anhydride to modify chitosan and found that N-succinylated chitosan (NSC) was more effective in inhibiting inflammation. The results showed that the stimulation of TNF-α and high glucose induces overexpression of capase-1 and TNF-α in human umbilical vein endothelial cells (HUVEC), and down-expression of CD31. However, the expression of capase-1 and TNF-α decreased, while the expression of CD31, VEGF and IL-10 was up-regulated significantly in dysfunctional HUVEC cells after treated by NSC. Moreover, NSC can speed wound healing, histological examination results showed that wounds treated with NSC exhibited faster epithelial tissue regeneration and thicker collagen deposition. Overall, this study results suggested that NSC has the function of restoring the physiological functions of dysfunctional HUVEC cells induced by high glucose and TNF-α, and can accelerate wound healing, indicating that NSC has good potential to be applied in inflammatory chronic wounds such as diabetic foot., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Understanding energy expenditure in children with chronic disease is critical due to the impact on energy homeostasis and growth. This systematic review aimed to describe available literature of resting (REE) and total energy expenditure (TEE) in children with chronic disease measured by gold-standard methods of indirect calorimetry (IC) and doubly labeled water (DLW), respectively. A literature search was conducted using OVID Medline, Embase, CINAHL Plus, Cochrane, and Scopus until July 2023. Studies were included if the mean age of the participants was ≤18 y, participants had a chronic disease, and measurement of REE or TEE was conducted using IC or DLW, respectively. Studies investigating energy expenditure in premature infants, patients with acute illness, and intensive care patients were excluded. The primary outcomes were the type of data (REE, TEE) obtained and REE/TEE stratified by disease group. In total, 271 studies across 24 chronic conditions were identified. Over 60% of retrieved studies were published >10 y ago and conducted on relatively small population sizes (n range = 1-398). Most studies obtained REE samples (82%) rather than that of TEE (8%), with very few exploring both samples (10%). There was variability in the difference in energy expenditure in children with chronic disease compared with that of healthy control group across and within disease groups. Eighteen predictive energy equations were generated across the included studies. Quality assessment of the studies identified poor reporting of energy expenditure protocols, which may limit the validity of results. Current literature on energy expenditure in children with chronic disease, although extensive, reveals key future research opportunities. International collaboration and robust measurement of energy expenditure should be conducted to generate meaningful predictive energy equations to provide updated evidence that is reflective of emerging disease-modifying therapies. This study was registered in PROSPERO as CRD42020204690., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Artificial light at night has become an emerging environmental pollutant, posing a serious threat to biodiversity. Cave-roosting animals are vulnerable to light pollution due to long-term adaptation to nocturnal niches, and the problem is especially severe in the context of cave tourism and limestone mining. Mitigating the adverse impacts of artificial light on cave-dwelling animals presents a challenge. This study aimed to assess the relative contributions of spectral parameters and light intensity to the emergence behavior of nine cave-roosting bat species: Rhinolophus macrotis, Rhinolophus pearsonii, Rhinolophus rex, Rhinolophus pusillus, Rhinolophus siamensis, Rhinolophus sinicus, Hipposideros armiger, Myotis davidii, and Miniopterus fuliginosus. We manipulated light spectra and intensities through light-emitting diode (LED) lighting and gel filters at the entrance of bat roost. We monitored nightly passes per species to quantify bat emergence under the dark control and ten lighting conditions (blue, green, yellow, red, and white light at high and low intensities) using ultrasonic recording. Our analyses showed that the number of bat passes tended to be reduced in the presence of white, green, and yellow light, independent of light intensity. In contrast, the number of bat passes showed no pronounced differences under the dark control, blue light, and red light. The number of bat passes was primarily affected by LED light's blue component, red component, peak wavelength, and half-width instead of light intensity. These results demonstrate that spectral parameters of LED light can significantly affect emergence behavior of cave-dwelling bats. Our