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Immune checkpoint inhibitors (ICIs) are revolutionizing cancer treatment, and Artificial Intelligence (AI) is a key player in this field. A comprehensive analysis of AI's impact on these inhibitors was lacking, but this study addresses that by analyzing literature for trends and future predictions. It reveals rapid growth and international collaboration. We utilized analytical tools such as CiteSpace, VOSviewer, and PlotDB to analyze 774 documents from the Web of Science Core Collection from 2018 to May 2024, discovering a steady increase in annual publications, with China and the United States leading the way. Sun Yat Sen University and researchers like Ock Chan-young, Zhang Hao, and Newman AM are prominent. The most productive journal is Frontiers in Immunology, while the New England Journal of Medicine has the highest citation rate. The most cited reference is Newman, AM's 2019 article in Nature Biotechnology. Keywords like "immunotherapy," "pembrolizumab," "cancer," "machine learning," and "expression" are central to the discourse. Research focuses on the application of inhibitors in non-small cell lung cancer, bioinformatics, and cancer immunotherapy, showing AI's potential to improve oncology precision medicine. Although AI's application in ICIs shows promise, significant challenges still demand exploration and resolution. Continued investment in AI research in this context could lead to significant advancements in cancer treatment. Global collaboration is needed to overcome these challenges and fully leverage AI's potential. This study provides a foundation for future research and interdisciplinary collaboration in this critical field.

To explore role of NAALADL2-AS2 as ceRNA in DLBCL. Fluorescence in situ hybridization was used to determine location of NAALADL2-AS2 in cells and to verify its expression in DLBCL tissues. The miRNAs interacting with NAALADL2-AS2 and related regulatory genes were identified by small interfering RNA (siRNA) assay, luciferase reporter assay, fluorescent quantitative polymerase chain reaction, western blotting. DLBCL cells transfected with NAALADL2-AS2 siRNA or control siRNA were treated with doxorubicin, rituximab at different concentrations alone or in combination. The growth curves, drug sensitivity changes of cells before and after transfection were detected by MTT assay, ATP-TCA drug sensitivity test. Cell proliferation was detected by BrdU cell proliferation assay, and apoptosis was detected by Annexin V-fluorescein isothiocyanate/propidium iodide staining. The effects and mechanisms of NAALADL2-AS2 on proliferation, apoptosis, drug resistance of DLBCL cells were studied at cellular level. We confirmed expression of NAALADL2-AS2 in both cytoplasm and nuclei of DLBCL cells. Additionally, we observed elevated levels of NAALADL2-AS2 in DLBCL tissues. We discovered that NAALADL2-AS2 functions as ceRNA to inhibit expression of miR-34a, miR-125a, whereas overexpression of NAALADL2-AS2 indirectly upregulates expression of BCL-2. Interfering with NAALADL2-AS2 promoted apoptosis in DLBCL cells, resulting in approximately a 40% increase in sensitivity to doxorubicin and rituximab. In vivo experiments further confirmed that targeting NAALADL2-AS2 effectively suppressed tumor growth, leading to upregulation of miR-34a and miR-125a, downregulation of BCL-2, and enhanced apoptosis in DLBCL cells, which significantly improved their sensitivity to doxorubicin and rituximab by approximately 50%. These results indicate that NAALADL2-AS2/miR-34a, miR-125a/BCL-2 networks hold promise as therapeutic targets for treatment of DLBCL.

This study aimed to evaluate the seroprevalence of Bordetella pertussis and persistence of antibodies following vaccination. We recruited 6060 healthy subjects from five provinces of China during 2017-2018. Serum IgG antibodies against pertussis toxin (anti-PT IgG) and filamentous hemagglutinin (anti-FHA IgG), and serum IgA antibodies against pertussis toxin (anti-PT IgA) were measured by ELISA. Geometric mean concentration (GMC), seropositivity rate, and recent infection rate were calculated. Among 0-6 years-olds, the anti-PT IgG, anti-PT IgA, and anti-FHA IgG GMCs were 6.4 IU/ml (95% CI 6.1-6.8), 2.8 IU/ml (95% CI 2.7-2.8), and 13.3 IU/ml (95% CI 12.4-14.2), respectively. The anti-PT IgG GMC increased in accordance with the primary vaccination series (4-6 months) and the toddler booster (18-24 months), but declined thereafter through to age 5 years [4.7 IU/ml (95% CI 4.2-5.4)]. The seropositivity rate of pertussis in >6 year-olds was 9.0% (95% CI 8.1-9.9) and the recent infection rate was 3.3% (95% CI, 2.7-3.8). Recent infection rate began to increase from 6 years of age, with peaks at 9, 20, 40, and ≥60 years of age. The anti-PT IgG GMCs of children aged 0-6 years who were vaccinated with DTaP, DTaP-IPV//PRP～T, and DTaP-Hib were 5.9 IU/ml (95% CI 5.6-6.3), 20.7 IU/ml (95% CI 15.6-27.8), and 11.7 IU/ml (95% CI 7.5-18.1) ( p  < .001), respectively ( p  < .001). Pertussis vaccination improves anti-PT IgG levels, however these wane soon after vaccination. Sero-estimated recent infection rates appear to increase from school age into adolescence and adulthood. Pertussis vaccine boosters should be considered in these age groups.

The aim of this study was to analyze the incidence and characteristics of adverse events following immunization (AEFI) with post-licensure vaccines used in Hebei province from 2018 to 2020 and to evaluate the safety of vaccines. All information of AEFI was gained from national adverse event following immunization surveillance system (NAEFISS) in Hebei Province from 2018 to 2020. Descriptive epidemiology method was used to analyze the data about AEFI in Hebei province. Reporting rates of AEFI were calculated by sex, age, city, categories of AEFI, severity of AEFI, reaction categories, etc. A total of 35,999 AEFI were reported through NAEFISS, and the average annual rate was 47.64/100,000 doses. The reporting rates of common adverse reactions and rare adverse reactions were 46.37/100,000 doses and 1.05/100,000 doses. The male-to-female ratio was 1.26:1. Most of the AEFI were concentrated in the ≤1 year age group and were reported in the second quarter and third quarter. The majority of AEFI were reported to be recovered or improved, and about 62% of the AEFI occurred within 24 hours after vaccination. Vaccines associated with the highest reporting rate of AEFI were diphtheria, tetanus and acellular pertussis combined vaccine (DTaP, 170.45/100,000 doses). The reporting rate of allergic rash was found to be the highest in the adverse reactions (0.29/100,000 doses). The majority of AEFI cases were common adverse reactions, while serious rare adverse reactions caused by vaccines were extremely uncommon, and all vaccines used in Hebei Province were safe.

Trial Registration: The LTFU study was registered at the Chinese Clinical Trial Registry, ChiCTR2100052313.

Objective: To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment., Methods: The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively., Results: IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs)., Conclusion: IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.

DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease. Currently, no hexavalent vaccines have been approved for use in China. Evidence of parental acceptance and interest in hexavalent vaccines can help policy makers and manufacturers make decisions about entering the vaccine market and the immunization program in China. We measured parental acceptance and willingness-to-pay (WTP) for a hexavalent vaccine to provide such evidence. We conducted a cross-sectional survey of children's caregivers in 16 vaccination clinics in seven cities in China and obtained information on socio-demographics, knowledge of disease, confidence in vaccines, previous vaccination experience, and acceptance of and WTP for hexavalent vaccine. Multivariate logistic regression was used to determine factors influencing acceptance, and multivariate tobit regression was used to identify factors impacting WTP. Between April 28 and June 30, 2023, a total of 581 parents of children aged 0-6 years participated in the survey; 435 (74.87%, 95% CI:71.3%-78.4%) parents indicated acceptance of hexavalent vaccine. Residence location, parents' education level, experience paying for vaccination, and disease knowledge scores were key factors affecting parents' choices for vaccination. Mean (SD) and median (IQR) willingness to pay for full 4-dose course vaccination were 2266.66 (1177.1) CNY and 2400 (1600-2800) CNY. Children's age ( p  < .001), parents' education level ( p  = .024), and perceived price barriers ( p  < .001) were significantly associated with WTP. Parents have high acceptance and willingness to pay for hexavalent vaccine. The less money parents have to pay out of pocket, the more willing they can be to accept the vaccine. Therefore, acceptance may increase even further if the vaccine is covered by medical insurance, provided free of charge by the government, or if its price is reduced. Our results provide reference for optimizing and adjusting immunization strategies in China.

