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Hypertrophic cardiomyopathy (HCM) is an inherited disease of the heart muscle that is dominated by variations in eight genes encoding sarcomere proteins. Although there are clinical or basic research reports that carrying double mutations can lead to more severe HCM phenotypes, there are also research reports that after reanalyzing the reported mutations, the severity of clinical symptoms in patients with double mutations did not significantly increase compared to patients with only one mutation. To determine whether double pathogenic mutations can aggravate the phenotype of hypertrophic cardiomyopathy in mice, we constructed mice carrying single pathogenic heterozygous mutation Myh6-R453C or Tnnt2-R92W and mice carrying both pathogenic heterozygous mutations. Our results showed that mice with double heterozygous mutations exhibited significant hypertrophic cardiomyopathy phenotypes at 4 weeks of age, and the degree of hypertrophy was significantly higher than that of single heterozygous mutant mice of the same age. Our study suggests that carrying the two pathogenic heterozygous mutations simultaneously can aggravate the phenotype of HCM in mice, which provides experimental evidence for the genotype-phenotype relationship of double pathogenic mutations and provides reference significance for clinical risk stratification of HCM patients., 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.)

Mining activities disrupt the natural oxidative balance underground, increasing the oxidation of metal sulfides like pyrite. This process leads to the formation of highly acidic mine drainage (AMD) with elevated concentrations of iron (Fe) and sulfate (SO 4 2- ). However, generic plugging and backfilling methods, when applied without considering the specific post-mining oxidative environments of different metal mines, often yields minimal results. To clarify the distribution of the underground redox environment after mining of a metal mine in Dexing, China, fifteen water samples from flood and dry periods, as well as fifteen borehole samples, were collected for hydrogeological and chemical analysis. For the first time, the study proposed that the redox zone could be identified and delineated through vertical analysis of water storage media, mineral composition, and hydrochemical characteristics. A hydrogeochemical cause model was constructed, revealing that AMD formation primarily occurs in oxidative and transition zones. Based on the redox zone characteristics of the study area, actual engineering sealing was performed on the oxidation and transition zones of cavity No. 23. As a result, the pH increased from 2.5 before remediation to 4.5, indicating a reduction in acidity. The concentrations of SO 4 2- and Fe significantly decreased, reducing from 1360.0 mg/L and 147.0 mg/L before treatment to 726.0 mg/L and 23.6 mg/L after treatment; the total decrease amounting to 46.6 % and 84.0 %, respectively. The concentrations of Mn and Cu similarly, decreased by 10.7 % and 15.6 %, respectively. This study provides a novel approach and valuable reference for the refined identification and classification of redox zones after metal mine exploitation, as well as for the targeted plugging and treatment of cavities that produce AMD., 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.)

Grasslands are the most extensively distributed terrestrial ecosystems on Earth, providing a range of ecosystem services that are vital for sustaining human life and critical for sustainable development at the global scale. However, the relationship between the two most important attributes of grassland, plant diversity, and productivity, remains controversial even after many years of research. Here, we develop an analysis of covariance (ANCOVA) model based on decadal-scale experimental data from a degraded meadow steppe in northeastern Inner Mongolia, China to quantify the response of aboveground biomass (AGB) to plant species diversity under varying management regimes. We report that AGB responds negatively to the plant diversity in fallow grasslands and positively in grazing grasslands, transiting from negative to positive in mowing grasslands as mowing became more frequent. We show that the changing diversity-productivity relationships are driven by changes in species composition of the plant community, given the significant productivity gap between rare and non-rare species. This highlights the role of management in regulating the diversity-productivity relationships in grasslands. These results not only provide provocative insights into the relationships between plant diversity and productivity but also support more sustainable use and management of grassland resources., 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 growing demand for natural rubber products has driven the expansion of rubber plantations in recent decades. While much attention has been given to studying the long-term effects of rubber and rubber-based agroforestry systems on surface soil properties, there has been a tendency to overlook changes in soil properties in deeper layers. Our study addresses this gap by examining alterations in nitrogen (N), phosphorus (P), and metal ion levels in deep soil layers resulting from the prolonged cultivation of rubber and rubber-based agroforestry systems. We found notable shifts in soil NH 4 + and NO 3 - concentrations within the 0-30 cm soil layer across different-aged rubber and rubber-based agroforestry systems. Particularly in mature systems, NO 3 - and available P levels were close to zero below 30 cm soil depth. Introducing Flemingia macrophylla into young rubber plantations increased soil NH 4 + and NO 3 - in the 0-90 cm soil layer and available P in the 0-10 cm soil layer. Over the long term, cultivation of rubber plantations increased the depletion of total P in the 0-50 cm soil layer, available iron (Fe) and manganese (Mn) in the 30-90 cm soil layer, available copper (Cu) and zinc (Zn) in the 0-90 cm soil layer, accompanied by a decrease in soil pH and increase in exchangeable aluminum (Al) in the 0-90 cm soil layer. Notably, soil exchangeable Al levels exceeding 2.0 cmol kg -1 appeared to induce aluminum toxicity. Furthermore, soil pH below 5.2 triggered a sharp release of exchangeable Al within the 0-90 cm soil layer of rubber plantations, with soil available P nearing zero when exchangeable Al levels assed 7.3 cmol kg -1 . Our findings underscore the profound impact of long-term rubber plantation cultivation on surface and deep soil properties. Addressing soil degradation in these deep soil layers poses significant challenges for future soil restoration efforts., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The growth in municipal solid waste incineration (MSWI) has resulted in a substantial rise in the production of fly ash in China. It is anticipated that during the "14th Five-Year Plan", the accumulated amount of fly ash stocked and disposed of at landfills will surpass 100 million tons. With the development of the economy and the implementation of garbage classification relevant policies, the pollution characteristics of heavy metal change in spatiotemporal distribution. Solidification/stabilization (S/S) pre-treatment coupled with landfill disposal is the mainstream method for fly ash. This study provides a systematic overview and comparison of the current application status and research on the mechanism of S/S technology, and the long-term stability of solidified/stabilized fly ash is a crucial factor in controlling the risks of landfills. Subsequently, it examines the influencing factors and mechanisms associated with heavy metals leaching under different environmental scenarios (meteorological factors, leachate and acid rain erosion, and carbonation, etc.), and concludes that single stabilization technology is difficult to meet long-term landfill requirements. Finally, the limits of heavy metal leaching toxicity evaluation methods and landfilled fly ash supervision were discussed, and relevant suggestions for future development were proposed. This study can provide theoretical instruction and technical support for the risk control of potential environmental risks of heavy metals in solidified/stabilized fly ash from landfills in China., 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.)

Establishing a method similar to ICP-MS that can quantitatively analyze multiple heavy metals simultaneously, conveniently, and in situ is highly anticipated. In this study, we integrated the sensing elements of multiple targets and different fluorescence reporting elements to construct an engineered Escherichia coli. When these targets are present, the engineered bacteria can emit a fluorescent signal at the corresponding wavelength. To avoid the inability to accurately distinguish and quantify the content of each target due to the overlap of fluorescence signals when multiple targets coexist, a hydrogel-based separation platform similar to a separation column was constructed. The hydrogel platform can change the detection limit (LOD) and sensitivity by adjusting the adsorption strength towards different targets, so as to realize the differentiation and recognition of their respective detection signals. The LODs of this new detection method for Cd(II), Hg(II), As(III), and Pb(II) are 1.249, 0.380, 3.917, and 0.755 μg/L, respectively. In addition, this biosensor system was applied to detect coexisting Cd(II), Hg(II), As(III), and Pb(II) in actual samples with a recovery rate of 85.61-110.30 %, which is consistent with the classical ICP-MS detection results, confirming the accuracy and reliability of the method for detecting multiple heavy metal coexisting samples., 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.)

Introduction: In the transition to the postpandemic era, adolescents are working to shift their focus back to school. However, the prevalence of academic procrastination is reflective of that the aftereffects of the pandemic are persisting. Literature documents the increases in the negative parenting behaviors and internet use of adolescents during the pandemic. The excessive internet use has to do with adolescents' self-regulatory capabilities and self-regulation is profoundly shaped by parents' parenting practices. Given the connections among these factors, the present study seeks to understand how maladaptive parenting practices during the pandemic influenced adolescents' academic procrastination postpandemic through the mediation of self-regulation and problematic internet use., Method: Using three waves of data from a total of 1062 Chinese adolescents (Mage = 14.9 years old, SD = 1.6, 13-18 years old; 45% female), we used structural equation modeling to examine the direct effect of maladaptive parenting on academic procrastination and its indirect effect via self-regulation and problematic internet use., Results: Maladaptive parenting during the pandemic did not directly predict adolescent academic procrastination post-pandemic. Yet, maladaptive parenting indirectly influenced academic procrastination both through self-regulation solely and self-regulation and problematic internet use sequentially., Conclusion: The findings demonstrate that parents can contribute to adolescents' academic procrastination by influencing their self-regulation ability, which further impacts their internet use. Self-regulation serves as a robust mediator between parenting and adolescents' problematic behaviors related to internet use and learning. Implications for parents and intervention oriented toward adolescents are discussed., (© 2024 Foundation for Professionals in Services to Adolescents.)