findings highlight the importance of manipulating light colors to reduce the negative impacts of light pollution on cave-roosting bats as a function of their spectral sensitivity. We recommend the use of gel filters to manage existing artificial lighting systems at the entrance of bat-inhabited caves., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Temperature has been recognized as an important environmental factor affecting the composition and function of gut microbiota (GM). Although research on high-temperature impacts has been well studied, knowledge about the effect of cold exposure on GM remains limited. This narrative review aims to synthesize the latest scientific findings on the impact of cold exposure on mammalian GM, and its potential health implications. Chronic cold exposure could disrupt the α-diversity and the composition of GM in both experimental animals and wild-living hosts. Meanwhile, cold exposure could impact gut microbial metabolites, such as short-chain fatty acids. We also discussed plausible biological pathways and mechanisms by which cold-induced changes may impact host health, including metabolic homeostasis, fitness and thermogenesis, through the microbiota-gut-brain axis. Intriguingly, alterations in GM may provide a tool for favorably modulating the host response to the cold temperature. Finally, current challenges and future perspectives are discussed, emphasizing the need for translational research in humans. GM could be manipulated by utilizing nutritional strategies, such as probiotics and prebiotics, to deal with cold-related health issues and enhance well-being in populations living or working in cold environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Effective control of wound bleeding and sustained promotion of wound healing remain a major challenge for hemostatic materials. In this study, the hemostatic sponge with controllable antibacterial and adjustable continuous promotion of wound healing (CMNCu) was prepared by chitosan, aminated MXene and copper ion. Interestingly, the internal topological point-line-surface interaction endowed the CMN-Cu sponge longitudinal staggered tubular porous microstructure, combined with the lipophilic properties obtained by modified MXene, which greatly improved its flexibility, wet elasticity and blood enrichment capacity. In addition, the sponge achieved controlled release of active ingredients, which made it present highly effective antibacterial activity and long-lasting ability to promote wound healing. In vitro and in vivo experiments confirmed that CMN-Cu sponge presented high-efficient hemostatic performance. Last but not least, a series of cell experiments showed that the CMN-Cu sponge had excellent safety as a hemostatic material., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The unknown daytime source of HONO has been extensively investigated due to unexplained atmospheric oxidation capacity and current modelling bias, especially during cold seasons. In this study, abrupt morning increases in atmospheric HONO at a rural site in the North China Plain (NCP) were observed almost on daily basis, which were closely linked to simultaneous rises in atmospheric water vapor content and NH 3 concentrations. Dew and guttation water formation was frequently observed on wheat leaves, from which water samples were taken and chemically analyzed for the first time. Results confirmed that such natural processes likely governed the daily nighttime deposition and daytime release of HONO and NH 3 , which have not been considered in the numerous HONO budget studies investigating its large missing daytime source in the NCP. The dissolved HONO and NH 3 in leaf surface water droplets reached 1.4 and 23 mg L -1 during the morning on average, resulting in averaged atmospheric HONO and NH 3 increases of 0.89 ± 0.61 and 43.7 ± 29.3 ppb during morning hours, with relative increases of 186 ± 212 % and 233 ± 252 %, respectively. The high atmospheric oxidation capacity contained within HONO was stored in near surface liquid water (such as dew, guttation and soil surface water) during nighttime, which prevented its atmospheric dispersion after sunset and protected it from photodissociation during early morning hours. HONO was released in a blast during later hours with stronger solar radiation, which triggered and then accelerated daytime photochemistry through the rapid photolysis of HONO and subsequent OH production, especially under high RH conditions, forming severe secondary gaseous and particulate pollution. Results of this study demonstrate that global ecosystems might play significant roles in atmospheric photochemistry through nighttime dew formation and guttation processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

