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ClO 2 has been ever-increasingly used as an alternative disinfectant to alleviate antibiotic resistance risk in aquaculture. However, the feasibility of ClO 2 disinfection in reducing antibiotic resistance has not been clarified yet. We comparatively explored the aggregation mechanisms and their effect on extracellular DNA (exDNA) partition and settlement in disinfected aquaculture waters and natural waters. In contrast to the unimodal aggregation in natural non-aquaculture waters, a unique bimodal size distribution pattern of micron-sized aggregates was found in aquaculture waters regardless of the disinfectants (macro-aggregates - 200-700 μm in diameter and micro-aggregates - 2-200 μm in diameter). The bimodal aggregates had 2-4 orders of magnitude higher content of Ferron cations and enriched hundred-fold exDNA in aquaculture waters than in natural waters. ExDNA was adsorbed on the surface of aggregates and conglutinated mainly by carbohydrates and coagulative cations. Macro-aggregates had lower fractal dimension but greater sedimentation velocities compared with micro-aggregates. Polylithionite was the key ballast mineral facilitating fast sedimentation of aggregates in aquaculture waters. Loading more antibiotic resistance genes and mobile gene elements, the aquaculture aggregates sank more rapidly from water to sediments than the natural-water aggregates. It indicates that disinfection with ClO 2 or antibiotics facilitated the spatial transfer of antibiotic resistance risk with high horizontal transfer potential from water column to sediment through forming bimodal aggregates. These findings imply that the adoption of antibiotic alternatives such as the oxidant of ClO 2 is far from sufficient to alleviate antibiotic resistance in aquaculture., 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.)

Rapid economic development has led to oil pollution and energy shortage. Thus, it is highly desirable to develop an efficient and environment-friendly approach for oil/water (O/W) separation. Herein, we report a simple and green method for preparing macroscopic COF AG and AG. COF AG was rapidly synthesized at room temperature, washed and freeze-dried to prepare COF AG without any adhesives or additives. Due to its strong hydrophobicity, COF AG is used as an absorbent for removing organic pollutants in O/W separation, and has a certain demulsification performance, which has a certain application prospect in the field of O/W separation. The hydrophobic COF AG material was combined with MA, which was synthesized in one step at room temperature, avoiding the long reaction conditions of traditional high temperature and high-pressure reaction, as well as the post-modification process and complex washing steps. The superhydrophobic sponge material was rapidly prepared. The introduction of MA reduced the amount of COF monomer, improved the adsorption capacity of the material for organic solvents and oil samples, increased from 37 times of the previous maximum adsorption weight to more than 120 times, and the demulsification capacity of O/W emulsion increased to more than 99%, with the ability of direct separation and continuous separation of O/W. Therefore, the prepared superhydrophobic sponge has high adsorption capacity and good reusability, and can be used for O/W separation. This work not only provides a strategy for the construction of functional COF, but also opens up a way for the growth of COF on different carriers for O/W separation., Competing Interests: 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., (This journal is © The Royal Society of Chemistry.)

Fatigue is a common health complaint in older adults, but its prevalence varies widely among studies due to differences in populations and assessment tools. The objective of this review is to systematically evaluate the prevalence of fatigue and perceived fatigability in older adults with PRISMA 2020. Four databases-PubMed, Embase, Web of Science (WoS), and Cochrane Library-were systematically searched as of December 27, 2023. Cochrane Q tests and the I 2 statistic were used using Stata16.0 to assess between-study heterogeneity. A total of 21 studies involving 17843 participants were included in this study. The prevalence of fatigue in older adults was 42.6%, and the prevalence of perceived physical fatigability and mental fatigability was 58.2% and 24.0%. Meta-analysis showed that the prevalence of perceived physical fatigability among older adults was very high. This prevalence varied with regional economic development level, age of the subjects, sample size, and representativeness of the subjects. Fatigue is a health dilemma faced by most older adults. To improve quality of life, early and regular fatigue assessment should be part of routine health screening for older adults., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

We first demonstrate that carrimycin, as an antibiotic, shows broad-spectrum anti-coronavirus activity by targeting frameshifting element (FSE) RNA. Herein, taking carrimycin as the lead, 26 new 16-membered macrolides were synthesized and evaluated for antiviral activity against coronavirus strains. Compound 2d exhibited the elevated antiviral efficacy against HCoV-OC43 and HCoV-229E with EC 50 values of 0.85 μM and 1.45 μM by directly targeting coronaviral FSE RNA pseudoknot. Molecular simulations revealed that the introduction of a 4″-substituent transforms the macrocyclic core into U-shaped conformation, enabling the higher binding with FSE. Meanwhile, using thermal proteome profiling (TPP) technology, we identified DIS3L2 as a potential host target, which probably assisted 2d to exert the antiviral effect. Therefore, the 16-membered macrolides constituted a new class of RNA inhibitors against coronaviruses, and 2d owns a dual-target mechanism that acts on both viral FSE RNA and host DIS3L2., 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 © 2025 Elsevier Masson SAS. All rights reserved.)

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high morbidity and mortality worldwide. Angiogenesis is essential for HCC progression and metastasis. Some angiogenesis-related genes promote this process, whereas other antiangiogenic genes inhibit HCC growth and metastasis. Therefore, finding new potential biomarkers for HCC prognosis prediction and treatment is essential. Public RNAseq and clinical data from TCGA and GEO database, download angiogenesis-related genes from the GeneCards, MSigDB database, through the single factor analysis of Cox, LASSO build risk score-Cox regression analysis model and external validation verified from the GEO. Cox regression analysis, Kaplan Meier (KM) curve, ROC curve, and decision-curve analysis will be used to evaluate and examine the risk score prediction effect of the model. GSVA analysis was used to assess the variation of gene sets between groups, and ClBERSOFT, ESTIMATE, and TIMER databases were used to analyze the immune infiltration in the single-cell level analysis of gene expression differences between cells. Finally, in the three pairs of HCC tissues and tissue adjacent to carcinoma by real-time fluorescent quantitative PCR (qRT_PCR) and western blotting (WB) to evaluate angiogenesis-related genes (ATP2A3 AEBP1 PNMA1, PLAT) expression level in HCC, and AEBP1 was knocked out in HCCLM3 cells, which is to study AEBP1 biological function in HCC. We established a prognostic risk assessment model based on 13 significant genes associated with HCC prognosis by Cox analysis and LASSO-Cox regression analysis. The median was used to divide these patients into high-risk and low-risk groups, and the prognosis of the high-risk group was worse than that of the low-risk group. Through the multivariate Cox regression analysis, it was found that the risk score was an independent predictor of overall survival (OS). The GSVA analysis suggested that the predicted high-risk population showed higher activity in the purine, pyrimidine, and riboflavin metabolic pathways. Compared with the low-risk group, the tumor microenvironment in the high-risk group showed a reduction in the number of cells promoting anti-tumor immunity and an increase in the number of cells inhibiting anti-tumor immunity, as well as a reduction in overall immune infiltration and matrix components. On the single-cell level, it was confirmed that the key genes (AEBP1, ATP2A3, PLAT, and PNMA1) expressed differently between liver cancer and adjacent tissue cell groups. Finally, qRT_PCR and WB results showed that ATP2A3, AEBP1, PNMA1, and PLAT were highly expressed in liver cancer tissue compared to adjacent tissue, and the proliferation, migration, and invasion of HCCLM3 cells were inhibited after knocking out AEBP1. We constructed novel risk score models as prognostic biomarkers for HCC, which has the potential to guide the development of more personalized treatment strategies for HCC patients. In addition, AEBP1 is a potential therapeutic target for HCC., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The study involving human participants were approved by the Ethics Review Committee of Guizhou Medical University (NO.2022375). The all patients provided their written informed consent in accordance with the Declaration of Helsinki., (© 2025. The Author(s).)

