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A growing percentage of diabetes-related deaths has been attributed to cancer, with environmental factors playing important contributions. Thus, we studied the potential relationship between endocrine disruptors polychlorinated biphenyls (PCBs) and cancer risk in diabetes. We aimed to evaluate the association between serum seven indicator-PCB (PCB-28/52/101/118/138/153/180) levels and incident cancer, and further explore the possible modifying role of lifestyle. A total of 2806 type 2 diabetes mellitus (T2DM) cases were included from the Dongfeng-Tongji cohort at the baseline in 2008 and tracked until December 2018, and 320 incident cancers were identified during about 10-year follow-up. Cox proportional hazards models and competing risk regression models were used to reveal associations of baseline concentrations of PCBs with total cancer and specific cancer, respectively. Lifestyle score was determined by body mass index, waist circumference, physical activity, smoking, alcohol drinking, and diet. Each interquartile range (IQR) increment of non-dioxin-like PCBs (NDL-PCBs) generated an 8%-30% increase in cancer incidence. Individuals in the highest quartile for PCB-52, PCB-101, PCB-138, and lowly chlorinated PCBs had 1.44- to 1.68-fold higher cancer risk compared to those in the lowest quartile. Restricted cubic spline analyses and the quantile g-computation model showed similar results. Significant interactions were found between PCBs and fasting blood glucose or simplified insulin resistance assessment indicators. NDL-PCBs were positively and significantly associated with gastrointestinal cancer and respiratory cancer, especially with liver cancer, colorectal cancer, and lung cancer. Higher PCBs showed a significant increase in total cancer risk among participants with an unhealthy lifestyle, however, no associations were observed in those with a relatively healthy lifestyle (P interaction < 0.05). Our findings indicated an increased cancer risk associated with NDL-PCBs, highlighted the role of a healthy lifestyle in potentially reducing adverse impact, and provided preliminary data for environmental and public health interventions to alleviate the risk of cancer among diabetes., 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.)

Mesenchymal stem cell-derived exosomes(MSCs-Exos) offer promising therapeutic potential for a wide range of tissues and organs such as bone/cartilage, nerves, skin, fat, and endocrine organs. In comparison to the application of mesenchymal stem cells (MSCs), MSCs-Exos address critical challenges related to rejection reactions and ethical concerns, positioning themselves as a promising cell-free therapy. As exosomes are extracellular vesicles, their effective delivery necessitates the use of carriers. Consequently, the selection of hydrogel materials as scaffolds for exosome delivery has become a focal point of contemporary research. The diversity of hydrogel scaffolds, which can take various forms such as injectable types, dressings, microneedles, and capsules, leads to differing choices among researchers for treating diseases within the same domain. This variability in hydrogel materials poses challenges for the translation of findings into clinical practice. The review highlights the potential of hydrogel-loaded exosomes in different fields and introduces the advantages and disadvantages of different forms of hydrogel applications. It aims to provide a multifunctional and highly recognized hydrogel scaffold option for tissue regeneration at specific sites, improve clinical translation efficiency, and benefit the majority of patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Previous studies suggested that pyrethroid exposure was associated with elevated type 2 diabetes (T2D) risk, while it remains uncertain whether genetic predisposition modifies this association. A nested case-control study within the prospective Dongfeng-Tongji cohort comprised 1832 T2D cases, age- (±5 years) and sex-matched controls with qualified genotyping data. Serum pyrethroids were measured by gas chromatography-tandem mass spectrometry. Overall diabetes-related genetic risk score (GRS) or pathway-specific GRS, including unweighted GRSs (uGRS) and weighted GRSs (wGRS), was developed by genetic variants identified in Asian populations. Higher overall diabetes-related GRS and GRS specific to the pathway of impaired beta cell function (Beta-cell GRS) were associated with a higher incident T2D risk. Beta-cell uGRS significantly modified the association of serum permethrin (P interaction =0.04) and deltamethrin (P interaction =0.01) with T2D. Specifically, for each doubling increase in serum deltamethrin, the odds ratios (ORs) (95 % confidence intervals [CIs]) for T2D were 1.23 (0.98-1.56) and 0.91 (0.77-1.07) in the highest and lowest Beta-cell uGRS group, as well as 1.23 (1.02-1.47) and 0.95 (0.78-1.15) for Beta-cell wGRS group, respectively. When considering jointly, those with the highest deltamethrin levels and highest Beta-cell GRS had a substantially higher T2D risk, compared with the reference group (OR for uGRS: 3.79 [95 % CI: 2.03-7.07], P interaction =0.03 and 3.23 [95 % CI: 1.78-5.87], P interaction =0.05 for wGRS). Our findings suggested that genetic susceptibility to impaired beta-cell function should be considered for T2D prevention targeting pyrethroid exposure, particularly deltamethrin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to explore the association between phthalates (PAEs) exposure and all-cause mortality among diabetic cases, and potential molecular mechanisms of the effect. We followed 2806 diabetes cases from 2008 to the end of 2018 based on the Dongfeng-Tongji study, of which 446 cases died. We measured serum levels of six PAEs (DMP, DEP, DiBP, DnBP, BBP, and DEHP). Cox models were used to investigate the associations between PAEs and all-cause mortality. Genes related to PAEs are obtained from the Comparative Toxicogenomics Database. We constructed polygenic scores for sex hormone-binding globulin (SHBG) and testosterone, and functional SNPs for IL-6, PPARG, and GPX1 from genotyping data, and further analyzed the environment-gene interactions. The positive associations of PAEs (DMP, DiBP, DnBP, DEHP) with mortality were only observed in males but not in females. Comparing with the extreme quartile 1, the HRs (95% CI) for quartile 4 were 1.63 (0.17, 2.26) for DMP, 1.82 (1.29, 2.56) for DiBP, 1.68 (1.18, 2.40) for DnBP, 1.66 (1.17, 2.36) for DEHP. Enrichment analysis showed that PAEs-related genes were mainly associated with hormones and IL-6-related pathways. Genetic variants of SHBG, testosterone, and IL-6 modified the association between PAEs mixture and all-cause mortality. PAEs exposure are associated with all-cause mortality among diabetic cases, and PAE exposure increases the risk of all-cause mortality only in males. Effects on the hormonal system and IL6-related pathways may be potential mechanisms., 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.)

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19., Competing Interests: The authors declare no conflict of interest.

Emerging evidence has linked arsenic exposure and metabolic homeostasis, but the mechanism is incompletely understood, especially at relatively low concentrations. In this study, we used a mouse model to evaluate the health impacts and metabolic toxicity of arsenic exposure in drinking water at environmentally relevant levels (0.25 and 1.0 ppm). Our results indicated that arsenic damaged intestinal barrier and induced arsenic accumulation, oxidative stress, and pathological changes in the liver and illum. Interestingly, arsenic increased the hepatic triglyceride (TG) and total cholesterol (TC), while reduced serum TG and TC levels. The liver transcriptome found that arsenic exposure caused transcriptome perturbation and promoted hepatic lipid accumulation by regulating the exogenous fatty acids degradation and apolipoproteins related genes. The serum metabolomics identified 74 and 88 differential metabolites in 0.25 and 1.0 ppm, respectively. The KEGG disease and subcellular location analysis indicated that arsenic induced liver and intestinal diseases, and the mitochondrion might be the target organelle for arsenic-induced toxicity. Co-enrichment of transcriptome and metabolome identified 24 metabolites and 9 genes as metabolic toxicity biomarkers. Moreover, 40 male (20 nonalcoholic fatty liver disease (NAFLD) cases and 20 healthy controls) was further selected to validate our findings. Importantly, the significantly changed L-palmitoylcarnitine, 3-hydroxybutyric acid, 2-hydroxycaproic acid and 6 genes of Hadha, Acadl, Aldh3a2, Cpt1a, Cpt2, and Acox1 were found in the NAFLD cases. The results from integrated multi-omics and chemical-protein network analysis indicated that L-palmitoylcarnitine played a critical role in metabolic toxicity by regulating mitochondrial fatty acids β-oxidation genes (Cpt1a, Cpt2). In conclusion, these findings provided new clues for the metabolic toxicity of arsenic exposure at environmentally relevant levels, which involved in the late-life NAFLD development. Our results also contribute to understanding the human responses and phenotypic changes to this hazardous material exposure in the environment., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Glioma is a highly vascularized tumor of the central nervous system. Angiogenesis plays a predominant role in glioma progression and is considered an important therapeutic target. Our previous study showed that vasorin (VASN), a transmembrane protein, is overexpressed in glioma and promotes angiogenesis; however, the potential mechanism remains unclear. In this study, we found that human vascular endothelial cells (hEC) co-cultured with VASN-overexpressing glioma cells exhibited accelerated migration ability and increased expression of VASN originated from glioma cells. VASN was found in exosomes secreted by glioma cells and could be taken up by hECs. hECs showed more edge filopodia and significantly upregulated expression of endothelial tip cell marker gene and protein levels after co-culture with VASN-overexpressing glioma cells. In clinical glioma tissue and orthotopic transplantation glioma tissue, the vascular density and the number of vascular endothelial cells with a tip cell phenotype in VASN-overexpressed tissues were significantly higher than in tissues with low expression. At the molecular level, VASN interacted with VEGFR2 and caused internalization and autophosphorylation of VEGFR2 protein, and then activated the AKT signaling pathway. Our study collectively reveals the function and mechanism of VASN in facilitating angiogenesis in glioma, providing a new therapeutic target for glioma., Implications: These findings demonstrate that VASN exocytosed from glioma cells enhanced the migration of vascular endothelial cells by VEGFR2/AKT signaling pathway., (©2024 American Association for Cancer Research.)

