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Objectives The type of electronic nicotine delivery system (ENDS) used by different age groups may be associated with ENDS and cigarette use behaviours. This study sought to identify differences in the use of ENDS device type based on age and cigarette use status to inform policy about regulating ENDS.Design This was a cross-sectional study.Setting Data was derived from a national survey conducted in 2021 in the USA.Participants Participants include 2369 US youth and adults (13 years or older) who reported past 30-day ENDS use.Outcome measures Past 30-day fairly regular use (i.e., several times a week or more) of ENDS device types, namely cigalikes, disposables, refillable tank/box mods, closed pods, refillable pods and drippers. Cigarette smoking status was also measured.Results We used weighted regression models to determine the association between ENDS device type current regular use and age group and the association between each ENDS type current regular use and smoking status separately for each age group. Youth ENDS users 13–17 years old were more likely to regularly use cigalikes (OR=2.71), disposables (OR=3.44), closed pods (OR=2.57) and drippers (OR=2.86) and 18–29 years old were more likely to regularly use disposables (OR=3.67), closed pods (OR=1.58) and drippers (OR=1.94), compared with 30+ years old ENDS users (all p

With the rapid development of optics and nanotechnology, optical therapy is recognized as a potential strategy to combat bacterial drug resistance. Unfortunately, the limitation of band structure on the therapeutic effect of photocatalytic nano-antimicrobial materials has become a major challenge in the development of optical therapy. Here, Co 9 S 8 and Co 9 S 8 -T200 were prepared by facet engineering design with major exposed facets (311) and (222), respectively. The experimental results demonstrate that the antimicrobial ability of Co 9 S 8 -T200 was significantly higher than that of Co 9 S 8 under the excitation of near-infrared light. Theoretical calculations show that the (222) facets can modulate the d-band center of Co 9 S 8 -T200 closer to the Fermi energy level. This promotes the binding of the intermediate to the active site. The strong adsorption capacity for O 2 and H 2 O and the high efficiency of electron-hole pair separation facilitate the production of reactive oxygen species dominated by singlet oxygen, and the photocatalytic therapy is effectively enhanced. In addition, Co 9 S 8 -T200 has a narrow bandgap to promote photothermal conversion efficiency and light absorption capacity and exhibits excellent photothermal therapy. This work expands new ideas for the development of superior optical antimicrobial agents with synergistic photothermal and photocatalytic therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Efficient magnesium-lithium separation is a critical step in extracting lithium ions from salt lakes brine. Precipitation of Mg 2+ from liquid to solid is the simplest separation method, but a side reaction of Li + adsorption by precipitated floc leads to incomplete Mg/Li separation and lithium loss. In this study, we grafted phosphorus atomic sites onto silica-based nuclei with self-floating separation capability to prepare adsorbents with specific capture ability for Mg 2+ , achieving efficient Mg/Li separation from brine. Surface composition analysis shows that the content of P element is 0.99 %, which contributed 82.20 mg g⁻ 1 of Mg 2+ adsorption capacity of at room temperature. During this process, the content of Na and Ca elements in the material decreased by 1.47 % and 0.85 %, respectively, due to ion exchange and surface coverage. In samples of the same water quality as Smackover brine, the Li content in the Mg 2+ -captured material was only 3.20 % of that in directly precipitated Mg(OH) 2 , due to the adsorption selectivity coefficient of the material for Mg²⁺ to Li⁺ reaching 62.26. The outcomes of this research enlighten the selective capture ability and mechanism of phosphorus atomic sites for Mg 2+ , providing new insights for efficient Mg/Li separation from salt lakes to improve raw brain grade., 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: Promoting coronavirus disease 2019 (COVID-19) vaccination is crucial among older adults, particularly those geriatric. This study aimed to analyze the association between chronic conditions, multimorbidity, and vaccination status in adults aged ≥80 years old to provide recommendations for vaccine-preventable diseases., Methods: A cross-sectional study was conducted in Beijing from April 5, 2023, to May 5, 2023, including participants aged ≥80 years old who did not receive the booster COVID-19 vaccination. Data on vaccination status, COVID-19 infection history, nine underlying conditions, and disease-control status were collected via cluster sampling through door-to-door interviews and telephone surveys using questionnaires. A multiple logistic regression model adjusted for age, sex, location, COVID-19 infection history, and education level were used to analyze the association between underlying conditions and vaccination status., Results: In total, 51,834 participants were included of whom 41,209 (76.6 %) were unvaccinated. Underlying diseases (92.3 %) and multimorbidities (65.7 %) were prevalent among the participants. Hypertension (74.6 %), cardiovascular disease (48.5 %), and diabetes (42.0 %) were the most prevalent conditions. Participants diagnosed with underlying conditions were significantly associated with being unvaccinated (Odds ratio [95 % confidential interval] OR [95 %CI]: 2.21 [2.05-2.37]). Furthermore, the proportion of unvaccinated individuals increased with both the number and severity of underlying conditions., Conclusions: The number and severity of underlying conditions were associated with unvaccinated status. To promote vaccination for geriatrics, standardized vaccination guidelines for individuals with underlying conditions should be developed. Additionally, family doctors play an essential role in vaccination assessment and recommendations during disease diagnosis and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Herein, we present an unprecedented electrochemical approach for aminooxygenation of enamides with azoles under transition-metal- and oxidizing-reagent-free conditions. This method affords 4-azolated oxazolines directly from readily available starting materials in up to 95% yield. Central to our success is the utilization of electrical energy as the primary driving force and NaBr as a mediator. Importantly, the resulting 4-azolated oxazolines exhibit potential utility as ligands (pyrazole-oxazoline ligands) in transition-metal-catalyzed reactions.

Background: The prevalence of adolescent mental health conditions such as depression and anxiety has significantly increased. Despite the potential of machine learning (ML), there is a shortage of models that use real-world data (RWD) to enhance early detection and intervention for these conditions., Objective: This study aimed to identify depression and anxiety in adolescents using ML techniques on RWD and social determinants of health (SDoH)., Methods: We analyzed RWD of adolescents aged 10-17 years, considering various factors such as demographics, prior diagnoses, prescribed medications, medical procedures, and laboratory measurements recorded before the onset of anxiety or depression. Clinical data were linked with SDoH at the block-level. Three separate models were developed to predict anxiety, depression, and both conditions. Our ML model of choice was Extreme Gradient Boosting (XGBoost) and we evaluated its performance using the nested cross-validation technique. To interpret the model predictions, we used the Shapley additive explanation method., Results: Our cohort included 52,054 adolescents, identifying 12,572 with anxiety, 7812 with depression, and 14,019 with either condition. The models achieved area under the curve values of 0.80 for anxiety, 0.81 for depression, and 0.78 for both combined. Excluding SDoH data had a minimal impact on model performance. Shapley additive explanation analysis identified gender, race, educational attainment, and various medical factors as key predictors of anxiety and depression., Conclusions: This study highlights the potential of ML in early identification of depression and anxiety in adolescents using RWD. By leveraging RWD, health care providers may more precisely identify at-risk adolescents and intervene earlier, potentially leading to improved mental health outcomes., (© Mamoun T Mardini, Georges E Khalil, Chen Bai, Aparna Menon DivaKaran, Jessica M Ray. Originally published in JMIR Mental Health (https://mental.jmir.org).)