Clinical guidelines have recently advised combination therapy involving immunotherapy (IO) and tyrosine kinase inhibitors (TKI) as the first-line therapy approach for advanced renal cell carcinoma (RCC). Nevertheless, there is currently no available biomarker that can effectively distinguish the progression-free survival (PFS). RNA-sequencing and immunohistochemistry were conducted on our cohort of metastatic RCC patients, namely ZS-MRCC, who received combination therapy consisting of IO and TKI. We further applied RNA-sequencing, immunohistochemistry, and flow cytometry to examine the immune cell infiltration and functionality inside the tumor microenvironment of high-risk localized RCC samples. SPP1 expression was significantly higher in non-responders to IO-TKI therapy. Elevated levels of SPP1 were associated with poor PFS in both the ZS-MRCC cohort (HR = 2.73, p  = .018) and validated in the JAVELIN Renal 101 cohort (HR = 1.61, p  = .004). By multivariate Cox analysis, SPP1 was identified as a significant independent prognosticator. Furthermore, there existed a negative correlation between elevated levels of SPP1 and the presence of GZMB + CD8 + T cells (Spearman's ρ= -0.48, p  < .001). Conversely, SPP1 expression is associated with T cell exhaustion markers. A significant increase in the abundance of Tregs was observed in tumors with high levels of SPP1. Additionally, a machine-learning-based model was constructed to predict the benefit of IO-TKI treatment. High SPP1 is associated with therapeutic resistance and unfavorable PFS in IO-TKI therapy. SPP1 expression have also been observed to be indicative of malfunction and exhaustion in T cells. Increased SPP1 expression has the potential to serve as a potential biomarker for treatment selection of metastatic RCC.

IGFALS forms stable ternary complexes with insulin-like growth factors (IGF1 and IGF2) and IGF-binding proteins (IGFBP3 and IGFBP5), which prolong the half-lives of IGFs. Through immunohistochemical analysis of 90 pairs of clinical samples and bioinformatics analysis, we observed downregulation of IGFALS in hepatocellular carcinoma tissues, which was associated with poor patient prognosis. This prompted us to explore the specific molecular mechanism of action of IGFALS in the inhibition of hepatocellular carcinoma (HCC), which could be a potential new target for the treatment of HCC. In vitro experiments demonstrated that IGFALS inhibits the proliferation, invasion, and migration of hepatocellular carcinoma cells and suppresses epithelial-mesenchymal transition. Gene Set Enrichment Analysis (GSEA) revealed a positive correlation between IGFALS and the activation of the PPAR pathway. Western blotting, immunofluorescence colocalization, and co-immunoprecipitation assays confirmed that IGFALS binds to PPAR-γ and stabilizes it through deubiquitination. Inhibition of PPAR-γ reversed the anticancer effects of IGFALS. Furthermore, we showed that IGFALS/PPAR-γ upregulates the expression of HMGCS2. The tumor xenograft model supported our findings. Mass spectrometry analysis and co-immunoprecipitation assays indicated that IGFALS promotes the binding of PPAR-γ with USP9X, a deubiquitinating enzyme, thereby facilitating the deubiquitination of PPAR-γ. In conclusion, our findings demonstrate that IGFALS can suppress hepatocellular carcinoma via the PPAR-γ/HMGCS2 pathway., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ximing 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.)

Butyrate can strengthen the intestinal epithelial barrier. However, the mechanisms by which butyrate affects intestinal epithelial cells (IECs) pyroptosis in Crohn's disease (CD) remain unclear. In this study, we collected colonic biopsy samples from CD patients and healthy controls to assess pyroptosis levels. Our findings indicated elevated expression of pyroptosis markers in CD patients, alongside distinct morphological evidence of pyroptosis in IECs. We further investigated the effects of tributyrin on pyroptosis and the cGAS-STING pathway in a trinitrobenzene sulfonic acid-induced colitis rat model. Tributyrin significantly mitigated intestinal inflammation, reduced pathological progression, and inhibited pyroptosis and cGAS-STING pathway activation in the colitis rat model. Similarly, in an in vitro model of IECs pyroptosis, sodium butyrate inhibited pyroptosis and cGAS-STING pathway activation in HT-29 cells. Co-treatment with a cGAS-STING pathway activator and butyrate demonstrated that the activator reversed the inhibitory effects of butyrate on pyroptosis and cGAS-STING pathway activation in both the colitis rat model and HT-29 cells. Mechanistically, the cGAS-STING pathway was found to interact with NLRP3. Taken together, butyrate may mitigate intestinal inflammation in CD by suppressing cGAS-STING-NLRP3 axis-mediated IECs pyroptosis. These findings offer new insights into potential therapeutic strategies for managing CD., 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 clinical syndrome of sepsis arises from severe infection, triggering an abnormal immune response that can lead to multiple organ dysfunction and ultimately the death of the host. Current therapies for sepsis are often limited in efficacy and fail to target the complex interplay of infection, inflammation and coagulation, leading to high mortality rates, which underscores the urgent need for novel therapeutics to combat sepsis. We previously identified Cath-HG, a compound capable of alleviating platelet dysfunction by suppressing GPVI-mediated platelet activation, thereby improving the survival of septic mice subjected to cecal ligation and puncture. Here, we further explored the antimicrobial, anti-inflammatory, LPS-neutralizing and anticoagulant properties of Cath-HG, as well as its protective effects in LPS-induced septic mice. Our results demonstrated that Cath-HG can bind to LPS, aggregate bacteria, and disrupt bacterial cell membranes, subsequently resulting in microbial death. Unlike most other Cathelicidins, Cath-HG displayed anticoagulation properties by regulating the enzymes plasmin, thrombin, β-tryptase, chymase and tissue plasminogen activator. In septic mice, Cath-HG provided protection against sepsis induced by LPS injection and exhibited bactericidal killing, LPS neutralization and inhibition of coagulation and MAPK signal transduction. Furthermore, Cath-HG obviously reduced the expression of pro-inflammatory cytokines and improved the pathological manifestations of tissue injury across multiple organs. Thus, Cath-HG emerges as a promising drug candidate for protecting against sepsis., 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.)

