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Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options, often exhibiting resistance to standard radiotherapy (RT) and chemotherapy. Recent advancements in nanomedicine provide an opportunity to enhance treatment efficacy through innovative drug delivery systems and radiosensitizers. In this study, we present a novel nanotheranostic platform, MOs-G@DOX, engineered to enhance the therapeutic efficacy of RT in the treatment of TNBC. This platform consists of gadolinium-containing mesoporous organosilica nanoparticles (MOs-G) that serve a dual function as a drug carrier and a radiosensitizer. The MOs-G were synthesized via a surfactant-mediated sol-gel process, followed by gadolinium incorporation through nanoprecipitation. The antitumor drug doxorubicin (DOX) was subsequently loaded into the mesoporous structure, forming the MOs-G@DOX nanoplatform. Comprehensive in vitro and in vivo studies demonstrated that MOs-G@DOX exhibits excellent biocompatibility and significantly enhances the radiosensitivity of TNBC cells, leading to superior tumor growth inhibition compared to conventional treatments. The stability of MOs-G, with minimal gadolinium ion leakage, further underscores its potential as a safe and effective nanomedicine. Additionally, the combination of MOs-G@DOX with RT showed a marked increase in reactive oxygen species (ROS) generation and tumor cell apoptosis, which were confirmed through histological analyses. These findings suggest that MOs-G@DOX is a promising candidate for advancing cancer therapy, particularly in the context of RT for TNBC., 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.)

Legumes are a widespread and cheap source of starch. However, legume starches are prone to retrogradation in applications. Therefore, enhancing the resistance to retrogradation is important to ensure the quality of starch products. In this study, the effects of amines, alcohols, and carboxylic acids deep eutectic solvents (DESs) on the retrogradation properties of pea starch (PS) were investigated. The results showed that the starches treated with carboxylic acid DESs for only 30 min exhibited low paste viscosity, high paste clarity and anti-retrogradation. The carboxylic acid DESs treatment resulted in holes or cracks appearing on the starch surface, a decrease in molecular ordering, relative crystallinity, and amylose content. The thermal enthalpy of starch as well as the pasting viscosity were substantially reduced after the treatment. The paste clarity and the resistance to retrogradation were significantly improved. Conversely, the structure, pasting and retrogradation properties of starch treated with amine and alcohol DESs exhibited only slight differences compared to PS. The carboxylic acid DESs took a short time for the starch modification, and the modified starch paste with low viscosity, high clarity, and resistance to retrogradation. The study could provide an environmentally-friendly and cost-effective method for the preparation of starch with well anti-retrogradation properties., 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 integrity of the skin barrier is essential for maintaining skin health, with the stratum corneum and filaggrin 2 (FLG-2) playing a key role. FLG-2 deficiency or mutation has been linked to diseases such as atopic dermatitis, while external stressors such as ultraviolet B (UVB) radiation further damage the epidermal barrier. This study investigated the effects of recombinant filaggrin (rFLG) on skin barrier function and UVB induced epidermal destruction. Cell experiments showed that 10 μg/mL of rFLG could increase the mobility of HaCaT cells from 20 % to 42 %, increase the epithelial resistance (TEER) value by about 2 times, and up-regulate the tight junction associated protein by about 2 times. In mouse models of UVB-induced epidermal barrier destruction, rFLG at concentrations of 0.5, 1, and 2 mg/mL showed effective cell uptake and skin penetration, alleviating erythema, and reducing skin thickness in mice by 1.5-3 times. Among them, 2 mg/mL of rFLG treatment restored the expression of tight junction proteins (LOR, ZO-1, and caspase-14), reduced collagen degradation, and reduced oxidative stress by normalizing serum hydroxyproline and superoxide dismutase levels. In addition, 2 mg/mL of rFLG inhibited UVB-induced upregulation of matrix metalloproteinases (MMP-3 and MMP-9) and reduced pro-inflammatory factors (IL-10, IL-1α, IL-6, and TNF-α) and apoptotic markers (P38, Bax, and Bcl-2) to normal levels. These findings suggested that rFLG effectively enhanced skin barrier integrity and mitigated UVB-induced epidermal barrier destruction, highlighting its potential as a therapeutic agent for diseases associated with skin barrier dysfunction., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The microsatellite stable (MSS) colon cancer (CC) has long been considered resistant to immunotherapy. Cuproptosis, as a novel form of cell death, may interact with tumor immunity. This project focused on the impact of cuproptosis on the cytotoxicity of CD8 + T in MSS CC, aiming to provide effective clues for improving the treatment strategy of MSS CC. The study developed an MSS CC cuproptosis model using 50 nM elesclomol and 1 μM CuCl 2 . Cuproptotic SW480 cells were directly co-cultured with CD8 + T cells. Cuproptosis levels were assessed via intracellular copper ion detection, Western blot, and confocal laser scanning microscopy. CCK-8, Hochest/PI staining, CFSE cell proliferation assay, LDH cytotoxicity detection, and ELISA were used to evaluate CD8 + T cell immune activity and cytotoxicity. Transcriptome sequencing and bioinformatics analysis identified regulated signals in cuproptotic SW480 cells. A rescue experiment utilized a WNT pathway activator (BML-284). PD-L1 expression in cells/membranes was analyzed using qRT-PCR, Western blot, and flow cytometry. NSG mice were immunoreconstituted, and the effects of cuproptosis on immune infiltration and cancer progression in MSS CC mice were assessed using ELISA and immunohistochemistry (IHC). Treatment with 50 nM elesclomol and 1 μM CuCl 2 significantly increased cuproptosis in SW480 cells. Co-culture with CD8 + T cells enhanced their cytotoxicity. Sequencing revealed cuproptosis-mediated modulation of immune and inflammatory pathways, including WNT signaling. Rescue experiments showed downregulation of WNT signaling in cuproptotic SW480 cells. Indirectly, CD8 + T cell immune function was enhanced by reducing PD-L1 expression. In mice, cuproptosis resulted in increased infiltration of CD8 + T cells in tumor tissue, leading to delayed cancer progression compared to the control group. Cuproptosis in MSS CC cells enhances the cytotoxicity of CD8 + T cells, which may be achieved through downregulation of the WNT signaling pathway and decreased expression of PD-L1. In the future, drugs that can induce cuproptosis may be a promising approach to improve MSS CC 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 © 2024. Published by Elsevier B.V.)