The elderly face elevated mortality risk due to rising temperature. Previous assessments of temperature-related mortality, however, lack a comprehensive analysis of distinct impacts of temperature change across different timescales and characteristics. Using a longitudinal survey of 27,233 elderly Chinese citizens from 2005 to 2018, we establish connections between rising temperatures, temperature variability, and extreme heat with increased mortality risk, assessed through four annual metrics that combine temperature and humidity. The intensity and prolonged duration of extreme heat are found to have the greatest impact on mortality risk. Furthermore, by identifying heterogeneous impacts based on location, sex, age, obesity, income, and diet, we reveal the pathways through which temperature metrics are likely to influence mortality risk. Our study highlights the compound effects of rising temperatures for elderly populations, and it could be expanded to other countries and regions experiencing similar challenges due to an aging population experiencing warming conditions.

Large enhancement of nonlinear absorption and nonlinear refraction are achieved simultaneously in highly ordered two dimensional (2D) covalent organic framework (COF) films prepared by solidliquid interface one-step method to overcome the weakness of COF powders in solubility. In the intrinsic nonlinear optical response obtained at 532 nm with 5 ns pulse, the nonlinear absorption coefficients (β) of two COF films are -4.87 × 10 -5  and -1.29 × 10 -5  m W -1 , respectively. Simultaneously, the fitted closed-aperture curves also show large nonlinear refractive indexes (n 2 ), -5.62 × 10 -12 m 2  W -1 and -0.76 × 10 -12 m 2  W -1 . The 4f coherent imaging performed at the same condition with a single-shot pulse further verifies the outstanding nonlinear optical response without any damage probably experienced in the Z-scan technique. Moreover, the differences in framework electronic structure and photoexcited states between two COF films are compared to explain the difference in nonlinear optical response. All the results indicate that two COF crystalline films with intrinsic giant nonlinear optical response can be capable of modulating both amplitude and phase of light, providing huge potential in all-optical manipulating and switching at the nanoscale as outstanding nonlinear optical materials., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

With the rapid advancement of soft electronics, particularly the rise of fiber electronics and smart textiles, there is an urgent need to develop high-performance fiber materials with both excellent electrical and mechanical properties. However, existing fiber materials including metal fibers, carbon-based fibers, intrinsically conductive polymer fibers, and composite fibers struggle to simultaneously meet the requirements. Here, we introduce a metalgel fiber with a unique structure. In metalgel fibers, liquid metal forms a continuum, extending throughout the entire volume of nanostructured fucoidan polymer networks, which are immobilized by electrostatic interactions. The distinctive structure imparts the fiber with metallic conductivity (2.8 × 10 6 S·m -1 ), softness (Young's modulus of 1.8 MPa), and stable electromechanical coupling properties (resistance change <5% after 20,000 times pressing, stretching, bending, and twisting cycles). The metalgel fibers were woven into multifunctional smart textiles, highlighting their potential for practical applications.

Miniaturized and wearable electronic products require electromagnetic interference shielding (EMI) materials with sensing functions to cope with complex application situations. Herein, an effective dual-network structure is designed to fabricate two-dimensional transition metal carbides and nitrides/bacterial cellulose-thermoplastic polyurethane (MXene/BC-TPU) foams with intriguing EMI shielding property and piezoelectric sensing ability under both compressive and tensile strains. Anisotropic MXene/BC aerogels, as conductive networks, with impressive conductivity (1912 S m -1 ), ultrahigh EMI shielding effectiveness (SE) of 86 dB, and absolute SE up to 63,608 dB cm 2 g -1 can be built by directional freezing. Interpenetrated neuro-like TPU network is embedded into the MXene/BC aerogels by controllable coagulation to provide elasticity. Inheriting the elastic TPU network, the light weight MXene/BC-TPU foams show superb elasticity and remarkable fatigue resistance suffering both compressive and tensile strains with a wide strain range (-80-80%). Meanwhile, benefiting from the separated conductive MXene/BC network and the elastic TPU network, the MXene/BC-TPU foams display an outstanding EMI SE (76 dB) with an EMI SE retention of 86.8% after 5000 compression-release cycles and an EMI SE retention of 69.7% after 100 stretch-release cycles, respectively. Furthermore, the MXene/BC-TPU foams reveal stable resistance signal output as piezoresistive sensors in a wide strain range of -80-80%. The highly conductive, stretchable, and compressible MXene/BC-TPU foams are suitable as EMI shielding and motion monitoring materials for wearable electronics.

Vat photopolymerization (VP) elastomers show great promise across various fields, yet they face significant challenges in achieving adequate mechanical strength, elasticity, and durability due to incomplete polymerization and weak interfacial bonding between printed layers. In this study, we introduce high-performance poly(urethane-urea) elastomers (PUEs) utilizing a dual cross-linked network (DCN) strategy compatible with VP 3D printing. This innovative approach enhances mechanical properties by incorporating multiple hydrogen-bonded urethane and urea groups. The presence of multiple hydrogen bonds facilitates energy dissipation under external mechanical stress and improves interfacial interlocking, while the covalent cross-linked network provides stability and flexibility during deformation. The resulting elastomer exhibits a tensile strength of 28.30 ± 1.10 MPa, a recovery strain of approximately 300%, and a fracture energy of 22.90 ± 4.20 kJ m -2 . As a proof of concept, we demonstrate the rapid fabrication of 3D-printed stents with intricate architectures, outstanding load-bearing capabilities, and excellent biocompatibility. This strategy not only paves the way for the development of mechanically robust, complex-structured PUEs but also broadens their application scope in engineering and biomedical fields.

Unexpected toxicity has become a significant obstacle to drug candidate development, accounting for 30% of drug discovery failures. Traditional toxicity assessment through animal testing is costly and time-consuming. Big data and artificial intelligence (AI), especially machine learning (ML), are robustly contributing to innovation and progress in toxicology research. However, the optimal AI model for different types of toxicity usually varies, making it essential to conduct comparative analyses of AI methods across toxicity domains. The diverse data sources also pose challenges for researchers focusing on specific toxicity studies. In this review, 10 categories of drug-induced toxicity is examined, summarizing the characteristics and applicable ML models, including both predictive and interpretable algorithms, striking a balance between breadth and depth. Key databases and tools used in toxicity prediction are also highlighted, including toxicology, chemical, multi-omics, and benchmark databases, organized by their focus and function to clarify their roles in drug-induced toxicity prediction. Finally, strategies to turn challenges into opportunities are analyzed and discussed. This review may provide researchers with a valuable reference for understanding and utilizing the available resources to bridge prediction and mechanistic insights, and further advance the application of ML in drugs-induced toxicity prediction., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: The thalamus plays a pivotal role in functional brain networks, yet its contribution to motor function recovery following stroke remains elusive. We aim to explore changes in thalamocortical functional connectivity poststroke and its correlation with motor function., Methods: Thirty-nine subacute ischemic stroke patients and 32 healthy individuals underwent resting-state functional magnetic resonance imaging (MRI). The Fugl-Meyer Assessment (FMA) was employed to evaluate upper and lower extremity motor function before and 1 year after stroke rehabilitation. The ipsilesional thalamus and contralesional thalamus were parceled into functional regions of interest (ROIs) based on connectivity with six cortical ROIs: prefrontal, motor, temporal, posterior parietal, somatosensory, and occipital cortex. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was calculated and compared between groups. Differences identified in the ROI-to-ROI analysis were further investigated through seed-to-voxel whole-brain connectivity analyses to pinpoint thalamic dysconnectivity. Correlations with upper and lower extremity motor function were also analyzed., Results: Significant changes in thalamocortical functional connectivity were observed after stroke in ROI-to-ROI analysis, with bilateral somatosensory-thalamic connectivity decreased and ipsilesional temporal-thalamic and bilateral occipital-thalamic connectivity increased. Seed-to-voxel analysis localized ipsilesional thalamic hypoconnectivity to the ipsilesional rolandic operculum and ipsilesional precentral gyrus. Ipsilesional somatosensory-thalamic connectivity was positively correlated with baseline upper extremity FMA scores and negatively correlated with upper extremity motor function change rate at 1-year postdischarge., Conclusions: This study provides new insights into the role of the thalamus in motor function recovery after stroke, offering preliminary evidence for its potential as a therapeutic target in poststroke rehabilitation., (© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