Background: Primary non-function (PNF) and early allograft failure (EAF) after liver transplantation (LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function (MEAF), PNF score by King's College (King-PNF) and Balance-and-Risk-Lactate (BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF., Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic (ROC) and the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses., Results: Of all 720 patients, 28 (3.9%) developed PNF and 67 (9.3%) developed EAF in 3 months. The overall early allograft dysfunction (EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0 (3.5-6.3), -2.1 (-2.6 to -1.2), and 5.0 (2.0-11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves (AUCs) of 0.872 and 0.891, superior to BAR-Lac (AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF., Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Surface sulfidation has been widely investigated to effectively enhance the utilization and selectivity of iron electrons for enhanced pollutant reduction. However, there is relatively less knowledge on whether sulfidation facilitates the catalytic oxidation process and the mechanism of enhancement. Therefore, in this study, the role of surface sulfidation in modulating the oxidant decomposition pathway and reactive oxygen species generation was investigated with the sulfidated zerovalent iron (S-ZVI) activated persulfate (PS) system. The results revealed that sulfur on the surface of S-ZVI not only facilitates PS activation to generate more SO 4 •- , but also acts as an essential in the dynamic equilibrium between SO 4 •- and • OH. Specifically, the S-ZVI surface sulfide first forms sulfur monomers during catalysis, which promotes electron transfer to accelerate Fe 3+ to Fe 2+ cycling, prompting the generation of more SO 4 •- also generates SO 3 2- . Then, SO 3 2- is further reacted with • OH to generate the [O - -O-SO 3 - ] intermediate of SO 4 •- , which leads to a dynamic equilibrium of SO 4 •- and • OH, mitigating the further conversion of SO 4 •- to • OH. These findings unveiled the dynamic variation of sulfur on the surface of S-ZVI during PS activation, elevating new insights for the sulfate radical-based efficient degradation., 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.)

Arsenate [As(V)] pollution is a challenge for water treatment, and the effect of coexisting microplastics (MPs) on As(V) removal is still not clear. In this study, series novel covalently bonded organic silicon-aluminum/iron composite coagulants (CSA/F) with different Al/Fe molar ratios were prepared for enhancing As(V) removal. The effect mechanism of MPs (PS MPs and PS-COOH MPs) on As(V) removal by using CSAF coagulation was analyzed. CSAF and CSF showed significantly better As(V) removal performance than other coagulants under the same conditions, especially CSF, more than 90 % As(V) removal was achieved at dosage of 20 mg/L and pH of 4.0-8.0. Interestingly, the introduction of silane coupling agent and the increase of Fe content in CSA/F changed the Al/Fe species distribution. Charge neutralization dominant in As(V) removal by using CSA, whereas adsorption and net sweeping contributed to As(V) coagulation by using CSAF and CSF with higher iron proportion at neutral pH. 3 µm MPs were removed by net sweeping of amorphous Al/Fe hydroxides, while 26 µm MPs were charge-neutralized or surface adsorbed by coagulant hydrolysates. The aliphatic C-H and -COOH functional groups of MPs were the main sites of hydrogen bonding adsorption with the hydroxyl groups of coagulant hydrolysates. This study is conducive to mitigating the environmental toxicity of arsenic and provides new insights into the interaction mechanism between composite pollutants and coagulants in waters., 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.)

Microplastics (MPs) are a global concern as an emerging pollutant, and the investigation on MPs in Antarctic aids in informing their global pollution assessments. Therefore, there are urgent scientific concerns regarding the environmental behavior, origins, influencing factors, and potential hazards of MPs in Antarctica. This study presents the characteristics of MPs from one ornithogenic sediment profile (coded CC) and two ornithogenic soil profiles (coded MR1 and MR2) from ice-free areas on Ross Island, Antarctica. We explored the potential sources of MPs and the main influencing factors for deposition based on their distribution with depth in the profiles. Through laser-infrared imaging spectroscopy (LDIR), a total of 30 polymer types were identified in all samples, with polyethylene terephthalate (PET) and polyvinyl chloride (PVC) as the dominant types, accounting for more than 70% of the total. The abundance of MPs in the CC sediment profile ranged from 2.83 to 394.18 items/g, while in MR1 and MR2 soil profiles, the abundance ranged from 2.25 to 1690.11 and 8.24 to 168.27 items/g, respectively. The size of MPs was mainly concentrated in the range of 20-50 μm, and possible downward movement of certain polymer types was revealed. From the perspective of temporal variation, we suggest that MPs were heavily influenced by local human activities including scientific research, fishing, and tourism, balanced by protective regulations, while no solid evidence was obtained to support strong influence from biological transport through penguins. This research enhances our understanding on the environmental behavior of MPs in the terrestrial systems of remote polar regions., 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.)

4-n-butylresorcinol (4nBR) is a frequently utilized as whitening ingredients in skincare cosmetics. Compared with other whitening ingredients, it can effectively inhibit tyrosinase with lower toxicity and superior inhibition efficacy. Under alkaline conditions, an induced oxidative coupling reaction can occur between 4nBR and dopamine (DA) to generate strong fluorescent substance azamonardine with an intense emission band centering at 476 nm when excited at 440 nm. This phenomenon can be used to establish a fluorescence analysis method for 4nBR. The results indicated that the linear range of the method was 1.0-24.0 nmol L -1 , and the detection limit was as low as 0.25 nmol L -1 . The method showed high sensitivity, good selectivity, mild experimental conditions and low cost. The proposed method was successfully used to detect 4nBR in cosmetics, and the results were consistent with those of HPLC. The spiking recoveries were between 98.2% and 108 %., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: End-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations., Objective: This study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers., Methods: ESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates., Results: Among 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs., Conclusion: Elevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population., 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.)

From both environment and health perspectives, sustainable management of ever-growing soil contamination by heavy metal is posing a serious global concern. The potential ecotoxicity of cadmium (Cd) to soil and ecosystem seriously threatens human health. Developing efficient, specific, and long-term remediation technology for Cd-contaminated soil is impending to synchronously minimize the bioavailability and ecotoxicity of Cd. In the present study, zinc oxide/graphene oxide nanocomposite (ZnO/GO) was developed as a novel amendment for remediating Cd-contaminated soil. Our results showed that ZnO/GO effectively decreased the available soil Cd content, and increased pH and cation exchange capacity (CEC) in both Cd-spiked standard soil and Cd-contaminated mine field soil through the interaction between ZnO/GO and soil organic acids. Using Caenorhabditis elegans (C. elegans) as a model organism for soil safety evaluation, ZnO/GO was further proved to decrease the ecotoxicity of Cd-contaminated soil. Specifically, ZnO/GO promoted Cd excretion and declined Cd storage in C. elegans by increasing the expression of gene ttm-1 and decreasing the level of gene cdf-2, which were responsible for Cd transportation and Cd accumulation, respectively. Moreover, the efficacy of ZnO/GO in remediating the properties and ecotoxicity of Cd-contaminated soil increased gradually with the time gradient, and could maintain a long-term effect after reaching the optimal remediation efficiency. Our findings established a specific and long-term strategy to simultaneously improve soil properties and reduce ecotoxicity of Cd-contaminated soil, which might provide new insights into the potential application of ZnO/GO in soil remediation for both ecosystem and human health., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: An Xu reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they 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.)

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.)