The environmental impact of dissolved trace element (DTE) pollution is becoming increasingly well understood. The southeastern edge of the Qinghai-Tibet Plateau is a region with high environmental vulnerability, making it highly susceptible to various anthropogenic disturbances. The Lancang River (LCR), as the most representative river in this area, serving as the largest international river in Southeast Asia, the LCR is crucial for the downstream regions, supporting fisheries, agriculture, and even economic development, earning it the title of the "water tower" for these areas. This study mainly focuses on the upstream unbuilt dam area. In this study, we gathered 25 surface water samples from the upstream of the LCR and examined the geographical distribution, primary sources, and associated human health risks of seven dissolved trace elements (Mn, Cr, Fe, Co, Cu, Ni, Zn). Cr, Fe, Co, Ni, and Cu in the main stream are primarily associated with natural sources, including rock weathering, soil erosion, and similar processes. Mn, however, predominantly originates from human activities such as industrial construction and road transportation. Zn mainly originates from the specialized fertilizers used for highland barley in plateau regions. Almost all DTE concentrations exhibited a downward trend from upstream to downstream. However, due to inputs from various sources along the way, there will be some abnormal points. The concentrations of DTE in the study area were within the acceptable limits set by drinking water standards in China, the USA, and the WHO. Overall, the water quality in this region is considered good. The results from a Monte Carlo simulation assessing health risks indicate that the non-carcinogenic health risk caused by DTE in the upper reaches of Lancang River was very weak. The primary pathway through which DTE can harm human health is ingestion, with children being particularly vulnerable. These findings offer a critical scientific basis for understanding the migration of DTE in aquatic environments and for the ecological stewardship of the Lancang River., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Aspartic proteases (APs) constitute a large family in plants and are widely involved in diverse biological processes, like chloroplast metabolism, biotic and abiotic stress responses, and reproductive development. In this study, we focused on overall analysis of the APs genes in tobacco. Our analysis included the phylogeny and cis-elements in the cell wall-associated promoters of these genes. To characterize the expression patterns of APs genes in stem vascular development. The tissue expression analysis showed that NtAED3-like was preferentially expressed in the differentiating xylem and phloem cells of the vascular system. Based on histochemical staining analysis showed that the NtAED3-like gene was specifically expressed in stem vascular tissue, root vascular tissue, and petiole vascular tissue. The TdT-mediated dUTP nick-end labeling (TUNEL) assay illustrated a delayed progression of programmed cell death (PCD) within the xylem of the ko-ntaed3a-like mutant, relative to the wild type. The mutant ko-ntaed3a-like exhibited a phenotype of thinning stem circumference and changed in xylem structure and lignin content. In addition, the two-dimension heteronuclear single quantum coherent nuclear magnetic resonance (2D-HSQC) analysis of three milled wood lignins (MWLs) showed that the content of β-O-4 connection in ko-ntaed3a-like decreased slightly compared with wild type. In conclusion, this study provides our understanding of the regulation of vascular tissue development by the NtAED3-like gene in tobacco and provides a better basis for determining the molecular mechanism of the aspartic protease in secondary cell wall (SCW) development., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

The pathogenesis of this condition is intricate, characterized by the aberrant activation of numerous cytokines and signaling pathways. This study aimed to delve into the association between the expression of the MAPK14 protein and immune cell infiltration in patients suffering from Acute Respiratory Distress Syndrome (ARDS). Additionally, it sought to assess the viability of autophagy-related genes as potential diagnostic biomarkers. To achieve this, the researchers employed various techniques such as immunohistochemistry, real-time quantitative PCR, and western blotting to measure the MAPK14 protein levels in the lung tissues of ARDS patients. These measurements were then correlated with clinical data to provide a comprehensive analysis.In this study, the researchers conducted a gene expression profile analysis to identify genes associated with autophagy. The relationship between these genes, MAPK14 expression, and immune cell infiltration was thoroughly evaluated. The findings revealed a marked increase in the expression of MAPK14 protein in the lung tissues of ARDS patients. This increased expression was found to be positively correlated with the extent of immune cell infiltration. The study's further analysis highlighted that several genes associated with autophagy exhibited expression levels that were correlated with both MAPK14 expression and the degree of immune infiltration. This suggests a complex interplay between MAPK14 protein levels, autophagy-related genes, and immune responses in the pathogenesis of ARDS. The results underscore the potential of these molecular markers in understanding the disease mechanisms and possibly aiding in the diagnosis and treatment of ARDS., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cadmium (Cd), a toxic heavy metal pollutant, inflicts widespread damage on various organs and tissues, including cartilage, where it induces chondrocyte apoptosis. Angelica sinensis polysaccharides (ASP), a key active component of the traditional Chinese medicine Angelica sinensis, have been shown to possess anti-apoptotic effects on chondrocytes. This study investigates the in vitro effects of ASP on alleviating Cd-induced apoptosis in layer chicken chondrocytes, focusing on the mitochondrial apoptosis pathway mediated by the c-Jun N-terminal kinase (JNK) signaling pathway. Chondrocytes were isolated from layer chicken embryos and confirmed to express collagen type II alpha 1 (Col2a1). We found that Cd triggered apoptosis in the chondrocytes; however, the use of the JNK inhibitor SP 600125 mitigated mitochondrial structural damage casused by Cd, indicating the involvement of JNK signaling in this process. Furthermore, ASP effectively alleviated Cd-induced apoptosis in layer chicken chondrocytes by inhibiting JNK signaling in vitro. Our findings provide a theoretical foundation for the clinical application of ASP in preventing Cd-induced cartilage diseases in poultry., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript, and manuscript is approved by all authors for publication. The author would like to declare on behalf of his co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alkaline phosphatase (ALP) is an enzyme that can hydrolyze phosphate groups, and its activity is related to algal bloom outbreaks in eutrophic waters. A magnetic ALP-responsive material named Fe 3 O 4 @INV/Zn-AMP was synthesized at room temperature by using zinc ions and adenosine monophosphate (AMP) as building blocks integrated invertase (INV). When ALP is present, it hydrolyzes the phosphate group of AMP, causing the disassembly of the Fe 3 O 4 @INV/Zn-AMP material and the release of signaling molecule (INV). After magnet separation, the released INV can digest sucrose into glucose measured by a personal glucometer (PGM), providing a signal that indicates the activity of ALP. This method allows for selective, sensitive, and easy detection of ALP in field settings without the need for complicated labeling operations. Benefit from the selective stimulus-response and the enzyme catalyzed amplification, a simple and portable method for the monitoring of ALP using PGM was established, with linear range of 0.005-0.2 U/mL and a detection limit of 0.001 U/mL, which showed the potential of field monitoring for alkaline phosphatase in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gut digestion by earthworms (GDE) is a crucial step in vermicomposting, affecting the fate of antibiotic resistance genes (ARGs) in vermicompost sludge. The extracellular polymeric substance (EPS) matrix of sludge is an important space for ARG transfer. However, the effect of GDE on EPS-associated ARGs remains unclear. Therefore, this study explored the role of GDE in driving the transfer of ARGs within different EPS layers in sludge. For this, the changes in intracellular ARGs and EPS-associated ARGs in sludge were analyzed after 5 days of the GDE process. The results showed that after the GDE process, both nitrate and dissolved organic carbon significantly increased in all EPS layers of sludge, while the proteins and polysaccharides only enhanced in soluble and loosely bound EPS of sludge. In addition, a 7.0% decrease in bacterial diversity was recorded after the GDE process, with a functional bacterial community structure emerging. Moreover, the absolute abundance of total ARGs and mobile genetic elements decreased by 90.71% and 61.83%, respectively, after the GDE process. Intracellular ARGs decreased by 92.1%, while EPS-associated ARGs increased by 4.9%, indicative of intracellular ARG translocation into the EPS during the GDE process. Notably, the ARGs exhibited significant enrichment in both the soluble and loosely bound EPS, whereas they were reduced in the tightly bound EPS. The structural equation modeling revealed that the GDE process effectively mitigated the ARG dissemination risk by modulating both the EPS structure and microenvironment, with the organic structure representing a primary factor influencing ARGs in the EPS., 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.)