The biological enhanced activated carbon (BEAC) system, utilizing the bioaugmentation with Acinetobacter harbinensis HITLi7 T , demonstrated remarkable performance in removing ammonia nitrogen (NH 4 + -N) from aquatic environments. However, the mechanism through which HITLi7 T bioaugmentation influenced microbial communities remains incompletely understood. Therefore, a comparative analysis of startup speed and NH 4 + -N removal efficiency was conducted between biological activated carbon (BAC) and BEAC bench-scale systems, with an in-depth examination of microbial dynamics and mechanisms within BEAC. Within 16 days post bioaugmentation, the biomass of BEAC (BEAC&#95;1 and BEAC&#95;2) was 4.75/9.07 times that of BAC, with NH 4 + -N removal efficiencies 29.36%/28.68% higher. 16-135 days, there was no significant difference in biomass among the groups. Specifically, from day 17-90, the NH 4 + -N removal efficiency of BEAC was still 25.80%/25.37% higher than that of BAC. After 90 days, the effluent NH 4 + -N levels from BEAC were more stable. In BEAC, the abundance of HITLi7 T decreased while the abundance of Nitrosomonas increased, exhibiting a characteristic of "species compensation". Subsequently, Candidatus&#95;Nitrotoga and Nitrospira became enriched. After 16 days, the total abundance of Nitrosomonas, Candidatus&#95;Nitrotoga, and Nitrospira in BEAC was 3.21%-5.66% and 3.68%-10.07% higher than that in BAC. The microbial community in BEAC was more influenced by diffusion limitation, especially for Nitrosomonas and Nitrospira. Within the microbial co-occurrence network, while Nitrosomonas and Nitrospira lacked a direct correlation with HITLi7 T , the presence of intermediates might potentially hinder the diffusion of Nitrosomonas and Nitrospira. This study deepened our understanding of how HITLi7 T bioaugmentation affects microbial community structure, dynamics, and co-occurrence patterns., 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.)

Introduction: Traumatic brain injury (TBI) is a prevalent type of disabling and fatal injury in infants/toddlers, which is usually caused by falls or traffic accidents. Considering that it is difficult to collect realistic material properties and validation data of child heads due to ethical reasons, experiments on the piglet heads and the finite element (FE) models are generally used as a substitute for the investigations of child TBI., Methods: In this study, first, a high-quality FE model of a 4-week-old piglet head, including brain (cerebrum, cerebellum, brainstem), skull, soft tissue, cerebrospinal fluid, dura matter, pia matter and mandible, is developed. Then, test for the material properties of the piglet head and that for the global validation data are conducted. For the former, the mechanical properties of the brain, overlying soft tissue and skull of the 4-week-old piglet head are tested, and the constitutive models and corresponding parameters are further defined. For the latter, the quasi-static compression test and dynamic impact test (free-fall drop impact test, drop-hammer impact test) are performed on the piglet head. Finally, the piglet head FE model was validated against tests in terms of the contact force and intracranial pressure (ICP) under eight conditions (one for the compression condition, four for the free-fall impact condition, and three for the drop-hammer impact condition)., Results: The trends of simulated curves are consistent with the experimental results under all conditions. For the contact force, the average error of the peak values between simulations and tests is about 12.9 %, and the average error of time durations is about 6.8 %. For the ICP, the average errors of peak values and time durations between simulations and tests are about 8.9 % and 9.9 %., Conclusions: The results show that the piglet head model has high bio-fidelity, which can be used to predict the head global response and the ICP, and further to assist the investigation of child TBI. The model provides another effective way to evaluate the modeling strategies and material constitute models suitable for child head FE model, and can better to understand the inducement and mechanism of child TBI under different external loading conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Intestinal organoid has emerged as an energetic tool for modeling intestine physiology and relevant diseases in vitro. Here, we reported that development of intestinal organoids could be used to explore the toxicology mechanism for combination effects of low dose nanoplastic (NPs) chronic exposure and acute radiation on intestine injury, the two classical chemical and physical substances., Methods: Integrated acute radiation-induced intestine injury model in vivo and mice intestinal organoids in vitro were conducted in this study., Results: First, through in vivo study, we found low dose NPs exposure could aggravate acute radiation-induced intestine injury including exacerbating damaged intestinal epithelial structure, shortened and fractured intestinal villi. Second, using an intestinal organoid model, we observed that low-dose NPs reduced radiation-induced proliferation and exacerbated inflammatory damage, which promoted inflammatory damage through elevated TGF-β1 expression, increased Smad3 phosphorylation, and diminished Smad7 expression. Furthermore, immunohistochemical and Western blot analyses of intestinal tissues further confirmed that low-dose nanoplastics enhance radiation-induced intestinal damage via activation of the TGF-β1/p-Smad3 signaling pathway., Conclusion: This study demonstrates that low-dose NPs may exacerbate the radiation-induced intestinal damage and inflammation process in vivo and in vitro. Our study highlights, for the first time, the potential for intestine organoids serving as powerful tool for explore the combination effects of two chemical and physical substances in toxicology investigation., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Gemcitabine (GEM) has been extensively applied in treating various solid tumors. Nonetheless, GEM is easily metabolized in vivo by cytidine deaminase (CDA) to inactive 2', 2'-Difluorodeoxyuridine (dFdU) results in a low oral bioavailability, which limit its clinical application. It was found that Cedazuridine (CDZ) could effectively inhibit the deamination of the drug by CDA, and its combination with GEM might affect the oral bioavailability of GEM. To investigate the effect of CDZ on the bioavailability and metabolism of GEM after oral administration, an HPLC-MS/MS method was developed for the simultaneous determination of CDZ, GEM, and its metabolite dFdU in mouse plasma. The separation of CDZ, GEM and dFdU was performed on an acetonitrile and water containing 0.1 % formic acid in isocratic elution on a COSMOSIL® 5C18-PAQ packed column (150 × 4.6 mm, 2.6 µm). The three analytes and the internal standard were determined in a multiple reaction monitoring (MRM) mode under positive ion conditions. The three analytes showed good linearity in the range of 5-10,000 ng/mL, and all quality control samples showed good precision and accuracy. The method was successfully applied to the pharmacokinetic study of GEM with CDZ. The results showed that CDZ significantly improved the oral bioavailability of GEM by reducing the metabolism of CDA to GEM in mice, which will provide a reference for the combined application of GEM and CDZ in clinical therapy., 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.)