Some nano-biochars (nano-BCs) as electron mediators could enter into cells to directly promote intracellular electron transfer and cell activities. However, little information was available on the effect of nano-BCs on SMX degradation. In this study, nano-BCs were prepared using sludge-derived humic acid (SHA) and their effects on SMX degradation by Shewanella oneidensis MR-1 were investigated. Results showed that nano-BCs (Carbon dots, CDs, <10 nm) synthesized using SHA performed a better accelerating effect than that of the nano-BCs with a larger size (10-100 nm), which could be attributed to the better electron transfer abilities of CDs. The degradation rate of 10 mg/L SMX in the presence of 100 mg/L CDs was significantly increased by 84.6% compared to that without CDs. Further analysis showed that CDs could not only be combined with extracellular Fe(III) to accelerate its reduction, but also participate in the reduction of 4-aminobenzenesulphonic acid as an intermediate metabolite of SMX via coupling with extracellular Fe(III) reduction. Meanwhile, CDs could enter cells to directly participate in intracellular electron transfer, resulting in 32.2% and 25.2% increases of electron transfer system activity and ATP level, respectively. Moreover, the activities of SMX-degrading enzymes located in periplasm and cytoplasm were increased by around 2.2-fold in the presence of CDs. These results provide an insight into the accelerating effect of nano-BCs with the size of <10 nm on SMX degradation and an approach for SHA utilization., 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.)

Gliomas are highly vascularized malignancies, but current anti-angiogenic treatments have not demonstrated practical improvements in patient survival. Studies have suggested that glioma-derived endothelial cell (GdEC) formed by glioma stem cell (GSC) differentiation may contribute to the failure of this treatment. However, the molecular mechanisms involved in GSC endothelial differentiation remain poorly understood. We previously reported that vasorin (VASN) is highly expressed in glioma and promotes angiogenesis. Here, we show that VASN expression positively correlates with GdEC signatures in glioma patients. VASN promotes the endothelial differentiation capacity of GSC in vitro and participates in the formation of GSC-derived vessels in vivo. Mechanistically, vascular endothelial growth factor receptor 2 (VEGFR2) is a critical factor that mediates the regulation of VASN on GSC endothelial differentiation. Separation of cell chromatin fractionation and chromatin immunoprecipitation-sequencing analysis show that VASN interacts with Notch1 and co-translocates into the cell nuclei, where VASN binds to the VEGFR2 gene promoter to stimulate its transcription during the progression of GSC differentiation into GdEC. Together, these findings elucidate the role and mechanisms of VASN in promoting the endothelial differentiation of GSC and suggest VASN as a potential target for anti-angiogenic therapy based on intervention in GdEC formation in gliomas., (© 2024 Federation of American Societies for Experimental Biology.)

Objective . Precise hepatocellular carcinoma (HCC) detection is crucial for clinical management. While studies focus on computed tomography-based automatic algorithms, there is a rareness of research on automatic detection based on dynamic contrast enhanced (DCE) magnetic resonance imaging. This study is to develop an automatic detection and segmentation deep learning model for HCC using DCE. Approach : DCE images acquired from 2016 to 2021 were retrospectively collected. Then, 382 patients (301 male; 81 female) with 466 lesions pathologically confirmed were included and divided into an 80% training-validation set and a 20% independent test set. For external validation, 51 patients (42 male; 9 female) in another hospital from 2018 to 2021 were included. The U-net architecture was modified to accommodate multi-phasic DCE input. The model was trained with the training-validation set using five-fold cross-validation, and furtherly evaluated with the independent test set using comprehensive metrics for segmentation and detection performance. The proposed automatic segmentation model consisted of five main steps: phase registration, automatic liver region extraction using a pre-trained model, automatic HCC lesion segmentation using the multi-phasic deep learning model, ensemble of five-fold predictions, and post-processing using connected component analysis to enhance the performance to refine predictions and eliminate false positives. Main results . The proposed model achieved a mean dice similarity coefficient (DSC) of 0.81 ± 0.11, a sensitivity of 94.41 ± 15.50%, a precision of 94.19 ± 17.32%, and 0.14 ± 0.48 false positive lesions per patient in the independent test set. The model detected 88% (80/91) HCC lesions in the condition of DSC > 0.5, and the DSC per tumor was 0.80 ± 0.13. In the external set, the model detected 92% (58/62) lesions with 0.12 ± 0.33 false positives per patient, and the DSC per tumor was 0.75 ± 0.10. Significance. This study developed an automatic detection and segmentation deep learning model for HCC using DCE, which yielded promising post-processed results in accurately identifying and delineating HCC lesions., (© 2024 Institute of Physics and Engineering in Medicine.)

Macrophage-mediated bone immune responses significantly influence the repair of bone defects when utilizing tissue-engineered scaffolds. Notably, the scaffolds' physical structure critically impacts macrophage polarization. The optimal pore size for facilitating bone repair remains a topic of debate due to the imprecision of traditional methods in controlling scaffold pore dimensions and spatial architecture. In this investigation, we utilized fused deposition modeling (FDM) technology to fabricate high-precision porous polycaprolactone (PCL) scaffolds, aiming to elucidate the impact of pore size on macrophage polarization. We assessed the scaffolds' mechanical attributes and biocompatibility. Real-time quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of macrophage-related genes, and enzyme linked immunosorbent assay for cytokine secretion levels. In vitro osteogenic capacity was determined through alkaline phosphatase and alizarin red staining. Our findings indicated that macroporous scaffolds enhanced macrophage adhesion and drove their differentiation towards the M2 phenotype. This led to the increased production of anti-inflammatory factors and a reduction in pro-inflammatory agents, highlighting the scaffolds' immunomodulatory capabilities. Moreover, conditioned media from macrophages cultured on these macroporous scaffolds bolstered the osteogenic differentiation of bone marrow mesenchymal stem cells, exhibiting superior osteogenic differentiation potential. Consequently, FDM-fabricated PCL scaffolds, with precision-controlled pore sizes, present promising prospects as superior materials for bone tissue engineering, leveraging the regulation of macrophage polarization., (© 2024 IOP Publishing Ltd.)