Anthropogenic pressure in areas of biodiversity importance erodes the integrity of the ecosystems they harbour, making features of biodiversity less buffered against extreme climatic events. We define the combination of these disturbances as compound events. We assessed compound event risk in protected areas (PAs) applying a spatial framework guided by criteria and quantitative thresholds associated with exposure to cyclones, drought, and intense human pressure. This assessment was used in a relational matrix to classify PAs with different risk of compound event occurrence. We identified PAs of higher conservation concern by quantifying the extent of human pressure in their surrounding landscape while harbouring large numbers of threatened vertebrate species. Of the 39,694 PAs assessed, very high risk of compound events was determined for 6965 PAs (17.5 %) related to cyclones and human pressure (mainly island hotspots), 6367 PAs (16 %) related to droughts and human pressure (island and continental hotspots), and 2031 PAs (5 %) to cyclones, drought and human pressure (mainly in island hotspots). From the subset of 2031 PAs assessed at very high risk, we identified 239 PAs of higher conservation concern distributed predominantly in the Caribbean Islands, Japan, North America Coastal Plain, Philippines, and Southwest Australia. Our work highlights PAs in the biodiversity hotspots where high risk of compound event occurrence poses a greater threat to species. We encourage researchers to adapt and apply this framework across other globally significant sites for conserving biodiversity to identify high risk-prone areas, and prevent further biodiversity decline., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The establishment of marine ranching demonstration areas is crucial for restoring offshore fishery resources, fostering ecosystem harmony, and creating blue "carbon sinks" in China. While their ecological benefits are evident, their impact on surrounding areas remains uncertain. This study takes the first batch of national marine ranching demonstration areas established in 2015 as a quasi-natural experiment and uses synthetic control methods to empirically evaluate the effects and mechanisms of their construction on regional ecological efficiency. Results show heterogeneous impacts, with positive effects in Jiangsu and Liaoning but negligible elsewhere. Mechanism analysis reveals that marine ranching demonstration areas enhance ecological efficiency through economic growth, and industrial structure optimization. Differences in marine ranching types and regulations influence their impact, with public welfare-oriented marine ranching showing greater positive effects compared to aquaculture-oriented ones. Overall, these findings hold theoretical and practical implications for advancing modern marine ranching construction., Competing Interests: Declaration of competing interest We hereby declare that we do not have any financial or personal relationships with individuals or organizations that could potentially exert undue influence on our work. Furthermore, we have no professional or personal interests, of any kind, in any product, service, or company that could be perceived as influencing our position or the manuscript review process., (Copyright © 2024. Published by Elsevier Ltd.)

Thiosulfate has been considered as a more environmentally-friendly alternative to cyanide salts for the extraction of gold from gold ores and the development of affordable, green and efficient adsorbents for the isolation of gold-thiosulfate complex (Au(S 2 O 3 ) 2 3- ) from the leaching solution remains a significant challenge. To address this issue, chitosan, a natural macromolecule, was selected as a carrier and chemically modified with ionic liquids. The ionic liquids modified chitosan showed greater adsorption capacity towards Au(S 2 O 3 ) 2 3- compared with pristine chitosan. The adsorption of Au(S 2 O 3 ) 2 3- on ionic liquid modified chitosan followed Freundlich isotherm and pseudo-second order kinetic models, involving an anion-exchange mechanism with liquid film diffusion as the rate-limiting step. The chitosan modified with butylimidazolium-based ionic liquid had an adsorption capacity of 5.0 mg g -1 for gold (10 mg L -1 of gold, pH 6, 2 g L -1 of adsorbent dosage), outperforming other reported adsorbents. The ionic liquid modified chitosan showed a high adsorption efficiency of up to 96.7 % for Au(S 2 O 3 ) 2 3- in an actual thiosulfate leaching solution with a desorption efficiency of 98.4 %, suggesting that the ionic liquid modified chitosan has the potential to be a eco-friendly, biocompatible and effective adsorbent for the recovery of Au(S 2 O 3 ) 2 3- ., 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.)

Integrins are heterodimers composed of two subunits, α(120-185kD) and β (90-110kD), which mediate the connection between cells and their external environment, such as extracellular matrix (ECM), and play an important role in the regulation of cell shape, proliferation and migration. Herein, we identified a potent anti-tumor migration peptide Accutin from crude venom of Agkistrodon acutus using an A549 3D tumor sphere model, and simulation tools and RNA sequencing were performed to reveal the mechanism of Accutin. Accutin is a disintegrin and docking, molecular dynamics simulations and ITC assay indicate that the RGD motif in the Accutin sequence can stably bind to integrins α5β1. 9.22 nM Accutin can significantly inhibit the migration and invasion of lung cancer cell lines. Transcriptome analysis indicated that many genes are involved in tumor cell adhesion-related biological processes. Several pathways, like the "mTOR signaling pathway", "TGF-β signaling pathway", and "Focal adhesion" were enriched. Interestingly, pathways involved in "N-Glycan biosynthesis" etc. were significantly inhibited. These transcriptomics data suggested that the molecular basis of Accutin-mediated inhibition of cancer cell migration may be by inhibiting N-glycosylation of integrin, then inhibiting signaling pathways such as PI3K/AKT/mTOR and TGFβ/smad. Western blotting analysis further confirmed that Accutin could suppress migration via down-regulating the phosphorylation of FAK and AKT and inhibiting EMT (epithelial-mesenchymal transition). Taken together, as a disintegrin with high efficiency, Accutin may be a potential precursor of a therapeutic agent for the treatment of lung cancer migration., 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.)

Echinococcosis and tuberculosis are two common zoonotic diseases that can cause severe pulmonary infections. Early screening and treatment monitoring are of great significance, especially in areas with limited medical resources. Herein, we designed an operation-friendly and rapid magnetic enrichment-silver acetylene chromogenic immunoassay (Me-Sacia) to monitor the antibody. The main components included secondary antibody-modified magnetic nanoparticles (MNP-Ab2) as capture nanoparticles, specific peptide (EG95 or CFP10)-modified silver nanoparticles (AgNP-PTs) as detection nanoparticles, and alkyne-modified gold nanoflowers as chromogenic nanoparticles. Based on the magnetic separation and plasma luminescence techniques, Me-Sacia could completely replace the colorimetric assay of biological enzymes. It reduced the detection time to approximately 1 h and simplified the labor-intensive and equipment-intensive processes associated with conventional ELISA. Meanwhile, the Me-Sacia showed universality for various blood samples and intuitive observation with the naked eye. Compared to conventional ELISA, Me-Sacia lowered the detection limit by approximately 96.8 %, increased the overall speed by approximately 15 times, and improved sensitivity by approximately 7.2 %, with a 100 % specificity and a coefficient of variation (CV) of less than 15 %., 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.)

With the development of monitoring technology, the variety of ozone precursors that can be detected by monitoring stations has been increased dramatically. And this has brought a great increment of information to ozone prediction and explanation studies. This study completes feature mining and reconstruction of multi-source data (meteorological data, conventional pollutant data, and precursors data) by using a machine learning approach, and built a cross-stacked ensemble learning model (CSEM). In the feature engineering process, this study reconstructed two VOCs variables most associated with ozone and found it works best to use the top seven variables with the highest contribution. The CSEM includes three base models: random forest, extreme gradient boosting tree, and LSTM, learning the parameters of the model under the integrated training of cross-stacking. The cross-stacked integrated training method enables the second-layer learner of the ensemble model to make full use of the learning results of the base models as training data, thereby improving the prediction performance of the model. The model predicted the hourly ozone concentration with R 2 of 0.94, 0.97, and 0.96 for mild, moderate, and severe pollution cases, respectively; mean absolute error (MAE) of 4.48 μg/m 3 , 5.01 μg/m 3 , and 8.71 μg/m 3 , respectively. The model predicted ozone concentrations under different NO x and VOCs reduction scenarios, and the results show that with a 20 % reduction in VOCs and no change in NO x in the study area, 75.28 % of cases achieved reduction and 15.73 % of cases got below 200 μg/m 3 . In addition, a comprehensive evaluation index of the prediction model is proposed in this paper, which can be extended to any prediction model performance comparison and analysis. For practical application, machine learning feature selection and cross-stacked ensemble models can be jointly applied in ozone real-time prediction and emission reduction strategy analysis., 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.)

As a typical energetic compound widely used in military activities, 2,4,6-trinitrotoluene (TNT) has attracted great attention in recent years due to its heavy pollution and wide distribution in and around the training facilities, firing ranges, and demolition sites. However, the subcellular targets and the underlying toxic mechanism of TNT remain largely unknown. In this study, we explored the toxic effects of TNT biological reduction on the mitochondrial function and homeostasis in Caenorhabditis elegans (C. elegans). With short-term exposure of L4 larvae, 10-1000 ng/mL TNT reduced mitochondrial membrane potential and adenosine triphosphate (ATP) content, which was associated with decreased expression of specific mitochondrial complex involving gas-1 and mev-1 genes. Using fluorescence-labeled transgenic nematodes, we found that fluorescence expression of sod-3 (muls84) and gst-4 (dvls19) was increased, suggesting that TNT disrupted the mitochondrial antioxidant defense system. Furthermore, 10 ng/mL TNT exposure increased the expression of the autophagy-related gene pink-1 and activated mitochondrial unfolded protein response (mt UPR), which was indicated by the increased expression of mitochondrial stress activated transcription factor atfs-1, ubiquitin-like protein ubl-5, and homeobox protein dve-1. Our findings demonstrated that TNT biological reduction caused mitochondrial dysfunction and the development of mt UPR protective stress responses, and provided a basis for determining the potential risks of energetic compounds to living organisms., 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.)