Colorectal polyps are one of the most direct causes of colorectal cancer. Polypectomy can effectively block the process of colorectal cancer, but accurate polyp segmentation methods are required as an auxiliary means. However, there are several challenges associated with achieving accurate polyp segmentation, such as the large semantic gap between the encoder and decoder, the incomplete edges, and the potential confusion between folds in uncertain areas and target objects. To address the aforementioned challenges, an advanced polyp segmentation network (C 2 E-Net) is proposed, leveraging a cascaded attention mechanism and context-aware cross-level fusion guided by edge learning. Firstly, a cascade attention (CA) module is proposed to capture local feature details and increase the receptive field by setting different dilation rates in different convolutional layers, and combines the criss-cross attention mechanism for bridging the semantic gap between codecs. Subsequently, an edge learning guidance (ELG) module is designed that employs parallel axial attention operations to capture complementary edge information with sufficient detail to enrich feature details and edge features. Ultimately, to effectively integrate cross-level features and obtain rich global contextual information, a context-aware cross-level fusion (CCF) module is introduced through a multi-scale channel attention mechanism to minimize potential confusion between folds in uncertain areas and target objects. A plethora of experimental results has shown that C 2 E-Net is superior over the state-of-the-art methods, with average Dice coefficients on five polyp datasets of 94.54 %, 92.23 %, 82.24 %, 79.53 % and 89.84 %., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In recent decades, the threats of ticks and tick-borne diseases (TBDs) increased extensively with environmental change, urbanization, and rapidly changing interactions between human and animals. However, large-scale distribution of tick and TBD risks as well as their relationship with environmental change remain inadequately unclear. Here, we first proposed a "tick-pathogen-habitat-human" model to project the global potential distribution of main pathogenic ticks using a total of 70,714 occurrence records. Meanwhile, the effects of ecological factors and socio-economic factors driving the distribution pattern were evaluated. Based on this, the risk distribution of TBDs was projected by large-scale "tick-pathogen-disease" analysis. Furthermore, the distribution shifts of tick suitability were projected under different shared socio-economic pathways in the future. Our findings demonstrate that warm temperate countries (e.g., the United States, China and European countries) in the Northern Hemisphere represent significant high risk regions for ticks and TBDs. Specifically, solar radiation of January emerges as the main decisive factor determining the risk distribution pattern. Future shifts of tick suitability showed decrease trend under low greenhouse gas emission scenarios but increase trend under high scenarios. These suitability shifts were significantly correlated with future temperature- (9 species) and precipitation- (19 species) related factors. Collectively, in this study we first shaped the global risk distribution of main ticks and TBDs as well as tick suitability shifts correlated with future global climate change, which will provide helpful references for disease prevention and administration. The methods proposed here will also shed light on other emerging and recurrent zoonotic diseases (e.g., COVID-19, monkeypox) in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Large language models (LLMs) have the potential to enhance evidence synthesis efficiency and accuracy. This study assessed LLM-only and LLM-assisted methods in data extraction and risk of bias assessment for 107 trials on complementary medicine. Moonshot-v1-128k and Claude-3.5-sonnet achieved high accuracy (≥95%), with LLM-assisted methods performing better (≥97%). LLM-assisted methods significantly reduced processing time (14.7 and 5.9 min vs. 86.9 and 10.4 min for conventional methods). These findings highlight LLMs' potential when integrated with human expertise., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The indigenous species Artemisia lavandulaefolia, widespread in areas co-contaminated with Cd and Hg, has the potential for phytoremediation. However, the mechanisms that underlie these plants' resistance to combined Hg and Cd stress are unelucidated. The influence of the dosage of one metal on another has also not been adequately quantified. We investigated the combined and interactive effects of varying doses of Cd and Hg on this species' growth, heavy metal accumulation, and physiological responses. We found that increased Hg and Cd in the co-contaminants inhibited biomass by 16-59 %. The interaction between these heavy metals on growth was concentration-dependent, with an antagonistic effect (concentration addition index (CAI) and effect addition index (EAI) < 0) at low concentrations and an additive effect at high concentrations. An increase in one metal had a beneficial effect on the aboveground accumulation of the other metal, reaching bioconcentrations of 20.16 and 2.25 for Cd and Hg, respectively. Furthermore, the elevation of Cd in the solution increased the proportion of Hg in the cell walls to 31.5 %; however, increasing the Hg dose did not change the Cd concentration in this substructure. Our results also demonstrate that different physiological responses occurred with increased Hg and Cd in the co-contaminants. The elevation of Hg in the mixture had a greater effect on photosynthetic systems than the increased Cd levels. The antioxidant systems of roots and leaves play important roles in attenuating Hg and Cd stress, respectively. Principal component analysis (PCA) revealed concentration-dependent trade-offs between heavy metal accumulation and plant growth and between the above- and belowground antioxidant activities of Artemisia lavandulaefolia for the first time. With increasing Hg, plants preferred to stimulate belowground antioxidant activity, whereas high concentrations of Cd followed the opposite trend. This study provides a theoretical basis for the phytoremediation of this species under combined heavy metal pollution. It highlights that the concentration-dependent interaction between Hg and Cd on plant toxicity should not be ignored during phytoextraction in co-contaminated environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

The parathyroid hormone type 1 receptor (PTH1R) plays a crucial role in modulating various physiological functions and is considered an effective therapeutic target for osteoporosis. However, a lack of detailed molecular and energetic information about PTH1R limits our comprehensive understanding of its activation process. In this study, we performed computational simulations to explore key events in the activation process, such as conformational changes in PTH1R, Gs protein coupling, and the release of guanosine diphosphate (GDP). Our analysis identified kinetic information, including the rate-determining step, transition state, and energy barriers. Free-energy and structural analyses revealed that GDP could be released from the Gs protein when the binding cavity is partially open. Additionally, we predicted important residues, including potential pathogenic mutations, and verified their significance through site-directed mutations. These findings enhance our understanding of class B GPCR activation mechanisms. Furthermore, the methodology employed in this study can be applied to other biophysical systems.