As the representative item of environmental chemical carcinogen, MNNG was closely associated with the onset of Gastric cancer (GC), while the underlying mechanisms remain largely unknown. Here, we comprehensively analyzed the potential clinical significance of METTL3 in multiple GC patient cohorts. Additionally, we demonstrated that long-term exposure to MNNG elevated METTL3 and EMT marker expression by in vitro and in vivo models. Furthermore, the depletion of METTL3 impacted the proliferation, migration, invasion, and tumorigenesis of MNNG malignant transformation cells and GC cells. By me-RIP sequencing, we identified a panel of vital miRNAs potentially regulated by METTL3 that aberrantly expressed in MNNG-induced GC cells. Mechanistically, we showed that METTL3 meditated miR-1184/TRPM2 axis by regulating the process of miRNA-118. Our results provide novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: The impact of global warming on health due to climate change is increasingly studied, but the global burden of self-harm and interpersonal violence attributable to high temperature is still limited. This study aimed to systematically assess the burden of self-harm and interpersonal violence attributable to high temperature globally or by region and climate zone from 1990 to 2019., Methods: We obtained the global, regional, and national deaths, disability-adjusted life years (DALYs), age-standardized mortality rates (ASMR), and age-standardized disability-adjusted life year rates (ASDR) of self-harm and interpersonal violence due to high temperature from 1990 to 2019 through the Global Burden of Disease Study (GBD) 2019. The burden of self-harm and interpersonal violence due to high temperature was estimated by age, sex, climate zone, the socio-demographic index (SDI), and the healthcare access and quality index (HAQ). Average annual percentage changes (AAPCs) in ASMR and ASDR were calculated for 1990-2019 using the Joinpoint model., Results: From 1990 to 2019, the global deaths and DALYs related to self-harm and interpersonal violence due to high temperature increased from 20,002 (95% UI, 9243 to 41,928) and 1,107,216 (95% UI, 512,062 to 2,319,477) to 26,459 (95% UI, 13,574 to 47,265) and 1,382,487 (95% UI, 722,060 to 2,474,441), respectively. However, the ASMR and ASDR showed varying degrees of decreasing trends, with decreases of 13.36% and 12.66%, respectively. The ASMR was high and declining in low and low-middle SDI regions, particularly in tropical and subtropical regions. In addition, SDI and HAQ index were negatively correlated with ASMR in 204 countries and regions., Conclusions: The global burden of self-harm and interpersonal violence attributed to high temperature has decreased over the past 30 years, but the number of deaths and DALYs continues to rise. Climate change continues to make heat stress a significant risk factor for self-harm and interpersonal violence worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A pea starch (PS) and pulp cellulose nanofibers (CNF-P) hybrid matrix biodegradable film was prepared using apple polyphenol (AP) as the active substance. SEM and thermogravimetric analyses showed that apple polyphenols could be uniformly distributed and form hydrogen bonds with the matrix, and the increase in crystallinity improved the thermal stability of the films (the final residue of the films increased from 22.66 % to 31.82 %). The TS and EAB of the films reached their maximum values of 11.14 ± 1.73 MPa and 71.55 ± 8.8 %, respectively, at an AP content of 1.5 %. It should be noted that the antioxidant properties of the films were significantly positively correlated with the AP content, and the DPPH radical scavenging rate of the films reached 73.77 % at an AP content of 4.5 %, which was about 49 times higher than that of the control film. The same trend was observed in the UV-vis spectra. In addition, the total color difference and water solubility of the membranes increased from 4.29 ± 0.29 to 31.86 ± 1.90 and from 20.01 ± 0.97 % to 21.70 ± 1.99 %, respectively, and the biodegradability also showed an upward trend. These findings provide a theoretical basis and data support for the development of multifunctional biodegradable food packaging materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In continuation of our program to search for novel potential anti-ischemic stroke agents, a series of 1,3,4-oxadiazole and sulfoxide hybrids of phthalide derivatives was designed and synthesized in this study to evaluate their anti-ischemic stroke activity. Among them, compounds 5b, 5d, 5 l, and 5 m exhibited excellent inhibitory effects on platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid (AA). In particular, compound 5b possessed considerable antithrombotic activity in animal models, as demonstrated by the