Hematopoietic Progenitor Kinase 1 (HPK1, also known as MAP4K1) is a hematopoiesis-specific serine/threonine kinase that belongs to the MAP4K family of Ste20-related protein kinases. HPK1 has been identified as a negative regulator of T-cell receptor signaling. Recent studies have indicated that the inhibition or knockout of HPK1 kinase function can effectively alleviate T cell exhaustion, enhance T cell functionality, and improve the therapeutic efficacy of tumor immunotherapy. In recent years, small molecule chemical drugs targeting HPK1 have made significant progress and have become a hot topic in the research and development of tumor immunotherapy drugs. However, the advancement of small molecule drugs that target HPK1 is hindered by various challenges, including the limited selectivity, insufficient immune stimulation, and the ambiguity surrounding role of non-kinase scaffold functions of HPK1 in tumor immune responses. This review briefly describes the biological structure of HPK1 and its related signaling pathways in tumor immunity, systematically discusses the latest research progress in small molecule chemical drugs targeting HPK1. Finally, we summarize and prospect the opportunities and challenges in the drug development of small molecule chemical drugs targeting HPK1 in tumor immunity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wenhai huang reports financial support was provided by Huadong Medicine-Joint Funds of the Zhejiang Provincial Natural Science Foundation of China. Wenhai huang reports financial support was provided by Zhejiang Provincial Key Research & Development Plan. Wenhai huang reports financial support was provided by Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province. Shenxin zeng reports financial support was provided by Hangzhou Medical College 2022 College basic research funds basic research project. Shenxin zeng reports financial support was provided by National Innovation and Entrepreneurship Training Program for College Students. Shenxin zeng reports financial support was provided by Innovation and Entrepreneurship Training Program for College Students of Zhejiang Province. Shenxin zeng reports financial support was provided by Scientific and Technological Innovation Project for College students in Zhejiang Province. The authors declare no conflicts of interest. 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 Inc. All rights reserved.)

Hexavalent chromium [Cr(VI)] is a widely distributed carcinogen in industrial contexts and general environmental contexts. Emerging research highlights the central role of ribosomal DNA (rDNA) in DNA Damage Responses (DDRs). However, there remains a lack of investigation into the potential dose-dependent relationship between exposure to Cr(VI) and alterations in rDNA copy number (CN), as well as the related mechanisms underlying these effects. A molecular epidemiological investigation involving 67 workers exposed to Cr(VI) and 75 unexposed controls was conducted. There was a notable increase in ZNF385A expression, variations in rDNA CN, and elevated γH2AX levels in the peripheral blood of Cr(VI)-exposed workers. Restricted cubic spline (RCS) models showed that blood Cr levels in the exposed population exhibited non-linear dose-dependent relationships with γH2AX, rDNA CN, and ZNF385A. Of considerable interest, there were robust and positive associations between ZNF385A and both γH2AX and rDNA CN. Further in vitro experiments provided concrete evidence that Cr(VI) simultaneously caused an increase in ZNF385A expression and variations in rDNA CN. ZNF385A-depleted cells showed increased sensitivity to Cr(VI)-mediated DDRs and alterations in rDNA CN. This study indicated that ZNF385A played a highly significant role in the rDNA CN variation in response to Cr(VI)-induced DNA damage., 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.)

Sodium alginate (SA) has gained widespread acclaim as a carrier medium for three-dimensional (3D) bioprinting of cells and a diverse array of bioactive substances, attributed to its remarkable biocompatibility and affordability. The conventional approach for fabricating alginate-based tissue engineering constructs entails a post-treatment phase employing a calcium ion solution. However, this method proves ineffectual in addressing the predicament of low precision during the 3D printing procedure and is unable to prevent issues such as non-uniform alginate gelation and substantial distortions. In this study, we introduced borate bioactive glass (BBG) into the SA matrix, capitalizing on the calcium ions released from the degradation of BBG to incite the cross-linking reaction within SA, resulting in the formation of BBG-SA hydrogels. Building upon this fundamental concept, it unveiled that BBG-SA hydrogels greatly enhance the precision of SA in extrusion-based 3D printing and significantly reduce volumetric contraction shrinkage post-printing, while also displaying certain adhesive properties and electrical conductivity. Furthermore, in vitro cellular experiments have unequivocally established the excellent biocompatibility of BBG-SA hydrogel and its capacity to actively stimulate osteogenic differentiation. Consequently, BBG-SA hydrogel emerges as a promising platform for 3D bioprinting, laying the foundation for the development of flexible, biocompatible electronic devices., 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.)

Objectives: This study investigated the transmission patterns of tuberculosis (TB) and its associated risk factors in Hunan province to inform the development of prevention and control strategies in the region., Methods: An 8-year retrospective population-based genomic epidemiological study was conducted. Genomic clusters were defined using distance thresholds of 12-single-nucletide-polymorphisms. Risk factors associated with TB transmission were analyzed using logistic regression model. Kernel Density analysis was used to locate hotspots where transmission occurred., Results: Among 2649 TB cases included in this study, 275 clusters were identified, with an overall clustering rate of 24.7% (654/2649). Nearly 95% (620/654) of clustered strains were isolated from the same county. Of the 275 clusters, 23 (8.4%, 23/275) had differences in drug-resistant profiles, with FQs resistance mutations occurring most frequently (52.2%, 12/23). Multivariate analysis identified male TB patients, those aged 30-60 years, ethnic minorities, nonfarmers, retreated TB patients, and individuals infected with MDR/RR-TB as independent risk factors for TB transmission (P < 0.05). Kernel density analysis showed that among the 5 drug-resistant surveillance sites, Leiyang had the highest clustering rate, followed by Yongshun, Qidong, Hecheng, and Taojiang., Conclusion: Recent transmission in the region is predominantly occurring within counties. The risk factors related to TB transmission and the hotspots where transmission occurs can provide a scientific basis for the formulation of targeted TB prevention and control strategies., Competing Interests: Declarations 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 article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Coronary artery disease poses a significant threat to human health. In clinical settings, coronary angiography remains the gold standard for diagnosing coronary heart disease. A crucial aspect of this diagnosis involves detecting arterial narrowings. Categorizing these narrowings can provide insight into whether patients should receive vascular revascularization treatment. The majority of current deep learning methods for analyzing coronary angiography are mostly confined to the theoretical research domain, with limited studies offering direct practical support to clinical practitioners. This paper proposes an integrated deep-learning model for the localization and classification of narrowings in coronary angiography images. The experimentation employed 1606 coronary angiography images obtained from 132 patients, resulting in an accuracy of 88.9 %, a recall rate of 85.4 %, an F1 score of 0.871, and a MAP value of 0.875 for vascular stenosis detection. Furthermore, we developed the "Hemadostenosis" web platform (http://bioinfor.imu.edu.cn/hemadostenosis) using Django, a highly mature HTTP framework. Users are able to submit coronary angiography image data for assessment via a visual interface. Subsequently, the system sends the images to a trained convolutional neural network model to localize and categorize the narrowings. Finally, the visualized outcomes are displayed to users and are downloadable. Our proposed approach pioneers the recognition and categorization of arterial narrowings in vascular angiography, offering practical support to clinical practitioners in their learning and diagnostic processes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sodium alginate has good biocompatibility and is widely used in the study of drug carriers. In this paper, a method to prepare calcium alginate microspheres with high sphericity based on double emulsion droplets was proposed, in which sodium alginate is used as the innermost phase. By adjusting the density of the system, the double-emulsion droplets could be suspended in the collecting solution, leading to the homogeneous reaction between the sodium alginate droplets and the calcium ions. By changing the flow rate, the size of the droplets could be changed, and by changing the concentration of calcium ions in the collecting solution, the sphericity of the calcium alginate microspheres could be changed. Then the swelling properties and drug release properties of calcium alginate microspheres were determined. The drug delivery study revealed that the insulin-loaded Ca-Alginate microspheres were able to decrease blood glucose by 41.4 % after oral administration to mice. Thus, the Ca-Alginate microsphere is a suitable candidate for controlled pH-sensitive drug delivery., 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.)