Dictamnine(DIC), as the key pharmacological component of the classical Chinese herbal medicine cortex dictamni, possesses multiple pharmacological activities such as anti-microbial, anti-allergic, anti-cancer, and anti-inflammatory activities, however it is also the main toxicant of cortex dictamni induced hepatic damage, yet the underlying molecular mechanisms causing hepatic damage are still largely unknown. With the purpose of explore possibilities hepatotoxicity of dictamnine in zebrafish and to identify the key regulators and metabolites involved in the biological process, we administered zebrafish to dictamnine at a sub-lethal dose (

Greenhouse gas emissions from the livestock industry are recognized as a major environmental issue. This includes emissions from livestock wastewater. However, the common methods used for carbon sequestration (CS) rarely involve treatment of livestock wastewater, due to an absence of standardized emission points and difficulties in gas collection. To remedy this knowledge gap, this review discusses the sequestration capacity, technical classification, mechanisms, and factors influencing carbon sequestration by microalgae (MCS) in livestock wastewater. First, the carbon emission characteristics of livestock farm are discussed, concluding that, compared with those from enteric fermentation, emissions from waste management are characterized by dispersed emission points, lack of obvious emission patterns, and difficulties in gas collection. Secondly, the use and potential of MCS in livestock wastewater are summarized, with emphasis on the mechanisms involved (both heterotrophic and autotrophic MCS). It was found that development of the heterotrophic microalgal mechanism or combining the use of autotrophic microalgae with bacteria was key to the effective use of MCS for treating livestock wastewater. Finally, physical and chemical factors directly influencing MCS, as well as biological factor (species), were found to determine the potential of MCS. Furthermore, a model for recycling MCS in livestock farms is proposed, providing a novel solution to the achievement of carbon neutrality, resource recycling and ecological environmental protection., 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.)

Kidney cancer rates are increasing in the US and worldwide. Arsenic, a known human carcinogen, is a suspected contributor to this rise, particularly in areas with arsenic-rich groundwater. However, research on the connection between low-level arsenic in drinking water and kidney cancer is limited. In our ecological study, we assessed the association between county-level drinking water arsenic levels and kidney cancer incidences using data from 240 counties in Texas. The analysis included 28,896 cancer cases among adults aged ≥20 years and 101,776,294 person-years during the period 2016-2020. Spatial Poisson regression models estimated the risk ratio (RR) for incident kidney cancer based on drinking water arsenic levels, adjusting for demographic, socioeconomic, and other risk factors, as well as spatial factors. Population-weighted drinking water arsenic levels were calculated using data from water testing for both public water systems and private wells, adjusted for populations served from each source. After adjusting for spatial factors and covariates, we observed 6% and 22% higher incidence of cancer in the medium (1-5 ppb) (RR 1.06, 95% CI 1.01, 1.11) and high arsenic (>5 ppb) group counties (RR 1.22, 95% CI 1.12, 1.34) compared to the low arsenic level ones (<1 ppb), showing a dose-response relationship (p-trend <0.001). Additionally, when arsenic was treated as a continuous variable, the incidence increased by 4% for each doubling of drinking water arsenic level (RR 1.04, 95% CI 1.02, 1.07) when considering drinking water arsenic level as a continuous variable. Our study suggests that exposure to low-level drinking water arsenic may be associated with an increased risk of kidney cancer. Further prospective studies are required to confirm our findings., 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.)

Panax ginseng C. A. Meyer (ginseng) is a medicinal plant widely used for promoting longevity. Recently, homogalacturonan (HG) domain-rich pectins purified from some plants have been reported to have anti-aging-related activities, leading us to explore the longevity-promoting activity of the HG pectins from ginseng. In this study, we discovered that two of low methyl-esterified ginseng HG pectins (named as WGPA-2-HG and WGPA-3-HG), whose degree of methyl-esterification (DM) was 16 % and 8 % respectively, promoted longevity in Caenorhabditis elegans. Results showed that WGPA-2-HG/WGPA-3-HG impaired insulin/insulin-like growth factor 1 (IGF-1) signalling (IIS) pathway, thereby increasing the nuclear accumulation of transcription factors SKN-1/Nrf2 and DAF-16/FOXO and enhancing the expression of relevant anti-aging genes. BLI and ITC analysis showed that the insulin-receptor binding, the first step to activate IIS pathway, was impeded by the engagement of WGPA-2-HG/WGPA-3-HG with insulin. By chemical modifications, we found that high methyl-esterification of WGPA-2-HG/WGPA-3-HG was detrimental for their longevity-promoting activity. These findings provided novel insight into the precise molecular mechanism for the longevity-promoting effect of ginseng pectins, and suggested a potential to utilize the ginseng HG pectins with appropriate DM values as natural nutrients for increasing human longevity., 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.)

The structure-function relationship of functionalized microcrystalline cellulose (MCC) composites as adsorbents remains unclear. Herein, the orange peel-derived MCC (i.e., OP-OH-H-25) was treated by different functional agents to prepare adsorbents for cadmium (Cd(II)) removal. Mercaptoacetic acid and orthophosphoric acid did not apparently impact MCC's surface site types and contents. Alternatively, they efficiently purified OP-OH-H-25 and generated OP-OH-SH and OP-OH-P samples with increased cellulose amounts. In contrast, the glycine modification produced OP-OH-NH 2 with fewer sulfhydryl/carboxyl functional groups and more amide/amino sites. The pH-dependent Cd(II) removal trends by the MCC-related materials showed three successive stages with disparate sorption modes. The Cd(II) sorption kinetics processes on OP-OH-SH, OP-OH-P, and OP-OH-NH 2 reached equilibrium after 0.25 h, faster than 0.5 h on OP-OH-H-25. The maximum Cd(II) sorption capacities of MCC-related adsorbents were OP-OH-P (151.81 mg/g) > OP-OH-SH (150.80 mg/g) > OP-OH-H-25 (124.90 mg/g) > > OP-OH-NH 2 (55.23 mg/g). OP-OH-P exhibited the strongest Cd(II) sorption ability under the interference of mixed aquatic components. The intrinsic Cd(II) sorption mechanisms were identified as inner-sphere complexation and cation-π bond interaction. Overall, the select priority of modifying agents is orthophosphoric acid > mercaptoacetic acid > > glycine when preparing functionalized MCC adsorbents for purifying Cd(II)-polluted water systems., 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.)

Background: Social Anxiety Disorder is traditionally diagnosed using subjective scales that may lack accuracy. Recently, EEG technology has gained importance for anxiety detection due to its ability to capture stable and objective neurophysiological activities. However, existing methods mainly focus on extracting EEG features during resting states, with limited use of psychologically features like Event-Related Potential (ERP) in task-related states for anxiety detection in deep learning frameworks., Methods: We collected EEG data from 63 participants exposed to four facial expressions and extracted task-relevant features. Using the EEGNet model, we predicted social anxiety and evaluated its performance using metrics such as accuracy, F1 score, sensitivity, and specificity. We compared EEGNet's performance with Deep Convolutional Neural Network (DeepConvNet), ShallowConvNet, Bi-directional Long Short-Term Memory (BiLSTM), and SVM. To assess the generalizability of the results, we carried out the same procedure on our prior dataset., Results: EEGNet outperformed other models, achieving 99.16 % accuracy with Late Positive Potential (LPP). ERP components yielded higher accuracy than time-domain and frequency-domain features for social anxiety recognition. Accuracy was better for neutral and negative facial stimuli. Consistency across two datasets indicates stability of findings., Limitations: Due to limited publicly available task-state datasets, only our own were used. Future studies could assess generalizability on larger datasets from different sources., Conclusions: We conducted the first test of ERP features in anxiety recognition tasks. Results show ERP features have greater potential in social anxiety recognition, with LPP exhibiting high stability and accuracy. Outcomes indicate recognizing social anxiety with negative or neutral facial stimuli is more useful., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Malnutrition is an important risk factor for multiple organ dysfunction syndrome in the elderly (MODSE) and seriously affects the occurrence, progression and prognosis of MODSE. Shenling Baizhu Power (SBP), a classic formula from traditional Chinese medicine (TCM), when integrated with enteral nutrition, has been proven to be an effective clinical strategy for treating the patients of MODSE with malnutrition. This study aimed to investigate the metabolic changes during disease occurrence and SBP treatment, and to discover potential metabolic biomarkers for the diagnosis and efficacy evaluation. An untargeted metabolomics strategy based on UHPLC-Q-Orbitrap-HRMS was performed to reveal the differential serum metabolites between MODSE patients with malnutrition (n=59) and healthy controls (n=33), and those between patients treated with enteral nutrition (n=31) and SBP combined with enteral nutrition (n=28). Significantly different metabolites were identified and mapped onto the network of metabolic pathways to explore the metabolic disorders caused by the disease and the metabolic regulatory mechanism of SBP. Additionally, the area under the curve (AUC) of the potential biomarkers was investigated for predicting the disease and the efficacy of SBP. Sixty differential metabolites were identified between the disease and control groups, which were mainly related to amino acid metabolism, energy metabolism and carbohydrate metabolism. In the same way, 50 differential metabolites associated with SBP treatment were identified, which improved metabolic abnormalities in vivo mainly by regulating the above-mentioned metabolic pathways. Finally, 13 differential metabolites in common were selected as the potential biomarkers and the AUC value of each biomarker was within the range of 0.8-1.0, indicating that these biomarkers had high prediction accuracy for the diagnosis and efficacy evaluation of MODSE with malnutrition. This study demonstrates that serum metabolomics approaches based on the UHPLC-Q-Orbitrap-HRMS platform can be applied as a tool to reveal the metabolic changes induced by MODSE with malnutrition and SBP can play an important role in the clinical application., 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.)