Hydrogen production from organic waste by gasification and reforming technologies offers major benefits to both the environment and climate. The long-term stability and regeneration of the reforming catalyst are still the biggest challenges because of carbon deposition. Here we report a recyclable salt-supported nickel oxide NiO/NaX (X: F, Cl, Br) catalyst for effective autothermal reforming of the oxygenated volatile organic compound (OVOC) ethyl acetate to hydrogen. The optimal hydrogen selectivity achieved 82.0% at 650 °C and the durability reached 43 h. Interestingly, with the decreasing of halogen electronegativity (F > Cl > Br) in NaX, the corresponding hydrogen selectivity of the catalysts decreased. Although NiO/NaX catalysts possess a very small specific surface area and a dense microstructure, their catalytic performance is better than that of normal Ni-based catalysts loaded on high-specific-surface-area supports. Detailed investigations revealed the critical roles played by halogen during the reforming reaction. First, the strong electronegative halogen in NaX induced the formation of hydrogen bonds with the reactants and reaction intermediates, which may prolong the surface residence time of such species, thus ensuring efficient hydrogen production over small-specific-surface-area catalysts under high-temperature conditions. Second, the halogen of the support NaX weakening the Ni-O bonds of the exposed Ni atoms in NiO/NaX made it easier for NiO to be reduced to Ni 0 , thus reducing the reaction activation energy and prompting the rapid catalytic reaction. The strength of such metal-support interaction can be easily modulated by varying the halogen electronegativity. This study provides a new prospect for the design of innovative recyclable heterogeneous catalysts with low specific surface area but high activity.

Liver sinusoidal endothelial cells (LSECs) are highly specific endothelial cells which play an essential role in the maintenance of liver homeostasis. During the progression of liver fibrosis, matrix stiffening promotes LSEC defenestration, however, the underlying mechanotransduction mechanism remains poorly understood. Here, we applied stiffness-tunable hydrogels to assess the matrix stiffening-induced phenotypic changes in primary mouse LSECs. Results indicated that increased stiffness promoted LSEC defenestration through cytoskeletal reorganization. LSECs sensed the increased matrix stiffness via focal adhesion kinase (FAK), leading to the activation of p38-mitogen activated protein kinase activated protein kinase 2 (MK2) pathway, thereby inducing actin remodeling via LIM Kinase 1 (LIMK1) and Cofilin. Interestingly, inhibition of FAK or p38-MK2 pathway was able to effectively restore the fenestrae to a certain degree in LSECs isolated from early to late stages of liver fibrosis mice. Thus, this study highlights the impact of mechanotransduction in LSEC defenestration, and provides novel insights for potential therapeutic interventions for liver fibrosis., 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: Contrast-associated acute kidney injury (CA-AKI) is a prevalent complication following coronary angiography (CAG). However, there is ongoing controversy surrounding its precise definition. Although previous studies have demonstrated the successful application of appropriate definitions in managing high-risk CA-AKI patients, there remains limited research on the association between different definitions and prognosis specifically in patients with chronic kidney disease (CKD)., Methods: A total of 4197 CKD patients undergoing coronary angiography (CAG) were included in this study. Two definitions of contrast-associated acute kidney injury (CA-AKI) were used: CA-AKI A , which was defined as an increase of ≥0.5 mg/dL or >25% in serum creatinine (SCr) from baseline within 72 hours after CAG, and CA-AKI B , which was defined as an increase of ≥0.3 mg/dL or >50% in SCr from baseline within 48 hours after CAG. Cox regression analysis was employed to assess the association between these two definitions and long-term mortality. Additionally, population attributable risks (PARs) were calculated to evaluate the impact of CA-AKI definitions on long-term prognosis., Results: During the median follow-up period of 4.70 (2.50-7.78) years, the overall long-term mortality was 23.6%, and the long-term mortality in patients with CA-AKI according to both CA-AKI A and CA-AKI B criteria were 33.5% and 33.8%, respectively. We found that CA-AKI A (HR: 1.45, 95% CI: 1.23-1.70, p<0.001) and CA-AKI B (HR: 1.44, 95% CI: 1.23-1.69, p<0.001) were associated with long-term mortality. The PARs were the highest for CA-AKI A (5.87%), followed by CA-AKI B (5.70%)., Conclusion: Contrast-associated acute kidney injury (CA-AKI) is a frequently observed complication in CKD patients undergoing coronary angiography (CAG), and both definitions of CA-AKI are significantly correlated with a poor long-term prognosis. Consequently, in the clinical management of CKD patients, it is crucial to prioritize CA-AKI, irrespective of the specific CA-AKI definition used., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Feng et al.)

Bulk carbon-based materials can enhance anaerobic biodenitrification when they are present in extracellular matrices. However, little information is available on the effect of nitrogen and iron co-doped carbon dots (N, Fe-CDs) with sizes below 10 nm on this process. This work demonstrated that Fe-N X formed in N, Fe-CDs and their low surface potentials facilitated electron transfer. N, Fe-CDs exhibited good biocompatibility and were effectively absorbed by Pseudomonas stutzeri ATCC 17588. Intracellular N, Fe-CDs played a dominant role in enhancing anaerobic denitrification. During this process, the nitrate removal rate was significantly increased by 40.60% at 11 h with little nitrite and N 2 O accumulation, which was attributed to the enhanced activities of the electron transport system and various denitrifying reductases. Based on proteomics and metabolomic analysis, N, Fe-CDs effectively regulated carbon/nitrogen/sulfur metabolism to induce more electron generation, less nitrite/N 2 O accumulation, and higher levels of nitrogen removal. This work reveals the mechanism by which N, Fe-CDs enhance anaerobic denitrification and broaden their potential application in nitrogen removal.

The problem of surface icing poses a serious threat to people's economy and safety, especially in the fields of aerospace, wind power generation and circuit transmission. Super-hydrophobic has excellent anti-icing performance, so it has been widely studied. As the most promising anti-icing technology, superhydrophobic anti-icing surface should not only be simple to prepare, but also have excellent comprehensive performance, which can meet the anti-icing task under harsh working conditions and long-term durability. This paper summarizes the basic performance requirements of superhydrophobic surface for anti-icing operation, and then summarizes the preparation methods and existing problems of superhydrophobic surface in recent years. Finally, the future development trend of superhydrophobic anti-icing surface is prospected and discussed, hoping to provide certain technical guidance for the subsequent research of high-performance superhydrophobic anti-icing surface., 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.)

Viruses have threatened human lives for decades, causing both chronic and acute infections accompanied by mild to severe symptoms. During the long journey of confrontation, humans have developed intricate immune systems to combat viral infections. In parallel, vaccines are invented and administrated to induce strong protective immunity while generating few adverse effects. With advancements in biochemistry and biophysics, different kinds of vaccines in versatile forms have been utilized to prevent virus infections, although the safety and effectiveness of these vaccines are diverse from each other. In this review, we first listed and described major pathogenic viruses and their pandemics that emerged in the past two centuries. Furthermore, we summarized the distinctive characteristics of different antiviral vaccines and adjuvants. Subsequently, in the main body, we reviewed recent advances of nanoparticles in the development of next-generation vaccines against influenza viruses, coronaviruses, HIV, hepatitis viruses, and many others. Specifically, we described applications of self-assembling protein polymers, virus-like particles, nano-carriers, and nano-adjuvants in antiviral vaccines. We also discussed the therapeutic potential of nanoparticles in developing safe and effective mucosal vaccines. Nanoparticle techniques could be promising platforms for developing broad-spectrum, preventive, or therapeutic antiviral vaccines.