Breast phyllodes tumor (PT) is a rare fibroepithelial neoplasm with potential malignant behavior. Long non-coding RNAs (lncRNAs) play multifaceted roles in various cancers, but their involvement in breast PT remains largely unexplored. In this study, microarray was leveraged for the first time to investigate the role of lncRNA in PT. We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT, and its overexpression endowed PT with high tumor grade and adverse prognosis. Furthermore, we elucidated that ZFPM2-AS1 promotes the proliferation, migration, and invasion of malignant PT in vitro . Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft (PDX) model could effectively inhibit tumor progression in vivo . Mechanistically, our findings showed that ZFPM2-AS1 is competitively bound to CDC42, inhibiting ACK1 and STAT1 activation, thereby launching the transcription of TNFRSF19. In conclusion, our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT, and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors.)

4-NP (4-nonylphenol), a prevalent environmental endocrine disruptor with estrogenic properties, is commonly detected in drinking water and food sources. It poses a significant risk of endocrine disruption, thereby influencing the onset and progression of diverse diseases, including tumorigenesis. However, its specific impact on cervical cancer remains to be fully elucidated. Our study focused on the biological effects of sustained exposure to low-dose 4-NP on human normal cervical epithelial cells (HcerEpic). After a continuous 30-week exposure to 4-NP, the treated cells exhibited a significant malignant transformation, whereas the solvent control group showed limited malignant phenotypes. Subsequent analyses of the metabolomic profiles of the transformed cells unveiled marked irregularities in glutathione metabolism and unsaturated fatty acid metabolism. Analyses of transcriptomic profiles revealed significant activation of the MAPK signaling pathway and suppression of ferroptosis processes in these cells. Furthermore, the expression of MT2A was significantly upregulated following 4-NP exposure. Knockdown of MT2A restored the aberrant activation of the MAPK signaling pathway, elevated antioxidant capacity, ferroptosis inhibition, and ultimately the development of malignant phenotypes that induced by 4-NP in the transformed cells. Mechanistically, MT2A increased cellular antioxidant capabilities and facilitated the removal of toxic iron ions by enhancing the phosphorylation of ERK1/2 and JNK MAPK pathways. The administration of activators and inhibitors of the MAPK pathway confirmed that the MAPK pathway mediated the 4-NP-induced suppression of ferroptosis and, ultimately, the malignant transformation of cervical epithelial cells. Overall, our findings elucidated a dynamic molecular transformation induced by prolonged exposure to 4-NP, and delineated comprehensive biological perspectives underlying 4-NP-induced cervical carcinogenesis. This offers novel theoretical underpinnings for the assessment of the carcinogenic risks associated with 4-NP., 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 ubiquitinproteasome system (UPS) is the main mechanism responsible for the intracellular degradation of misfolded or damaged proteins. Under inflammatory conditions, the immunoproteasome, an isoform of the proteasome, can be induced, enhancing the antigen-presenting function of the UPS. Furthermore, the immunoproteasome also serves nonimmune functions, such as maintaining protein homeostasis and regulating signalling pathways, and is involved in the pathophysiological processes of various cardiovascular diseases (CVDs). This review aims to provide a comprehensive summary of the current research on the involvement of the immunoproteasome in cardiovascular diseases, with the ultimate goal of identifying novel strategies for the treatment of these conditions., 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.)