Achieving chemical accuracy in describing reactions involving both main-group elements and transition metals poses a substantial challenge for density functional approximations (DFAs), primarily due to the significantly different behaviors for electrons moving in the s,p-orbitals or in the d,f-orbitals. MOR41, a representative dataset of transition metal chemistry, has highlighted the PWPB95-D3(BJ) functional, a B2PLYP-type doubly hybrid (bDH) approximation equipped with an empirical dispersion correction, as the leading functional thus far (Dohm et al., J Chem Theory Comput 2018;14: 2596-2608). However, this functional is not among the top bDH methods for main-group chemistry (Goerigk et al., Phys Chem Chem Phys. 2017;19: 32184). Conversely, bDH methods such as DSD-BLYP-D3, proficient in main-group chemistry, often falter for transition metal chemistry. Herein, taking advantage of the home-made Rust-based Electronic-Structure Toolkits, we examine a suite of XYG3-type doubly hybrid (xDH) methods. We confirm that the trade-off in descriptive accuracy between main-group and transition metal systems persists within the realm of perturbation theory (PT2)-based xDH methods. Notably, however, our study ushers in a pivotal advance with the recently proposed renormalized xDH method, R-xDH7-SCC15. This method not only distinguishes itself among the elite methods for main-group chemistry, but also achieves an unprecedented accuracy for the MOR41 dataset, outperforming all other reported DFAs. The efficacy of R-xDH7-SCC15 stems from the successful integration of a renormalized PT2 correlation model (rPT2) and a machine-learning strong-correlation correction (SCC15), marking a significant step forward in the realm of computational chemistry., (© 2024 Wiley Periodicals LLC.)

This study aimed to enhance bread functionality while maintaining its organoleptic attributes by employing superfine grinding and purple wheat, through characterizing dough properties, bread quality attributes, and in vitro starch digestibility. Compared with dough made from commercial-superfine-whole-wheat flour, the superfine-whole-purple-wheat dough was less strong, comparably extensible, and higher in gassing power during mixing, moulding and proofing, respectively. The subsequent bread quality analysis of crumb grain features and texture indicated that the bread made from superfine-whole-purple-wheat flour was more porous and softer with a larger specific volume (3.21 ± 0.20 cm 3 /g) than that made from commercial-superfine-whole-wheat flour (2.30 ± 0.17 cm 3 /g). Additionally, the superfine-whole-purple-wheat bread had a significantly slower glucose release (k = 0.0048 min -1 ) during in vitro starch digestion as compared to the superfine-whole-wheat bread (k = 0.0065 min -1 ). Therefore, this study demonstrates that using superfine-whole-purple-wheat flour leads to bread with desirable quality attributes and potential health benefits compared to conventional whole-wheat flour., 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 Ltd.)

The bioactivity of polysaccharide was closely related to its fermentation utilization by gut Bacteroides, and its utilization degree was determined by various gut Bacteroides species and different polysaccharides characteristics. The effects of longan polysaccharide (LP) and LP treated by ultrasonic-assisted hydrogen peroxide for 8 h (DLP-8) on gut Bacteroides growth, and their fermentation utilization were compared. The results of LP and DLP-8 on the proliferation of six Bacteroides species showed that Bacteroides uniformis had the highest proliferation index. In fermentation by B. uniformis, DLP-8 (with a lower molecular weight), the viable count of which was higher than that of LP, was degraded more and especially utilized more glucose and glucuronic acid. The microstructure of the two polysaccharides changed differently during fermentation. Moreover, DLP-8 promoted greater short-chain fatty acids production than LP. These results indicated that the fermentation properties of DLP-8 by B. uniformis were superior to those of LP., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication., (Copyright © 2024. Published by Elsevier Ltd.)

Due to the sensitivity to water, the all-inorganic CsPbBr 3 nanocrystals have been widely applied in information encryption with spatial dimensions. However, the absence of time-dimension information limits the information capacity for the application of CsPbBr 3 . In this work, the CsPbBr 3 nanocrystal was combined with water-sensitive borophosphate glass, achieving decomposing/recrystallization of CsPbBr 3 nanocrystal with multi-dimension. The addition of SiO 2 confirms that the collapse of the borophosphate glass network structure causes the exposure of the CsPbBr 3 nanocrystals. The decomposition and recrystallization mechanism of CsPbBr 3 nanocrystals in glass-ceramics upon encountering water has been verified. Finally, an information encryption strategy, using the mixture of CsPbBr 3 glass ceramic and sodium carboxymethylcellulose as ink, is designed via adopting screen-printing technology, which not only provides a new idea for the preparation of CsPbBr 3 nanocrystals, but also establish a new avenue for the information encryption technology., 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.)

Debris flow disasters can directly indicate the quality of an area's ecological and geological (eco-geological) environment. Coordinating the coupling mechanism between these environments is crucial for reducing debris flow incidents and promoting sustainable socio-economic development. Nevertheless, comprehensive research on the coupling coordination mechanisms of the eco-geological environment in high-prone areas of debris flow has yet to be reported. This study focuses on the Bailong River Basin (BRB) and proposes two main hypotheses: (1) There is a coupled relationship with mutual influences among the eco-geological environmental systems; (2) The eco- geological environment affects debris flows, with geo-environmental factors having the most significant impact. To validate first hypotheses, this study developed an assessment index system for the eco-geological environment, encompassing geological environment, ecological environment, and human activities. We applied the projection pursuit model and the coupling coordination degree (CCD) model to calculate indicator weights and analyze the coupling coordination mechanisms. The results indicate that the three subsystems interact with each other. To validate second hypotheses, the self-organizing maps (SOM) method categorized the eco-geological subsystems. Building on this foundation, we analyzed the impact of the eco-geological environment on debris flow using variance decomposition analysis (VDA) and redundancy analysis (RDA) methods. The results indicate that eco-geological environment account for 87.8 % of the variation in debris flow frequency, with geological factors having the most significant impact. Notably, the area with the highest frequency of debris flow (four times per year) is located near the urban center of Wudu District, where the human environment subsystem is overwhelmingly dominant and the quality of the ecological and geological systems is comparatively low. Consequently, we analyzed the reasons behind the differences in clustering areas and proposed specific recommendations, including enhancing geological disaster prevention and monitoring potential hazardous areas. Future research should focus on enhancing data accuracy and exploring more effective methods for integrating ecological and geological environments with debris flow disaster management for functional zoning. In conclusion, this study provides scientific support for strategies to prevent or mitigate debris flow disasters and protect the BRB ecosystem by validating the above two hypotheses., 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.)