Five new alkyl zinc complexes supported by different formylfluorenimide ligands were prepared and characterized. Complex 1 was obtained by the reaction of 9-[N(CH 3 ) 2 -Cy-NCH]Fl (Cy = 2-cyclohexyl) (Fl = fluorenyl ) ( L1 ) with diethylzinc (ZnEt 2 ) in tetrahydrofuran. Reacting 9-[2-pyridyl-CH-NCH]Fl ( L2 ) with ZnEt 2 in tetrahydrofuran yielded complex 2. Under analogous conditions, complexes 3 and 4 were obtained through the reaction of 9-[2-pyridyl-CH(CH 3 )-NCH]Fl ( L3 ) and 9-[8-quinoline-CH-NCH]Fl ( L4 ) with ZnEt 2 in tetrahydrofuran, respectively. The above ligands formed a tridentate four-coordinate structure with the introduction of a THF molecule along with the elimination of one ethyl group during its coordination with zinc. Notably, the formylfluorenimide ligand 9-[2-phenoxy-Ph-NCH]Fl (Ph = phenyl) (L5) bearing a phenoxy group exhibited unique reactivity compared to the other ligands and formed a bidentate three-coordinated structure when reacting with ZnEt 2 in THF. All complexes were characterized via 1 C NMR spectroscopy, and elemental analysis, with structural determination confirmed through single-crystal X-ray diffraction. Furthermore, the catalytic properties of these complexes were investigated. All these complexes exhibited excellent catalytic activities for the hydroboration of benzaldehyde, among which complex 5 demonstrated excellent catalytic performance (up to 99% yield) with a versatile substrate scope and high tolerance to functional groups (27 substrates) at a low catalyst loading (0.8 mol%) under mild reaction conditions.13 C NMR spectroscopy, and elemental analysis, with structural determination confirmed through single-crystal X-ray diffraction. Furthermore, the catalytic properties of these complexes were investigated. All these complexes exhibited excellent catalytic activities for the hydroboration of benzaldehyde, among which complex 5 demonstrated excellent catalytic performance (up to 99% yield) with a versatile substrate scope and high tolerance to functional groups (27 substrates) at a low catalyst loading (0.8 mol%) under mild reaction conditions.

Introduction: To analyze and summarize the clinical and pathological features of breast hamartoma to enhance clinicians' awareness of this rare and benign lesion of the breast., Methods: We retrospectively described the clinical data, imaging results, and pathological findings of 56 patients with breast hamartoma who underwent surgical treatment at the First Hospital of Jilin University between January 2005 and December 2020, and summarized the features. Additionally, a literature review was conducted using the PubMed database for clinical reports on breast hamartoma and analyzed them., Results: This study included 56 female patients. Preoperative ultrasound revealed round or elliptical heterogeneous echoes with clear boundaries: hypoechoic in 35 cases (63%), iso-echoic in 8 cases (14%), hyperechoic in 1 case (2%), mixed echo in 9 cases (16%), slightly strong echo in 1 case (2%), and uneven echo of fat in 2 cases (4%). Mammography was performed in 33 cases, revealing clear and dense shadows in 20 cases (61%) and dense shadows on the outer edges in 16 cases (48%). The excised masses were solid, with light yellow and gray cut surfaces. Pathological analysis identified ducts and fibrous tissue, with intra-tumoral fat content ranging from 10 to 90%., Conclusion: Breast hamartoma is prevalent among perimenopausal women and is characterized by ultrasound and radiography; surgical intervention remains the primary treatment with a good prognosis., 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 Su, Bai, Fan, Wu and Qu.)

Increased tree species diversity can promote forest production by reducing intra-specific competition and promoting an efficient unitization of resources. However, questions remain on whether and how mixed stands affect the dynamics of intra-annual xylem formation in trees, especially in subtropical forests. In this study, we randomly selected 18 trees from a monoculture of 63-year-old Masson pine ( Pinus massoniana ) growing in pure stands and mixed them with 39-year-old Castanopsis hystrix in Pinxiang, southern China. A total of 828 microcores were collected biweekly throughout the growing season from 2022 to 2023 to monitor the intra-annual xylem formation. Cell production started in early March and ended in late December and lasted about 281 to 284 days. Xylem phenology was similar between mixed and pure stands. During both seasons, the Masson pine in mixed stands showed higher xylem production and growth rates than those in pure stands. The Masson pine in mixed stands produced 45-51 cells in 2022 (growth rate of 0.22 cells day -1 ) and 35-41 cells in 2023 (0.17 cells day -1 ). Growth rate, and not growth seasons, determined the superior xylem growth in the mixed stands. Our study shows that after 39 years of management, Masson pine and C. hystrix unevenly aged mixed stands have a significant positive mixing effect on Masson pine xylem cell production, which demonstrates that monitoring intra-annual xylem growth dynamics can be an important tool to evaluate the effect of species composition and reveal the mechanisms to promote tree growth behind the mixing effect.

Background: Pulmonary hypertension (PH) is associated with endothelial dysfunction. However, the cause of endothelial dysfunction and its impact on PH remain incompletely understood. We aimed to investigate whether the hypoxia-inducible FUNDC1 (FUN14 domain-containing 1)-dependent mitophagy pathway underlies PH pathogenesis and progression., Methods: We first analyzed FUNDC1 protein levels in lung samples from patients with PH and animal models. Using rodent PH models induced by HySu (hypoxia+SU5416) or chronic hypoxia, we further investigated PH pathogenesis and development in response to global and cell-type-specific Fundc1 loss/gain-of-function. We also investigated the spontaneous PH in mice with inducible loss of endothelial Fundc1 . In addition, histological, metabolic, and transcriptomic studies were performed to delineate molecular mechanisms. Finally, findings were validated in vivo by compound deficiency of HIF2α (hypoxia-inducible factor 2α; Epas1 ) and pharmacological intervention., Results: FUNDC1 protein levels were reduced in PH lung vessels from clinical subjects and animal models. Global Fundc1 deficiency exacerbated PH, while its overexpression was protective. The effect of FUNDC1 was mediated by endothelial cells rather than smooth muscle cells. Further, inducible loss of endothelial Fundc1 in postnatal mice was sufficient to cause PH spontaneously, whereas augmenting endothelial Fundc1 protected against PH before and after the onset of disease. Mechanistically, Fundc1 deficiency impaired basal mitophagy in endothelial cells, leading to the accumulation of dysfunctional mitochondria, metabolic reprogramming toward aerobic glycolysis, pseudohypoxia, and senescence, likely via a mtROS-HIF2α signaling pathway. Subsequently, Fundc1 -deficient endothelial cells increased IGFBP2 (insulin-like growth factor-binding protein 2) secretion that drove pulmonary arterial remodeling to instigate PH. Finally, proof-of-principle in vivo studies showed significant efficacy on PH amelioration by targeting endothelial mitophagy, pseudohypoxia, senescence, or IGFBP2., Conclusions: Collectively, we show that FUNDC1-mediated basal mitophagy is critical for endothelial homeostasis, and its disruption instigates PH pathogenesis. Given that similar changes in FUNDC1 and IGFBP2 were observed in PH patients, our findings are of significant clinical relevance and provide novel therapeutic strategies for PH., Competing Interests: None.