Persistent organochlorine pesticide (OCP) has been associated with type 2 diabetes (T2D), and genetic polymorphism might modify such an association. However, prospective evidence remains scarce. We conducted a nested case-control study comprising 1006 incident diabetic cases and 1006 matched non-diabetic controls [sex and age (±5 years)] from 2008 to 2013 (mean follow-up period: ∼4.6 years) based on the Dongfeng-Tongji cohort in Shiyan City of China, determined baseline levels of nineteen OCPs, and examined the associations of circulating OCPs, both individually and collectively, with incident T2D risk. We also constructed overall genetic risk score (GRS) based on 161 T2D-associated variants and five pathway-specific cluster GRSs based on established variants derived from the Asian population. Compared with the first quartile of serum β-BHC levels, the multivariable-adjusted ORs (95% CIs) of incident T2D risk in the second, third, and fourth quartiles were 0.98 (0.70-1.39), 1.43 (0.99-2.07), and 1.75 (1.14-2.68), respectively (FDR-adjusted P trend  = 0.03). A positive association was observed between serum OCP mixture and incident T2D risk and can be largely attributed to β-BHC. Furthermore, serum β-BHC and p,p'-DDE showed significant interactions with the GRS for lipodystrophy, a T2D-related pathway representing fat redistribution to viscera, on T2D risk (P interaction < 0.05). In conclusion, higher circulating OCP levels were independently associated with an increased risk of T2D, with β-BHC possibly being the major contributor. Genetic predisposition to T2D-related morbidity, such as visceral adiposity, should be considered when assessing the risk of T2D conferred by OCPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Minimal invasive surgery (MIS) has been reported to increase the risk of cancer relapse and death compared with traditional open surgery in patients with early-stage cervical cancer (CC). Pre-operative conization is a protective procedure that as developed to reduce the risk caused by MIS., Methods: Relevant publications were identified by searching medical databases prior to the December 31, 2022. The primary aim of this meta-analysis was to evaluate the efficacy of pre-operative conization on disease-free survival (DFS) in early-stage CC. The secondary objective was to assess the efficacy of pre-operative conization on overall survival (OS) in early-stage CC., Results: Twelve studies were eligible for analysis. The pooled result of pre-operative conization showed a significantly improved DFS when compared with non-conization patients (HR, 0.28; 95% CI, 0.19-0.41), furthermore, pre-operative conization improved DFS by 75% (HR, 0.25; 95% CI, 0.13-0.46) in stage IB1 patients. In patients who underwent MIS, pre-operative conization also led to a significant improvement in DFS when compared with non-conization patients (HR, 0.21; 95% CI, 0.09-0.54). However, in patients who underwent pre-operative conization, MIS increased the risk of recurrence by 34% when compared with open abdominal radical hysterectomy (HR, 1.34; 95% CI, 0.41-4.38), although this difference was not statistically significant. Finally, the OS of early-stage CC was not significantly affected by surgical approach or conization., Conclusion: Pre-operation conization represents a protective effect and can improve DFS when compared with non-conization in early-stage CC, especially in stage IB CC. There was no statistical evidence to indicate that pre-operation conization could improve OS. High-quality randomized controlled trials are required to verify these results., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (© 2023 Published by Elsevier Ltd.)

Prospective epidemiological evidence was lacking on the association of phthalates (PAEs) exposure with incident type 2 diabetes mellitus (T2DM) risk. In present nested case-control study, we identified 1006 T2DM cases and matched 1006 controls based on Dongfeng-Tongji cohort study, and 6 PAEs were detected in baseline serum. The conditional logistic regression model, Bayesian kernel machine regression (BKMR) model and Quantile-based g-computation were applied to evaluate the associations of determined PAEs, either as individuals or as a mixture, with incident T2DM risk. Subgroup analysis was conducted to identify the potential sensitive population of PAEs effects on T2DM. After multiple adjustment, no statistically significant association was observed between single or mixture of PAEs and incident T2DM risk in the whole population. However, serum levels of Di-n-butyl phthalate (DnBP) [OR= 2.06; 95% CI: (1.11-3.96)], Σdibutyl phthalate (ΣDBP) [OR= 1.96; 95% CI: (1.06-3.76)], and Σlow-molecular- weight phthalate (ΣLMW) [OR= 2.27; 95% CI: (1.17-4.57)] were significantly associated with T2DM in current drinker group. Moreover, significant potential interactions were observed among Di-iso-butyl phthalate (DiBP), DnBP, Butyl-benzyl phthalate (BBP), ΣDBP, and ΣLMW with drinking status on T2DM risk (P for interaction = 0.036, 0.005, 0.049. 0.010, and 0.005). We did not find significant associations between serum PAEs levels and T2DM in the whole population. However, current alcohol drinkers expose to higher levels of DnBP, ΣDBP, and ΣLMW had higher risk of T2DM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Emerging evidence revealed that pyrethroids and circulating lipid metabolites are involved in incident type 2 diabetes (T2D). However, the pyrethroid-associated lipid profile and its potential role in the association of pyrethroids with T2D remain unknown. Metabolome-wide association or mediation analyses were performed among 1006 pairs of T2D cases and matched controls nested within the prospective Dongfeng-Tongji cohort. We identified 59 lipid metabolites significantly associated with serum deltamethrin levels, of which eight were also significantly associated with serum fenvalerate (false discovery rate [FDR] < 0.05). Pathway enrichment analysis showed that deltamethrin-associated lipid metabolites were significantly enriched in the glycerophospholipid metabolism pathway (FDR = 0.02). Furthermore, we also found that several deltamethrin-associated lipid metabolites (i.e., phosphatidylcholine [PC] 32:0, PC 34:4, cholesterol ester 20:0, triacylglycerol 52:5 [18:2]), and glycerophosphoethanolamine-enriched latent variable mediated the association between serum deltamethrin levels and T2D risk, with the mediated proportions being 44.81%, 15.92%, 16.85%, 16.66%, and 22.86%, respectively. Serum pyrethroids, particularly deltamethrin, may lead to an altered circulating lipid profile primarily in the glycerophospholipid metabolism pathway represented by PCs and lysophosphatidylcholines, potentially mediating the association between serum deltamethrin and T2D. The study provides a new perspective in elucidating the potential mechanisms through which pyrethroid exposure might induce T2D., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Motorized spiral enteroscopy (MSE) is a novel advance in small bowel examination that is characterized as fast with a deep insertion. The aim of this study was to elucidate the effectiveness and safety of MSE., Methods: Relevant articles that were published before November 1, 2022 were identified by searching PubMed, EMBASE, Cochrane, and the Web of Science. The technical success rate (TSR), total (pan)-enteroscopy rate (TER), depth of maximum insertion (DMI), diagnostic yield, and adverse events were extracted and analyzed. Forest plots were graphed based on random effects models., Results: A total of 876 patients from 8 studies were eligible for analysis. The pooled results of the TSR were 95.0% [95% confidence interval (CI) 91.0-98.0%, I 2  = 78%, p < 0.01] and the pooled outcome of the TER was 43.1% (95% CI 24.7-62.5%, I 2  = 95%, p < 0.01). The pooled results of the diagnostic and therapeutic yields were 77.2% (95% CI 69.0-84.5%, I 2  = 84%, p < 0.01) and 49.0% (95% CI 38.0-60.1%, I 2  = 89%, p < 0.01), respectively. The pooled estimates of adverse and severe adverse events were 17.2% (95% CI 11.9-23.2%, I 2  = 75%, p < 0.01) and 0.7% (95% CI 0.0-2.1%, I 2  = 37%, p = 0.13), respectively., Conclusion: MSE is a novel alternative approach for small bowel examination that can achieve high TER and diagnostic and therapeutic yields, and relatively low rates of severe adverse events. Head-to-head studies comparing MSE and other device-assisted enteroscopies are warranted., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Humans show a remarkable ability in solving the cocktail party problem. Decoding auditory attention from the brain signals is a major step toward the development of bionic ears emulating human capabilities. Electroencephalography (EEG)-based auditory attention detection (AAD) has attracted considerable interest recently. Despite much progress, the performance of traditional AAD decoders remains to be improved, especially in low-latency settings. State-of-the-art AAD decoders based on deep neural networks generally lack the intrinsic temporal coding ability in biological networks. In this study, we first propose a bio-inspired spiking attentional neural network, denoted as BSAnet, for decoding auditory attention. BSAnet is capable of exploiting the temporal dynamics of EEG signals using biologically plausible neurons and an attentional mechanism. Experiments on two publicly available datasets confirm the superior performance of BSAnet over other state-of-the-art systems across various evaluation conditions. Moreover, BSAnet imitates realistic brain-like information processing, through which we show the advantage of brain-inspired computational models.

Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum therapeutic and prophylactic drugs against infection by SARS-CoV-2 and its variants, as well as future emerging CoVs, is urgently needed. In this study, we screened several US FDA-approved drugs and identified phenothiazine derivatives with the ability to potently inhibit the infection of pseudotyped SARS-CoV-2 and distinct variants of concern (VOCs), including B.1.617.2 (Delta) and currently circulating Omicron sublineages XBB and BQ.1.1, as well as pseudotyped SARS-CoV and MERS-CoV. Mechanistic studies suggested that phenothiazines predominantly inhibited SARS-CoV-2 pseudovirus (PsV) infection at the early stage and potentially bound to the spike (S) protein of SARS-CoV-2, which may prevent the proteolytic cleavage of the S protein, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that phenothiazines can serve as a potential broad-spectrum therapeutic drug for the treatment of SARS-CoV-2 infection as well as the infection of future emerging human coronaviruses (HCoVs).

Glioma is the most common primary brain tumor. Glioma stem cells (GSCs) are the origin of gliomagenesis and may develop from normal neural progenitor cells (NPCs). However, how neoplastic transformation occurs in normal NPCs and the role of the Ras/Raf/MAPK pathway in NPC transformation is unclear. The present study generated NPCs from human embryonic stem cells (ESCs) carrying gene alterations in the Ras/Raf/MAPK pathway. The CCK‑8 proliferation, single‑cell clonal expansion, cell migration, RT‑qPCR, immunofluorescence staining, western blotting, transcriptome and Seahorse analyses, and intracranial implantation assay were performed to identify the characterization of transformed NPCs in vitro and in vivo . Brain organoids were used to verify the phenotypes transforming in NPCs. KRAS ‑activated NPCs exhibited increased proliferation and migration in vitro . KRAS ‑activated NPCs showed atypical morphology and formed aggressive tumors in immunodeficient mice. At the molecular level, KRAS ‑activated NPCs displayed neoplasm‑associated metabolic and gene expression profiles. Moreover, activation of KRAS led to substantial cell proliferation and abnormal structure in ESC‑derived brain organoids. The present study showed that activated KRAS transformed normal NPCs to GSC‑like cells and established a simple cellular model to investigate gliomagenesis.

Background: Previous epidemiological studies indicated that the association between polychlorinated biphenyls (PCB) and type 2 diabetes mellitus (T2DM) was inconclusive., Objective: We investigated the association between PCBs exposure and incident T2DM in a nested case-control study, and further explored the relationship between PCBs and 5-year fasting blood glucose (FBG) changes., Methods: Baseline concentrations of seven indicator-PCB (PCB-28, 52, 101, 118, 138, 153, 180) were measured in 1006 pairs of incident T2DM cases and matched controls nested within the Dongfeng-Tongji cohort. Conditional logistic regression models and pre-adjusted residuals method were used to assess the associations between PCBs and incident T2DM. We further computed beta coefficients (βs) of 5-year FBG changes using multivariable generalized linear regression., Results: Non-dioxin-like PCBs (NDL-PCBs) were significantly associated with higher T2DM incidence after adjustment for all covariates. Significant differences were observed for extreme quartiles comparisons (Q4 vs. Q1) of PCBs except PCB-138, and the incidence of T2DM were 1- to 3-fold higher among those in the highest versus lowest PCBs quartiles. Serum NDL-PCBs were positively associated with changes in FBG (P for overall association ≤0.01). Additionally, triglycerides mediated the associations between PCBs and T2DM incidence., Conclusion: Our findings showed positive associations of NDL-PCBs with incident T2DM and 5-year FBG changes. PCBs increased incident T2DM via lipid metabolic pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: As the third generation of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib has demonstrated more significant cardiotoxicity than previous generations of EGFR-TKIs. Investigating the mechanism of osimertinib cardiotoxicity can provide a reference for a comprehensive understanding of osimertinib-induced cardiotoxicity and the safety of the usage of this drug in clinical practice. Methods: Multichannel electrical mapping with synchronous ECG recording was used to investigate the effects of varying osimertinib concentrations on electrophysiological indicators in isolated Langendorff-perfused hearts of guinea pigs. Additionally, a whole-cell patch clamp was used to detect the impact of osimertinib on the currents of hERG channels transfected into HEK293 cells and the Nav1.5 channel transfected into Chinese hamster ovary cells and acute isolated ventricular myocytes from SD rats. Results: Acute exposure to varying osimertinib concentrations produced prolongation in the PR interval, QT interval, and QRS complex in isolated hearts of guinea pigs. Meanwhile, this exposure could concentration-dependently increase the conduction time in the left atrium, left ventricle, and atrioventricular without affecting the left ventricle conduction velocity. Osimertinib inhibited the hERG channel in a concentration-dependent manner, with an IC 50 of 2.21 ± 1.29 μM. Osimertinib also inhibited the Nav1.5 channel in a concentration-dependent manner, with IC 50 values in the absence of inactivation, 20% inactivation, and 50% inactivation of 15.58 ± 0.83 μM, 3.24 ± 0.09 μM, and 2.03 ± 0.57 μM, respectively. Osimertinib slightly inhibited the currents of L-type Ca 2+ channels in a concentration-dependent manner in acutely isolated rat ventricular myocytes. Discussion: Osimertinib could prolong the QT interval; PR interval; QRS complex; left atrium, left ventricle, and atrioventricular conduction time in isolated guinea pig hearts. Furthermore, osimertinib could block the hERG, Nav1.5, and L-type Ca 2+ channels in concentration-dependent manners. Therefore, these findings might be the leading cause of the cardiotoxicity effects, such as QT prolongation and decreased left ventricular ejection fraction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Tian, Wang, Jiang, Li and Hao.)

Diabetes has made it challenging to repair alveolar bone defects. A successful method for bone repair utilizes a glucose-sensitive osteogenic drug delivery. This study created a new glucose-sensitive nanofiber scaffold with controlled dexamethasone (DEX) release. DEX-loaded polycaprolactone/chitosan nanofibers scaffolds were created using electrospinning. The nanofibers had high porosity (>90%) and proper drug loading efficiency (85.51 ± 1.21%). Then, glucose oxidase (GOD) was immobilized on the obtained scaffolds by a natural biological cross-linking agent, genipin (GnP), after soaking in the mixture solution containing GOD and GnP. The enzyme properties and glucose sensitivity of the nanofibers were investigated. The results showed that GOD was immobilized on the nanofibers and exhibited good enzyme activity and stability. Meanwhile, the nanofibers expanded gradually in response to the increase in glucose concentration, followed by the release of DEX increased. The phenomena indicated that the nanofibers could sense glucose fluctuation and possess favorable glucose sensitivity. In addition, the GnP nanofibers group showed lower cytotoxicity in the biocompatibility test compared with a traditional chemical cross-linking agent. Lastly, the associated osteogenesis evaluation found that the scaffolds effectively promoted MC3T3-E1 cells' osteogenic differentiation in high-glucose environments. As a result, the glucose-sensitive nanofibers scaffolds offer a viable treatment option for people with diabetes with alveolar bone defects., (© 2023 IOP Publishing Ltd.)

Background: Existing cross-sectional studies indicated a positive association of bisphenol A (BPA) with overweight and obesity. However, the relationship and potential mechanisms underlying this association remain to be elucidated in prospective studies., Objective: This study was designed to investigate whether serum BPA is associated with incident overweight and obesity risk, and to further explore whether adiponectin plays a mediating role in the association., Methods: We measured blood BPA and adiponectin in Chinese populations. The association of serum BPA with overweight and obesity risk was evaluated using multivariable logistic regression models. We further examined the mediating effect of adiponectin by causal mediation analysis., Results: Among 796 participants free of overweight and obesity at baseline, 133 individuals developed overweight and obesity during the follow-up period. Compared with those in the lowest quartile of serum BPA, those in the second and third quartiles were positively associated with incident overweight and obesity risk adjusting for covariates (all P-values < 0.05), whereas this association was not observed in the fourth quartile. Further spline analysis showed an inverted U-shaped dose-response relationship (P non-linear  = 0.04). Furthermore, each unit of serum log 10 -transformed BPA levels was associated with higher changes in waist-to-height ratio and body roundness index (all P-values < 0.05). Mediation analysis indicated significant indirect effects of adiponectin on the associations of BPA with overweight and obesity prevalence (mediation proportion: 46.08%; P = 0.02), and BMI levels (mediation proportion: 30.32%; P = 0.03)., Conclusion: Serum BPA displayed a positive association with incident overweight and obesity risk in a non-monotonic pattern, and adiponectin might mediate the association. Further mechanistic studies are warranted., 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 © 2022 Elsevier Ltd. All rights reserved.)