effective alleviation of carrageenan-induced and FeCl 3 -induced thrombosis in tail and carotid arteries, respectively. Notably, intraperitoneal administration of compound 5b could better protect the brain from injury caused by ischemia/reperfusion in rats compared with precursor 3-n-butylphthalide. Further pharmacokinetics, liver microsomal stability, and PAMPA-BBB assays also indicated that compound 5b had relatively high bioavailability, metabolic stability, and BBB permeability. Moreover, compound 5b showed a safety profile that was superior to the clinical drugs clopidogrel, aspirin, and 3-n-butylphthalide in the mouse-tail bleeding assay. Finally, molecular docking predicted that the potential target of the antiplatelet aggregation activity of compound 5b was P2Y12 receptor. This research provides a novel candidate compound for the treatment of ischemic stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Prymnesium parvum is a toxin-producing haptophyte that causes harmful algal blooms worldwide, which are often associated with massive fish-kills and subsequent economic losses. In here, we present nuclear and plastid genome assemblies using PacBio HiFi long reads and DNBseq short reads for the two P. parvum strains UTEX 2797 and CCMP 3037, representing producers of type A prymnesins. Our results show that the P. parvum strains have a moderate haptophyte genome size of 97.56 and 107.32 Mb. The genome assemblies present one of highest contiguous assembled contig sequences to date consisting of 463 and 362 contigs with a contig N50 of 596.99 kb and 968.39 kb for strain UTEX 2797 and CCMP 3037, respectively. The assembled contigs of UTEX 2797 and CCMP 3037 were anchored to 34 scaffolds, with a scaffold N50 of 5.35 Mb and 3.61 Mb, respectively, accounting for 93.2 % and 97.9 % of the total length. Each plastid genome comprises a circular contig. A total of 20,578 and 19,426 protein-coding genes were annotated for UTEX 2797 and CCMP 3037. The expanded gene family analysis showed that starch and sucrose metabolism, sulfur metabolism, energy metabolism and ABC transporters are involved in the evolution of P. parvum. Polyketide synthase (PKS) genes responsible for the production of secondary metabolites such as prymnesins displayed different expression patterns under nutrient limitation. Overlap with repeats and horizontal gene transfer may be two contributing factors to the high number of PKS genes found in this species. The two high quality P. parvum genomes will serve as valuable resources for ecological, genetic, and toxicological studies of haptophytes that can be used to monitor and potentially manage harmful blooms of ichthyotoxic P. parvum in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Fine particulate matter (PM 2.5 ) adversely affects blood lipids, while residential greenspace exposure may improve blood lipids levels. However, the association between exposure to residential greenspace and blood lipids has not been adequately studied, especially in vulnerable populations (e.g. people with essential hypertension). This study aimed to assess the association between residential greenspace exposure and blood lipids, and to clarify whether PM 2.5 and chemical constituents was mediator of it. We used a period (May 2010 to December 2011) from the Chinese national hypertension project. The residential greenspace was estimated using satellite-derived normalized difference vegetation index (NDVI). The generalized additive mixed model (GAMM) was used to assess the association between exposure to residential greenspace and blood lipids, and the mediation model was used to examine whether there was a mediating effect of PM 2.5 and chemical constituents on that association. The exposure to residential greenspace was negatively associated with the decreased risk of dyslipidemia, especially short-term exposure. For example, the odd ratio short-term for dyslipidemia was 0.915 (95% CI：0.880 to 0.950). This association was strengthened by physical activity and participants living in the North. PM 2.5 and chemical constituents were important mediators in this association, with the proportion of mediators ranging from -5.02% to 26.33%. The association between exposure to residential greenspace and dyslipidemia in this essential hypertensive population, especially participants living in the North and doing daily physical activity, was mediated by PM 2.5 and chemical constituents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Sepsis represents a profound proinflammatory response with a major contribution from oxidative injury. Here we evaluated possible impact of heavy metal scavenger metallothionein (MT) on endotoxin lipopolysaccharide (LPS)-induced oxidative stress, endoplasmic reticulum (ER) stress, autophagy, and ferroptosis