Background: Intratumoral oncolytic herpes simplex virus 2-GM CSF (OH2) injection has shown safety and antitumor efficacy in patients with solid tumors. Here, we examined the safety and efficacy of OH2 as a single agent or in combination with HX008, an NMPA-approved PD-1 inhibitor, in locally advanced or metastatic sarcoma patients., Methods: This multicenter, phase 1/2 trial enrolled patients with injectable sarcoma lesions, who had failed at least 1 or more lines of standard treatment. Patients were treated with OH2 at three dose levels (10 6 , 10 7 and 10 8 CCID 50 /mL) as single agent or in combination with a fixed dose of HX008. The primary endpoints were safety and tolerability in phase 1 and objective response rate determined by RECIST (V.1.1) criteria and immune-RECIST in phase 2., Results: Between October 20, 2020 and December 30, 2023, 26 patients were enrolled. Seven patients were treated with single-agent OH2 and 19 with HX008 and OH2 combination. No dose-limiting toxicities were observed during the dose escalation. We documented four partial or complete responses in injected lesions, and one partial response in non-injected lesions, which were all from the combination group. Hence, the overall response rate was 0% and 16.7% in the single agent and combination groups, respectively. The duration of response was 3.9-6.5 months. The most frequent treatment-related adverse events (TRAEs) were fever (n=9). Grade 3 or 4 TRAEs were reported in four patients (15.4%). A clear increase in CD8+cell density in the tumor microenvironment was observed in the patients' post-treatment specimens compared with baseline., Conclusions: Intratumoral injection of oncolytic virus OH2 is well tolerable in patients with sarcoma. Further investigation of OH2 with HX008 in select sarcoma subtypes is warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Radiation-induced bone injury (RBI) has a multifaceted mechanism of occurrence, is influenced by various factors, and is difficult to prevent. Clinicopathologic features and manifestations of disease progression were observed in two patients with distinct fractures: one with a left-sided fourth rib fracture after postoperative radiotherapy for lung cancer, and the other with a right-sided intertrochanteric femur fracture following accidental exposure to a 192 Ir radiation source 5 years prior. These two clinical case reports discussed the clinicopathologic features of RBI and disease progression and utilized transcriptome sequencing to explore potential new targets for treating this type of RBI. Both patients exhibited similar incurable osteolytic bone destruction and fatty infiltration in their pathology. It is proposed that XIST, the most significantly upregulated gene identified by transcriptome sequencing analysis, maybe a potential target for understanding these molecular mechanisms., Competing Interests: None., (AJCR Copyright © 2025.)

Direct and consistent monitoring of respiratory patterns is crucial for disease prognostication. Although the wired clinical respiratory monitoring apparatus can operate accurately, the existing defects are evident, such as the indispensability of an external power supply, low mobility, poor comfort, and limited monitoring timeframes. Here, we present a self-powered in-nostril hydrogel sensor for long-term non-irritant anti-interference respiratory monitoring, which is developed from a dual-network binary-solvent thermogalvanic polyvinyl alcohol hydrogel fiber (d = 500 μm, L=30 mm) with Fe 2+ /Fe 3+ ions serving as a redox couple, which can generate a thermoelectrical signal in the nasal cavity based on the temperature difference between the exhaled gas and skin as well as avoid interference from the external environment. Due to strong hydrogen bonding between solvent molecules, the sensor retains over 90 % of its moisture after 14 days, exhibiting great potential in wearable respiratory surveillance. With the assistance of deep learning, the hydrogel fiber-based respiration monitoring strategy can actively recognize seven typical breathing patterns with an accuracy of 97.1 % by extracting the time sequence and dynamic parameters of the thermoelectric signals generated by respiration, providing an alert for high-risk respiratory symptoms. This work demonstrates the significant potential of thermogalvanic gels for next-generation wearable bioelectronics for early screening of respiratory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this Letter, we propose a high-performance optimized detection scheme based on a neural network (NN) in a receiver digital signal processing (DSP) for bandwidth-limited intensity modulation and direct detection (IM/DD) transmission systems. The NN-based optimized detection scheme consists of two components, an NN-based lookup table (NN-LUT) and an NN-based log-maximum a posteriori estimation with a fixed number of surviving state (NN-MAP) decoder. The NN-LUT provides more accurate and sufficient a priori information (PI) to the decoder than the conventional filter-form PI without increasing computational complexity. The NN-MAP decoder can be optimized for detection using the NN-form PI. The proposed scheme is implemented in a 122-Gbps IM/DD optical 4-level pulse amplitude modulation (PAM-4) system with a 3.7-GHz 3-dB bandwidth. The results demonstrate that the proposed NN-MAP scheme can enhance receiver sensitivity by 1.4 dB under the same complexity compared to conventional optimized detection, achieving a 20% forward error correction threshold. To the best of our knowledge, this represents the inaugural instance of NN being employed for optimized detection.

Ophiocordyceps sinensis is widely used to treat various diseases and as a health supplement. The present study comprehensively compared the metabolic differences between wild and cultivated O. sinensis through 2D 1 H- 13 C HSQC-based metabolomics, and assessed their anti-lung cancer activity on A549 cells. To characterize the global metabolic profile, sample preparation was scrutinously optimized, and both polar (1:4 methanol-water) and non-polar (1:4 methanol-chloroform) extracts of O. sinensis were investigated. A total of 47 and 10 metabolites were identified in the polar and non-polar extracts, respectively. Principal Component Analysis (PCA) revealed greater differences between the two types of O. sinensis in the polar extracts than in the non-polar extracts. Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) together with univariate tests captured 23 and 19 differential spectral features (with 22 and 11 of them assigned) between wild and cultivated O. sinensis in the polar and non-polar extracts, respectively. Meanwhile, the anti-lung cancer activities of both polar and non-polar extracts of wild and cultivated O. sinensis were assessed by MTS assay on A549 cells, and the sterols found in non-polar extracts, such as ergosterol, ergosterol peroxide, and 9,11-dehydroergosterol peroxide, and β-sitosterol, are the active ingredients with potential anti-lung cancer properties. In this study, we introduced a comprehensive strategy integrating 2D NMR-based metabolomics with in vitro assays for comparing the chemical composition and assessing the pharmacological activity of wild and cultivated O. sinensis. Our results provided a scientific basis for the potential viability of cultivated O. sinensis as an alternative to the wild counterpart., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The four major Chinese carps are highly popular for their distinctive nutritional benefits. However, the differences in flavor among these carps remain unclear. This study investigated the flavor profiles of these carps using headspace solid-phase micro-extraction gas chromatography-mass spectrometry (HS-SPME-GC/MS) combined with ultra-fasted gas chromatography electronic nose (GC E-nose). The four major Chinese carps had high protein content (16.68-18.61 %) and low fat levels (0.42-1.29 %). A total of 45 volatile compounds were identified in these carps. Both the GC E-nose and HS-SPME-GC-MS results consistently showed significant flavor profiles differences among these carps, with Ctenopharyngodon Idella (CI) exhibiting the most pronounced distinctions compared to the other three species. Based on VIP >1 and p < 0.05, 10 key compounds including 2-Nonanone, Cyclodecanol, Eugenol, 1,3-Cyclooctadiene, etc., largely contributed to the distinctive overall flavor profile of four major Chinese carps derived mainly from amino acid and fatty acid metabolism., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Diabetic neuropathy (DN), a common and debilitating complication of diabetes, significantly impairs the quality of life of affected individuals. While multiple studies have indicated changes in the expression of specific matrix metalloproteinases (MMPs) in patients with DN, and basic research has reported the impact of MMPs on DN, there is a lack of systematic research and the causal relationship remains unclear. The objective of this research is to investigate the casual relationship between MMPs and DN through two-sample Mendelian randomization (MR)., Methods: Data for this investigation were derived from genome-wide association studies (GWAS) of MMPs and DN. For the analysis using two-sample MR, methods such as inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger were utilized, with IVW serving as the primary measure for determining causative impacts. To evaluate the analysis' heterogeneity and potential pleiotropy, sensitivity examinations including MR-PRESSO analysis, Cochran's Q test, and the leave-one-out test were conducted., Results: IVW analysis revealed that genetically decreased serum MMP-2 level were causally associated with a high risk of DN (OR = 0.88, 95% CI: 0.79-0.99, P = 0.026). Genetically elevated serum MMP-16 level were causally associated with a high risk of DN (OR = 1.15, 95% CI: 1.01-1.32, P = 0.038). Genetic prediction results showed no causal association between other MMPs (MMP14/17/9/12/7/3) and DN. Sensitivity analyses showed no significant heterogeneity or pleiotropy., Conclusion: In summary, this research uncovered a genetic causal relationship between heightened MMP-16 levels and reduced MMP-2 concentrations, and DN risk. These discoveries offer new perspectives on the role of MMPs in DN etiology and establish a foundational premise for further investigations into MMP-targeted therapeutic interventions., 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. The handling editor LX declared a past co-authorship with the author TL., (Copyright © 2025 Bai, Yang, Qi, Yang, Wu, Peng, Wang and Liu.)