Neuropeptides are the most ubiquitous neurotransmitters in the immune system, regulating various biological processes. Neuropeptides play a significant role for the discovery of new drugs and targets for nervous system disorders. Traditional experimental methods for identifying neuropeptides are time-consuming and costly. Although several computational methods have been developed to predict the neuropeptides, the accuracy is still not satisfactory due to the representability of the extracted features. In this work, we propose an efficient and interpretable model, NeuroPpred-SHE, for predicting neuropeptides by selecting the optimal feature subset from both hand-crafted features and embeddings of a protein language model. Specially, we first employed a pre-trained T5 protein language model to extract embedding features and twelve other encoding methods to extract hand-crafted features from peptide sequences, respectively. Secondly, we fused both embedding features and hand-crafted features to enhance the feature representability. Thirdly, we utilized random forest (RF), Max-Relevance and Min-Redundancy (mRMR) and eXtreme Gradient Boosting (XGBoost) methods to select the optimal feature subset from the fused features. Finally, we employed five machine learning methods (GBDT, XGBoost, SVM, MLP, and LightGBM) to build the models. Our results show that the model based on GBDT achieves the best performance. Furthermore, our final model was compared with other state-of-the-art methods on an independent test set, the results indicate that our model achieves an AUROC of 97.8 % which is higher than all the other state-of-the-art predictors. Our model is available at: https://github.com/wenjean/NeuroPpred-SHE., Competing Interests: Declaration of competing interest All authors declared no potential conflicts of interest with respect to this article., (Copyright © 2024. Published by Elsevier Ltd.)

Numerous investigations have shown that the municipal solid waste incineration (MSWI) has become one of the major sources of dioxin (DXN) emissions. Currently, the primary issue that needs to be addressed for DXN emission reduction control is the online measurement of DXN. Data-driven AI algorithms enable real-time DXN concentration measurement, facilitating its control. However, researchers mainly focus on building models for DXN emissions at the stack. This approach does not allow for the construction of models that online measurement of DXN generation and absorption throughout the whole process. To achieve optimal pollution control, models that encompass the whole process are necessary, not just models focused on the stack. Therefore, this article focuses on modeling the whole process of DXN concentrations, including generation, adsorption, and emission. It uses machine learning techniques based on advanced tree-based data-driven deep and broad learning algorithms. The determination of data characteristics at different phases is grounded in the understanding of the DXN mechanism, offering a novel framework for DXN modeling. State-of-the-art tree-based models, including adaptive deep forest regression algorithm based on cross layer full connection, tree broad learning system, fuzzy forest regression, and aid modeling technologies, are applied to handle diverse data characteristics. These characteristics encompass high-dimensional small samples, low-dimensional ultra-small size samples, and medium-dimensional small samples across different phases related to DXN. The most interesting is the robust validation where the proposed a whole process tree-based model for DXN is validated using nearly one year of authentic data on DXN generation, adsorption, and emission phases in an MSWI plant of Beijing. The proposed modeling framework can be used to explore the mechanism characterization and support the pollution reduction optimal control., 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.)

Environmental pollutants are considered as a cause of tumorigenesis, but approaches to assess their risk of causing tumors remain insufficient. As an alternative approach, the adverse outcome pathway (AOP) framework is used to assess the risk of tumors caused by environmental pollutants. Arsenic is a pollutant associated with lung cancer, but early assessment of lung cancer risk is lacking. Therefore, we applied the AOP framework to arsenic-induced lung cancer. A systematic review revealed increased risks of lung cancer following exposure to a range of arsenic concentrations in drinking water (OR = 1.83, 95 % CI = 1.46-2.30). We obtained, from public databases, genes related to risk of arsenic-induced lung cancer. Then, Cox and LASSO regressions were used to screen target genes from the risk genes. Subsequently, target genes, phenotypes, and pathways were used to construct the computational AOP network, which was determined by Cytoscape to have 156 edges and 45 nodes. Further, target genes, phenotypes, and pathways were used as molecular initiating events and key events to construct the AOP framework depending on upstream and downstream relationships. In the AOP framework, by Weight of Evidence, arsenic exposure increased levels of EGFR, activated the PI3K/AKT pathway, regulated cell proliferation by promoting the G1/S phase transition, and caused generation of lung cancers. External validation was achieved through arsenite-induced, malignant transformed human bronchial epithelial (HBE) cells. Overall, these results, by integration into existing data to construct an AOP framework, provide insights into the assessment of lung cancer risk for arsenic exposure. Special attention needs to be focused on populations with low-dose arsenic exposure., 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.)

Dysregulated super-enhancer (SE) results in aberrant transcription that drives cancer initiation and progression. SEs have been demonstrated as novel promising diagnostic/prognostic biomarkers and therapeutic targets across multiple human cancers. Here, we sought to develop a novel prognostic signature derived from SE-associated genes for head and neck squamous cell carcinoma (HNSCC). SE was identified from H3K27ac ChIP-seq datasets in HNSCC cell lines by ROSE algorithm and SE-associated genes were further mapped and functionally annotated. A total number of 133 SE-associated genes with mRNA upregulation and prognostic significance was screened via differentially-expressed genes (DEGs) and Cox regression analyses. These candidates were subjected for prognostic model constructions by machine learning approaches using three independent HNSCC cohorts (TCGA-HNSC dataset as training cohort, GSE41613 and GSE42743 as validation cohorts). Among dozens of prognostic models, the random survival forest algorithm (RSF) stood out with the best performance as evidenced by the highest average concordance index (C-index). A prognostic nomogram integrating this SE-associated gene signature (SEAGS) plus tumor size demonstrated satisfactory predictive power and excellent calibration and discrimination. Moreover, WNT7A from SEARG was validated as a putative oncogene with transcriptional activation by SE to promote malignant phenotypes. Pharmacological disruption of SE functions by BRD4 or EP300 inhibitor significantly impaired tumor growth and diminished WNT7A expression in a HNSCC patient-derived xenograft model. Taken together, our results establish a novel, robust SE-derived prognostic model for HNSCC and suggest the translational potentials of SEs as promising therapeutic targets for HNSCC., 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.)

Microplastics (MPs) are emerging as anthropogenic vectors to form plastisphere, facilitating microbiome colonization and pathogenic dissemination, thus contributing to environmental and health crises across various ecosystems. However, a knowledge gap persists regarding MPs risks and their driving factors in certain unique and vulnerable ecosystems, such as Karst travertine lakes, some of which are renowned World Natural Heritage Sites under ever-increasing tourism pressure. We hypothesized that tourism activities serve as the most important factor of MPs pollution, whereas intrinsic features, including travertine deposition can exacerbate potential environmental risks. Thus, metagenomic approaches were employed to investigate the geographical distribution of the microbiome, antibiotic resistance genes (ARGs), virulence factor genes (VFGs), and their combined environmental risks in Jiuzhaigou and Huanglong, two famous tourism destinations in Southwest China. The plastisphere risks were higher in Huanglong, contradicting our hypothesis that Jiuzhaigou would face more crucial antibiotic risks due to its higher tourist activities. Specifically, the levels of Lipopolysaccharide Lewis and fosD increased by sevenfold and 20-fold, respectively, from upstream to downstream in Huanglong, whereas in Jiuzhaigou, no significant accrual was observed. Structural equation modeling results showed that travertine deposition was the primary contributor to MPs risks in alpine karstic lakes. Our findings suggest that tourism has low impact on MPs risks, possibly because of proper management, and that travertine deposition might act as an MPs hotspot, emphasizing the importance of considering the unique aspects of travertine lakes in mitigating MPs pollution and promoting the sustainable development of World Natural Heritage Sites., 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.)