enroute to myocardial injury along with interplay among these stress domains., Materials and Methods: Echocardiographic, cardiomyocyte mechanical and intracellular Ca 2+ responses were monitored in myocardia from WT and transgenic mice with cardiac-selective MT overexpression challenged with LPS. Oxidative stress, stress signaling (p38, ERK, JNK), ER stress, autophagy, and ferroptosis were scrutinized., Key Findings: RNAseq analysis revealed discrepant patterns in ferroptosis between LPS-exposed and normal murine hearts. LPS insult enlarged LV end systolic dimension, suppressed fractional shortening, ejection fraction, maximal velocity of shortening/relengthening and peak shortening, as well as elongated relengthening along with dampened intracellular Ca 2+ release and reuptake. In addition, LPS triggered oxidative stress (lowered glutathione/glutathione disulfide ratio and O 2 - production), activation of stress cascades (p38, ERK, JNK), ER stress (GRP78, PERK, Gadd153, and IRE1α), inflammation (TNFα and iNOS), unchecked autophagy (LCB3, Beclin-1 and Atg7), ferroptosis (GPx4 and SLC7A11) and interstitial fibrosis. Although MT overexpression itself did not reveal response on cardiac function, it attenuated or mitigated LPS-evoked alterations in echocardiographic, cardiomyocyte contractile and intracellular Ca 2+ characteristics, O 2 - production, TNFα level, ER stress and ferroptosis (without affecting autophagy, elevated AMP/ATP ratio, and iNOS). In vitro evidence revealed beneficial effects of suppression of oxidative stress, ER stress and ferroptosis against LPS-elicited myocardial anomalies., Significance: These data strongly support the therapeutic promises of MT and ferroptosis in septic cardiomyopathy., Competing Interests: Declaration of competing interest No potential conflict of interest exists for any authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A flame retardant high-performance gelatinized starch (GS)-ammonium dihydrogen phosphate (ADP) wood adhesive, named GS-ADP adhesive was prepared by condensation of GS and ADP under acidic condition. The preparation process of GS-ADP adhesive is very simple by mixing and stirring GS and ADP evenly at room temperature. The results revealed that the GS-ADP adhesive has good storage stability and water resistance, and its wet shear strength is much higher than that of phenolic resin (PF) adhesive. Markedly, the cone calorimeter test results show that G-ADP adhesive has good flame retardancy, and the plywood based on GS-ADP adhesive has good flame retardancy. Meanwhile, it can be seen from dynamic mechanical analysis (DMA) and thermogravimetric analysis (TGA) that GS-ADP has excellent modulus of elasticity (MOE), high glass transition temperature (Tg) and good thermal stability. The findings suggest that GS-ADP could be a viable substitute for PF resin in structural wood fabrication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Antipsychotic drug treatment for schizophrenia (SZ) can alter brain structure and function, but it is unclear if specific regional changes are associated with treatment outcome. Therefore, we examined the effects of antipsychotic drug treatment on regional grey matter (GM) density, white matter (WM) density, and functional connectivity (FC) as well as associations between regional changes and treatment efficacy. SZ patients (n = 163) and health controls (HCs) (n = 131) were examined by structural magnetic resonance imaging (sMRI) at baseline, and a subset of SZ patients (n = 77) were re-examined after 8 weeks of second-generation antipsychotic treatment to assess changes in regional GM and WM density. In addition, 88 SZ patients and 81 HCs were examined by resting-state functional MRI (rs-fMRI) at baseline and the patients were re-examined post-treatment to examine FC changes. The Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were applied to measure psychiatric symptoms and cognitive impairments in SZ. SZ patients were then stratified into response and non-response groups according to PANSS score change (≥50 % decrease or <50 % decrease, respectively). The GM density of the right cingulate gyrus, WM density of the right superior frontal gyrus (SFG) plus 5 other WM tracts were reduced in the response group compared to the non-response group. The FC values between the right anterior cingulate and paracingulate gyrus and left thalamus were reduced in the entire SZ group (n = 88) after treatment, while FC between the right inferior temporal gyrus (ITG) and right medial superior frontal gyrus (SFGmed) was increased in the response group. There were no significant changes in regional FC among the non-response group after treatment and no correlations with symptom or cognition test scores. These findings suggest that the right SFG is a