Introduction: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown., Methods: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022. Kaplan-Meier method was used to estimate real-world progression-free survival (rwPFS, primary end point) and overall survival (secondary end point). Treatment-related adverse events (trAEs) during consolidation treatment were defined using Common Terminology Criteria for Adverse Events version 5.0. Multivariable Cox regression analysis was used., Results: Of 136 patients with stage III EGFRmut NSCLC treated with definitive concurrent CRT, 56 received consolidation durvalumab, 33 received consolidation osimertinib, and 47 was on observation alone. Baseline characteristics were similar across the three cohorts. With a median follow-up of 46 months for the entire cohort, the median duration of treatment was not reached (NR) for osimertinib (interquartile range: NR-NR) and was 5.5 (interquartile range: 2.4-10.8) months with durvalumab. After adjusting for nodal status, stage III A/B/C, and age, patients treated with consolidation osimertinib had significantly longer 24-month rwPFS compared to those treated with durvalumab or in the observation cohorts (osimertinib: 86%, durvalumab: 30%, observation: 27%, p < 0.001 for both comparisons). There was no difference in rwPFS between the durvalumab and the observation cohorts. No significant difference in overall survival across the three cohorts was detected, likely due to the limited follow-up. Any-grade trAE occurred in 52% (2 [6.1%] grade ≥3) and 48% (10 [18%] grade ≥3) of patients treated with osimertinib and durvalumab, respectively. Of 45 patients who progressed on consolidation durvalumab, 37 (82%) subsequently received EGFR tyrosine kinase inhibitors. Of these, 14 (38%) patients developed trAEs including five patients with pneumonitis (14%; 2 [5.4%] grade ≥3) and five patients with diarrhea (14%; 1 [2.7%] grade ≥3)., Conclusions: This study suggests that among patients with stage III unresectable NSCLC with a sensitizing EGFR mutation, consolidation osimertinib was associated with a significantly longer rwPFS compared to durvalumab or observation. No unanticipated safety signals were observed with consolidation osimertinib., Competing Interests: Disclosure Dr. Nassar receives honoraria from OncLive, TEMPUS, and Korean Society for Medical Oncology and consulting fees from Guidepoint Global. Dr. Kim is on the advisory board for Amgen. Dr. Shepherd reports having stock and other ownership interests from Eli Lilly and AstraZeneca; receiving honoraria from AstraZeneca, Merck Serono, Takeda, and Daiichi Sankyo; having consulting/advisory role at AstraZeneca and Merck Serono; and receiving research funding from Eli Lilly (inst), Pfizer (inst), Bristol-Myers Squibb (inst), AstraZeneca/MedImmune (inst), and Roche Canada (inst). Dr. Gray reports receiving grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, G1 Therapeutics, Ludwig Institute of Cancer Research, Merck & Co., Inc., Novartis, and Pfizer; receiving consulting fees from AbbVie, AstraZeneca, Blueprint Medicines, EMD Serono, Gilead Sciences, Inc., Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Loxo Oncology Inc., Merck & Co., Inc., Novartis, OncoCyte Biotechnology, Spectrum ODAC, Takeda Pharmaceuticals, and Triptych Health Partners; and having leadership role as SWOG Lung Committee Chair, IASLC Board of Director member, and ASCO Education Committee Ex-Chair. Dr. Dilling reports receiving consulting fees from AstraZeneca and support for travel from NCCN. Dr. Neal reports receiving grants from Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Nektar Therapeutics, Takeda Pharmaceuticals, Adaptimmune, GlaxoSmithKline, Janssen, AbbVie, and Novocure; receiving consulting fees from AstraZeneca, Genentech/Roche, Exelixis, Takeda Pharmaceuticals, Eli Lilly and Company, Amgen, Iovance Biotherapeutics, Blueprint Pharmaceuticals, Regeneron Pharmaceuticals, Natera, Sanofi/Regeneron, D2G Oncology, Surface Oncology, Turning Point Therapeutics, Mirati Therapeutics, Gilead Sciences, AbbVie, Summit Therapeutics, Novartis, Novocure, Janssen Oncology, and AnHeart Therapeutics; and receiving honorarium from CME Matters, Clinical Care Options CME, Research to Practice CME, Medscape CME, Biomedical Learning Institute CME, MLI Peerview CME, Prime Oncology CME, Projects in Knowledge CME, Rockpointe CME, MJH Life Sciences CME, Medical Educator Consortium, and HMP Education. Dr. Wakelee reports receiving grants from Arrys Therapeutics Research, AstraZeneca/Medimmune, Bristol-Myers Squibb, Genentech/Roche, Merck, Helsinn, Seagen, and Xcovery; and serving on the advisory board of Mirati (compensated)—ended November 2022, IOBiotech (compensated)—October 2023, Merck (NOT compensated), and Genentech/Roche/Bristol-Myers Squibb/AstraZeneca (NOT compensated). Dr. S.H. Lin reports receiving grants from STCube Pharmaceuticals, Beyond Spring, and Nektar Therapeutics; consulting fees from XRAD Therapeutics; serving on the advisory board of AstraZeneca; having stock/stock options from Apple, Google, Amazon, Tesla, Meta, Rivian, and CreatvMicrotech; and having other support from SEEK Diagnostics (co-founder). Dr. Patil reports receiving grants from Gilead Research Scholars and LUNGevity Foundation Award; consulting fees from AstraZeneca, Boehringer Ingelheim, Bicara, Daiichi, Janssen, Jazz Pharmaceuticals, Mirati Therapeutics, Pfizer, Sanofi, Regeneron, Roche/Genentech, Takeda, Gilead Research Scholars, and LUNGevity Foundation Award; and honorarium from Janssen. Dr. Bar reports receiving grants from Merck Sharp & Dohme, AstraZeneca, Roche, Bristol-Myers Squibb, Takeda, AbbVie, Bayer, Boehringer Ingelheim, and Pfizer; receiving consulting fees from AstraZeneca, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Takeda, AbbVie, Pfizer, Bayer, and VBL; and having leadership role from Lung Ambition Consortium, Israel Lung Cancer Group, and IASLC committee. Dr. Marron receives grants from Regeneron, Bristol-Myers Squibb, Merck, Boehringer Ingelheim, NCI, and Cancer Research Institute; and serving on the advisory board of AbbVie, Celldex, and Rockefeller University. Dr. Yu receives grants/contracts from AstraZeneca, Pfizer, Daiichi Cullinan Oncology, Janssen, Novartis, Blueprint med, Black Diamond, and Systimmune and consulting fees from AstraZeneca, Daiichi, Taiho, Takeda, Janssen, Amgen, AbbVie, Novocure, and Ipsen. Dr. Owen receives grants/contracts from Bristol-Myers Squibb, Merck, Palobiofarma, Genentech, Onc.AI, and Pfizer; and travel support from Amgen, AstraZeneca, and Genentech. Rocha receives grants/contracts from SEOM, ESMO Fellowship, and AECC; and travel support from Merck Sharp & Dohme, AstraZeneca, and Bristol-Myers Squibb. Dr. Arriola receives grants/contracts from AstraZeneca and Bristol-Myers Squibb; honorarium from Eli Lilly, AstraZeneca, Roche, Takeda, Merck Sharp & Dohme, Pfizer, Janssen, and Bristol-Myers Squibb; and travel support from AstraZeneca, Roche, and Pfizer. Dr. Cheng receives grants/contracts from AstraZeneca and Genentech; and serving on the advisory board of Janssen, G1 Therapeutics, and AstraZeneca. Dr. Parikh receives consulting fees from Jazz Pharmaceuticals, Guardant Health, and AstraZeneca; and honorarium from MJH Life Sciences. Dr. Harris receives grants/contract from NIH P30CA062203, the UC Irvine Comprehensive Cancer Center using UCI Anti-Cancer Challenge Grant, and ACS Seed Grant 129801-IRG-16-187-13-IRG; and serving on the advisory board of UC Irvine as DSMB member. Dr. Nagasaka receives consulting fees from Caris Life Sciences; honorarium/speaker fees from AstraZeneca, Daiichi, Novartis, EMD Serono self, Pfizer, Eli Lilly, Genentech, Regeneron, Takeda, Janssen, Blueprint, and Mirati; travel support from AnHeart Therapeutics; and stock/stock options from Mbrace Therapeutics. Dr. Valazquez receives grants/contracts from ASCO, American Association for Cancer Research (AACR), LUNGevity, NIA P30AG015272, NCI 5U54CA242646-03 Conquer Cancer and Niarchos Foundation, UCSF Clinical Practice Group, and AAMC; consulting fees from AstraZeneca, Merus, Novocure, and Cadence Communications & Research; and having stock/stock options from Corbus Pharmaceuticals. Dr. J.J. Lin receives grants/contracts from Hengrui Therapeutics, Turning Point Therapeutics, Neon Therapeutics, Relay Therapeutics, Bayer, Elevation Oncology, Roche, Linnaeus Therapeutics, Nuvalent, and Novartis; consulting fees from Genentech, C4 Therapeutics, Blueprint Medicines, Nuvalent, Bayer, Elevation Oncology, Novartis, Mirati Therapeutics, AnHeart Therapeutics, Takeda, CLaiM Therapeutics, Regeneron, Pfizer, Turning Point Therapeutics, Daiichi Sankyo, AstraZeneca, and Merus. Dr. Piotrowska receives grants/contracts from Novartis, Takeda, Spectrum, AstraZeneca, Tesaro/GlaxoSmithKline, Cullinan Oncology, Daiichi Sankyo, AbbVie, Janssen, and Blueprint; consulting fees from Taiho, Janssen, Takeda, AstraZeneca, Cullinan Oncology, C4 Therapeutics, Jazz Pharmaceuticals, and Blueprint; and honorarium from Daiichi Sankyo, Janssen, and Eli Lilly (honoraria for nonpromotional educational events). Dr. Reuss receives grants/contracts from Genentech/Roche, Verastem, Nuvalent, and LUNGevity Foundation; consulting fees from Genentech/Roche, Sanofi/Genzyme, Personalis, Guardant, AstraZeneca, Bristol-Myers Squibb, Arcus, AbbVie, Daiichi Sankyo, Catalym, Seagen, and Gilead; and honorarium from AstraZeneca and Merck. Dr. Baena Espinar receives consulting fees from AstraZeneca, Roche, and Merck Sharp & Dohme; honorarium from AstraZeneca, Roche, and Merck Sharp & Dohme; payment for expert testimony from Roche; and travel support from Roche and Janssen. Leal receives research funding to institution from Pfizer, Advaxis, and Bayer, outside the submitted work. Dr. Mak receives grants/contracts from ViewRay; consulting fees from AstraZeneca, Novartis, and Sio Capital Management; and other support from Founder of HealthAI. Dr. Naqash receives grants/contracts from SWOG Hope Foundation and FDA Broad Agency Contract; serving on the advisory board of JCO Precision Oncology; receiving travel support from SITC/American Association for Cancer Research (AACR)/Conquer Cancer Foundation/BinayTara Foundation and Foundation Med/Caris Life Sciences, and Jazz Pharmaceuticals; and funding to institution for trials from Loxo@Lilly, Surface Oncology, ADC Therapeutics, IGM Biosciences, EMD Serono, Aravive, Nikang Therapeutics, Inspirna, Exelexis, Revolution Medicine, Jacobio, Pionyr, Jazz Pharmaceuticals, NGM Biopharmaceuticals, Immunophotonics, and Selexine. Dr. Goldberg receives grants/contracts from AstraZeneca, Boehringer Ingelheim, and Mirati; and serving on the advisory board of AstraZeneca, Bristol-Myers Squibb, Amgen, Sanofi, Genzyme, Daiichi Sankyo, Regeneron, Takeda, Janssen, Summit, and Merck. The remaining authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Selective serotonin reuptake inhibitor (SSRI) antidepressants are of increasing concern worldwide due to their ubiquitous occurrence and detrimental effects on aquatic organisms. However, little is known regarding their effects on the dominant bloom-forming cyanobacterium, Microcystis aeruginosa. Here, we investigated the individual and joint effects of two typical SSRIs fluoxetine (FLX) and sertraline (SER) on M. aeruginosa at physio-biochemical and molecular levels. Results showed that FLX and SER had strong growth inhibitory effects on M. aeruginosa with the 96-h median effect concentrations (EC 50 s) of 362 and 225 μg/L, respectively. Besides, the mixtures showed an additive effect on microalgal growth. Meanwhile, both individual SSRIs and their mixtures can inhibit photosynthetic pigment synthesis, cause oxidative damage, destroy cell membrane, and promote microcystin-leucine-arginine (MC-LR) synthesis and release. Moreover, the mixtures enhanced the damage to photosynthesis, antioxidant system, and cell membrane and facilitated MC-LR synthesis and release compared to individuals. Furthermore, transcriptomic analysis revealed that the dysregulation of the key genes related to transport, photosystem, protein synthesis, and non-ribosomal peptide structures was the fundamental molecular mechanism underlying the physio-biochemical responses of M. aeruginosa. These findings provide a better understanding of the toxicity mechanisms of SSRIs to microalgae and their risks to aquatic ecosystems., 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.)

Background: Theranostic nanoplatforms with integrated diagnostic imaging and multiple therapeutic functions play a vital role in precise diagnosis and efficient treatment for breast cancer, but unfortunately, these nanoplatforms are usually stuck in single-site imaging and single mode of treatment, causing unsatisfactory diagnostic and therapeutic efficiency. Herein, a dual biomarkers-activatable facile hollow mesoporous MnO 2 (H-MnO 2 )-based theranostic nanoplatform, DNAzyme@H-MnO 2 -MUC1 aptamer (DHMM), was constructed for the simultaneous multi-site diagnosis and multiple treatment of breast cancer., Results: The DHMM acted as an integrated diagnostic and therapeutic nanoplatform that realizes multi-site fluorescence imaging-guided high-efficient photothermal/chemodynamic/gene synergistic therapy (PTT/CDT/GT) for breast cancer. The H-MnO 2 exhibits high loading capacity for Cy5-MUC1 aptamer (3.05 pmoL μg -1 ) and FAM-DNAzyme (3.37 pmoL μg -1 ), and excellent quenching for the probes. In the presence of MUC1 on the cell membrane and GSH in the cytoplasm, Cy5-MUC1 aptamer and FAM-DNAzyme was activated triggering dual-channel fluorescence imaging at different sites. Moreover, the self-supplied Mn 2+ was further supplied as DNAzyme cofactors to catalytic cleavage intracellular EGR-1 mRNA for high-efficient GT and stimulated the Fenton-like reaction for CDT. The H-MnO 2 also showcases a favorable photothermal performance with a photothermal conversion efficiency of 44.16%, which ultimately contributes to multi-site fluorescence imaging-guided synergistic treatment with an apoptosis rate of 71.82%., Significance: This dual biomarker-activatable multiple therapeutic nanoplatform was realized multi-site fluorescence imaging-guided PTT/CDT/GT combination therapy for breast cancer with higher specificity and efficiency, which provides a promising theranostic nanoplatform for the precision and efficiency of breast cancer 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 © 2024 Elsevier B.V. All rights reserved.)