Zero-valent iron biochar composites (ZVI/BC) are considered as effective amendments for arsenic (As)-contaminated soils. However, the mechanisms of transformation of various soil As species during ZVI/BC amendments remain unclear. This study investigated As transformation in four soils (namely, GX, ZJ, HB, and HN) treated with ZVI/BC for 65 days under two soil moisture conditions, unsaturated and oversaturated. Results showed that the 65-day treatment was divided into two stages based on the variation of labile As content. Within 2 days (stage 1), ZVI/BC addition quickly reduced labile As content by 5.91-90.3 % in soils under unsaturated conditions. During days 2-65 (stage 2), labile As ultimately decreased by 0.06-0.31 mg/kg in GX, ZJ, and HB while increasing by 22.1 mg/kg in HN soil, due to its lower pH value and Fe content. The variations of labile As were attributed to changes in multiple Fe minerals and associated As species. In stage 1, the corrosion of ZVI/BC generated amorphous Fe oxides to immobilize labile As, resulting in the accumulation of meta-stable As. In stage 2, amorphous Fe oxides were transformed into crystalline Fe oxides, resulting in the release and re-precipitation of As along with transformation, thus redistributing immobilized As into labile and stable As, which was evidenced by multiple methods, including chemical extraction, XRD, and TEM-EDX. The elevated soil moisture condition would enhance the corrosion of ZVI/BC in stage 1, further forming a reductive environment to facilitate the transformation of Fe minerals in stage 2. Besides, As bioaccessibility in soils was reduced by 10.8-38.7 % after ZVI/BC treatment in in-vitro gastrointestinal simulations. Overall, our study revealed the time-dependent transformation mechanism of soil As species and associated Fe minerals under different soil moisture with ZVI/BC treatments, and highlighted the effectiveness of ZVI/BC as a long-term amendment for As-contaminated soils., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The Amazon, the Earth's largest tropical forest, plays a critical role in the global carbon cycle, acting as a significant carbon sink. Recent studies, however, indicate a decline in its carbon sequestration capacity due to climate variability, intensive deforestation, and fires. This study aims to examine the impacts of these factors on the carbon dynamics of the Amazon over a centennial scale based on dynamic global vegetation models (DGVMs) of Trendy-v11. It was found that the Amazon region exhibited significant spatiotemporal variations in net land carbon (C) fluxes, and was a net C sink (40.02 ± 242.64 Tg C yr -1 ) during 1901-2021. The Amazonian net biome productivity (NBP) showed a 6-decades-scale shift from a decreasing trend (-3.78 Tg C yr -2 ) during 1901-1959 to an increasing trend (2.39 Tg C yr -2 ) during 1960-2021. The Amazonian NBP was negatively related to air temperature while positively related to dry-season precipitation during 1901-2021. Furthermore, the increase of atmospheric CO 2 concentration during 1901-2020 enhanced Amazonian NBP by 36.40 ± 8.39 Pg C, which was largely offset by land use change (-18.84 ± 12.02 Pg C) and climate change (-10.03 ± 5.00 Pg C). Our findings underscore the critical need for sustainable management practices in the Amazon to enhance its C sink and preserve its function in the global climate system., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

To tackle the challenge of ensuring food security while managing water availability and quality constraints in the Haihe Basin, a critical grain-producing region in China with a dense population and severe water degradation issues, we have developed a comprehensive spatial optimization (CSO) strategy. This approach integrates various crop and soil management practices, land consolidation, and cutting-edge breeding technologies. It also uses a spatial planning model based on linear programming, considering water quantity and quality constraints. Our research shows that crop yields may drop by 14 % (3780 Kt) compared to levels in 2017 due to restrictions on groundwater extraction and nitrogen (N) concentrations in leaching or runoff. However, by strategically maximizing overall crop yields through the integrated CSO strategy without changing the crop production structure, the total crop yield could potentially increase by 81 % (21,817 Kt) while using 3.0 % (86 Kha) less cultivated land than in 2017. This would help to fulfill the projected food demand in 2050. If the integrated aims to minimize the sown area after fulfilling the demand for crops in 2050, around 28 % of the sown area, or 820 Kha cropland, could be reduced compared with 2017. This reduction may save more land for natural conversation. Furthermore, total N losses, including ammonia, nitrous oxide emissions, runoff, and leaching, could be reduced by 23 %-43 % (139-252 Kt), depending on the specific optimization strategy goals. The stepwise integrated optimization strategy provides a feasible framework for the Haihe Basin, enabling the maintenance or even enhancing current crop yields while safeguarding water quality and quantity., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The hippocampus and amygdala, as important components of the limbic system, play crucial roles in central remodeling in congenital hearing loss. This study aimed to investigate the morphological integrity and network properties of the subfields of hippocampus and amygdala in children with congenital hearing loss., Methods: A total of 24 children with congenital hearing loss and 17 age- and sex- matched healthy controls (HC) are included in the study. T1-weighted images are analyzed by segmenting the brain into cortical and subcortical regions. Intergroup difference of volumes were explored. Structural covariance networks for the whole brain and hippocampus-amygdala subregions were constructed. Between-group differences of network property are investigated by comparing area under a range of network sparsity., Results: Patients with congenital hearing loss exhibited significantly larger volumes in the right dentate gyrus and CA3 of the hippocampus. However, there were no significant differences in total hippocampal or showed decreased global efficiency and increased characteristic path length, indicating reduced network integration. Lower betweenness centrality was observed in the left hippocampal fissure in the hearing loss group. The changes in volume and network topological properties are not affected by age and sex., Conclusion: Children with congenital hearing loss display specific volumetric increases in hippocampal subregions, suggesting compensatory adaptations to auditory deprivation. The hippocampus-amygdala network shows significant reorganization, potentially underpinning cognitive and behavioral development issues associated with congenital hearing loss. These findings highlight the importance of targeted neural substrates in understanding and addressing the developmental challenges faced by children with congenital hearing loss., 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 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Biochar has great potential for simultaneously improving soil ecological functions and eliminating environmental pollutants. However, studies on this strategy in the restoration of ecological functions in chelator-washed soil are lacking, and the effect of biochar on the structure, functions, and microbial interactions of washed soil microbiomes are unclear. Hence, the effect of rice husk biochar (RHB, 2 %) on the physicochemical properties, heavy metal fractions, and microbial community structure of glutamate-N, N-diacetic acid (GLDA)- and ethylenediaminetetraacetic acid (EDTA)- washed remediated soil were investigated. Results showed that the RHB addition restored the washed soil physical structure (pores and agglomerates) and meanwhile, the soil colloidal sheet sweeps increased by 20.49 % and 102.07 % in the z-axis, respectively. Additionally, RHB significantly increased washed soil pH (P < 0.05) and alkaline phosphatase and urease activities, while decreased acid phosphatase and glucosidase activities. The Observed - species and Shannon index were significantly higher in soil treated by RHB combined with GLDA and EDTA than those treated with GLDA and EDTA alone (P < 0.05). GLDA washing coupled RHB treatment enriched key bacterial groups such as MND1, Chelativorans, and Ellin6067, while EDTA washing coupled RHB treatment enriched Sreroidobacter, Micromonospora, and Reyranella, that both related to C-, N-, and P- cycles. Importantly, RHB addition could enrich functional bacteria by increasing bacterial resistance, including glucose metabolic homeostasis and metal ion resistance. The observed enrichment of functional bacteria provided evidence for the enhancement of soil nutrient cycles, indicative of improved soil functions by combination of chelator washing and biochar amended., 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 use of nano-chemicals in agriculture has been shown to enhance crop production through soil additions or foliar sprays. However, the accumulation pattern, translocation efficiency, mode of action of nanomaterials (NMs) via different application methods remain unclear. In this study, wheat was treated with CuO-NPs/CeO 2 -NPs (50 and 100 nm) for 21 days using soil and foliar application separately. Foliar spray resulted in higher accumulation and more efficient translocation of NMs compared to soil addition. Smaller NMs exhibited higher accumulation and transfer capabilities under the same application method. The accumulation of CuO-NPs was approximately 20 times greater than that of CeO 2 -NPs, particularly under the soil addition treatment. Scanning electron microscopy analysis demonstrated that NMs could directly enter wheat leaves via stomata during foliar application. Wheat growth was inhibited by roughly 15 % following CuO-NPs exposure, whereas no significant effects on growth were observed with CeO 2 -NPs. By integrating nontargeted metabolomics analysis with targeted physiological characteristics assessments, it was revealed that CuO-NPs mainly disturbed nitrogen metabolism pathways and induced oxidative damage. In contrast, CeO 2 -NPs enhanced carbohydrates related biological processes such as starch and sucrose metabolism, glycolysis, and TCA cycle, which are crucial for carbon metabolism. These findings suggest that the type of nanomaterial is a crucial factor to consider when evaluating their foliar or soil application in agriculture., 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.)