Silent magnetic resonance angiography (S-MRA) is primarily utilized to assess the blood flow in aneurysms and parent vessels of treated intracranial aneurysms. This study aimed to compare the diagnostic value of S-MRA and three-dimensional time of flight (3D-TOF) MRA for unruptured intracranial aneurysms. We included patients diagnosed with unruptured intracranial aneurysms using digital subtraction angiography (DSA) who subsequently underwent S-MRA and 3D-TOF MRA. Two independent neuroimaging and neurointerventional doctors evaluated the DSA images and measured aneurysm dimensions. Using DSA results as the gold standard, we determined the sensitivity and specificity of S-MRA and 3D-TOF MRA, as well as their accuracy in measuring aneurysm size and identifying aneurysms with daughter sacs. We detected a total of 41 intracranial aneurysms (in 37 patients) on both S-MRA and 3D-TOF MRA, with both techniques achieving a sensitivity and specificity of 100%. For aneurysm height, the intraclass correlation coefficient (ICC) was 0.977 (P < 0.001) between S-MRA and DSA, and 0.908 (P < 0.001) between 3D-TOF MRA and DSA. For neck width, the ICC was 0.663 (P < 0.001) between S-MRA and DSA, and 0.563 (P < 0.001) between 3D-TOF MRA and DSA. In terms of daughter aneurysm detection, 3D-TOF MRA Sensitivity 40%; specificity 92%: positive predictive value 100%; S-MRA sensitivity 60%; specificity 89%; positive predictive value 42%. In conclusion, S-MRA and 3D-TOF MRA did not significantly differ in aneurysm detection ability. For the detection of aneurysm with dauthger sacs indicators, the sensitivity is also higher., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Chronic cerebral hypoperfusion (CCH) is a critical pathophysiological mechanism underlying cerebral small vessel disease (CSVD). Accumulating evidence have demonstrated that resident pericytes and deposit extracellular matrix (ECM) and play a key role in mediating fibrosis in hypoxic changes. Edaravone dexborneol (EDB) is known to target multiple pathways involved in fibrosis., Methods: We constructed the CCH mouse models that were subjected to either PBS or EDB at different concentrations. Measures of cognitive function, neuronal damage, white matter lesion (WML), the fibrous profiles of pericytes and ECM protein were investigated to assess the effect of EDB. RNA sequencing of OGD in pericytes was performed to identify a key signaling pathway., Results: We observed that both medium and high concentrations of EDB could ameliorate CCH-induced cognitive impairment and emotional disorders. Neuronal damage in cortical layer and hippocampus and WML in corpus callosum were improved by EDB, which was consistent with the tends of fibrous pericytes and ECM proteins in these regions. RNA sequencing suggested that TGF-β1/IL-11 plays an important role in mechanism of pericytes fibrosis. Subsequently, the results of sequencing were confirmed in both cellular and mouse model., Conclusions: Our findings reveal the role of pericyte-mediated fibrosis in depositing ECM in the pathogenesis of CSVD. EDB could improve symptoms and the underlying pathogenesis of CCH mice and decrease the expression of the fibrous profiles of pericytes and ECM proteins, which may be regulated by TGF-β1/ IL-11. EDB treatment, targeting pericytes fibrosis, may be a novel therapeutic strategy for CSVD., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were approved by the Animal Care and Use Ethics Committee of Laboratory Animal Research Center (No. 2019034) and the Research Ethics Committee of Guangdong Provincial People’s Hospital (No. GDREC2019133A). Consent for publication: Not applicable. Competing interests: All authors have declared that there are no competing interests. Declaration of generative AI in scientific writing: Not applicable., (© 2025. The Author(s).)

Petroleum-based films have triggered a serious global pollution crisis because they are difficult to recycle, degrade, and reuse. Developing alternative sustainable active films represents a powerful strategy to address these issues. Here, a multifunctional biodegradable bacterial cellulose (BC) film incorporated with guanidine-based polymer (PHGH)/gallic acid (GA) was constructed (termed OBC-PHGH/GA). The resulting OBC-PHGH/GA film exhibited a highly interweaved nanofiber network structure with excellent tensile strength and ductility. The OBC-PHGH/GA film showed an excellent antibacterial effect against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) with inhibition efficiencies of ∼99.99 % compared with the OBC film. Moreover, the as-prepared film showed excellent UV-shielding, antioxidant, and antifungal activities, showing great potential in food packaging. More importantly, the OBC-PHGH/GA film can be degraded into safe and reusable sugars, demonstrating outstanding environmental friendliness and sustainability. This work provides a promising and unique strategy for designing and fabricating green active packaging materials., Competing Interests: Declaration of competing interest The authors declare that the work was not influenced by competing financial interests or personal relationships., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Clear cell renal cell carcinoma (ccRCC) is characterized by its aggressive invasion and metastasis, presenting significant clinical challenges. Gaining insights into the molecular mechanisms underlying its progression is crucial for the development of effective therapeutic strategies. Addressing a critical knowledge gap in understanding ccRCC tumorigenesis, this study aims to elucidate the expression patterns of TRIM21 in ccRCC, unravel its impact on ccRCC patient prognosis, and investigate the regulatory role of TRIM21 in ASS1 expression and urea cycle dysregulation within the context of ccRCC. The results demonstrate that TRIM21 is downregulated in ccRCC, and low expression of TRIM21 predicts an unfavorable prognosis for ccRCC patients. Furthermore, the upregulation of TRIM21 can inhibit the migration and invasion of ccRCC cells by regulating the ubiquitination modification of ASS1. This not only expands the functional role of TRIM21 in ccRCC tumorigenesis but also demonstrates its ability to reverse urea cycle dysregulation through stabilizing ASS1 expression. Specifically, abnormal downregulation of TRIM21 in ccRCC reduces K63 ubiquitination modification of ASS1, leading to decreased stability of the ASS1 protein, aggravated urea cycle dysregulation, and facilitated migration and invasion of ccRCC cells. Additionally, reduction in ASS1 reverses the depressed migration and invasion caused by overexpression of TRIM21 in ccRCC cells. In summary, our findings contribute to a deeper understanding of the functional role played by TRIM21 in ccRCC progression, pinpoint a unique and novel regulatory mechanism involving ectopic downregulation-mediated ASS1 ubiquitination modification and urea cycle dysfunction during ccRCC progression, and provide fresh insights for further investigation into the pathogenesis and metabolic reprogramming associated with ccRCC., (© 2024 Wiley Periodicals LLC.)

Analysis of the musculoskeletal movements (gait analysis) is needed in many scenarios. The in vivo method has some difficulties. For example, recruiting human subjects for the gait analysis is challenging due to many issues. In addition, when plenty of subjects are required, the follow-up experiments take a long period and the dropout of subjects always occurs. An efficient and reliable in silico simulation platform for gait analysis has been desired for a long time. Therefore, a technique using three-dimensional (3D) muscle modeling to drive the 3D musculoskeletal model was developed and the application of the technique in the simulation of lower limb movements was demonstrated. A finite element model of the lower limb with anatomically high fidelity was developed from the MRI data, where the main muscles, the bones, the subcutaneous tissues, and the skin were reconstructed. To simulate the active behavior of 3D muscles, an active, fiber-reinforced hyperelastic muscle model was developed using the user-defined material (VUMAT) model. Two typical movements, that is, hip abduction and knee lifting, were simulated by activating the responsible muscles. The results show that it is reasonable to use the improved CFD-FE method proposed in the present study to simulate the active contraction of the muscle, and it is feasible to simulate the movements by activating the relevant muscles. The results from the present technique closely match the physiological scenario and thus the technique developed has a great potential to be used in the in silico human simulation platform for many purposes.