critical target of antipsychotic drugs and that WM density and FC alterations within this region could be used as potential indicators in predicting the treatment outcome of antipsychotics of SZ., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFN γ ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFN γ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFN γ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy., Competing Interests: The authors declare no conflicts of interest., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Breast cancer is one of the most common malignant tumors in women worldwide, and thus, it is important to enhance its treatment efficacy [1]. Copper has emerged as a critical trace element that affects various intracellular signaling pathways, gene expression, and biological metabolic processes [2], thereby playing a crucial role in the pathogenesis of breast cancer. Recent studies have identified cuproptosis, a newly discovered type of cell death, as an emerging therapeutic target for breast cancer treatment, thereby offering new hope for breast cancer patients. Tsvetkov's research has elucidated the mechanism of cuproptosis and uncovered the critical genes involved in its regulation [3]. Manipulating the expression of these genes could potentially serve as a promising therapeutic strategy for breast cancer treatment. Additionally, using copper ionophores and copper complexes combined with nanomaterials to induce cuproptosis may provide a potential approach to eliminating drug-resistant breast cancer cells, thus improving the therapeutic efficacy of chemotherapy, radiotherapy, and immunotherapy and eventually eradicating breast tumors. This review aims to highlight the practical significance of cuproptosis-related genes and the induction of cuproptosis in the clinical diagnosis and treatment of breast cancer. We examine the potential of cuproptosis as a novel therapeutic target for breast cancer, and we explore the present challenges and limitations of this approach. Our objective is to provide innovative ideas and references for the development of breast cancer treatment strategies based on cuproptosis., Competing Interests: Declaration of Competing Interest No potential conflicts of interest are disclosed., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cadmium (Cd) causes severe toxicity in plants. However, the molecular mechanisms underlying plant resistance to Cd in relation to nitrogen (N) supply remain unclear. The non-symbiotic hemoglobin gene Hb1 plays an important role in scavenging nitric oxide (NO) in plants. In this study, there was no differential effect of Cd on the biomass of wild-type (WT) and AHb1-overexpressing (H7) plants when NH 4 + -N was used as a nitrogen source. However, under NO 3 - -N conditions, Cd exerted less biomass stress on AHb1-silenced (L3) plants and more stress on H7 plants than on WT plants. The Cd tolerance index followed the order: L3 > WT > H7. However, there was no difference in Cd concentrations in the roots or shoots of the WT, L3, and H7 plants, indicating that differences in AHb1 expression were unrelated to Cd uptake. Further investigation showed that Cd exposure enhanced H 2 O 2 accumulation and aggravated oxidative damage in H7 plants. The application of an NO donor effectively reversed growth inhibition, H 2 O 2 burst, and oxidative stress induced by Cd in H7 plants. Thus, we suggest that NO 3 - -induced AHb1 expression suppresses Cd-induced NO production in plants, increasing the ROS burst and exacerbating Cd toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

DNA topoisomerase I (TOP1) catalytic inhibitors are a promising class of antitumor agents. Oleanolic acid derivatives are potential TOP1 catalytic inhibitors. However, their inhibitory activity still needs to be enhanced, and the stability and hotspot residue sites of their interaction with TOP1 remain to be elucidated. Herein, a novel oleanolic acid derivative, OA4 (N-(3-(methyl(3-(orotic amido)propyl)amino)propyl)oleanolamide), was identified by rational design. Subsequently, molecular dynamics simulations were performed to explore the stability and conformational dynamics of the TOP1-OA4 complex. The molecular mechanics/generalized Born surface area method calculated the binding free energy and predicted Arg488, Ile535, and His632 to be hotspot residues. Biological experiments verified that OA4 is a nonintercalative TOP1 catalytic inhibitor. OA4 exhibits better proliferation inhibitory activity against tumor cells than normal cells. Furthermore, OA4 can induce apoptosis and effectively suppress the proliferation and migration of cancer cells. This work provides new insights for the development of novel TOP1 catalytic inhibitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)