Iron nanoparticles synthesized using Euphorbia cochinchinensis leaf extracts (Ec-FeNPs) showed high selectivity for rare earth elements (REEs) recovery from mining wastewater. REEs recovery efficiencies were > 90 %, with distribution coefficients ranging from 2483.9 to 37500 mL/g, which were consistently much higher than non-REEs (15.0 - 234.8 mL/g). Moreover, even after 5 consecutive reuse cycles, Ec-FeNPs effectively adsorbed > 60 % of REEs. Application of advanced characterization techniques found that the high selectivity of Ec-FeNPs for REEs was mainly due to the biomolecules present in the Ec extract. During the synthesis of FeNPs, these biomolecules are modified on the surface of Ec-FeNPs, giving Ec-FeNPs an enhanced ability to separate REEs from non-REEs. The biomolecule capping layer, which is modified on the surface of Ec-FeNPs, constitutes a primary source of high selectivity. LC-MS identified amino acids, carbohydrates, and organic acids as the major biomolecule categories in the capping layer. Density functional theory (DFT) confirmed that the biomolecule capping layer of Ec-FeNPs had the strongest interaction with REEs; an association confirmed by Spearman's correlation analysis. The adsorption mechanism of REEs by Ec-FeNPs mainly involved a combination of ion exchange, electrostatic adsorption, and surface complexation. Overall, the novel findings reported here provide new perspectives for the design of absorbents with highly selective recovery of REEs from mining wastewater., 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.)

Heavy metal pollution (HMP) directly affects the safety of agricultural products, thereby impacting human health. Industrial emissions, as the main source of soil HMP in China, require in-depth research on their pollution risks. Based on national heavy metal (HM) enterprise data, this paper analyzes the spatial distribution characteristics of key enterprises involved in the HMP across the country. It constructs the risk assessment index system of enterprise HMP based on the "source-pathway-receptor" (SPR) process of the HMP, evaluates and partitions the risk of the HMP from enterprises nationwide. The results show that: (1) Enterprises and pollutant discharge outlets are mainly distributed in the eastern and southeastern coastal regions. Jiangxi, Yunnan, Guangdong, and Hunan Province are the main distribution regions of smelting enterprises, with the most types of HM pollutants. The hazard of pollution sources shows a spatial distribution pattern of higher risk in the southwest and north, and lower risk in the central region. Counties with high-risk pollution sources are mainly distributed in Yunnan, Hunan, Guangdong, Inner Mongolia, and Jiangxi Province. (2) The hazard of pollutant transmission pathways shows a spatial distribution pattern of higher risk in the southeast and lower risk in the central region. About 31.5 % of counties are at extremely high risk, mainly distributed in the southeastern coastal regions of Guangdong, Jiangsu, Zhejiang, Jiangxi, Shandong, and Fujian Province. (3) The vulnerability of the receptors shows significant clustering characteristics in the northeast and central regions. About 3.3 % of counties have a receptor vulnerability level of "extremely high," mainly distributed in Inner Mongolia, Jilin, Heilongjiang, Liaoning Province in the northeast, as well as Hubei and Jiangsu Province. (4) About 1.55 % of counties nationwide have a comprehensive risk level of the HMP classified as "extremely high," mainly distributed in Guangdong Province and Inner Mongolia. Additionally, some counties in Yunnan, Hunan, Jiangsu, Jiangxi, and Zhejiang Province have a risk of exceeding pollution standards, requiring further preventive measures to reduce pollution risks in the future. This paper can provide a scientific basis for the prevention and control (P&C) of the HMP 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.)

The Beijing-Tianjin-Hebei (BTH) region is severely polluted by ozone (O 3 ). Accurate O 3 estimates are essential for identifying high-polluted zones and developing targeted interventions to relieve the burden of diseases. Although many studies have estimated high-resolution O 3 concentrations in BTH, the estimation accuracies are still insufficient. In this study, we incorporated data-driven spatial weight matrices (DDWs) into a random forest (RF) model to fully utilize both the spatial homogeneity and heterogeneity of maximum daily 8-h ozone concentration (MDA8O 3 ), and obtained full-coverage MDA8O 3 concentrations at 1 km×1 km in BTH from 2014 to 2022. DDW-RF exhibited satisfactory accuracy (10-fold cross-validation R 2 =0.937, RMSE=13.919 μg/m 3 ). Overall O 3 level presented a spatial pattern of lower in the north and higher in the southeast and showed a distinct temporal trend, i.e., first increasing and then decreasing during 2014-2021 and increasing slightly in 2022. The accurate MDA8O 3 estimates indicates that more attention and resources should be poured into the areas adjacent to Bohai Rim, Shandong and Henan. Regulated operation of factories under specific meteorological conditions and upgrading industrial structure and production modes are recommended to mitigate the formation of O 3 precursors and reduce O 3 generation. Our findings provide evidence and reference for environmental cleaning policies and targeted interventions., 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 xenobiotic metabolism driven by the gut microbiota significantly regulates the bioavailability and toxic effects of environmental pollutants such as plasticizers on aquatic organisms. However, it is still unknown whether the gut microbiota can exhibit variable metabolic ability across host species and which functional bacteria and genes are involved in xenobiotic transformation. This study investigated the enriched gut microbiota community composition and diversity of in vitro enrichment cultures from 6 marine species, namely, yellowfin seabream (Acanthopagrus latus), thorn fish (Terapon jarbua), shortnose ponyfish (Leiognathus brevirostris), mussel (Perna viridis), prawn (Parapenaeopsis hungerfordi) and crab (Charybdis riversandersoni). Pseudomonadota, Bacteroidota and Bacillota were the dominant phyla and Enterobacter, Raoultella, Klebsiella, Dysgonomanas and Lactococcus were the dominant genera in the enriched flora according to 16S rRNA sequencing. Furthermore, the metagenomic results revealed that all enriched gut microbiota presented metabolic genes for carbohydrates, amino acids, lipids, and xenobiotics. In particular, the gut microbiota of yellowfin seabream had the highest abundance of glycoside hydrolase family genes and CYP450 enzyme genes. Klebsiella was identified as a common potential degrader of xenobiotic metabolism. In addition, the Biolog plate test system confirmed that the gut microbiota can metabolize various carbon sources and drive the xenobiotic transformation. According to AWCD analysis of community level physiological profiling (CLPP), yellowfin seabream > mussel > prawn > shortnose ponyfish > crab > thorn fish. The gut microbiota of yellowfin seabream presented a stronger metabolic profile of phthalates and bisphenol analogs which reflected by their AWCD results and concentration variations. Overall, our results demonstrated the diverse metabolic abilities of the gut microbiota from six marine organisms and their potential for altering of the fate of xenobiotics in the ecosystem on the basis of combined taxonomic, metagenomic, and in vitro transformation 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.)