Objectives: This study aimed to analyze the possible role of rDNA copy number variation in the association between hexavalent chromium [Cr (VI)] exposure and semen quality in semen donors and further confirm this association in mice., Methods: In this cross-sectional study, whole blood and semen samples were collected from 155 semen donors in the Zhejiang Human Sperm Bank from January 1st to April 31st, 2021. Adult C57BL/6 J male mice were treated with different doses of Cr (VI) (0, 10, or 15 mg/kg b.w./day). Semen quality, including semen volume, total spermatozoa count, sperm concentration, progressive motility, and total motility, were analyzed according to the WHO laboratory manual. Cr concentration was detected using inductively coupled plasma mass spectrometry. The rDNA copy number was measured using qPCR., Results: In semen donors, whole blood Cr concentration was negatively associated with semen concentration and total sperm counts. Semen 5 S and 45 S rDNA copy numbers were negatively associated with whole blood Cr concentration and whole blood 5.8 S rDNA copy number was negatively associated with semen Cr concentration. In mice, Cr (VI) damaged testicular tissue, decreased semen quality, and caused rDNA copy number variation. Semen quality was related to the rDNA copy number in whole blood, testicular tissue, and semen samples in mice., Conclusion: Cr (VI) was associated with decreased semen quality in semen donors and mice. Our findings suggest an in-depth analysis of the role of the rDNA copy number variation in the Cr (VI)-induced impairment of semen quality., 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.)

Polygonum hydropiper (PH) is a rich source of active compounds and serves as a pivotal ingredient in Chinese rice wine (Huangjiu) production. This study investigates the impact of PH and Polygonum hydropiper extract (PHE) on ethyl carbamate (EC) production during Huangjiu fermentation. Our findings reveal that PH enhances the relative abundance of Bacillus subtilis in Huangjiu fermentation, thereby facilitating its interaction with Saccharomyces cerevisiae. Furthermore, PH modulates the urea metabolism of S. cerevisiae. In the PH-B. subtilis-S. cerevisiae fermentation system, the expression of DUR1,2 and DUR3 genes in S. cerevisiae is upregulated. This augmentation leads to increased urea uptake and metabolism by S. cerevisiae in the fermentation broth, subsequently reducing the urea concentration in the fermentation medium (The EC content in the CK group was approximately 355.55 % and 356.05 % higher than those in the PH and PHE groups, respectively). Consequently, PH demonstrates promise in reducing the EC concentration of Huangjiu, offering a novel approach to enhance the safety of Huangjiu consumption., 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.)

Ponatinib is approved for use in patients with chronic myeloid leukemia (CML) who are resistant to or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. Given that ponatinib can induce significant cardiotoxicity when taken, and that most Chinese medicines have cardioprotective effects, it is possible to administer them in combination in clinic to alleviate adverse effects. The quantitative determination of ponatinib and its metabolite N-desmethyl ponatinib was optimized and fully verified by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). And the drug-drug interactions (DDI) of ponatinib with lycopene and shikonin, both in vivo and in vitro, were studied. The results of bioanalytical methodology showed that ponatinib and N-desmethyl ponatinib had good linearity in plasma samples, and their selectivity, accuracy, precision, stability, matrix effect and recovery were all satisfied with the need of quantitative analysis of samples. In animal experiments, compared with the control group, lycopene and shikonin significantly changed the pharmacokinetic parameters of ponatinib, including AUC (0-t) , AUC (0-∞) and CL z/F , while having no effect on the pharmacokinetic parameters of N-desmethyl ponatinib. In vitro interaction studies indicated that lycopene showed mixed inhibition mechanism on ponatinib metabolism in both rat liver microsomes (RLM) and human liver microsomes (HLM). And, shikonin displayed mixed inhibition mechanism in RLM and competitive inhibition mechanism in HLM, respectively. In summary, the UPLC-MS/MS method can accurately and sensitively quantify ponatinib and N-desmethyl ponatinib, and provide further reference for clinical drug combination between ponatinib and lycopene or shikonin., 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.)

Theoretical research has explained the process of dioxin (DXN) formation in the municipal solid waste incineration (MSWI). This process includes the generation, adsorption, and emission of DXN. Actual DXN concentrations often significantly deviate from theoretical models. This discrepancy is influenced by several key factors: the type of integrated municipal solid waste (MSW) treatment process, the characteristics of the waste, and the operational controls. The progression of DXN generation, adsorption, and emission concentrations within the MSWI process remains unclear. This lack of clarity is especially pronounced when examining the accounting for the specific components of the MSW. To unravel the evolution of DXN, this article proposes a comprehensive numerical simulation model for the entire process of DXN concentration in an MSWI plant. The model is designed based on existing knowledge of MSW combustion and DXN mechanisms, leveraging FLIC and ASPEN simulation software. It incorporates six key stages to facilitate the DXN simulation: precipitation and formation, high-temperature pyrolysis, high-temperature gas-phase synthesis, low-temperature catalytic synthesis, adsorption on activated carbon, and emission to the atmosphere. Under both benchmark and multiple operating conditions, the simulated experiments confirm the effective representation of the evolution of DXN concentrations throughout the process. Consequently, this study presents a model designed to enhance the development of strategies aimed at reducing DXN emissions and to foster innovation in intelligent control technologies., 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 article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Monitoring the spatiotemporal distribution of formaldehyde (HCHO) is crucial for reducing volatile organic compounds (VOCs) emissions, and the long-term evolution of socio-natural sources contributions to tropospheric HCHO over China is still unclear. We propose an oversampling algorithm for quantitatively tracking the evolution of uncertainty, which lowers the uncertainty of the original Level 2 OMI HCHO data (50 % -105 %) to 0-50 %, and then we examine the evolution of contributions from various emissions sources applying multi-scale correlation. We found that the high formaldehyde vertical column densities (VCD) caused by human activities in eastern China are crossing the Hu Huanyong Line, which was formerly used to demarcate the population distribution. National-scale analysis indicate that HCHO VCD are significantly correlated with per capita Gross Domestic Product (per capita GDP) (r = 0.948) and Normalized Difference Vegetation Index (r = 0.864), while no substantial correlation with land surface temperature (LST) (r = 0.233). A valuable finding at city-scale is that the vast majority of cities exhibits clear latitude zoning characteristics in the correlation between HCHO VCD and per capita GDP. Diagnosis at pixel scale reveals that anthropogenic emissions continue to weaken the contributions of emissions caused by the increase in vegetation proportion. NDVI = 0.8 is the critical characteristic point where the contribution of natural source exceeds that of anthropogenic sources, while the point presents a decreasing trend in recent years due to the enhancement of human activities levels. Rise in LST over vegetation areas show positive driving effect on formaldehyde emissions, but continuous urbanization is diminishing this contribution. NDVI = 0.8 is a characteristic point to determine whether the contribution proportion of regional surface temperature to formaldehyde emissions from vegetation begun to rise. Our research identifies the evolutionary process and characteristics of the spatiotemporal distribution and socio-nature sources contributions of tropospheric formaldehyde of China from 2005 to 2022., 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.)