Kidney ischemia reperfusion injury (IRI) is a common and inevitable pathological condition in routine urological practices, especially during transplantation. Severe kidney IRI may even induce systemic damage to peripheral organs, and lead to multisystem organ failure. However, no standard clinical treatment option is currently available. It has been reported that kidney IRI is predominantly associated with abnormally increased endogenous reactive oxygen species (ROS). Scavenging excessive ROS may reduce the damage caused by oxidative stress and subsequently alleviate kidney IRI. Here, we reported a simple and efficient one-step synthesis of gold-platinum nanoparticles (AuPt NPs) with a gold core having a loose and branched outer platinum shell with superior ROS scavenging capacity to possibly treat kidney IRI. These AuPt NPs exhibited multiple enzyme-like anti-oxidative properties simultaneously possessing catalase- and peroxidase-like activity. These particles showed excellent cell protective capability, and alleviated kidney IRI both in vitro and in vivo without obvious toxicity, by suppressing cell apoptosis, inflammatory cytokine release, and inflammasome formation. Meanwhile, AuPt NPs also had an effect on inhibiting the transition to chronic kidney disease by reducing kidney fibrosis in the long term. Thus, AuPt NPs might be a good therapeutic agent for kidney IRI management and may be helpful for the development of clinical treatments for kidney IRI., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Ammonia is important, both as a fertilizer and as a carrier of clean energy, mainly produced by the Haber-Bosch process, which consumes hydrogen and emits large amounts of carbon dioxide. The ENRR (Electronchemical Nitrogen Reduction Reaction) is considered a promising method for nitrogen fixation owing to their low energy consumption, green and mild. However, the ammonia yield and Faraday efficiency of the ENRR catalysts are low due to the competitive reaction between HER and NRR, the weak adsorption of N2 andthe strong N≡N triple bond. Oxygen vacancy engineering is the most important method to improve NRR performance, not only for fast electron transport but also for effective breaking of the N≡N bond by capturing metastable electrons in the antibonding orbitals of nitrogen molecules. In this review, the recent progress of OVs (oxygen vacancies) in ENRR has been summarized. First, the mechanism of NRR is briefly introduced, and then the generation methods of OVs and their applicationin NRR are discussed, including vacuum annealing, hydrothermal method, hydrogen reduction, wet chemical reduction, plasma treatment and heterogeneous ion doping. Finally, the development and challenges of OVs in the field of electrochemical nitrogen fixation are presented. This review shows the important areas of development of catalysts to achieve industrially viable NRR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Wang, He, Pu, Li, He, Huang, Tang and Tang.)

Pyrethroid insecticides have been extensively used worldwide, but few studies explored the prospective association between pyrethroid exposure and incident type 2 diabetes (T2D). We conducted a nested case-control study of 2012 paired cases and controls, and measured eight pyrethroid insecticides in the baseline sera. We used conditional logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals, and constructed multiple-pollutant models to investigate the association of pyrethroid mixture with incident T2D risk. The median concentrations (detection rates) were 3.53 μg/L (92.45%), 0.52 μg/L (99.80%), 1.16 μg/L (90.61%) and 1.43 μg/L (99.95%) for permethrin, cypermethrin, fenvalerate, and deltamethrin, respectively. Compared to participants with serum fenvalerate levels in the first quartile, the multivariable-adjusted ORs of incident T2D were 1.20 (95% CI 0.86-1.67), 1.41 (0.97-2.05), and 2.29 (1.27-4.11) for the second, third and fourth quartile (P trend = 0.01). Spline analysis further confirmed the positive association between serum fenvalerate levels and incident T2D risk (P for overall association = 0.006). Furthermore, mixture models revealed a positive association of pyrethroid mixture with incident T2D risk, with serum fenvalerate ranked as the top contributor (proportion of relative contribution: > 70%). We found that high concentrations of serum pyrethroid insecticides were significantly associated with an increased risk of incident T2D. The elevated risk was largely explained by fenvalerate. Further investigations are urgently needed to confirm our findings and elucidate the underlying mechanisms, given the widespread use of pyrethroids and the global pandemic of diabetes., (© 2022. Springer Nature B.V.)

Previous evidences exploring the associations of BPA with lipid changes and dyslipidemia did not obtain consistent results. To evaluate whether serum BPA concentration was associated with changes in blood lipid levels and incident dyslipidemia risk in middle-elderly Chinese adults, we conducted a prospective study with 1093 participants (average 62.65 years old) derived from the Dongfeng-Tongji cohort which was founded in 2008 and followed up each 5 years. Serum BPA levels were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Changes in lipid levels were named as Δ lipids which equal to Lipid 2013 - Lipid 2008 . The diagnosis of dyslipidemia was according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in 2016. We used multivariable linear regression and Logistic regression to explore the relations between serum BPA levels and changes in lipid levels and incident dyslipidemia risk, respectively. Besides, restricted cubic splines were used to explore the dose-response relations. After 5 years' follow-up, 51 individuals developed with hypercholesterolemia, 87 with hypertriglyceridemia, 34 with high-LDL-cholesterolemia, 74 with low-HDL-cholesterolemia, and 199 with dyslipidemia. At baseline serum BPA levels were positively related to TC, LDL-c, and Non-HDL-c levels. In the prospective study, each Ln-BPA increase was associated with 0.05 (95% CI: 0.02, 0.09) mmol/L increase in Δ TC, 0.07 (95% CI:0.03, 0.11) mmol/L increase in Δ Non-HDL-c, 0.05 (95% CI: 0.01, 0.08) increase in Δ TC/HDL-c, and 0.05 (95% CI: 0.01, 0.08) increase in Δ Non-HDL-c/HDL-c. We only observed significant associations in females but not in males. Besides, serum BPA levels were positively associated with hypercholesterolemia (OR=1.12, 95% CI: 1.01, 1.25). The restricted cubic splines obtained similar results. In conclusion, serum BPA was associated TC and Non-HDL-c changes, and BPA was also associated with increased risk of hypertriglyceridemia. Further prospective studies with large sample size are warranted to validate our findings., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide with a low 5‑year survival rate due to the lack of effective therapeutic strategies. Accumulating evidence has indicated that maternal embryonic leucine zipper kinase (MELK) is highly expressed in several tumors and associated with tumor development. However, the biological effects of MELK in ESCC remain unknown. In the present study, cell phenotypical experiments and animal metastasis assays were performed to detect the influence of MELK knockdown in vitro and in vivo . The potential molecular mechanism of MELK‑mediated ESCC metastasis was further investigated by western blotting and immunofluorescence staining. The results revealed that the expression of MELK in human ESCC tissues was higher than that in adjacent normal tissues and was positively associated with the poor prognosis of patients. Reducing MELK expression resulted in growth inhibition and suppression of the invasive ability of ESCC cells in vitro and in vivo . MELK inhibition induced alterations of epithelial‑mesenchymal transition‑associated proteins. Mechanistically, MELK interacted with IκB kinase (IKK) and promoted the phosphorylation of IKK, by which MELK regulated activation of the NF‑κB pathway. Collectively, the present study revealed the function and mechanism of MELK in the cell metastasis of ESCC, which may be a potential therapeutic target for ESCC.

Phase-change materials (PCMs) are a unique and exciting class of materials with bright prospects in wide-ranging sustainable technologies such as thermal and electrochemical energy storage. While impressive, the effect of gaseous species on PCMs remains largely unexplored hitherto. Here, a gaseous co-solvent is reported that can facilitate melting and modulate physical properties such as viscosity and ion conduction of PCMs. Especially for the appealing application of PCMs as electrolytes, gaseous species also have a critical influence on both Li + -electrolyte structure and resultant solid electrolyte interphase (SEI). Specifically, theoretical simulations and experimental analysis evidence that CO 2 can promote melting while reconfiguring the solvation structure of a succinonitrile (SCL)-derived Li + phase-change electrolyte (Li + -PCE) model system. Due to the enhanced interaction between Li + cations and bis(trifluoromethanesulfonyl)imide (TFSI - ) anions in the reconfigured solvation structure, more TFSI - -derived F-rich component and extra CO 2 -derived Li 2 CO 3 form in the upgraded SEI layer, thereby endowing proof-of-concept Li-metal batteries with prolonged cyclability. These findings may stimulate widespread interest in gas leverage to innovate electrolyte chemistry., (© 2022 Wiley-VCH GmbH.)