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.

Cadmium (Cd) contamination poses a substantial threat to crop yields and human health. While magnesium hydride (MgH 2 ) has been reported as a hydrogen (H 2 ) donor that promotes plant growth under heavy metal contamination, its role in rice remains elusive. Herein, seedlings of Oryza sativa L. Japonica variety Zhonghua 11 (ZH11) were selected and exposed to 20 µL of 1-mol/L cadmium chloride (CdCl 2 ) solution via hydroponics to simulate Cd stress. Meanwhile, 0.1 mg of MgH 2 was used to slow-release H 2 to the experimental group to explore its potential effects on rice over a 2-week period. The results indicated that Cd exposure severely inhibited the growth and development of ZH11 rice seedlings. However, the exogenous slow-release of H 2 from MgH 2 effectively mitigated this inhibitory effect by restoring the balance of reactive oxygen species (ROS), maintaining endogenous H 2 homeostasis, and supporting the photosynthetic system. High-performance liquid chromatography analysis revealed that exogenous H 2 reduces m 6 A RNA methylation levels in mRNA under Cd stress. Consequently, MeRIP-seq was conducted to investigate the effect of Cd exposure in rice in the presence and absence of H 2 . The m 6 A modifications were enriched at the start codon, stop codon, and 3' UTR. By integrating RNA-seq data, 118 transcripts were identified as differentially methylated and expressed genes under Cd stress. These gene annotations were associated with ROS, biological stress, and hormonal responses. Notably, 297 differentially methylated and expressed genes were identified under Cd stress in the presence of H 2 , linked to heavy metals, protein kinases, and calcium signaling regulation. Cd strongly activates the MAPK pathway in response to stress. Exogenous H 2 reduces Cd accumulation as well as enhances plant tolerance and homeostasis by lowering m 6 A levels, thereby decreasing the mRNA stability of these genes. Our findings indicate that MgH 2 , by supplying H 2 , regulates gene expression through m 6 A RNA methylation and confers Cd tolerance in rice. This study provides potential candidate genes for studying the remediation of heavy metal pollution in plants., 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.)

Seawater-groundwater interactions can enhance the migration process of microplastics to coastal aquifers, posing increased associated environmental risks. Here, we aim to analyze the relationship between seawater intrusion (SWI) and groundwater microplastic pollution in Laizhou Bay (LZB), which is a typical area of sea-land interactions. The results showed that modern seawater intrusion was the main process controlling the migration of microplastics. The detected microplastics in the study area showed a migration pattern from nearshore marine areas to groundwater aquifers along the SWI direction. In addition, the microplastics also reached the brine formed by palaeo-saltwater intrusion through hydraulic exchange between aquifers. By comparing the spatial distributions of different microplastic parameters, we found that nearshore fisheries, commercial, tourism, textile, and agricultural activities were the main sources of microplastics in groundwater in the study area. A risk assessment model of microplastics associated with SWI was further optimized in this study using a three-level classification system by assigning appropriate weights to different potential influencing factors. The results showed moderate comprehensive ecological risks associated with microplastics from seawater intrusion in the study area, with high microplastic enrichment risks. This study provides a scientific basis for future research on seawater-groundwater interactions and microplastic pollution in coastal 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 B.V. All rights reserved.)

Constructed wetlands (CWs) are identified as significant ecological systems for the potential control of antibiotic resistance genes (ARGs) in the environment. However, the precise mechanisms governing removal, persistence, expression, and associated risks of ARGs during wetland treatment remain poorly understood. In this study, the distribution, mobility, expression, and hosts of ARGs in water, sediments, and plants of a field-scale CW and its parallel natural river were systematically investigated through metagenomic and metatranscriptomic approaches. Results showed that both the abundance and diversity of ARGs in water gradually decreased along the way of CW, reaching a final abundance removal rate of 72.28 % in the effluent. Source tracking analysis indicted that the reduction of ARGs in water was mainly achieved by the dynamic accumulation of ARGs in sediments and plants of the CW. Proteobacteria were identified as primary hosts for ARGs, particularly in sediments and plants during CW treatment. Moreover, although ESKAPE pathogens carrying multiple ARGs persisted in all media throughout the CW treatment, ARG expression levels and risk of water were also significantly decreased after CW treatment. Collectively, our comprehensive multi-omics study would enhance the understanding of ARG removal by CWs, offering insights for controlling antimicrobial resistance in wastewater treatment system., 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.)

Three-dimensional (3D) distributions of multiple soil pollutants in industrial site are crucial for risk assessment and remediation. Yet, their 3D prediction accuracies are often low because of the strong variability of pollutants and availability of 3D covariate data. This study proposed a patch-based multi-task convolution neural network (MT-CNN) model for simultaneously predicting the 3D distributions of Zn, Pb, Ni, and Cu at an industrial site. By integrating neighborhood patches from multisource covariates, the MT-CNN model captured both horizontal and vertical pollution information, and outperformed the widely-used methods such as random forest (RF), ordinary Kriging (OK), and inverse distance weighting (IDW) for all the 4 heavy metals, with R 2 values of 0.58, 0.56, 0.29 and 0.23 for Zn, Pb, Ni and Cu, respectively. Besides, the MT-CNN model achieved more stable predictions with reasonable accuracy, in comparison with the single-task CNN model. These results highlighted the potential of the proposed MT-CNN in simultaneously mapping the 3D distributions of multiple pollutants, while balancing the model training, maintaining and accuracy for low-cost rapid assessment of soil pollution at industrial 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.)

Sulfur dioxide (SO 2 ) has a wide range of applications in food additives and industrial production, and it is one of the main substances that form acid rain, causing serious harm to ecosystems and human health. Hence, it is necessary to construct an effective tool to quickly and accurately detect SO 2 derivatives in environmental, food, and biological samples. In this study, fluorescent probe NPMQ was built to detect SO 2 derivatives from nopinone with the merits of superior water solubility, high sensitivity (12 nM), excellent specificity, large Stokes shift (180 nm), and rapid response time (within 5 s). NPMQ was used to qualitatively and quantitatively detect SO 2 derivatives in environmental water, soil and food samples. In addition, an electrospinning film was prepared with the probe NPMQ to image SO 2 derivatives, and test strips are capable of rapidly, sensitively, and selectively detecting SO 2 derivatives with the naked eye. Moreover, the probe NPMQ was used to visualize endogenous SO 2 derivatives in Arabidopsis thaliana under Cd 2+ stress. Furthermore, the probe NPMQ was employed to image exogenous and endogenous SO 2 derivatives in living Hela, HepG-2 cells, and zebrafish. This study develops an effective tool for monitoring SO 2 derivatives in the environmental, food, and biological systems., 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 widespread emergence of antibiotic resistance poses a substantial challenge to global health. While polymyxin E serves as a final option in treatment, its effectiveness is hindered by dose-related toxicity. A crucial strategy for addressing this issue involves incorporating an antibiotic adjuvant to enhance the antibiotic's efficacy and decrease the required dosage. Here, we reported a multifunctional antibacterial compound A33, containing a 2-aminothiazole scaffold. In vitro studies demonstrated that A33 in combination with polymyxin E inhibited the growth of various Gram-negative bacteria, meanwhile with minimum inhibitory concentrations (MICs) of 0.5-4 μg/mL against twenty-three Gram-positive bacteria, including two drug-resistant strains. In vivo studies showed significant efficacy of the combined treatment of A33 and polymyxin E in a mouse infection model. The mice treated with compound A33 (64 mg/kg) and polymyxin E (0.5 mg/kg) in combination had a 100 % survival rate. Mechanistic studies suggested that A33 might exert its synergistic effect by targeting the outer membrane of Gram-negative bacteria. The ADMET data demonstrated that A33 possessed good pharmacokinetic profiles and drug-likeness properties. Overall, the optimized compound A33 assisted polymyxin E in combating various Gram-negative bacteria and exhibited bactericidal effects against drug-resistant Gram-positive bacteria, offering a new potential therapeutic approach for managing mixed bacterial infections., 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 Masson SAS. All rights reserved.)