Dabrafenib is a BRAF inhibitor that has been demonstrated to be efficacious in the treatment of melanoma and non-small-cell lung cancer patients with BRAF V600E mutations. The objective of this study was to investigate the effects of 51 traditional Chinese medicines on the metabolism of dabrafenib and to further investigate the inhibitory effect of imperatorin. The quantification of dabrafenib and its metabolite hydroxy-dabrafenib was carried out using a sensitive, rapid, and accurate assay method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The results of in vitro experiments showed that 20 drugs inhibited the metabolism of dabrafenib by more than 80 %. In a further study of imperatorin on dabrafenib, the half-maximal inhibitory concentration (IC 50 ) values of imperatorin on dabrafenib were 0.22 μM and 3.68 μM in rat liver microsomes (RLM) and human liver microsomes (HLM), respectively, while the inhibition mechanisms were non-competitive and mixed type inhibition, respectively. The results of in vivo experiments demonstrated that in the presence of imperatorin, the AUC (0-t) , AUC (0-∞) , C max , and T max of dabrafenib were increased by 2.38-, 2.26-, 1.05-, and 6.10-fold, respectively, while CL z/F was decreased by 67.9 %. In addition, T max of hydroxy-dabrafenib was increased by 1.4-fold. The results of the research showed that imperatorin had a consistent inhibitory effect on dabrafenib in vitro and in vivo. When the concurrent use of dabrafenib and imperatorin is unavoidable, clinicians should closely monitor for potential adverse events and make timely adjustments to the administered dosage., 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.)

Clothianidin, classified as a second-generation neonicotinoid, has achieved extensive application due to its high efficacy against insect pests. This broad-spectrum usage has resulted in its frequent detection in environmental surveys. CYP2C19 and CYP3A4 are crucial for converting clothianidin to desmethyl-clothianidin (dm-clothianidin). The expression of these CYP450s can be significantly influenced by genetic polymorphisms. The objective of our research was to examine the catalytic effects of 27 CYP3A4 variants and 31 CYP2C19 variants on the metabolism of clothianidin within recombinant insect microsomes. These variants were assessed through a well-established incubation procedure. In addition, the concentration of its metabolite dm-clothianidin was quantified by employing an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Lastly, the kinetic parameters of these CYP3A4 and CYP2C19 variants were calculated by applying Michaelis-Menten kinetic analysis to fit the data. The observed changes in enzyme activity were related to the metabolic transformation of clothianidin to dm-clothianidin. In the CYP2C19 metabolic pathway, one variant (CYP2C19.23) showed no notable change in intrinsic clearance (CL int ), four variants (CYP2C19.29, .30, .31 and L16F) demonstrated a marked increase in CL int (110.86-183.46 %), and the remaining 25 variants exhibited a considerable decrease in CL int (26.38-89.79 %), with a maximum decrease of 73.62 % (CYP2C19.6). In the CYP3A4 metabolic pathway, 26 variants demonstrated significantly reduced CL int (10.54-52.52 %), with a maximum decrease of 89.46 % (CYP3A4.20). Our results suggested that most variants of CYP3A4 and CYP2C19 significantly altered the enzymatic activities associated with clothianidin metabolism to various degrees. This study provides new insights into assessing the metabolic behavior of pesticides and delivers crucial data that can guide clinical detoxification strategies., 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.)

Apixaban is an oral anticoagulant that directly inhibits the target Factor Xa (FXa). In this study, we focused on the in vivo and in vitro effects of adagrasib and asciminib on apixaban metabolism, to discover potential drug-drug interactions (DDI) and explore their inhibitory mechanisms. The levels of apixaban and its metabolite, O-desmethyl-apixaban (M2), were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). In vitro evaluation, the maximum half inhibitory concentration (IC 50 ) of adagrasib in rat liver microsomes (RLM) and human liver microsomes (HLM) against apixaban was 7.99 μM and 117.40 μM, respectively. The IC 50 value of asciminib against apixaban in RLM and HLM was 4.28 μM and 18.42 μM, respectively. The results of the analysis on inhibition mechanisms showed that adagrasib inhibited the metabolism of apixaban through a non-competitive mechanism, while asciminib inhibited the metabolism of apixaban through a mixed mechanism. Moreover, the interaction of apixaban with adagrasib and asciminib in Sprague-Dawley (SD) rats was also investigated. It was found that the pharmacokinetic characteristics of apixaban were significantly changed when combined with these two antitumor drugs, where AUC (0-t) , AUC (0-∞) , t 1/2 , T max , and C max were increased, while CL z /F was significantly decreased. But both drugs did not appear to affect the metabolism of M2 in a significant way. Consistent results from in vitro and in vivo demonstrated that both adagrasib and asciminib inhibited the metabolism of apixaban. It provided reference data for the future clinical individualization of apixaban., 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: Long-term physical inactivity probably leads to a co-existence of osteoporosis and sarcopenia which result in a high risk of falls, fractures, disability and even mortality. However, universally applicable and feasible approaches are lacking in the concurrent treatment of osteoporosis and sarcopenia. In this study, we evaluated the effect of strontium zinc silicate bioceramic (SZS) extract on osteoporosis and sarcopenia and explored its underlying mechanisms., Methods: Hindlimb osteoporosis and sarcopenia were established in a tail-suspended rat model. The bones were conducted μCT scanning, histological examination, and gene expression analysis, and the muscles were conducted histological examination and gene expression analysis. In vitro,  the effect of SZS extract on osteoblasts was determined by alizarin red S staining, immunofluorescence and qPCR. Similarly, the effect of SZS extract on myoblasts was determined by immunofluorescence and qPCR.. At last, the role of Piezo1 and the change of intracellular calcium ion (Ca 2+ ) were explored through blockading the Piezo1 by GsMTx4 in MC3T3-E1 and C2C12 cells, respectively., Results: We found that SZS extract could concurrently and efficiently prevent bone structure deterioration, muscle atrophy and fibrosis in hind limbs of the tail-suspended rats. The in vivo study also showed that SZS extract could upregulate the mRNA expression of Piezo1, thereby maintaining the homeostasis of bones and muscles. In vitro study demonstrated that SZS extract could promote the proliferation and differentiation of MC3T3-E1 and C2C12 cells by increasing the intracellular Ca 2+ in a Piezo1-dependent manner., Conclusion: This study demonstrated that SZS extract could increase Piezo1-mediated intracellular Ca 2+ , and facilitate osteogenic differentiation of osteoblast and myogenic differentiation of myoblasts, contributing to alleviation of osteoporosis and sarcopenia in a tail-suspended rat model., The Translational Potential of This Article: The current study might provide a universally applicable and efficient strategy to treat musculoskeletal disorders based on bioactive ceramics. The verification of the role of Piezo1-modulated intracellular Ca 2+ during osteogenesis and myogenesis provided a possible therapeutic target against mechanical related diseases., (© 2024 The Authors.)