The integrated application of hydrological models and best management practices (BMPs) serves as a pivotal decision-making tool for managing nonpoint source (NPS) pollution in watersheds. Optimizing and selecting BMP options are critical challenges in managing NPS pollution, as these processes are typically computationally expensive and involve mixed discrete-continuous decision variables. Our study integrated a novel method, the multi-objective adaptive surrogate modeling-based optimization for constrained hybrid problems (MO-ASMOCH), with the distributed Soil and Water Assessment Tool (SWAT) model to efficiently optimize the deployment of BMPs in the Four Lakes watershed of China. We compared the optimization results with those obtained using the traditional non-dominated sorting genetic algorithm (NSGA-II) method. Our results demonstrate that MO-ASMOCH significantly outperforms NSGA-II in computational efficiency, achieving comparable Pareto-optimal solutions with just 1,150 model evaluations compared to NSGA-II's requirement of 10,000 model evaluations. This demonstrates that MO-ASMOCH is a more efficient optimization algorithm for BMP optimization problems with both discrete and continuous decision variables. We selected representative scenarios to calculate in-lake concentrations of total phosphorus (TP) and total nitrogen (TN) pollutant loads. The largest reduction scenario could reduce TN and TP loads by 18.3 % and 20.7 %, respectively, at a cost of 1.54 × 10 8 Chinese Yuan. Under this scenario, the water quality classification level of TN improves from inferior Class V to Class IV-V, while TP attains Class III throughout the year. The methods of this study could enhance our capability to manage NPS pollution in watersheds effectively and provide targeted decision-making insights for environmental management practices., 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 rational utilization of ROS is key to treating infected wounds. Exogenous ROS can destroy bacterial structures, quickly kill bacteria, and inhibit secondary infections. However, excess ROS at the wound will cause a secondary inflammatory response. Acute infections exacerbate this damage by increasing endogenous ROS, complicating the maintenance of ROS homeostasis. Therefore, regulating the balance of ROS production and scavenging in wounds has emerged as a promising strategy for wound treatment. Conventional ROS balancing platforms are mostly based on the " all for one" strategy of functional superposition and lack self-adaptability and integration. To subvert this conventional strategy, this study proposes a "one for all" self-adaptive integrated photodynamic therapy (PDT)-antioxidant model to actively regulate the ROS balance. A gelatin-hyaluronic acid hydrogel embedded with Se-modified cerium dioxide nanoparticles (Gel-HA-Se@CeO 2 NPs) is designed for treating infected wounds. The Se@CeO 2 NPs serve both as nanoenzymes and photosensitizers(PS). As nanoenzymes, they exhibit catalase and superoxide dismutase activities, converting hydrogen peroxide and superoxide anions into oxygen. As a PS, it synergizes with oxygen under NIR irradiation to rapidly produce singlet oxygen. Additionally, Se modification enhances the PDT effects by disrupting bacterial antioxidant systems. In vitro and in vivo experiments revealed that the ROS balance platform polarizes M1-type macrophages to M2-type macrophages, altering the wound microenvironment from proinflammatory to prohealing. RNA sequencing revealed that this hydrogel accelerated the reconstruction of the vascular network of the wound by activating the PI3K/AKT pathway and increasing VEGF secretion.This strategy is believed to be beneficial not only for infected wounds but also for treating other conditions that involve the regulation of reactive oxygen species, such as tumors and bacterial infections., (© 2024 Wiley‐VCH GmbH.)

Artificial light-harvesting systems (LHSs) are of growing interest for their potential in energy capture and conversion, but achieving efficient fluorescence in aqueous environments remains challenging. In this study, a novel tetraphenylethylene (TPE) derivative, TPEN, is synthesized and co-assembled with poly(sodium 4-styrenesulfonate) (PSS) to enhance its fluorescence via electrostatic interactions. The resulting PSS⊃TPEN network significantly increased blue emission, which is further harnessed by an energy-matched dye, 4,7-di(2-thienyl)benzo[2,1,3]thiadiazole (DBT), to produce an efficient LHS with yellow emission. Moreover, this system is successfully applied to develop color-tunable light-emitting diode (LED) devices. The findings demonstrate a cost-effective and environmentally friendly approach to designing tunable luminescent materials, with promising potential for future advancements in energy-efficient lighting technologies., (© 2024 Wiley‐VCH GmbH.)

Circular polarization points (C points), which evolve from bound states in the continuum and feature topological half vortices, are important in manipulating chiroptical effects and controlling valley exciton emission in photonic systems. The methods for generating and manipulating C points usually rely on symmetry breaking of structures, but new strategies are required for more refined control. In this work, we investigate the generation and evolution of C points in photonic crystal slabs (PCSs) composed of anisotropic media while keeping the geometrical structure unchanged. By adjusting the optical axis of the anisotropic media, we introduce two degrees of freedom including azimuth and rotation angles, leading to the V point to split into two C points with opposite handedness. Our approach offers flexible control of C points by tuning material properties, presenting new, to the best of our knowledge, opportunities for direction- and spin-dependent optical devices.

Breast cancer (BC) is a critical threat to women's lives. Radiotherapy (RT) is a pivotal treatment modality for BC, but the failure of RT due to radioresistance is still not well facilitated. Ginkgetin (GK) has a potent anti-tumor activity intimately associated with ferroptosis. This study applied in vitro and in vivo experimental models to ascertain the GK mechanism of action on BC radioresistance. The outcomes reported that GK could inhibit BC cell growth and increase apoptosis. In addition, when BC cells generated radioresistance, GK promoted ferroptosis of radioresistant BC cells by mitigating NRF2 expression, suppressing HO-1 and NQO1 expression, increasing the intracellular content of reactive oxygen species (ROS) and ferrous ions, accelerating the glutathione (GSH) depletion, and decreasing GPX4 expression. Notably, GK can damage intracellular mitochondria and cause a substantial increase in ferrous ions in BC cells. Therefore, GK shows immense potential for enhancing breast cancer radiotherapy sensitivity, which may provide pivotal evidence for subsequent RT sensitization., 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.)