Hydrogel strain sensors with extreme temperature tolerance have recently gained great attention. However, the sensing ability of these hydrogel strain sensors changes with temperature, resulting in the variety of output signals that causes signal distortion. In this study, double-network hydrogels comprising SiO 2 nanoparticles composed of polyacrylamide and phytic acid-doped polypyrrole were prepared and applied on strain sensors with a wide sensing range, high adhesiveness, and invariable strain sensitivity under flame and cold environments. The hydrogels had stable conductivity, excellent adhesive strength of up to 79.7 kPa on various substrates, and high elongation of up to 1896% at subzero temperature and after heating. They also exhibited effective flame retardancy with low surface temperature (71.2 °C) after 1200 s of heating (200 °C) and antifreezing properties at a low temperature of -20 °C. Remarkably, even under cold temperature and heat treatment, the hydrogel-based strain sensor displayed consistent sensing behaviors in detecting human motions with a broad strain range (up to 500%) and steady gauge factor (GF, ∼2.90). Therefore, this work paves the way for the applications of hydrogel sensors in robotic skin, human-mechanical interfaces, and health monitoring devices under harsh operating environments.

Aim: BRCA mutation carriers have a high lifetime risk of developing breast cancer (BC) and ovarian cancer (OC). Risk-reducing salpingo-oophorectomy (RRSO) has been shown to reduce OC risk. This meta-analysis was aim to analyze the effect of RRSO on the BC risk among BRCA1/2 mutation carriers., Methods: Embase, PubMed, Web of Science, and Cochrane databases were searched for all studies investigating the effect of RRSO on BC risk. The pooled results were used to evaluate the association between RRSO and BC risk., Results: This meta-analysis included 13,965 BRCA1 and 7,057 BRCA2 mutation carriers from 14 observational studies. The pooled results showed that RRSO lowered BC risk among BRCA1 mutation carriers [hazard ratio (HR) = 0.63, 95% confidence interval (CI): 0.49-0.81, P < 0.01] and BRCA2 mutation carriers (HR = 0.51, 95% CI: 0.34-0.75, P < 0.01). RRSO reduced BC risk in younger women with BRCA1 mutation (HR = 0.48, 95% CI: 0.30-0.77, P < 0.01) and BRCA2 mutation (HR = 0.22, 95% CI: 0.08-0.65, P < 0.01). Analysis of the efficacy of RRSO at different time intervals after surgery showed a reduction of BC risk at <5 years after surgery in BRCA1 mutation carriers (HR = 0.60, 95% CI: 0.40-0.89, P = 0.01) and BRCA2 mutation carriers (HR = 0.42, 95% CI: 0.20-0.86, P = 0.02)., Conclusions: RRSO is an effective way to reduce BC risk among women with BRCA1/2 mutation, especially in younger women. BRCA1/2 mutation carriers could benefit from RRSO in the immediate 5 years after surgery., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Medical education accreditation in China has been conducted by the Working Committee for the Accreditation of Medical Education (WCAME) and 129 medical schools have completed accreditation by December 2021. Despite studies on the standards, process and effectiveness of accreditation, the actual information transparency of accredited medical schools in China has not been examined. The study investigated the status of publicly available information from WCAME-accredited medical schools in China, and whether public availability of information had significant differences among different types of universities., Methods: The 129 medical schools' official websites were reviewed for the 21 criteria of the WFME Global Standards for Quality Improvement: Basic Medical Education. Dichotomous method was used to record information as presence or absence. SPSS was utilized for descriptive and ANOVA analyses., Results: The mean of the publicly available information on the 21 criteria was 13.77 ± 3.57, and only 5 (3.9%) accredited medical schools had all relevant information available. Publicly available information on Governance (100%) and Administration (100%) was the most, whereas information on Assessment in support of learning (16.3%) was the least. Public availability of information differed significantly among schools accredited with higher (18.15 ± 2.16), medium (13.69 ± 3.41) and lower results (12.79 ± 3.19) (F = 14.71, p < 0.05). Medical universities and comprehensive universities did not show significant differences in their overall information availability (F = 0.25, p > 0.05). Central government funded universities had a remarkably larger amount of publicly available information than local government funded universities (17.86 ± 1.98 vs. 12.75 ± 2.93, p < 0.05)., Conclusion: Public availability of information from the accredited medical schools in China needs to be improved to promote transparency and continuous quality improvement, especially with regard to information on curriculum, assessment and quality assurance. Explicit information availability requirements need to be considered to include in medical education standards, and further studies are warranted to explore which information elements should be made publicly available., (© 2022. The Author(s).)

Antibiotics are emerging contaminants that have recently attracted attention. They have been detected in natural water and pose health concerns owing to potential antibiotic resistance. Antibiotics are ubiquitous in aquatic environments, with a wide spectrum and trace levels. It is difficult to detect all types of antibiotics with completely different physicochemical properties. Solid phase extraction (SPE) is a common sample preparation procedure. For a fast and high-throughput continuous on-line analysis of these emerging contaminants, a method for the determination of 42 antibiotics (grouped into seven categories: sulfonamides, fluoroquinolones, lincosamides, macrolides, tetracyclines, cephalosporins, and chloramphenicols) in environmental water was developed based on ultra high performance liquid chromatography combined with tandem mass spectrometry (UHPLC-MS/MS) involving large volume direct injection without sample enrichment and cleanup. The collected water samples were filtered through a 0.22-μm filter membrane, their pH levels were adjusted to 6.0-8.0 after adding Na 2 EDTA, and then the solutions were mixed with an internal standard. The addition of Na 2 EDTA contributed to the release of tetracyclines and fluoroquinolones from the metal chelate. Improved recoveries were observed for all the compounds when the pH of the aqueous solution was set at 6.0-8.0. The optimized UHPLC conditions were as follows: chromatographic column, Phenomenex Kinetex C18 column (50 mm×30 mm, 2.6 μm); mobile phase, acetonitrile and 0.1% (v/v) formic acid aqueous solution; flow rate, 0.4 mL/min; injection volume, 100 μL. In the UHPLC-MS/MS experiment, chloramphenicol, thiamphenicol, and florfenicol were analyzed in the negative ionization scheduled multiple reaction monitoring mode (scheduled-MRM), while the other 39 antibiotics were analyzed in the positive scheduled-MRM mode. This acquisition method improved the response of each target compound by dividing the time of the analysis test cycle and scanning the ion channels of chromatographic peaks at different time periods. The ionspray voltage was set at 5500 and -4500 V in positive and negative modes, respectively. The source temperature for both ionization modes was set at 500 ℃, which was optimized to improve the sensitivity. Instrumental parameters like collision energy and declustering potential were also optimized. Good linearity was observed for all the tested antibiotics, with a correlation coefficient ( r ) greater than 0.995. The method detection limits (MDLs) were 0.015-3.561 ng/L. The average recoveries ranged from 80.1% to 125%, while the relative standard deviations (RSDs) were between 0.8% and 12.2%. The method was successfully applied to the determination of 10 source water samples and 5 tap water samples. Twelve antibiotics, viz. sulfachloropyridazine, sulfadiazine, sulfamethazine, sulfamethoxazole, sulfisomidine, clindamycin, lincomycin, roxithromycin, clarithromycin, erythromycin, thiamphenicol, and forfenicol, were detected in the 10 water samples with a detection frequency of 100%. The total antibiotic content in each sample ranged from not detected to 80.3 ng/L. Lincosamides and chloramphenicols were the predominant antibiotics in the water samples, with contents in the ranges of 3.83-13.7 and 4.23-33.6 ng/L, respectively. Therefore, the large volume direct injection method exhibited good performance in terms of MDL and recovery compared to standard methods and those reported previously. Compared with traditional pretreatment methods, the large volume direct injection method is simpler, more rapid, more precise, and more accurate. It is a viable alternative to SPE, and can be used for the determination of the 42 antibiotics at trace levels in cleaner water bodies, such as surface water, groundwater, and tap water.