Cellulose, renowned for its excellent biocompatibility, finds extensive applications in both industrial and laboratory settings. However, few studies have specifically addressed the mechanistic evolution of hydrogen bond networks in cellulose during the dissolution and regeneration processes. In this research, the regeneration mechanism of cellulose in water and ethanol is investigated through molecular dynamics simulations. The results indicate that the ability of water molecules to disrupt hydrogen bonds between cellulose and ionic liquids is stronger than that of ethanol, which is more conducive to promoting the regeneration of cellulose. Besides, the Fourier transform infrared spectroscopy coupled with two-dimensional correlation infrared spectroscopy techniques are employed to unveil the evolution sequence of hydrogen bonds during dissolution and regeneration: ν(OH) (absorbed water) → ν(O3-H3···O5) (intrachain) → ν(O6-H6···O3') (interchain) → ν(O2-H2···O6) (intrachain) → ν(OH) (free). This study not only enhances our understanding of the intricate hydrogen bond dynamics in cellulose dissolution and regeneration but also provides a foundation for the expanded application of cellulose in diverse fields., 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.)

Cardiovascular disease is a main cause of mortality in the world and the highest incidence of all diseases. However, the mechanism of the pathogenesis of cardiovascular disease is still unclear, and we need to continue to explore its mechanism of action. The occurrence and development of cardiovascular disease is significantly associated with genetic abnormalities, and gene expression is affected by transcriptional regulation. In this complex process, the protein-protein interaction promotes the RNA polymerase II to the initiation site. And in this process of transcriptional regulation, transcriptional cofactors are responsible for passing cues from enhancers to promoters and promoting the binding of RNA polymerases to promoters, so transcription cofactors playing a key role in gene expression regulation. There is growing evidence that transcriptional cofactors play a critical role in cardiovascular disease. Transcriptional cofactors can promote or inhibit transcription by affecting the function of transcription factors. It can affect the initiation and elongation process of transcription by forming complexes with transcription factors, which are important for the stabilization of DNA rings. It can also act as a protein that interacts with other proteins to affect the expression of other genes. Therefore, the aim of this overview is to summarize the effect of some transcriptional cofactors such as BRD4, EP300, MED1, EZH2, YAP, SIRT6 in cardiovascular disease and to provide a promising therapeutic strategy for the treatment of cardiovascular disease., 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.)

In rheumatoid arthritis (RA), macrophages infiltrate joints, while fibroblast-like synovial cells proliferate abnormally, forming a barrier against drug delivery, which hinders effective drug delivery to joint focus. Here we firstly designed a pH-responsive size-adjustable nanoparticle, composed by methotrexate (MTX)-human serum albumin (HSA) complex coating with pH-responsive liposome (Lipo/MTX-HSA) for delivering drugs specifically to inflamed joints in acidic environments. We showed in vitro that the nanoparticles can induce mitochondrial dysfunction, promote apoptosis of fibroblast-like synoviocytes and macrophages, further reduce the secretion of inflammatory factors (TNF-α, IL-1β, MMP-9), and regulate the inflammatory microenvironment. We also demonstrated similar effects in a rat model of arthritis, in which Lipo/MTX-HSA accumulated in arthritic joints, and at low pH, liposome phospholipid bilayer cleavage released small-sized MTX-HSA, which effectively reduced the number of fibroblast-synoviocytes and macrophages in joints, alleviated joint inflammation, and repaired bone erosion. These findings suggest that microenvironment-responsive size-adjustable nanoparticles show promise as a treatment against rheumatoid arthritis. STATEMENT OF SIGNIFICANCE: Abnormal proliferation of fibroblast synoviocytes poses a physical barrier to effective nanoparticle delivery. We designed size-adjustable nano-delivery systems by preparing liposomes with cholesterol hemisuccinate (CHEM), which were subsequently loaded with small-sized albumin nanoparticles encapsulating the cytotoxic drug MTX (MTX-HSA), termed Lipo/MTX-HSA. Upon tail vein injection, Lipo/MTX-HSA could be aggregated at the site of inflammation via the ELVIS effect in the inflamed joint microenvironment. Specifically, intracellular acidic pH-triggered dissociation of liposomes promoted the release of MTX-HSA, which was further targeted to fibroblasts or across fibroblasts to macrophages to exert anti-inflammatory effects. The results showed that liposomes with adjustable particle size achieved efficient drug delivery, penetration and retention in joint sites; the strategy exerted significant anti-inflammatory effects in the treatment of rheumatoid arthritis by inducing mitochondrial dysfunction to promote apoptosis in fibrosynoviocytes and macrophages., Competing Interests: Declaration of competing interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The aim of this study is to conduct a thorough evaluation of the association between Benzophenone-3 (BP-3) exposure and OA, offering critical insights into the underlying mechanisms involved. The National Health and Nutrition Examination Survey (NHANES) database was utilized to investigate the correlation between BP-3 and osteoarthritis. Proteomic sequencing from clinical sample and the PharmMapper online tool were employed to predict the biological target of BP-3. Cellular molecular assays and transfection studies were performed to verify the prediction from bioinformatics analyses. Through cross-sectional analysis of the NHANES database, we identified BP-3 as a risk factor for OA development. The results of proteomic sequencing showed that Secreted Protein Acidic and Rich in Cysteine (SPARC) was significantly elevated in the area of damage compared to the undamaged area. SPARC was also among the potential biological targets of BP-3 predicted by the online program. Through in vitro cell experiments, we further determined that the toxicological effects of BP-3 may be due to SPARC, which elevates intracellular GPX4 levels, activates the glutathione system, and promotes lipid peroxidation to mitigate ferroptosis. Inhibiting SPARC expression has been shown to reduce inflammation and ferroptosis in OA contexts. This research provides an expansive understanding of BP-3's influence on osteoarthritis development. We have identified SPARC as a potent target for combating chondrocyte ferroptosis in BP-3-associated osteoarthritis., 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 Inc. All rights reserved.)