Clear cell renal cell carcinoma (ccRCC) is a disease rooted in metabolic disorders, distinguished by abnormally high activity of glucose 6-phosphate dehydrogenase (G6PD). G6PD serves as a key rate-limiting enzyme in the pentose phosphate pathway. Meanwhile, BRAF-activated non-coding RNA (BANCR) has emerged as a crucial regulatory factor linked to various cancers. The expression pattern of BANCR varies across different cancer types, exhibiting apparent duality in its function. However, the precise role and underlying mechanisms of BANCR in ccRCC tumorigenesis remain incompletely understood. Our study indicated that BANCR was downregulated in ccRCC and influenced cell survival by modulating cell proliferation, apoptosis, and G6PD enzyme activity. The underlying mechanism was that BANCR could directly bind to G6PD through a lncRNA-protein interaction, ultimately inhibiting G6PD activity by impeding its dimer formation. Moreover, BANCR exhibited the capability to modulate the glucose metabolic flow in ccRCC cells. Subsequent experiments demonstrated a significant inhibition of tumor growth in vivo upon overexpression of BANCR, and G6PD played a pivotal role in mediating the tumor suppressive effect of BANCR in ccRCC cells. In conclusion, this study provides novel insights into the molecular pathogenesis of ccRCC, highlights a distinct and new regulatory mechanism responsible for the ectopic overactivation of G6PD in ccRCC progression, and suggests that BANCR-mediated suppression of G6PD activity could emerge as a potential therapeutic strategy for ccRCC treatment., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The role of epigenetic aging in the environmental pathogenesis and prognosis of fibrotic interstitial lung disease (fILD) is unclear. We evaluated whether ambient particulate matter ≤2.5 μm (PM 2.5 ) and neighbourhood disadvantage exposures are associated with accelerated epigenetic aging, and whether epigenetic age is associated with adverse clinical outcomes in patients with fILD., Methods: This multicentre, international, cohort study included patients with fILD from the University of Pittsburgh (UPitt, n=306) and University of British Columbia (UBC, n=170). Five-year PM 2.5 exposures were estimated using satellite-derived models. Neighbourhood disadvantage was calculated using U.S. and Canadian Census-based metrics. Epigenetic age difference (EAD=epigenetic age - chronological age) was calculated using GrimAge analysis of blood DNA methylation data. Linear models assessed associations of exposures with EAD. Cox models assessed associations of EAD with transplant-free survival. Causal mediation analysis evaluated EAD mediation of exposure-survival relationships., Results: Median epigenetic age was 11.7 years older than chronological age in patients with fILD. In combined cohort analysis, each interquartile range (IQR) PM 2.5 increase was associated with 2.88 years (95%CI 1.39-4.38, p<0.001) increased EAD. In UPitt, each IQR neighbourhood disadvantage increase was associated with 1.16 years (95%CI 0.22-2.09, p=0.02) increased EAD. Increased EAD was associated with worse transplant-free survival (HR=1.17 per 1-year increase EAD, 95%CI 1.10-1.24, p<0.001), with EAD mediating 40% of PM 2.5 -survival relationship and 59% of neighbourhood disadvantage-survival relationships. Epigenetic age was also more strongly associated with transplant-free survival than chronological age., Conclusions: Epigenetic age acceleration is associated with worse survival and mediates adverse exposure impacts in fILD., (Copyright ©The authors 2025. For reproduction rights and permissions contact permissions@ersnet.org.)

Addressing heavy metal contamination in water bodies is a critical concern for environmental scientists. Traditional detection methods are often complex and costly. Recent advancements in artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), have shown significant potential in analytical chemistry. However, these AI models require extensive spectral data, which traditional methods struggle to provide quickly. To overcome this challenge, we developed a new digital spectral imaging system and rapidly collected 3000 digital spectra from mixed heavy metal samples. We then created an end-to-end regression model for predicting heavy metal concentrations in mixed water samples using deep convolutional neural networks (ResNet-50, Inception V1, and SqueezeNet V1.1). The results indicated that the trained ResNet-50 model can effectively detect arsenic, chromium, and copper simultaneously, with a linear fitting coefficient exceeding 0.99 between true and predicted values. This study offers an efficient approach for rapid heavy metal detection in complex water environments and serves as a reference for developing intelligent analytical techniques.

Ethnopharmacological Relevance: Jieduquyuziyin prescription (JP) is an empirical prescription approved for application to treat systemic lupus erythematosus (SLE) in hospital within China. Despite the prominent treatment effect of JP clinically, further investigation is imperative to explore its underlying mechanisms., Aim of the Study: We aim to investigate the impact of JP on DN T cell apoptosis in the treatment of SLE and the specific regulation mechanisms., Materials and Methods: Firstly, female MRL/lpr mice were treated with JP and the therapeutic efficacy of JP was evaluated via skin lesions, lymphoid organ enlargement, accumulation of autoantibodies and renal function. Then, flow cytometer analysis was performed to evaluate the proportions and the apoptosis of T cell subpopulations. Based on the above results, double-negative (DN) T cells were subjected to proteomic with subsequent differential screening. The expression of Ube2m and Bim was further validated using real-time PCR and Western blot. Subsequently, DN T cells were incubated with JP-contained serum in vitro, and cell apoptosis was quantified using flow cytometry. Additionally, the expression levels of Ube2m, Bim and other associated proteins were also assessed through western blotting. To further clarify whether Ube2m serves as the key target of JP in regulating DN T cell apoptosis, the mice that Ube2m was specific deleted in T cells with spontaneous lupus (Ube2m -/- lpr) were utilized. JP was administered to WTlpr or Ube2m -/- lpr mice, followed by assessment of the lupus condition and DN T cell apoptosis., Results: JP administration effectively ameliorated the lupus phenotype. Then flow cytometry assay showed that JP treatment enhanced DN T cell apoptosis to reduce their accumulation and restored the immune homeostasis. Proteomic analysis revealed a significant inhibition of Ube2m for JP treatment, which is essential for maintaining homeostasis of DN T cells. Further experiments confirmed that JP treatment effectively downregulated the expression of Ube2m and subsequently upregulated the level of pro-apoptotic protein Bim with decreased Bim degradation. In vitro experiments also confirmed that JP-contained serum significantly facilitated DN T cell apoptosis and reduced DN T cell accumulation by inhibiting Ube2m expression. Furthermore, Ube2m -/- lpr mice were utilized and the impact of JP treatment on the apoptosis of DN T cells was found to be minimal in the absence of Ube2m. Mechanistic investigation reveals that JP exerts its effects by suppressing the expression of Ube2m, subsequently inhibiting CRL-dependent degradation of Bim, and ultimately promoting Bim-induced apoptosis in DN T cells. Furthermore, the blockade of Ube2m in T cells effectively prevents JP-induced apoptosis in DN T cells, underscoring Ube2m as one crucial therapeutic target of JP in mediating DN T cell apoptosis and managing SLE., Conclusions: Our findings indicate that JP treatment effectively restores the homeostasis of DN T cells in SLE by inhibiting Ube2m expression, thereby reducing Bim ubiquitination degradation. This ultimately enhanced DN T cell apoptosis and alleviated lupus phenotype., 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: Investigating the molecular epidemiological characteristics of multidrug-resistant tuberculosis (MDR-TB) in China's moderate-burden regions, such as Wuhan, is crucial for understanding and controlling disease transmission., Materials and Methods: This study analyzed MDR-TB isolates from pulmonary tuberculosis cases registered at Wuhan Pulmonary Hospital in 2017. Whole genome sequencing (WGS) was used to identify resistance-conferring mutations, examine their associations with specific Mycobacterium tuberculosis lineages or sublineages, and assess clustering profiles., Results: Among the 149 analyzed strains, the most prevalent mutations associated with resistance to 11 anti-tuberculosis drugs were identified as follows: rpoB Ser450Leu (59.73%, rifampicin), katG Ser315Thr (62.42%, isoniazid), embB Met306Val (42.86%, ethambutol), rpsL Lys43Arg (68.13%, streptomycin), pncA Trp68Arg (10.53%, pyrazinamide), gyrA Asp94Gly (22.50%, fluoroquinolones), and rrs 1401A > G (50.00-100.00%, second-line injectable aminoglycosides). Additional mutations were detected in fabG1 c-15C > T (42.86%, ethionamide) and thyX c-16C > T (21.43%, p-aminosalicylic acid). Notably, rare mutations absent from the WHO mutation catalog, such as ahpC c-52C > T and rpsL Lys43Thr, were also observed. The mutation frequency of embB Met306Ile was significantly higher in Lineage 4 (L4) strains than in Lineage 2 (L2) strains ( p  = 0.0150), while the rpsL Lys43Arg mutation frequency was lower in L4 compared to L2 ( p  = 0.0333). A total of 31 MDR MTB Mycobacterium tuberculosis isolates formed clusters, resulting in a clustering rate of 20.81% and a recent transmission rate of 11.41%. The clustering rates between L4 and L2 strains were not significantly different (χ 2  = 0.0017, p  > 0.05)., Conclusion: The genetic diversity of MDR-TB in Wuhan demonstrates unique characteristics, with evidence of localized transmission. These findings highlight the urgent need to strengthen measures to detect early cases of MDR-TB and control transmission of MDR-TB in the region., 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 © 2025 Wei, Chen, Deng, Zhang, Zhang and Duan.)