The clinical application of tumor necrosis factor-α (TNF-α) is limited by its short half-life, subeffective concentration in the targeted area and severe systemic toxicity. In this study, the recombinant polypeptide S4-TNF-α was constructed and coupled with chitosan-modified superparamagnetic iron oxide nanoparticles (S4-TNF-α-SPIONs) to achieve pH-sensitive controlled release and active tumor targeting activity. The isoelectric point (pI) of S4-TNF-α was reconstructed to approach the pH of the tumor microenvironment. The negative-charge S4-TNF-α was adsorbed to chitosan-modified superparamagnetic iron oxide nanoparticles (CS-SPIONs) with a positive charge through electrostatic adsorption at physiological pH. The acidic tumor microenvironment endowed S4-TNF-α with a zero charge, which accelerated S4-TNF-α release from CS-SPIONs. Our studies showed that S4-TNF-α-SPIONs displayed an ideal pH-sensitive controlled release capacity and improved antitumor effects. Our study presents a novel approach to enhance the pH-sensitive controlled-release of genetically engineered drugs by adjusting their pI to match the pH of the tumor microenvironment., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cellulose papers (CPs) possess a pore structure, rendering them ideal precursors for carbon scaffolds because of their renewability. However, achieving a tradeoff between high electromagnetic shielding effectiveness and low reflection coefficient poses a tremendous challenge for CP-based carbon scaffolds. To meet the challenge, leveraging the synergistic effect of gravity and evaporation dynamics, laminar CP-based carbon scaffolds with a bidirectional gradient distribution of Fe 3 O 4 nanoparticles were fabricated via immersion, drying, and carbonization processes. The resulting carbon scaffold, owing to the bidirectional gradient structure of magnetic nanoparticles and unique laminar arrangement, exhibited excellent in-plane electrical conductivity (96.3 S/m), superior electromagnetic shielding efficiency (1805.9 dB/cm 2  g), low reflection coefficients (0.23), and a high green index (g s , 3.38), suggesting its green shielding capabilities. Furthermore, the laminar structure conferred upon the resultant carbon scaffold a surprisingly anisotropic thermal conductivity, with an in-plane thermal conductivity of 1.73 W/m K compared to a through-plane value of only 0.07 W/m K, confirming the integration of thermal insulation and thermal management functionalities. These green electromagnetic interference shielding materials, coupled with thermal insulation and thermal management properties, hold promising prospects for applications in sensitive devices., 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 mycotoxigenic fungus Fusarium verticillioides is a common pathogen of grain and medicine that contaminates the host with fumonisin B1 (FB1) mycotoxin, poses serious threats to human and animal health. Therefore, it is crucial to unravel the regulatory mechanisms of growth, and pathogenicity of F. verticillioides. Mbp1 is a component of the MluI cell cycle box binding factor complex and acts as an APSES-type transcription factor that regulates cell cycle progression. However, no information is available regarding its role in F. verticillioides. In this study, we demonstrate that FvMbp1 interacts with FvSwi6 that acts as the cell cycle transcription factor, to form the heteromeric transcription factor complexes in F. verticillioides. Our results show that ΔFvMbp1 and ΔFvSwi6 both cause a severe reduction of vegetative growth, conidiation, and increase tolerance to diverse environmental stresses. Moreover, ΔFvMbp1 and ΔFvSwi6 dramatically decrease the virulence of the pathogen on the stalk and ear of maize. Transcriptome profiling show that FvMbp1-Swi6 complex co-regulates the expression of genes associated with multiple stress responses. These results indicate the functional importance of the FvMbp1-Swi6 complex in the filamentous fungi F. verticillioides and reveal a potential target for the effective prevention and control of Fusarium diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The high osmolarity glycerol 1 mitogen-activated protein kinase (Hog1-MAPK) cascade genes are important for diverse biological processes. The activated Hog1 upon multiple environmental stress stimuli enters into the nucleus where it directly phosphorylates transcription factors to regulate various physiological processes in phytopathogenic fungi. However, their roles have not been well-characterized in Fusarium verticillioides. In this study, FvHog1 is identified and functionally analyzed. The findings reveal that the phosphorylation level and nuclear localization of FvHog1 are increased in Fumonisin B1 (FB1)-inducing condition to regulate the expression of FB1 biosynthesis FUM genes. More importantly, the deletion mutants of Hog1-MAPK pathway show increased sensitivity to Ca 2+ stress and elevated intracellular Ca 2+ content. The phosphorylation level and nuclear localization of FvHog1 are increased with Ca 2+ treatment. Furthermore, our results show that FvHog1 can directly phosphorylate Ca 2+ -responsive zinc finger transcription factor 1 (FvCrz1) to regulate Ca 2+ homeostasis. In conclusion, our findings indicate that FvHog1 is required for FB1 biosynthesis, pathogenicity and Ca 2+ homeostasis in F. verticillioides. It provides a theoretical basis for effective prevention and control maize ear and stalk rot 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 B.V. All rights reserved.)

The concentration of trace elements (chromium, lead, zinc, copper, manganese, and iron) was determined in water, sediment and tissues of two Cyprinidae fish species - Labeo rohita and Tor putitora - collected from the eight sampling stations of Indus River in 2022 for four successive seasons (autumn, winter, spring, summer), and also study the present condition of macroinvertebrates after the construction of hydraulic structure. The obtained results of trace element concentrations in the Indus River were higher than the acceptable drinking water standards by WHO. The nitrate concentration ranges from 5.2 to 59.6 mg l -1 , turbidity ranges from 3.00 to 63.9 NTU, total suspended solids and ammonium ions are below the detection limit (<0.05). In the liver, highest dry wt trace elements (μg/g) such as Cr (4.32), Pb (7.07), Zn (58.26), Cu (8.38), Mn (50.27), and Fe (83.9) for the Labeo rohita; and Tor Putitora has significantly greater accumulated concentration (Cr, Pb, Zn, Cu, Mn, Fe) in muscle and liver than did Labeo rohita species. Additionally, lower number of macroinvertebrates were recorded during the monsoonal season than pre-monsoon and post-monsoon. Local communities surrounded by polluted environments are more probably to consume more fish and expose them to higher concentrations of toxic trace elements (lead and copper). The findings also provide a basis for broader ecological management of the Indus River, which significantly influenced human beings and socioeconomic disasters, particularly in the local community., 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.)

An investigation of EtOAc extract from the roots of Paeonia lactiflora yielded three new 30-noroleanane triterpenoids paeonenoides L-N (1-3) and one new oleanane triterpenoid paeonenoide O (4) together with 7 known compounds (5-11). Extensive spectrographic experiments were applied to identify the structures of 1-4, and their absolute configurations were unambiguously determined by theoretical calculations of ECD spectra, as well as the single-crystal X-ray diffraction analysis. Compounds 8, 9 and 10 were isolated from the Paeonia genus for the first time. Moreover, compounds 8, 9 and 11 showed inhibitory activities against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages with the IC 50 values of 72. 17 ± 4.74, 30.02 ± 2.03 and 28.34 ± 1.85 μM, respectively., 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.)

Hydrovoltaic is an emerging technology that aims to harvest energy from water flow and evaporation, in which the plasmonic hydrogen ions are generated by the interaction between water and hydrovoltaic device. However, the volume of the water sample for the interaction is usually ultra-small due to the compact size of hydrovoltaic device, making the quantification and characterization of the hydrogen ions in such water sample an elusive goal. To address this issue, a miniature fiber-optic pH probe is proposed using a unilaterally tapered-microfiber Bragg grating. The microfiber Bragg grating has an intrinsic Bragg reflection signal with a narrow linewidth. The fiber probe is functionalized by coating the sodium alginate, which can respond to the variation of pH mediated by the alteration of the hydrophilicity. The rigidity and robustness of microfiber Bragg grating facilitates the encapsulation of the sensor into a sampling capillary, allowing for the detection of trace aqueous sample less than 2 μL. The pH sensitivity of the tapered-μFBG-based sensor is 62.8 p.m./pH (R 2  = 0.995) with a limit resolution of 0.096 pH. The sensor performed a practical application in the monitoring and characterization of the hydrovoltaic microdevice, which can generate microcurrent as soaked in the water. This work demonstrates a promising technology in the fields of materials, energy, biology and medicine, in which the detection of the microsamples is inevitable., 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.)