Background: The highly heterogeneity of the tumor microenvironment (TME) in hepatocellular carcinoma (HCC) results in diverse clinical outcomes and therapeutic responses. This study aimed to investigate potential intercellular crosstalk and its impact on clinical outcomes and therapeutic responses., Methods: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST) and bulk RNA sequencing (RNA-seq) datasets were integrated to comprehensively analyze the intercellular interactions within the TME. Multiplex immunohistochemistry was conducted to validate the intercellular interactions. A machine learning-based integrative procedure was used in bulk RNA-seq datasets to generate a risk model to predict prognosis and therapeutic responses., Results: Survival analyses based on the bulk RNA-seq datasets revealed the negative impact of the naïve Cluster of Differentiation 4 + (CD4) T cells and Secreted Phosphoprotein 1 + (SPP1) macrophages on prognosis. Furthermore, their intricate intercellular crosstalk and spatial colocalization were also observed by scRNA-seq and ST analyses. Based on this crosstalk, a machine learning model, termed the naïve CD4 + T cell and SPP1 + macrophage prognostic score (TMPS), was established in the bulk-RNA seq datasets for prognostic prediction. The TMPS achieved C-index values of 0.785, 0.715, 0.692 and 0.857, respectively, across 4 independent cohorts. A low TMPS was associated with a significantly increased survival rates, improved response to immunotherapy and reduced infiltration of immunosuppressive cells, such as. regulatory T cells. Finally, 8 potential sensitive drugs and 6 potential targets were predicted for patients based on their TMPS., Conclusion: The crosstalk between naïve CD4 + T cells and SPP1 + macrophages play a crucial role in the TME. TMPS can reflect this crosstalk and serve as a valuable tool for prognostic stratification and guiding clinical decision-making., 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: Integrins are upregulated on endothelial cells and T-lymphocytes in autoimmune thyroid disease (AITD), potentially contributing to immune response localization. The role of integrins on B-cells in AITD remains unclear., Methods: Peripheral blood samples were collected from healthy controls (n = 56), patients with Graves' disease (GD) (n = 37) and Hashimoto's thyroiditis (HT) (n = 52). Ultrasound-guided fine-needle aspiration (FNA) of the thyroid was performed in patients with non-autoimmune thyroid disease (nAITD) (n = 19), GD (n = 11), and HT (n = 40). Integrins α4β7, α4β1, and αEβ7 in B cells were measured by flow cytometry. Serum zonulin levels were quantified via ELISA. Associations of integrins on B cells with thyroid hormones, thyroid autoantibodies, AITD duration, and zonulin were analyzed., Results: HT patients exhibited lower α4β7 and higher α4β1 expression on B cells compared to healthy controls and GD patients. While α4β7 was predominant on circulating B cells, the dominant integrin expressed on intrathyroidal B cells varied with specific thyroid diseases. In GD patients, α4β7 and α4β1 expression on circulating B cells correlated positively and negatively with thyroid function and thyroid stimulating immunoglobulins (TSI) levels, respectively. Intrathyroidal α4β1 + B cells positively correlated with TSH levels in HT patients. Additionally, serum zonulin was elevated in HT patients, and intrathyroidal α4β7 + B cells and α4β1 + B cells correlated negatively and positively with zonulin levels, respectively. Integrin αEβ7 on B cells showed no significant association with AITD., Conclusion: Integrins expressed on B cells potentially play a role in the pathogenesis of AITD and might serve as immune biomarkers for the 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.)

Sepsis-associated acute liver injury (ALI) is a deadly condition resulting from a systemic inflammatory response to liver cell damage and malfunction. Monotropein (MON) belongs to the iris group of compounds extracted from the natural product Mollen dae officinalis radix, which has strong anti-inflammatory and antioxidant pharmacological effects. The purpose of this study was to elucidate the underlying mechanism of MON in the treatment of sepsis ALI. In this study, an in vivo caecal ligation puncture (CLP)-induced ALI model and in vitro LPS-stimulated AML12 cells and RAW264.7 cells model were established. Additionally, a variety of experimental techniques, including CCK8, H&E staining, DHE probe labelling, biochemical, QPCR, and Western blotting and blocking tests, were used to explore the role of MON in ALI. The results showed that MON improved liver morphological abnormalities, oedema, histopathological injury, and elevated ALT and AST, providing a protective effect against ALI. MON reduced CYP2E1 expression, alleviated oxidative stress (downregulation of MDA levels and upregulation of GSH, CAT, and T-AOC levels) and ROS accumulation with the involvement of the NRF2-Keap-1 pathway. MON inhibited inflammation via the TLR4/NF-κB/NLRP3 inflammasome pathway. In addition, it activated the Akt (Ser473)/GSK3β (Ser9)/Fyn pathway and accelerated NRF2 nuclear accumulation; MK-2206 blockade reversed the NRF2 nuclear accumulation and anti-inflammatory function of MON. MON also restricted the mitochondrial apoptosis pathway, a process specifically blocked by MK-2206. In summary, we concluded that MON alleviated septic ALI by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3β (Ser9)/Fyn/NRF2 pathway., 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 widespread occurrence of liquid crystal monomers (LCMs) in the environment has raised concerns about their persistence, bioaccumulation, and toxicity (PBT). Here we review the lifecycle of environmental LCMs, focusing on their occurrences, emission sources, human exposure routes, and toxicity. Industrial emissions from Liquid Crystal Display (LCD) manufacturing and e-waste recycling are the primary point sources of LCMs. In addition, emissions from LCD products, air conditioning units, wastewater treatment plants, and landfills contribute to environmental occurrence of LCMs as secondary sources. Dietary routes were identified as the primary exposure pathways to humans. E-waste dismantling workers and infants/children are vulnerable populations to LCMs exposure. Exposure to LCMs has been shown to potentially induce oxidative stress, metabolic disorders, and endocrine disruption. Accumulation of LCMs in the brain and liver tissues of exposed animals highlights the need for toxicokinetic studies., 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 microplastics (MPs) vary in abundance, shape, size, color, and polymer type in freshwater ecosystems, yet their impact on bacterial community assembly in natural lakes is unclear. Here, we examined MPs and bacterial compositions in water and sediments of Taihu Lake, China, to reveal the influence of complex MPs on the bacterial community assembly. The results showed that the complexity index of MPs significantly influenced the turnover and nestedness components of bacterial communities. In the colder season, MP complexity was significantly correlated with the turnover componentin sediments (R 2 = 0.19, P < 0.0001), with turnover increasing as MP complexity increased. Conversely, under warmer season, MP complexity was significantly correlated with turnover and nestedness components. Additionally, the interaction effect of environmental and MP factors affected almost all components of beta diversity, particularly in cold water and sediment, with impacts on nestedness of 0.17 and 0.12, respectively, and should thus not be ignored. Our findings indicate for the first time that complex MPs significantly influence the assembly of bacterial communities in lake systems. The impact varies across seasons and future warming may exacerbate this effect, rendering it more uncertain and complex., 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.)