Objective: Transjugular intrahepatic portosystemic shunt (TIPS) is a useful approach in managing complications caused by severe portal hypertension (PH) in adults. In children, TIPS is technically challenging, and previous studies of TIPS in children have yielded inconsistent results. This study aimed to elucidate the feasibility and clinical effectiveness of TIPS in pediatric and adolescent patients., Methods: This meta-analysis study identified relevant publications through medical databases. The primary outcomes included technical success, hemodynamic success, and clinical success. The secondary outcomes were primary patency rate, shunt revision rate, and secondary patency rate., Results: A total of 286 patients representing 13 studies were eligible for analysis. The pooled rates of technical success, hemodynamic success, and clinical success were 95% (95% CI 88-99), 89% (95% CI 81-95), and 93% (95% CI 86-98), respectively. The portosystemic gradient decreased from 21.5 mmHg before TIPS to 8.3 mmHg after TIPS. The pooled estimates of primary patency rate, shunt revision rate, and secondary patency rate were 84% (95% CI 72-94), 35% (95% CI 21-51), and 100% (95% CI 92-100), respectively., Conclusion: Study results suggest that TIPS may be feasible and effective in children with PH of various etiologies as for long-term management., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Accumulating evidence suggests that a subpopulation of stem-cell-like tumor cells in glioma (GSCs) is the major factor accounting for intratumoral heterogeneity and acquired chemotherapeutic resistance. Therefore, understanding intratumoral heterogeneity of GSCs may help develop more effective treatments against this malignancy. However, the study of GSCs' heterogeneity is highly challenging because tumor stem cells are rare. To overcome the limitation, we employed a microfluidic single-cell culture approach to expand GSCs by taking advantage of the self-renewal property of stem cells. Stemness of the recovered cells was confirmed by immunofluorescence, RT-PCR, RNA-sequencing, and cell function assays. The recovered cells were classified into three groups based on their morphological characteristics, namely, the tight-format (TF), the loose-format (LF), and the limited-size group (LS). The serial passage assay showed that the LS group has a lower sphere-forming rate than the LF and TF group, and the invasion assay showed that the LF and TF cells migrated longer distances in Matrigel. The transcriptomic analysis also revealed differences in gene expression profiling among these GSC subtypes. The abovementioned results suggest that GSCs have transcriptional and functional heterogeneities that correlate with morphological differences. The presented microfluidic single-cell approach links morphology with function and thus can provide an enabling tool for studying tumor heterogeneity.

The present study aims to determine the associations of multiple plasma metal levels and plasma microRNAs (miRNAs) with diabetes risk, and further explore the mediating effects of plasma miRNAs on the associations of plasma metal with diabetes risk. We detected plasma levels of 23 metals by inductively coupled plasma mass spectrometry (ICP-MS) among 94 newly diagnosed and untreated diabetic cases and 94 healthy controls. The plasma miRNAs were examined by microRNA Array screening and Taqman real-time PCR validation among the same study population. The multivariate logistic regression models were employed to explore the associations of plasma metal and miRNAs levels with diabetes risk. Generalized linear regression models were utilized to investigate the relationships between plasma metal and plasma miRNAs, and mediation analysis was used to assess the mediating effects of plasma miRNAs on the relationships between plasma metals and diabetes risk. Plasma aluminum (Al), titanium (Ti), copper (Cu), zinc (Zn), selenium (Se), rubidium (Rb), strontium (Sr), barium (Ba), and Thallium (Tl) levels were correlated with elevated diabetic risk while molybdenum (Mo) with decreased diabetic risk (P < 0.05 after FDR multiple correction). MiR-122-5p and miR-3141 were positively associated with diabetes risk (all P < 0.05). Ti, Cu, and Zn were positively correlated with miR-122-5p (P = 0.001, 0.028 and 0.004 respectively). Ti, Cu, and Se were positively correlated with miR-3141 (P = 0.003, 0.015, and 0.031 respectively). In addition, Zn was positively correlated with miR-193b-3p (P = 0.002). Ti was negatively correlated with miR-26b-3p (P = 0.016), while Mo and miR-26b-3p were positively correlated (P = 0.042). In the mediation analysis, miR-122-5p mediated 48.0% of the association between Ti and diabetes risk. The biological mechanisms of the association are needed to be explored in further studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chronic kidney disease (CKD) is a common comorbidity among patients with type 2 diabetes. Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been linked to poorer kidney function in general population, but the related studies in individuals with diabetes were very limited. We aimed to examine the longitudinal associations of PFOA and PFOS exposure and CKD incidence among diabetes patients. Baseline levels of PFOA and PFOS were measured in serum in 967 diabetes patients from the Dongfeng-Tongji cohort. Multivariable logistic regression models were used to characterize the relationship between serum PFOA and PFOS levels and incident CKD risk (defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 ). During 10-years follow-up, 267 incident CKD cases were identified. Only PFOS level was significantly associated with lower risk of CKD incidence (adjusted OR: 0.67; 95%CI: 0.51, 0.88). Such inverse association was only observed among participants with lower eGFR levels (< 70 mL/min/1.73 m 2 ), although the interaction did not achieve statistical significance. Notably, an inverted U-shaped relationship between eGFR and serum PFOS level (P for nonlinearity < 0.001) was observed based on the 1825 subjects with available data at baseline. PFOS exposure was negatively associated with CKD incidence in patients with diabetes, especially in those with baseline eGFR levels < 70 mL/min/1.73 m 2 . This may be explained by the implication of baseline kidney function on the serum PFAS concentrations which in turn affect the relationship between PFOS exposure and the incident CKD risk among diabetes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Tumor cell clusters of varying sizes and densities have different metastatic potentials. Three-dimensional (3D) patterned structures with rational topographical and mechanical properties are capable of guiding the 3D clustering of tumor cells. In this study, single femtosecond laser pulses were used to fabricate individual high-aspect-ratio micropillars via two-photon polymerization (TPP). By combining this approach with capillary-force self-assembly, complex 3D microstructure patterns were constructed with a high efficiency. The microstructures were able to regulate the formation of cell clusters at different cell seeding densities and direct self-guided 3D assembly of cell clusters of various sizes and densities. Localization of cell clusters was achieved using grid-indexed samples to address individual cell clusters, which holds great promise for in situ cell cluster culture and monitoring and for applications such as RNA sequencing of cell clusters.

Drug-induced liver injury (DILI) is a leading cause of therapy failure in the clinic and also contributes much to acute liver failure cases. Investigations of predictive sensitivity in animal models have limitations due to interspecies differences. Previously reported in vitro models of liver injury based on primary human hepatocytes (PHHs) cannot meet the requirements of high physiological fidelity, low cost, simple operation, and high throughput with improved sensitivity. Herein, we developed an integrated biomimetic array chip (iBAC) for establishing extracellular matrix (ECM)-based models. A collagen-based 3D PHH model was constructed on the iBAC as a case for the prediction of clinical DILI at throughput. The iBAC has a three-layer structure with a core component of 3D implanting holes. At an initial cell seeding numbers of 5000-10,000, the collagen-based 3D PHH model was optimized with improved and stabilized liver functionality, including cell viability, albumin, and urea production. Moreover, basal activities of most metabolic enzymes on the iBAC were maintained for at least 12 days. Next, a small-scale hepatotoxicity screening indicated that the 3D PHH model on the iBAC was more sensitive for predicting hepatotoxicity than the 2D PHH model on the plate. Finally, a large-scale screening of liver toxicity using 122 clinical drugs further demonstrated that the collagen-based 3D PHH model on the iBAC had superior predictive sensitivity compared to all previously reported in vitro models. These results indicated the importance of 3D collagen for liver physiological functionality and hepatotoxicity prediction. We anticipant it being a promising tool for risk assessment of drug-induced hepatotoxicity with a widespread acceptance in drug industry., (© 2021 Wiley Periodicals LLC.)