The key flavor compound formation pathways resulting from indigenous microorganisms during the spontaneous fermentation of wine have not been thoroughly described. In this study, high-throughput metagenomic sequencing and untargeted metabolomics were utilized to investigate the evolution of microbial and metabolite profiles during spontaneous fermentation in industrial-scale wine production and to elucidate the formation mechanisms of key flavor compounds. Metabolome analysis showed that the total amount of esters, fatty acids, organic acids, aldehydes, terpenes, flavonoids, and non-flavonoids increased gradually during fermentation. Enrichment analysis indicated that metabolic pathways related to the synthesis, decomposition, transformation, and utilization of sugars, amino acids, and fatty acids were involved in the formation of key flavor compounds in wine. Metagenomic analysis revealed that Saccharomyces , Hanseniaspora , Zygosaccharomyces , Wickerhamiella , Lactobacillus , and Fructobacillus were the dominant taxa during spontaneous fermentation. They were significantly positively correlated with organic acids, fatty acids, esters, phenols, aldehydes, terpenes, and phenols. In conclusion, this research provides new insights into the metabolic pathways of key flavor compounds formed by indigenous microorganisms during wine fermentation.

N6-methyladenosine (m6A) modification is a key methylation modification involved in reproductive processes. Myostatin gene editing (MT) in cattle is known to enhance muscle mass and productivity. However, the changes in m6A modification in MT bull sperm remain poorly understood. In the MT and wild-type (WT) groups, we identified 25,542 and 22,253 m6A peaks, respectively, mainly concentrated in the coding sequence (CDS) and 3' untranslated region (UTR) of genes. The MT group showed an increase in gene transcription, but there was no significant difference in the overall m6A peaks pattern. There was also no significant difference in m6A motif and chromosome distribution between MT and WT groups. Most genes had less m6A modification sites. A total of 1120 m6A peaks were significantly different, corresponding to 1053 differentially m6A-methylated genes (DMMGs). These DMMGs are mainly associated with G protein-coupled receptor signaling pathways and the overall composition of the cell membrane. Furthermore, an MCL clustering analysis of 111 differentially m6A-methylated and expressed genes identified seven key genes ( RHOA , DAAM1 , EXOC4 , GNA12 , PRICKLE1 , SCN1A, and STXBP5L ), with the cytoskeleton and migration-related gene, RHOA , being the most important gene located at the center of the gene network. However, the analysis of sperm morphology and motility indicated no significant changes in semen volume, sperm count, sperm viability, plasma membrane integrity, acrosome membrane integrity, or mitochondrial membrane integrity. This study provides a map of m6A methylation in spermatozoa from MT and WT bulls, identifies key differential m6A genes that are affected by the myostatin gene but do not affect sperm morphology and viability in MT bulls, and provides a theoretical basis for the breeding quality of MT bulls.

Sperm cryopreservation is widely used in assisted reproductive technology (ART) and livestock breeding. Although sperm cryopreservation accelerates breeding, the quality of cryopreserved sperm tends to be decreased. Improving the quality of frozen sperm is a hot topic, and spirulina polysaccharide, known for its immunomodulatory and antioxidant properties, is considered a promising natural extract for extensive studies. In this study, a pectic polysaccharide was extracted from spirulina (PSP), and its effects on postthaw bovine sperm viability were evaluated. Phosphoproteomic analysis based on TMT labelling and LC-MS/MS was employed. The results revealed that 10 mg/L PSP had significant protective effects on postthaw sperm viability, plasma membrane integrity, acrosomal integrity, and mitochondrial membrane integrity. Moreover, PSP increased the antioxidant capacity by activating antioxidant enzymes such as SOD, CAT, and GSH-PX and reduced apoptosis, ROS release and MDA levels. In addition, PSP resulted in decreased phosphorylation levels of proteins related to the acrosome, flagellum, metabolism, energy acquisition, and apoptosis. This protective effect of PSP on frozen sperm was achieved by inhibiting the activation of protein kinase A(PKA) protein-related 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. The authors declare no conflict of interest., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

The development of biomass material is an important approach to alleviating the excessive using of plastic packaging, by which the product could be more environmentally friendly and lower toxicity. In this study, we developed a biodegradable photodynamic antibacterial food packaging film using nitrogen-doped carbon quantum dots (N-CQDs) synthesized from crayfish shells, combined with konjac glucomannan (KGM) and sodium alginate (SA). Casting method was used to prepare the composite film and results indicated that incorporation of N-CQDs significantly enhanced the mechanical and barrier properties of the film by reducing the number of micropores. The N-CQDs endowed the film with strong antioxidant activity and UV resistance. The DPPH scavenging rate of the composite film reached 77.92 %, while the transmittance of ultraviolet (300 nm) was reduced to 16.97 %. Furthermore, under blue light irradiation, the film exhibited excellent photodynamic antibacterial effects against Shewanella putrefaciens and Staphylococcus aureus, achieving inhibition rates of 99.2 % and 98.99 %, respectively. The film solution demonstrated no cytotoxicity, and the composite film preserved crayfish meat for up to 8 days at 4 °C. Furthermore, the film almost completely degrading in soil within 14 days. These findings suggest that the KGM/SA/N-CQD film is a promising degradable antimicrobial material for food packaging applications., 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. Published by Elsevier B.V.)