The environmental fate of arsenic (As) relies substantially on its speciation, which occurs frequently coupled to the redox transformation of manganese. While trivalent manganese (Mn(III)), which is known for its high reactivity, is believed to play a role in As mobilization by iron (oxyhydr)oxides in dynamic aquifers, the exact roles and underlying mechanisms are still poorly understood. Using increasingly complex batch experiments that mimick As-affected aquifer conditions in combination with time-resolved characterization, we demonstrate that Mn(III)-NOM complexes play a crucial role in the manganese-mediated immobilization of As(III) by ferrihydrite and goethite. Under anaerobic condition, Mn(III)-fulvic acid (FA) rapidly oxidized 31.8% of aqueous As(III) and bound both As(III) and As(V). Furthermore, Mn(III)-FA exerted significantly different effects on the adsorption of As by ferrihydrite and goethite. Mn(III)-FA increased the adsorption of As by 6-16% due to the higher affinity of oxidation-produced As(V) for ferrihydrite under circumneutral conditions. In contrast, As adsorption by crystalline goethite was eventually inhibited due to the competitive effect of Mn(III)-FA. To summarize, our results reveal that Mn(III)-NOM complexes play dual roles in As retention by iron oxides, depending on the their crystallization. This highlights the importance of Mn(III) for the fate of As particularly in redox fluctuating groundwater 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 word reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The Bouligand structure has been observed in a variety of biological materials, such as lamellar bone and exoskeleton of lobsters. It is a hierarchical and non-homogeneous architecture that exhibits excellent damage-resistant performance. This paper presents a multiscale fracture model considering the material inhomogeneity, the multiscale property, and the anisotropy to reveal the toughening mechanisms in the Bouligand structure. Firstly, the macro and micro constitutive properties of this composite are derived. Then, a multiscale fracture model is developed to characterize the local stress intensity factors and the energy release rates at the crack front of twisted cracks. Our results demonstrate that the decrease in the local energy release rate can be attributed to two-step mechanisms. The first mechanism is that the multiscale structure and the material inhomogeneity cause a release of stress near the initial crack tip. The second mechanism is that the twisted crack leads to the transformation from single-mode loading to mixed-mode loading, which enhances the fracture toughness. These results can not only reveal the toughening mechanism of the Bouligand structure but also provide guidelines for the design of high-performance composites. STATEMENT OF SIGNIFICANCE: Biological materials in nature often possess excellent mechanical properties that have not been achieved by synthetic materials. Bioinspired Bouligand structures provide prototypes for designing high-performance materials. In this study, we propose a multiscale theoretical fracture model to investigate the fracture properties of Bouligand structures with twisted cracks. We systematically consider the roles of material inhomogeneity, anisotropy, and multiscale properties. Our analysis demonstrates that the remarkable toughness of Bouligand structures results from the combined effects of material inhomogeneity and twisted cracks. This research contributes to unveiling the secret behind the outstanding toughness of Bouligand structures and provides inspiration for the development of novel designs for man-made composites., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Despite abundant theoretical investigations on the dynamic behavior of functionally graded (FG) structures, the study on frequency analysis of FG bio-composite structures is limited. FG bio-composite materials due to their biocompatibility potentials and good material properties can be applied in biomedical applications, especially dental implants. In this investigation, a natural frequency response of the FG bio-composite plate is analyzed within the framework of the newly developed refined higher-order shear deformation plate theory. Additionally, the imperfection impact on frequency behavior is evaluated while three imperfection distribution patterns are taken into account. The constitutive materials of FG bio-composite plate are Hydroxyapatite and Titanium. The effective material properties of the structure are determined with the help of the upper Hashin-Shtrikman bounds homogenization model. In continuation, to solve the derived governing equations of imperfect FG bio-composite plate, Galerkin's analytical method is employed. Also, the precision of the used theory is validated, the obtained outcomes are compared and an acceptable matching is found. Later, the sensitivity of different considerable variables is comprehensively assessed and discussed., 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 Ltd. All rights reserved.)

Mercury (Hg) is one of the major pollutants in the environment, which requires effective countermeasures to manage its risk to both human health and the ecosystem. The antagonistic effect of selenium (Se) against methyl mercury (MeHg) and HgCl 2 was evaluated using parent and offspring Caenorhabditis elegans (C. elegans) in this study. Through designated acute exposure of 24 h, our results showed that both MeHg and HgCl 2 induced dose-dependent reproductive toxicity, including increased germ cell apoptosis, decrease in the number of oocytes, brood size, and sperm activation. The increased germ cell apoptosis was even higher in F1 and F2 generations, but returned to control level in F3 generation. Pretreatment with Se significantly suppressed the reproductive toxicity caused by Hg in both parental worms and their offspring, but had little influence on Hg accumulation. The protective role of Se was found closely related to the chemical forms of Hg: mtl-1 and mtl-2 genes participated in reducing the toxicity of HgCl 2 , while the gst-4 gene was involved in the reduced toxicity of MeHg. The formation of Se-Hg complex and the antioxidant function of Se were considered as possible antagonistic mechanisms. Our data indicated that pretreatment with Se could effectively protect C. elegans and their offspring against the reproductive toxicity of Hg in different chemical forms, which provided a reference for the prevention of Hg poisoning and essential information for better understanding the detoxification potential of Se on heavy metals., Competing Interests: Declaration of competing interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pyrite has been extensively tested for oxidizing contaminants via the activation of water molecule or dissolved oxygen, while the changing of oxidation species induced by contaminant's concentration has been largely underestimated. In this study, we revealed a self-acclimation mechanism of pyrite in terms of • OH conversion to 1 O 2 during the sulfamethoxazole (SMX) degradation process under oxic conditions. Two reaction stages of SMX degradation by pyrite were observed. The SMX concentration decreased by 70% rapidly in the first 12 h after the reaction was initiated, then, the removal rate began to decrease as the SMX concentration decreased. Importantly, • OH and O 2 •- were the dominant oxidizing species in stage one, while 1 O 2 was responsible for the further degradation of SMX in stage two. The self-acclimated mechanism of pyrite was proven to be caused by the conversion of oxidative species at the surface of pyrite. This process can overcome the shortages of • OH such as ultrashort lifetime and limited effective diffusion in the decontamination of micropollutant. Moreover, different reactive oxygen species will lead to different degradation pathways and environmental toxicity while degrading pollutants. This finding of oxidizing species' self-acclimation mechanism should be of concern when using pyrite for water 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 Elsevier B.V. All rights reserved.)

In this study, two strains of symbiotic bacteria (SOB-1 and SOB-2) were isolated from Scenedesmus obliquus, and various algal-bacterial mutualistic systems were established under acetochlor (ACT) stress conditions. Following exposure to varying ACT concentrations from 2.0 to 25.0 μg/L, the capacity for co-cultured bacteria to degrade ACT was enhanced in 7 days by up to 226.9% (SOB-1) and 193.0% (SOB-2), compared with axenic algae, although bacteria exposed to higher ACT concentrations exacerbated algal metabolic stress, oxidative states, apoptosis and cellular lysis. ACT reduced carbohydrates in the phycosphere by up to 31.5%; compensatory nutrient plunder and structural damage by bacteria were the potential exploitation pathways determined based on the inhibition of bacterial infection using a glucanase inhibitor. The ACT-induced reduction in algal antimicrobial substances, including fatty acids and phenolics (by up to 58.1% and 56.6%, respectively), also facilitated bacterial exploitation of algae. ACT-dependent interspecific interaction coefficients between algae and bacteria generated from long-term symbiosis cultures implied that bacteria moved from mutualism (0 and 2.0 μg/L ACT) to exploitation (7.9 and 25.0 μg/L ACT). The population dynamic model under incremental ACT-concentration scenarios inferred that theoretical systematic extinction may occur in algal-bacterial systems earlier than in axenic algae. These outcomes provide interspecific insights into the distortion of algal-bacterial reciprocity due to the ecotoxicological effects of ACT., 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.)

CpG oligodeoxynucleotides (ODNs) strongly activate the immune system after binding to toll-like receptor 9 (TLR9) in lysosome, which demonstrated significant potential in cancer immunotherapy. However, their therapeutic efficacy is limited by drawbacks such as rapid degradation and poor cellular uptake. Although encouraging progress have been made on developing various delivery systems for CpG ODNs, safety risks of the synthetic nanocarriers as well as the deficient CpG ODNs release within lysosome remain big obstacles. Herein, we developed a novel nanovector for lysosome-targeted CpG ODNs delivery and enhanced cancer immunotherapy. Natural glycogen was simply aminated (NH 2 -Gly) through grafting with diethylenetriamine (DETA), which was spherical in shape with diameter of approximately 40 nm. NH 2 -Gly possessed good biocompatibility. Cationic NH 2 -Gly complexed CpG ODNs well and protected them from nuclease digestion. NH 2 -Gly significantly enhanced the cellular uptake of CpG ODNs. Efficient CpG ODNs release was observed in the presence of α-glucosidase that mimicking the environment of lysosome. Consequently, NH 2 -Gly/CpG complexes triggered potent antitumor immunity and effectively inhibit the tumor growth without causing any toxic effect or tissue damages. This work highlights the promise of glycogen for lysosome-targeted on-command delivery of CpG ODNs, which brings new hope for precision cancer immunotherapy., 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.)

An improved agglomerate formulation with melatonin and fine lactose for dry powder inhalation using Turbuhaler® was developed. Co-grinding lactose with 1 % magnesium stearate prior to air jet mixing served as a key factor to improve the in vitro aerosolization and in vivo efficacy. Elevated mixing pressure facilitated the dispersion and homogenization of the cohesive mixture for even distribution of agglomerate size after spheroidization and subsequent higher emitted dose with lower variation. Magnesium stearate was employed as a tertiary component to adjust the interparticle force for better aerosolization. At optimized mixing pressure, co-grinding lactose with magnesium stearate before jet mixing displayed further improvement of fine particle fraction to 71.6 ± 3.1 %. The superior fine particle deposition efficiency contributed to rapid onset of action and a high bioavailability of 67.0 % after intratracheal administration to rats. Overall, an inhalable melatonin dry powder formulation exhibiting good aerosol property and lung deposition with clinical translation potential was developed., 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 Inc. All rights reserved.)