Volatile organic compounds (VOCs) are ubiquitous in both indoor and outdoor environments. Evidence on the associations of individual and joint VOC exposure with all-cause and cause-specific mortality is limited. Measurements of 15 urinary VOC metabolites were available to estimate exposure to 12 VOCs in the National Health and Nutritional Examination Survey (NHANES) 2005-2006 and 2011-2018. The environment risk score (ERS) was calculated using LASSO regression to reflect joint exposure to VOCs. Follow-up data on death were obtained from the NHANES Public-Use Linked Mortality File through December 31, 2019. Cox proportional hazard models and restricted cubic spline models were applied to evaluate the associations of individual and joint VOC exposures with all-cause and cause-specific mortality. Population attributable fractions were calculated to assess the death burden attributable to VOC exposure. During a median follow-up of 6.17 years, 734 (8.34 %) deaths occurred among 8799 adults. Urinary metabolites of acrolein, acrylonitrile, 1,3-butadiene, and ethylbenzene/styrene were significantly associated with all-cause, cardiovascular disease (CVD), respiratory disease (RD), and cancer mortality in a linear dose-response manner. Linear and robust dose-response relationships were also observed between ERS and all-cause and cause-specific mortality. Each 1-unit increase in ERS was associated with a 33.6 %, 39.1 %, 109.8 %, and 67.8 % increase for all-cause, CVD, RD, and cancer mortality risk, respectively. Moreover, joint exposure to VOCs contributed to 17.95 % of all-cause deaths, 13.49 % of CVD deaths, 35.65 % of RD deaths, and 33.85 % of cancer deaths. Individual and joint exposure to VOCs may enhance the risk of all-cause and cause-specific mortality. Reducing exposure to VOCs may alleviate the all-cause and cause-specific death burden., 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.)

Earthworms play a pivotal role in the elimination of fecal coliforms during vermicomposting of fruit and vegetable waste (FVWs). However, the specific mechanisms underlying the action of earthworm mucus remain unclear. This study investigated the mechanisms of fecal coliform reduction related to earthworm mucus during FVWs vermicomposting by comparing treatments with and without earthworms. The results show that the secretion of earthworm mucus decreased by 13.93 % during the startup phase, but significantly (P < 0.001) increased by 57.80 % during the degradation phase. Compared to the control without earthworms, vermicomposting led to a significant (P < 0.05) 1.22 -fold increase in the population of active bacteria, with a strong positive correlation between mucus characteristics and dominant bacterial phyla. As the dominant fecal coliforms, Escherichia coli and Klebsiella pneumoniae significantly (P < 0.05) declined by 86.20 % and 93.38 %, respectively, in the vermi-reactor relative to the control. Bacterial dispersal limitation served as a key factor constraining the elimination of E. coli (r = 0.73, P < 0.01) and K. pneumoniae (r = 0.77, P < 0.001) during vermicomposting. This study suggests that earthworm mucus increases the active bacterial abundance and cooperation by weakening the bacterial dispersal limitation, thus intensifying competition and antagonism between fecal coliforms and other bacteria., 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.)

Lung cancer is the most common cancer and the leading cause of death in China. The current gold standard for clinical lung cancer diagnosis is based on histopathological examination of tumors, but it has the limitation for easy operation and convenient applications. Therefore, researchers are still striving to develop other tools and methods for non-invasive and rapid assessment of the health conditions of lung cancer patients. Hair, as a reflection of the metabolism of the body, is closely related to human health conditions. In principle, Fourier-transform infrared (FTIR) spectroscopy can probe the major chemical compositions in the hair. However, as indicated by previous studies, there is still the challenge to make good use of FTIR spectroscopy for achieving reliable analysis of hair from cancer patients. In this study, hair samples from 82 lung cancer patients were collected and subjected to FTIR measurements and analysis, which showed the protein content in the hair is closely related to the protein content in the blood serum of patients, and the contents of protein and lipid are statistically lower in the lung cancer patients. Furthermore, we demonstrated that FTIR spectroscopy could be employed to monitor the hair of lung cancer patients undergoing chemotherapy, and confirmed that the FTIR spectra of the hair may reflect the resultant effect of the chemotherapy. As such, this work validates the way of using FTIR spectroscopy in hair analysis for the assistance of medical diagnosis of lung cancer as well as monitoring the conditions of the patients under the medical 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.)

Recently, high-entropy alloys have superior physicochemical properties as compared to conventional alloys for their glamorous "cocktail effect". Nevertheless, they are scarcely applied to electrochemical immunoassays until now. Herein, uniform PtRhMoCoFe high-entropy alloyed nanodendrites (HEANDs) were synthesized by a wet-chemical co-reduction method, where glucose and oleylamine behaved as the co-reducing agents. Then, a series of characterizations were conducted to illustrate the synergistic effect among multiple metals and fascinating structural characteristics of PtRhMoCoFe HEANDs. The obtained high-entropy alloy was adopted to build a electrochemical label-free biosensor for ultrasensitive bioassay of biomarker cTnI. In the optimized analytical system, the resultant sensor exhibited a dynamic linear range of 0.0001-200 ng mL -1 and a low detection limit of 0.0095 pg mL -1 (S/N = 3). Eventually, this sensing platform was further explored in serum samples with satisfied recovery (102.0 %). This research renders some constructive insights for synthesis of high-entropy alloys and their expanded applications in bioassays and bio-devices., 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.)

A novel environmentally-friendly porous hydrogel adsorbent (GHPN) is firstly designed and prepared using dextran, phosphate, and calcium hydroxide for the adsorption of Be(II). GHPN shows good adsorption selectivity for Be(II) (K d  = 1.53 × 10 4  mL/g). According the adsorption kinetics and thermodynamics, the theoretical adsorption capacity of GHPN to Be(II) is 43.75 mg/g (35 °C, pH = 6.5), indicating a spontaneous exothermic reaction. After being reused for 5 cycles, the adsorption and desorption efficiencies of Be(II) with GHPN are obtained to be more than 80 %, showing acceptable recycling performance. Both of the characterizations and theoretical calculations indicate that the phosphate group, hydroxyl group, and amino group own the affinity to form stable complexes with Be(II). Benefiting from the introduction of phosphate and amino, the adsorption effect of the hydrogel adsorbent on Be(II) can be greatly improved, and surface precipitation, complexation, and ligand exchange are the dominant mechanisms of beryllium adsorption. The results suggest that GHPN has great potential to be utilized as an eco-friendly and useful adsorbent of Be(II) from aqueous solution., 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.)

Ovarian cancer (OvCa) is characterized by early metastasis and high mortality rates, underscoring the need for deeper understanding of these aspects. This study explores the role of glucose transporter 3 (GLUT3) driven by zinc finger E-box-binding homeobox 1 (ZEB1) in OvCa progression and metastasis. Specifically, this study explored whether ZEB1 promotes glycolysis and assessed the potential involvement of GLUT3 in this process in OvCa cells. Our findings revealed that ZEB1 and GLUT3 were excessively expressed and closely correlated in OvCa. Mechanistically, ZEB1 activates the transcription of GLUT3 by binding to its promoter region. Increased expression of GLUT3 driven by ZEB1 dramatically enhances glycolysis, and thus fuels Warburg Effect to promote OvCa progression and metastasis. Consistently, elevated ZEB1 and GLUT3 expression in clinical OvCa is correlated with poor prognosis, reinforcing the profound contribution of ZEB1-GLUT3 axis to OvCa. These results suggest that activation of GLUT3 expression by ZEB1 is crucial for the proliferation and metastasis of OvCa via fueling glycolysis, shedding new light on OvCa 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. Published by Elsevier B.V.)