Nanozymes play a pivotal role in mitigating excessive oxidative stress, however, determining their specific enzyme-mimicking activities for intracellular free radical scavenging is challenging due to endo-lysosomal entrapment. In this study, we employ a genetic engineering strategy to generate ionizable ferritin nanocages (iFTn), enabling their escape from endo-lysosomes and entry into the cytoplasm. Specifically, ionizable repeated Histidine-Histidine-Glutamic acid (9H 2 E) sequences are genetically incorporated into the outer surface of human heavy chain FTn, followed by the assembly of various chain-like nanostructures via a two-armed polyethylene glycol (PEG). Utilizing endosome-escaping ability, we design iFTn-based tetrameric cascade nanozymes with high superoxide dismutase- and catalase-mimicking activities. The in vivo protective effects of these ionizable cascade nanozymes against cardiac oxidative injury are demonstrated in female mouse models of cardiac ischemia-reperfusion (IR). RNA-sequencing analysis highlight the crucial role of these nanozymes in modulating superoxide anions-, hydrogen peroxide- and mitochondrial functions-relevant genes in IR injured cardiac tissue. These genetically engineered ionizable protein nanocarriers provide opportunities for developing ionizable drug delivery systems., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

In this paper, we studied the sidewall conditions of 28 × 52 µm 2 InGaN-based blue and green micro-LEDs with different sidewall angles and their effects on external quantum efficiency (EQE). Our findings indicate that steeper sidewall mesas can reduce non-radiative recombination and leakage current, which is beneficial for achieving high internal quantum efficiency (IQE). However, as the sidewall angle increases, the light output from the micro-LED tends to concentrate in the internal region, leading to a decrease in light extraction efficiency (LEE). Using microscopic hyperspectral imaging, we observed distinct chromaticity characteristic distributions in the internal area of mesas with different sidewall angles, compared to the entire micro-LEDs. Mesas with gentler sidewalls exhibited lower chromaticity stability. For both blue and green micro-LEDs, the optimal sidewall tilt angle was found to be 48°, yielding the highest EQE. This result reflects a trade-off between LEE and IQE. Notably, the improvement in IQE for green micro-LEDs was not as significant as that for blue micro-LEDs, likely due to the higher indium content in green InGaN micro-LEDs, which results in deeper localized potential wells and a higher dislocation density. This work demonstrates the variation of IQE and LEE for blue and green micro-LEDs fabricated on mesas with different sidewall angles, aimed at achieving the highest EQE.

Gas pipeline networks are vital urban infrastructure, susceptible to leaks caused by natural disasters and adverse weather, posing significant safety risks. Detecting and localizing these leaks is crucial for mitigating hazards. However, existing methods often fail to effectively model the time-varying structural data of pipelines, limiting their detection capabilities. This study introduces a novel approach for leak detection using a spatial-temporal attention network (STAN) tailored for small-hole leakage conditions. A graph attention network (GAT) is first used to model the spatial dependencies between sensors, capturing the dynamic patterns of adjacent nodes. An LSTM model is then employed for encoding and decoding time series data, incorporating a temporal attention mechanism to capture evolving changes over time, thus improving detection accuracy. The proposed model is evaluated using Pipeline Studio software and compared with state-of-the-art models on a gas pipeline simulation dataset. Results demonstrate competitive precision (91.7%), recall (96.5%), and F1-score (0.94). Furthermore, the method effectively identifies sensor statuses and temporal dynamics, reducing leakage risks and enhancing model performance. This study highlights the potential of deep learning techniques in addressing the challenges of leak detection and emphasizes the effectiveness of spatial-temporal modeling for improved detection accuracy.

Aptamers and aptamer-drug conjugates (ApDCs) have shown some success as targeted therapies in cancer theranostics. However, their stability in complex media and their capacity to evade lysosomal breakdown still need improvement. To address these challenges, we herein developed a one-step self-assembly strategy to improve the stability of aptamers or ApDCs, while simultaneously enhancing their delivery performance and therapeutic efficiency through a lysosome-independent pathway. This strategy involves the formation of stable complexes between disulfide monomer and aptamers (Sgc8) or ApDCs (Gem-Sgc8). Self-assembled Sgc8 NPs resisted nuclease degradation for up to 24 h, whereas the aptamer alone degraded within just 3 h. These self-assembled Sgc8 NPs, as well as Gem-Sgc8 NPs, demonstrated enhanced binding capabilities compared to Sgc8 aptamers or Gem-Sgc8 alone. Furthermore, lysosome-independent cellular uptake was significantly improved, which in turn increased the therapeutic efficacy of Gem-Sgc8 NPs by 2.5 times compared to Gem-Sgc8 alone. In vivo results demonstrated that Gem-Sgc8 NPs can effectively suppress the growth of tumors. The same self-assembly strategy was successfully applied to other aptamers, such as MJ5C and cMET, showing the generalizability of our method, Overall, this aptamer self-assembly strategy not only overcomes the limitations associated with instability and lysosomal degradation but also demonstrates its broad applicability, highlighting its potential as a promising avenue for advancing targeted cancer theranostics. STATEMENT OF SIGNIFICANCE: We developed a one-step self-assembly strategy to improve the stability of aptamers or ApDCs and enhance their drug therapeutic efficiency through a lysosome-independent pathway. The stability of self-assembled Sgc8 nanoparticles (NPs) was significantly improved. The resulting Sgc8 NPs or GEM-Sgc8 NPs exhibited enhanced binding ability compared to Sgc8 aptamers or GEM-Sgc8 alone, and they also facilitated lysosome-independent cellular uptake, resulting in a 2.5-fold increase in therapeutic efficacy of GEM-Sgc8-NPs. The same self-assembly strategy was successfully applied to other aptamers, such as MJ5C and cMET, showing the generalizability of our method., Competing Interests: Declaration of interest statement 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 © 2025 Acta Materialia Inc. Published by Elsevier Inc. All rights reserved.)

Context: Area-level predictive models are commonly used to screen children for blood lead levels (BLLs) greater than the Center for Disease Control and Prevention (CDC) blood lead reference value (BLRV) of 3.5 µg/dL., Objectives: To increase screening accuracy and precision by creating a parcel-level model incorporating housing characteristics to predict parcels where children are at high risk., Design: Residential addresses associated with child blood lead tests were linked to neighborhood- and parcel-level characteristics and proximity to lead sources. Regression forests were fit using different predictor combinations and compared using cross-validated accuracy and decile-based agreement across all residential parcels., Setting: Hamilton County, Ohio, United States., Participants: Children less than 6 years of age with blood lead tests between January 2020 and April 2023., Main Outcome Measure: Cross-validated model accuracy and decile-based agreement across residential parcels., Results: 27,782 tests were matched to a residential parcel. Regression forests using Parcel + Source (70.8% AUC) and Neighborhood + Parcel + Source predictors (70.3% AUC) had the highest cross-validated accuracy for predicting BLLs >3.5 µg/dL. Parcel-level predictions revealed heterogeneity of risk across parcels within the same tract., Conclusions: Parcel characteristics improved the accuracy of predicting locations of children with BLLs >3.5 µg/dL and can help identify children at high risk living in low-risk areas. A parcel-level identification of housing-based lead hazards could guide and support action to prevent pediatric lead exposure., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intrahepatic cholangiocarcinoma is a malignant tumor that starts from the epithelium of the bile duct and has a poor prognosis. They are characterized by poor response to chemotherapy and lack of effective targeted therapies; thus, therapeutic options are limited., Case Presentation: A 59-year-old man was admitted to the hospital for a workup of abnormal CA19-9 levels. He was diagnosed with ICC, underwent surgery and was found to have pT1bNx disease. He developed rapid disease recurrence on adjuvant gemcitabine + capecitabine. Following recurrence, he received first-line systemic pembrolizumab + lenvatinib and second-line pembrolizumab + lenvatinib + chemotherapy and had mild tumor regression followed by progression. Next-generation sequencing was performed on the baseline surgical sample. This revealed a novel RBPMS-MET fusion, and based on the literature, crizotinib 250 mg twice a day was administered. After 3 months of crizotinib treatment, magnetic resonance imaging revealed a significant reduction in liver lesions, and 4 months after initiating treatment, scans demonstrated a partial response., Conclusion: Our case report strengthens the evidence that crizotinib may be a viable treatment option for patients with ICC with a c-MET tyrosine kinase fusion, necessitating additional clinical investigation., (© The Author(s) 2024. Published by Oxford University Press.)