The transcription factor Olig2 is highly expressed throughout oligodendroglial development and is needed for the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and remyelination. Although Olig2 overexpression in OPCs is a possible therapeutic target for enhancing myelin repair in ischemic stroke, achieving Olig2 overexpression in vivo remains a formidable technological challenge. To address this challenge, we employed lipid nanoparticle (LNP)-mediated delivery of Olig2 synthetically modified messenger RNA (mRNA) as a viable method for in vivo Olih2 protein overexpression. Specifically, we developed CD140a-targeted LNPs loaded with Olig2 mRNA (C-Olig2) to achieve targeted Olig2 protein expression within PDGFRα + OPCs, with the goal of promoting remyelination for ischemic stroke therapy. We show that C-Olig2 promotes the differentiation of PDGFRα + OPCs derived from mouse neural stem cells into mature oligodendrocytes in vitro, suggesting that mRNA-mediated Olig2 overexpression is a rational approach to promote oligodendrocyte differentiation and remyelination. Furthermore, when C-Olig2 was administered to a murine model of ischemic stroke, it led to improvements in blood‒brain barrier (BBB) integrity, enhanced remyelination, and rescued learning and cognitive deficits. Our comprehensive analysis, which included bulk RNA sequencing (RNA-seq) and single-nucleus RNA-seq (snRNA-seq), revealed upregulated biological processes related to learning and memory in the brains of mice treated with C-Olig2 compared to those receiving empty LNPs (Mock). Collectively, our findings highlight the therapeutic potential of multifunctional nanomedicine targeting mRNA expression for ischemic stroke and suggest that this approach holds promise for addressing various brain diseases. STATEMENT OF SIGNIFICANCE: While Olig2 overexpression in OPCs represents a promising therapeutic avenue for enhancing remyelination in ischemic stroke, in vivo strategies for achieving Olig2 expression pose considerable technological challenges. The delivery of mRNA via lipid nanoparticles is considered aa viable approach for in vivo protein expression. In this study, we engineered CD140a-targeted LNPs loaded with Olig2 mRNA (C-Olig2) with the aim of achieving specific Olig2 overexpression in mouse OPCs. Our findings demonstrate that C-Olig2 promotes the differentiation of OPCs into oligodendrocytes in vitro, providing evidence that mRNA-mediated Olig2 overexpression is a rational strategy to foster remyelination. Furthermore, the intravenous administration of C-Olig2 into a murine model of ischemic stroke not only improved blood-brain barrier integrity but also enhanced remyelination and mitigated learning and cognitive deficits. These results underscore the promising therapeutic potential of multifunctional nanomedicine targeting mRNA expression in the context 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In the ionic liquids (ILs) method for processing regenerated cellulose fiber (RCF), which is a high-performance ecologically benign product, metal ion impurities (such as Fe 3+ and Cu 2+ ) of cellulose might inevitably remain in the recycled ILs and coagulation bath. The presence of metal ions might negatively impact the properties of the manufactured RCFs and obstruct their applications, which are urgent to be made clear. For this research, the solvent for dissolving wood pulp cellulose (WPC) was 1-ethyl-3-methylimidazolium diethyl phosphate ([Emim]DEP) with various metal ion concentrations. The effect of metal ions in IL on the dissolution of cellulose was investigated by Molecular Dynamics simulations. Rheological analysis and degree of polymerization (DP) analysis were adopted to evaluate the influence on fiber spinnability of different spinning solution metal ion concentrations and various dissolving times. Further, the morphology and mechanical performances of the RCFs variation regulation were also thoroughly researched. The findings showed that the presence of metal ions in the spinning solution affected the DP, crystallinity, and orientation factor of RCFs, which will influence their stress more sensitively than the strain. These findings can serve as a practical guide for the commercial manufacture of emerging fiber., 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.)

Magnetic nanoparticles (MNPs) are promising in tumor treatments due to their capacity for magnetic hyperthermia therapy (MHT), chemodynamic therapy (CDT), and immuno-related therapies, but still suffer from unsatisfactory tumor inhibition in the clinic. Insufficient hydrogen peroxide supply, glutathione-induced resistance, and high-density extracellular matrix (ECM) are the barriers. Herein, we hierarchically decorated MNPs with disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx) to form a nanosystem (MNPs-SS-R-GOx). Its outer GOx layer not only enhanced the H 2 O 2 supply to produce . OH by Fenton reaction, but also generated stronger oxidants (ONOO - ) together with the interfaced R layer. The inner S-S layer consumed glutathione to interdict its reaction with oxidants, thus enhancing CDT effects. Importantly, the generated ONOO - tripled the MMP-9 expression to induce ECM degradation, enabling much deeper penetration of MNPs and benefiting CDT, MHT, and immunotherapy. Finally, the MNPs-SS-R-GOx demonstrated a remarkable 91.7% tumor inhibition in vivo. STATEMENT OF SIGNIFICANCE: Magnetic nanoparticles (MNPs) are a promising tumor therapeutic agent but with limited effectiveness. Our hierarchical MNP design features disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx), which boosts H 2 O 2 supply for ·OH generation in Fenton reactions, produces potent ONOO - , and enhances chemodynamic therapy via glutathione consumption. Moreover, the ONOO - facilitates the upregulation of matrix metalloprotein expression beneficial for extracellular matrix degradation, which in turn enhances the penetration of MNPs and benefits the antitumor CDT/MHT/immuno-related therapy. In vivo experiments have demonstrated an impressive 91.7% inhibition of tumor growth. This hierarchical design offers groundbreaking insights for further advancements in MNP-based tumor therapy. Its implications extend to a broader audience, encompassing those interested in material science, biology, oncology, and beyond., Competing Interests: Declaration of Competing Interest The authors frankly declare that there was no conflict of interest regarding the publication of this article., (Copyright © 2023. Published by Elsevier Ltd.)

Micro- and nanoplastics have recently been detected in human blood and placentas, indicating inevitable embryonic exposure to these particles. However, their influence on human embryogenesis and the underlying mechanisms are still unknown. In this study, the effects of polystyrene nanoplastics (PS-NPs) exposure on cardiac differentiation of human embryonic stem cells (hESCs) were evaluated. Uptake of PS-NPs not only caused cellular injury, but also regulated cardiac-related pathways as revealed by RNA-sequencing. Consequently, the efficiency of cardiomyocyte differentiation from hESCs was compromised, leading to immature of cardiomyocytes and smaller cardiac organoids with impaired contractility. Mechanistically, PS-NPs promoted mitochondrial oxidative stress, activated P38/Erk MAPK signaling pathway, blocked autophagy flux, and eventually reduced the pluripotency of hESCs. Consistently, in vivo exposure of PS-NPs from cleavage to gastrula period of zebrafish embryo led to reduced cardiac contraction and blood flow. Collectively, this study suggests that PS-NPs is a risk factor for fetal health, especially for heart development., 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.)

Due to the characteristics of simple process, environmental friendliness and low operating costs, biometallurgy has become a popular technology for metals recovering from low-grade ores and tailings. In order to enhance the efficiency of bioleaching functional bacteria acquisition, the 9K agar was optimized by adjusting the ratio of two solutions to achieve better and faster solidification for the functional bacteria growth and isolation. By using the improved 9K agar, six functional stains within genera of Acidithiobacillus ferriphilus, A. ferrooxidans and Leptospirillum ferrooxidans were isolated from the enrichment of acid mine drainage. After the Fe 2+ oxidation ability evaluation, three strains of WT1-1, XT2-2, and YT3-1 within the three genera were selected and employed as the individual inoculum for the bioleaching from polymetallic sulfide tailings. Eventually, a maximum leaching efficiency of 58.37% Cu, 53.14% Al, 80.09% Mg, and 76.95% Zn were observed by A. ferriphilus WT1-1 after 28 d. To further improve the bioleaching efficiency, the three strains were mixed proportionally as the inoculum in both one-step and two-step bioleaching processes. Comparing to the pure cultures, the leaching efficiencies of Cu and Mg were significantly enhanced in both one- and two-steps, while no significant change in Zn. By comparing the one- and two-step processes, leaching efficiencies of Al, Mg, and Zn were higher in the one-step process, whereas Cu was observed to be higher in the two-step process. Therefore, the selection on leaching process of one or two steps should be determined based on tailings composition and target metals., 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.)

Talin protein (Talin 1/2) is a mechanosensitive cytoskeleton protein. The unique structure of the Talin plays a vital role in transmitting mechanical forces. Talin proteins connect the extracellular matrix to the cytoskeleton by linking to integrins and actin, thereby mediating the conversion of mechanical signals into biochemical signals and influencing disease progression as potential diagnostic indicators, therapeutic targets, and prognostic indicators of various diseases. Most studies in recent years have confirmed that mechanical forces also have a crucial role in the development of disease, and Talin has been found to play a role in several diseases. Still, more studies need to be done on how Talin is involved in mechanical signaling in disease. This review focuses on the mechanical signaling of Talin in disease, aiming to summarize the mechanisms by which Talin plays a role in disease and to provide references for further studies., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)