To clarify the effect of heating rate on the thermal decomposition process of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), this study employs molecular dynamic simulations to investigate the thermal decomposition of TATB at heating rates of 20, 40, 60, and 80 K/ps. The initial temperature is uniformly set to 300 K, while the final temperature is set to 3000 K. Results indicate that within the temperature range of 300-3000 K, the thermal decomposition rate of TATB decreases with increasing heating rate, whereas the initial decomposition temperature of TATB increases, consistent with the experimental pattern. Within the studied temperature range, a lower heating rate results in a higher number of decomposition fragments, leading to more effective collision between active fragments, facilitating more effective collisions between active species, and leading to the formation of more stable products such as H₂O, CO₂, and N₂. Conversely, higher heating rates reduce the quantities of these stable products. This study enhances the understanding of TATB's thermal decomposition mechanism, providing valuable insights for its safe handling and application. METHODS: The Gaussian09 software was used to calculate the BDEs of TATB molecules, while the MD simulation using the ReaxFF-lg force field was performed by the LAMMPS package. Visualization and postprocessing were conducted using the OVITO software, and a custom script was developed to analyze the reaction products and frequencies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Non-metallic heteroatom-doped carbon materials are promising catalysts for the oxidative dehydrogenation of propane (ODHP), but their controlled synthesis remains challenging. Herein, a novel three-dimensional N, P co-doped carbon nanosheet (NPC-NS-T) catalyst is prepared, which shows an impressive catalytic performance in the ODHP reaction with high propane conversion (20.0%) and high selectivity for propene (62.1%) and olefins (64.5%) at 500 °C along with good long-time stability. Comprehensive experimental characterizations revealed that incorporation of appropriate P can not only help to form more CO species on the surface of NPC-NS-T but also inhibit the consumption of CO species under ODHP conditions, thereby remarkably improving the catalytic performance. This work could pave the way for developing efficient biomass-derived carbon catalysts for the oxidative dehydrogenation reactions of propane.

African swine fever (ASF) is an acute hemorrhagic disease in pigs caused by the African swine fever virus (ASFV), which has a high mortality rate and brought great damage to global pig farming industry. At present, there is no effective treatment or vaccine to combat ASFV infection, so early detection of ASFV has become particularly important. Therefore, the PDMS/chitosan/MPMs composite film was proposed to detect ASFV P72. PDMS mixed with chitosan particles were used to provide biological modification sites for the ASFV P72 antibody, which simplified the functional modification process. The specific binding of antigen and antibody leads to the mechanical deformation of the composite film, which was observed through optical method to change the microsphere spacing. The polystyrene microsphere (PMs) spacing changes were acquired by simply measuring the diameters of the Debye ring diffracted by the PDMS/chitosan/PMs with a simple laser pointer. The conductive layer formed by AgNWs realize the transformation of biological signals to electrical signals. By conjugating PMs with Fe 3 O 4 nanoparticles (MPMs) and applying a magnetic field, a magnetic-stress-electric coupling system has been constructed, which amplifies the deformation of the composite film and enhances the sensitivity of the flexible film. The experimental results showed that the flexible film has wide linear range of 10 ng/mL-100 μg/mL, and the optimal detection limit (LOD) is 0.059 ng/mL, which was about one order of magnitude lower than that without magnetic field. In addition, the flexible film showed a good stability, specificity, and selectivity., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Non-functioning pituitary adenomas (NFPAs) are a highly heterogeneous group and often show invasion, but few studies have explored the invasion mechanism and biomarkers for specific subtypes. This study was designed to describe the role of HIF1α and its downstream genes in specific subtypes of NFPAs. Specimens were classified into two subtypes of NFPAs: 46 null cell adenomas (28 invasive and 18 noninvasive) and 46 oncocytomas (11 invasive and 35 noninvasive). HIF1α, TIMP1, MT6-MMP, ECAD and NCAD were detected by qRT-PCR, western blot or immunohistochemistry in tumor tissue. The transwell assay was performed to measure the effects of HIF1α on tumor cell invasion in GH3 and GT1-1 cells. TIMP1, MT6-MMP, ECAD and NCAD were detected by western blot in HIF1α overexpressed GT1-1 cells. HIF1α mRNA and protein level was significantly upregulated in invasive pituitary null cell adenomas but not in invasive pituitary oncocytoma. The TIMP1 mRNA and protein level was significantly downregulated and MT6-MMP mRNA and protein level was significantly upregulated in invasive pituitary null cell adenomas. Meanwhile, there were no significant differences in epithelial-mesenchymal transition (EMT) markers, ECAD and NCAD, between invasive and noninvasive pituitary null cell adenomas. The overexpression of HIF1α promoted the invasive capability of pituitary adenoma cells in vitro. Regarding the molecular mechanism, HIF1α overexpression could downregulate TIMP1 and upregulate MT6-MMP expression levels but did not affect EMT markers' expression. Our results suggested that HIF1α might contribute to the invasion of pituitary null cell adenomas through activating HIF1α/TIMP1/MT6-MMP pathway but not EMT.

With the increasing global focus on sustainable materials, paper is favored for its biodegradability and low cost. Their integration with triboelectric nanogenerators (TENGs) establishes broad prospects for self-powered, paper-based triboelectric materials. However, these materials inherently lack efficient charge storage structures, leading to rapid charge dissipation. This study introduced a paper-based triboelectric material with efficient charge storage using deep traps assembled by a hydrogen bonds strategy. Compared to pure paper, the material increased the deep trap density by ∼54 times, with an ∼10 times higher dielectric constant at high frequency. TENG based on the material had a peak output power density ∼45 times higher than paper-based TENG and maintained a stable voltage after 20,000 cycles. It also shows exceptional environmental stability and practicality with minimal voltage reduction in heat environments. This offers a practical and effective solution for powering and sustaining small electronic devices under extreme conditions.

Hydrocephalus is a neurological condition caused by aberrant circulation and/or obstructed cerebrospinal fluid (CSF) flow after cerebral ventricle abnormal dilatation. In the past 50 years, the diagnosis and treatment of hydrocephalus have remained understudied and underreported, and little progress has been made with respect to prevention or treatment. Further research on the pathogenesis of hydrocephalus is essential for developing new diagnostic, preventive, and therapeutic strategies. Various genetic and molecular abnormalities contribute to the mechanisms of hydrocephalus, including gene deletions or mutations, the activation of cellular inflammatory signaling pathways, alterations in water channel proteins, and disruptions in iron metabolism. Several studies have demonstrated that modulating the expression of key proteins, including TGF-β, VEGF, Wnt, AQP, NF-κB, and NKCC, can significantly influence the onset and progression of hydrocephalus. This review summarizes and discusses key mechanisms that may be involved in the pathogenesis of hydrocephalus at both the genetic and molecular levels. While obstructive hydrocephalus can often be addressed by removing the obstruction, most cases require treatment strategies that involve merely slowing disease progression by correcting CSF circulation patterns. There have been few new research breakthroughs in the prevention and treatment of hydrocephalus., 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 © 2025 Deng, Chen, Duan, Ding, Wang, Wang, Chen, Zhou and Zhao.)

Introduction: The high percentage of Omicron breakthrough infection in vaccinees is an emerging problem, of which we have a limited understanding of the phenomenon., Methods: We performed single-cell transcriptome coupled with T-cell/B-cell receptor (TCR/BCR) sequencing in 15 peripheral blood mononuclear cell (PBMC) samples from Omicron infection and naïve with booster vaccination., Results: We found that after breakthrough infection, multiple cell clusters showed activation of the type I IFN pathway and widespread expression of Interferon-stimulated genes (ISGs); T and B lymphocytes exhibited antiviral and proinflammatory-related differentiation features with pseudo-time trajectories; and large TCR clonal expansions were concentrated in effector CD8 T cells, and clonal expansions of BCRs showed a preference for IGHV3. In addition, myeloid cells in the BA.5.2 breakthrough infection with the fourth dose of aerosolized Ad5-nCoV were characterized by enhanced proliferation, chemotactic migration, and antigen presentation., Discussion: Collectively, our study informs the comprehensive understandings of immune characterization for Omicron breakthrough infection, revealing the positive antiviral potential induced by booster doses of vaccine and the possible "trained immunity" phenomenon in the fourth dose of aerosolized Ad5-nCoV, providing a basis for the selection of vaccination strategies., 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 © 2025 Zhang, Han, Sun, Liu, Wen, Yao, Zhang, Duan, Zhang, Pang, Kou and Jiang.)

Background: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society., Methods: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China., Results: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015., Conclusions: The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Microplastics (MPs) pose significant threats to ecosystems and human health due to their persistence and widespread distribution. This paper provides a comprehensive review of sampling methods for MPs in aquatic environments, soils, and biological samples, assessing pre-treatment procedures like digestion and separation. It examines the application and limitations of identification techniques, including microscopic observation, spectroscopic analysis, and thermal analysis. The review highlights the potential of AI technology to enhance detection efficiency and precision. It underscores the necessity of standardized protocols for consistent sampling and detection, and the importance of systematic risk assessment methodologies for managing environmental and health risks associated with MPs. The paper concludes with recommendations for future research, emphasizing the standardization of methods, advancement of detection technologies, integration of AI, and comprehensive health risk assessments. This review will be helpful for researchers to comprehensively understand the current main detection technologies and risk assessment methods of the MP, and to accelerate the establishment of an artificial intelligence regulatory framework for MPs., 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 © 2025 Elsevier Ltd. All rights reserved.)

Lilies are economically important monocots known for their ornamental flowers, bulbs, and large genomes. The absence of their genomic information has impeded evolutionary studies and genome-based breeding efforts. Here, we present reference genomes for Lilium sargentiae (lily, 35.66 Gb) and Gloriosa superba (flame lily, 5.09 Gb). The giant lily genome is shaped by recent long terminal repeat retroelements. Phylogenetic analysis reveals diverse, independent origins of lily cultivars. Gene families involved in sucrose and starch metabolism are significantly expanded in the lily genome. Key homologs of XTH22, SOC1, and AP1/FUL-like genes regulate the development, bud growth transition, and floral bud growth transition of lily bulbs. Colchicine biosynthetic gene clusters are identified in G. superba but are absent in L. sargentiae, highlighting independent colchicine evolution in Colchicaceae. These genomic insights enhance understanding of Liliales evolution, providing a foundation for future breeding and molecular research., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Posterior spinal fusion (PSF) surgery for correction of idiopathic scoliosis is associated with chronic postsurgical pain (CPSP). In this multicenter study, we describe perioperative multimodal analgesic (MMA) management and characterize postoperative pain, disability, and quality of life over 12 months after PSF in adolescents and young adults., Methods: Subjects (8-25 years) undergoing PSF were recruited at 6 sites in the United States between 2016 and 2023. Data were collected on pain, opioid consumption (intravenous morphine milligram equivalents (MME)/kg), and use of nonopioid analgesics through postoperative days (POD) 0 and 1. Pain descriptors, functional disability, and quality of life were assessed preoperatively, 2 to 6 and 10 to 12 months after surgery using questionnaires (PainDETECT, Functional Disability Inventory [FDI], and Pediatric Quality of Life Inventory [PedsQL]). Descriptive analyses of analgesic use across and within sites (by preoperative pain and psychological diagnoses), acute postoperative pain and yearly in-hospital analgesic trends are reported. Pain trajectories over 12 months were analyzed using group-based discrete mixture. CPSP (defined as pain score >3/10 beyond 2 months postsurgery), and associated FDI and PedsQL were analyzed., Results: In this cohort (343 patients, median [interquartile range {IQR}] 15.2 (13.7-16.6) years, 71.1% female), perioperative use of opioids and nonopioid analgesics significantly varied across sites (P < .001). Preoperatively, gabapentinoids were administered to 48.2% (157/343). Intraoperatively, opioid use included remifentanil (264/337 [78.3%]) and fentanyl (73/337 [21.7%]) infusions, and methadone boluses (159/338 [47%]). Postoperatively, patient-controlled analgesia was commonly used (342/343 [99.9%]). Within sites MMA use did not appear to differ by preoperative pain or psychological comorbidities. Median in-hospital opioid use declined over time (-0.08 [standard error {SE} 0.02] MME/kg/POD 0 to 1 per year, P < .001) while increased use of ketamine (P < .001), methadone (P < .001), dexmedetomidine (P < .001), and regional analgesia (P = .015) was observed. Time spent in moderate-to-severe pain on POD 0 to 1 was ≈33%. CPSP was reported by 24.2% (64/264) with ~17% reporting ongoing neuropathic/likely neuropathic pain. Four postsurgical pain trajectories were identified; 2 (71%) showed resolving pain and 2 (29%) showed persistent mild and moderate-to-severe pain. Although FDI and PedsQL improved over time in both CPSP and non-CPSP groups (P < .001), FDI was higher (P < .001) and PedsQL lower (P = .001) at each time point in the CPSP versus the non-CPSP group., Conclusions: MMA strategies showed site-specific variability and decreasing yearly trends of in-hospital opioid use without changes in acute or chronic pain after PSF. There was a high incidence of persistent pain associated with disability and poor quality of life warrants postoperative surveillance to enable functional recovery., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2025 International Anesthesia Research Society.)

With the rapid progression of industrialization, the application and release of endocrine disruptors (EDCs), including bisphenol A (BPA), octylphenol and nonylphenol have significantly increased, presenting substantial health hazards. Conventional analytical techniques, such as high-performance liquid chromatography and gas chromatography-mass spectrometry, are highly sophisticated but suffer from complex procedures and high costs. To overcome these limitations, this study introduces an innovative spectral methodology for the simultaneous detection of multiple aquatic multicomponent EDCs. By leveraging chemical machine vision, specifically with convolutional neural network (CNN) models, we employed a long-path holographic spectrometer for rapid, cost-effective identification of BPA, 4-tert-octylphenol, and 4-nonylphenol in aqueous samples. The CNN, refined with the ResNet-50 architecture, demonstrated superior predictive performance, achieving detection limits as low as 3.34, 3.71 and 4.36 μg/L, respectively. The sensitivity and quantification capability of our approach were confirmed through the analysis of spectral image Euclidean distances, while its universality and resistance properties were validated by assessments of environmental samples. This technology offers significantly advantages over conventional techniques in terms of efficiency and cost, offering a novel solution for EDC monitoring in aquatic environments. The implications of this research extend beyond improved detection speed and cost reduction, presenting new methodologies for analyzing complex chemical systems and contributing to environmental protection and public health., 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.)

Glycated albumin (GA) has been proposed as a reliable diabetes mellitus marker particularly useful in assessing intermediate glycemic control. Herein, we designed a bioinspired nanochannels for biochemical detection based on the host-guest interaction between β-cyclodextrin and azobenzene. Cyclodextrin was grafted on the inner surface of nanochannels of a nanoporous membrane and azobenzene was tagged to the terminal of GA aptamer, thereby facilitating the orientation of GA aptamer in the nanochannels. The presence of GA was monitored by recording the voltammetric signal of ferricyanide that transported across the nanochannel array. The peak current exhibited a linearity relationship with the GA concentration across a broad range of 1.0 ng mL -1 to 100 μg mL -1 , along with a detection limit of 0.18 ng mL -1 . Notably, the aptamer could be offloaded under ultraviolet light, regenerating the cyclodextrin functionalized nanochannels for subsequent re-immobilization of the fresh aptamer. The relative standard deviation for seven cycles of regeneration treatment was no more than 1.8 %. The remarkable reusability of the nanochannels offered a cost-effective, sensitive and reproducible aptasensing platform., 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.)

River flood forecasting and assessment are crucial for reducing flood risks, as they offer early alerts and allow for proactive actions to safeguard individuals from possible flood-related damage. Effective modeling in this field often multiple interconnected aspects of the hydrologic cycle, such as precipitation, infiltration, runoff, and evaporation, requiring collaboration among hydrology experts. Such collaboration enables experts to handle and manage their specialized processes more effectively, thereby enhancing the efficiency of the development of integrated flood forecasting models. Tight integration and loose integration are two common strategies for integrating different hydrologic cycle process models in river flood forecasting. However, most integration strategies rely on centralized models, necessitating experts to configure models and data on local computers. Currently, there is a deficiency in the capacity for effective collaboration in the integrated modeling of river flood forecasts. This issue arises from multiple obstacles: the complexity of understanding heterogeneous data and hydrologic cycle process models; the difficulty of integrating models with diverse runtime environments; and the challenge of synchronizing forecasting model changes among experts in real time. Therefore, we propose a web-based collaborative integrated modeling method, designed to support both tightly and loosely integrated modes, to enhance collaborative river flood forecasting and assessment. This method includes three core modules: (1) data and model description for providing a structured description of the execution logic of forecasting models and the internal structure of forecast data for expert understanding; (2) model access and integration for access and integration of data and multi-source heterogeneous models of hydrologic cycle processes; and (3) modeling scenario configuration for collaborative development of forecasting models and the execution of simulation tasks. Finally, we illustrate the application of the proposed method by utilizing the GEFS v12 (Global Ensemble Forecast System) rainfall ensemble forecasting dataset with the CREST (Coupled Routing and Excess STorage) hydrologic model. The results show enhanced efficiency in the collaborative development of river flood forecasts by hydrology experts, particularly in model accessibility, data processing, simulation, and evaluation, thereby potentially aiding 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 Ltd. All rights reserved.)

The epidermal growth factor receptor (EGFR) is a validated therapeutic target for RAS/RAF wild-type colorectal cancer (CRC). However, monoclonal antibody-based anti-EGFR therapies such as cetuximab have limited effectiveness. Herein, it is identified that EGFR internalization is associated with poor treatment response and prognosis in patients with CRC, based on a retrospective analysis of patients treated with cetuximab. It is further demonstrated that the endocytosis inhibitor prochlorperazine (PCZ) can move EGFR, which is hidden inside the cell, to the cell surface to improve therapeutic antibody binding. Thus, a thermosensitive hydrogel co-loaded with cetuximab and PCZ (Gel@Cmab/PCZ) is constructed for sustained inhibition of endocytosis and effective cetuximab delivery. Peritumoral injection of Gel@Cmab/PCZ shows strong antitumor efficacy in subcutaneous and orthotopic CRC tumor models and completely abrogated liver metastasis when combined with chemotherapy. In a humanized patient-derived xenograft model, a single injection of Gel@Cmab/PCZ with one-third of the conventional cetuximab dose achieved 91% tumor growth inhibition, which promoted NK cell infiltration into tumor tissues and their antibody-dependent cell-mediated cytotoxicity effect. This study represents a novel strategy to boost the monoclonal antibody-mediated anti-tumor response in CRC., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Ischemia brain injury is closely associated with the gut microbiota. Polysaccharides, as a typical prebiotic, have been extensively employed in stroke treatment. In our previous study, Pueraria lobata polysaccharide (PLP-3) with antioxidant activity was prepared via water extraction and alcohol precipitation combined with ultrasonic degradation. In this study, the effects of PLP-3 on ischemia brain injury and its regulatory effects on the gut microbiota were further investigated. The results demonstrated that PLP-3 effectively reduced the infarct area, improves neurological function, and alleviates neuronal damage of cerebral ischemia injury. Mechanistically, PLP-3 significantly reduces serum LPS levels in MCAO mice, inhibiting TLR-4 activation in brain tissue and thereby reducing IL-1β and TNF-α levels. Meanwhile, PLP-3 significantly repaired the intestinal barrier injury by increasing the expression of tight junction proteins (ZO-1 and Occludin) and increasing the number of goblet cells. Additionally, the structure and composition of gut microbiota in MCAO mice after PLP-3 intervention, were also significantly changed, especially the enrichment of Lactobacillus and the reduction of Corynebacterium and Staphylococcus. At the same time, short chain fatty acid, metabolites of gut microbiota, were also significantly increased and significantly correlated with the abundance of Lactobacillus. Moreover, LC-MS untargeted metabolomics revealed that PLP-3 significantly improves the intestinal metabolic profile after cerebral ischemia injury, upregulating the amino acid biosynthesis pathway and enriching amino acids such as glutamine and arginine, as well as neuroprotective flavonoids such as fisetin and liquiritigenin. These results suggested that PLP-3 could protect mice from cerebral ischemia-reperfusion injury by regulating gut microbiota and repairing gut barrier, inhibiting brain LPS/TLR4/MyD88 inflammatory pathway, therefore we provide a theoretical basis for PLP-3 as a functional food to prevent ischemic brain injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

COVID-19 reopening of China in the context of the highly transmissible Omicron variant has resulted in an unprecedented wave of infections, placing significant strain on healthcare systems and giving rise to a range of psychological responses, including perceptions of the pandemic's threat, emotional reactions, and prosocial intentions amid moral conflicts over medical resource scarcity and evolving public health responses. This study employed a comprehensive approach integrating surveys, behavioral experiments, and agent-based modeling (ABM) to examine these psychological impacts of COVID-19 reopening. A total of 1,675 participants from 34 Chinese provinces completed the surveys, with 587 also undertaking the reversal-learning task. The measures employed were primarily designed to assess perceptions of COVID-19 infection risk and medical resources, negative affect, and prosocial intentions in moral conflicts. Results found that the perception of infection risk and associated negative affects remained elevated until the pandemic decline. However, prosocial intentions initially increased, but subsequently decreased. Moreover, the influence of perceived public medical resources and negative affect on prosocial intentions is mediated by distinct pathways. ABM suggested that anxiety might accelerate the pandemic but increase overall fatalities through prosocial actions, while public medical resources perceptions might shape the pandemic by influencing healthcare-seeking behaviors. These findings underscore the crucial role of psychological factors in pandemic management, alongside physical aspects, providing a scientific foundation for future responses., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)