Objective: To explore the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) combined with a PD-1 antibody in improving complete clinical response (cCR) and organ preservation in patients with ultra-low rectal cancer., Methods: This was a prospective phase II, single-arm, open-label trial. Patients with confirmed pMMR status T1-3aN0-1M0 retcal adenocarcinoma were included. Long-course chemoradiotherapy was delivered to a dose of 50 Gy. A PD-1 antibody was added 2 weeks after the first radiotherapy session, and two courses were administered. After chemoradiotherapy, CapeOX plus PD-1 antibody was administered to patients for two cycles. After evaluation, patients with cCR were managed with a watch-and-wait (W&W) approach. Local excision or a W&W approach was performed for patients with near complete clinical response (ncCR) as per multidisciplinary team decision. Radical surgery was recommended for poorly regressed or progressed tumors., Results: Twenty-five patients were enrolled, but two patients withdrew from the study. A total of 23 patients completed the entire neoadjuvant therapy. Ten and five patients achieved cCR and ncCR, respectively, and the rest had a partial clinical response. Patients with cCR were managed with W&W. Four patients with ncCR underwent local excision and were managed using W&W. Eight patients with partial clinical response underwent anus-preserving surgery. At the last follow-up, the rectum and anus preservation rates were 63.4% (14/22) and 95.5% (21/22), respectively., Conclusion: nCRT combined with immunotherapy tended to achieve better cCR and rectum preservation rates with good tolerance in patients., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Identifying inflammation-induced leukocyte subsets and their derived circulating factors has been instrumental in understanding the progession of ALI/ARDS. Nevertheless, how primary inflammation-induced non-leukocyte populations in distal organs contribute to ALI/ARDS remains poorly defined. Here, we report one population of erythroblast-like cells (Ter-cells) deriving from megakaryocyte- erythroid progenitor cells with a unique Ter-119+CD45-CD71+ phenotype in ALI/ARDS. Ter-cells induced by spleen are chemoattracted into lung to inhibit the progression of ALI by secreting neurotrophic factor artemin into the blood and BALF. In vivo blockade of Ter-cell-derived artemin aggravates lung injury, and artemin deficiency abolishes Ter-cells' anti-inflammatory ability. We confirm the presence of circulating artemin in ARDS patients and show that significantly elevated artemin correlates with good prognosis. We propose that Ter-cells and the secreted artemin play important roles in ALI/ARDS with prognostic and therapeutic implications.

Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRAS G12C -mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC). Between 15 September 2022 and 28 September 2023, 119 patients with a median age of 62 years were enrolled. As of the data cut-off date on 28 March 2024, the ORR assessed by IRC was 47.9% (56/117; 95% confidence interval: 38.5-57.3%). The incidence of treatment-related adverse events (TRAEs) of any grade was 97.5% (116/119). The incidence of grades 3 and 4 TRAEs was 38.7% (46/119). A total of 5.0% (6/119) of patients discontinued the treatment due to TRAEs. No treatment-related deaths occurred. Glecirasib exhibited promising clinical efficacy and manageable safety profiles in these patient populations. ClinicalTrials.gov identifier: NCT05009329 ., Competing Interests: Competing interests: Y.W., Y.D., Qiao Li and Z.R. are employees of Jacobio Pharmaceuticals. A.W.-G. is an employee of Jacobio (US) Pharmaceuticals. The remaining authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Myostatin (MSTN) is a protein that plays a crucial role in regulating skeletal muscle development. Despite the known benefits of MSTN mutant cattle for increasing beef production, their potential impact on CH 4 emissions has not been quantified. The study comparing wild-type (WT) cattle to MSTN-knockout (MSTN-KO) cattle revealed that CH 4 production was lower. Macrogenomic analysis revealed a significant decrease in rumen archaea, with reduced Richness indices (P = 0.036). The MSTN-KO cattle also showed altered archaea distribution and composition at different taxonomic levels. LEfSe results showed changes in 21 methanogenic archaea clades, with obligately hydrogen (H 2 )-dependent methylotrophs Candidatus Methanoplasma termitum species belonging to Methanomassiliicoccales order demonstrating the most significant decrease. Rumen metabolites revealed a decrease in the ratio of acetate to propionate, indicating a shift in rumen fermentation pattern towards propionate fermentation. Additionally, the changing trend of methanogenic archaea is consistent with the evolution of methanogens, and this is correlated with the higher levels of linoleic acid in the rumen of MSTN-KO cattle. Linoleic acid affects the utilization of H 2 by methanogenic archaea, leading to a reduction in obligately H 2 -dependent methylotrophs. Our study suggests that MSTN-KO cattle have potential as an economically and ecologically benign breed for reducing methane emissions., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Polyunsaturated fatty acids (PUFAs) such as linoleic acid (18:2, n-6) and α-linolenic acid (18:3, n-3) are essential for the growth, development, and well-being of mammals. However, most mammals, including humans, cannot synthesize n-3 and n-6 PUFAs and these must be obtained through diet. The beneficial effect of converting n-6 polyunsaturated fatty acids (n-6 PUFAs) into n-3 polyunsaturated fatty acids (n-3 PUFAs) has led to extensive research on the flax fatty acid desaturase 3 ( Fad3 ) gene, which encodes fatty acid desaturase. Still, the plant-derived Fad3 gene is used much less in transgenic animals than the Fat-1 gene from Caenorhabditis elegans. To address this problem, we used somatic cell nuclear transfer (SCNT) technology to create codon-optimized Fad3 transgenic cattle. Gas chromatographic analysis showed that the n-3 PUFA content of transgenic cattle increased significantly, and the ratio of n-6 PUFAs to n-3 PUFAs decreased from 3.484 ± 0.46 to about 2.78 ± 0.14 ( p < 0.05). In conclusion, Fad3 gene knock-in cattle are expected to improve the nutritional value of beef and can be used as an animal model to study the therapeutic effects of n-3 PUFAs in various diseases.

Background: Polymyxin B sulfate (PBS) and colistin sulfate (CS) are the last-line treatments for infections caused by multidrug-resistant Gram-negative bacteria, but their efficacy and safety have not been validated. The aims of the current study were to (1) determine their efficacy and safety among critically ill patients and the influencing factors, and (2) determine the relationships of drug exposure with efficacy and safety, to provide evidence for the precision dosing., Method: This retrospective study included 100 critically ill patients treated with PBS and 80 treated with CS. The efficacy outcomes were clinical efficacy and 30-day mortality, while the safety indicator was acute kidney injury (AKI) incidence., Result: There was no significant difference between the two drugs in clinical efficacy, 30-day mortality, or overall AKI incidence, but the incidence of stage 3 AKI was significantly higher in the PBS cohort than the CS cohort. Therapeutic drug monitoring (TDM) and trough concentration (C min ) were significantly associated with clinical efficacy and AKI in both cohorts. Classification and regression tree analysis revealed that C min values of ≥0.91 mg/L for PBS and C min ≥ 0.53 mg/L for CS were associated with higher clinical efficacy., Conclusion: There is basically no significant difference in the efficacy and safety of PBS and CS. TDM can significantly improve the clinical efficacy of both drugs and reduce the incidence of AKI. TDM is therefore recommended to improve the clinical efficacy while reducing the adverse reactions., 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, Wang, Chen, Bai, Sun, Qiu, Teng and Dong.)

Acute and chronic inflammation are important pathologies of benign airway stenosis (BAS) fibrosis, which is a frequent complication of critically ill patients. cGAS-STING signalling has an important role in inflammation and fibrosis, yet the function of STING in BAS remains unclear. Here we demonstrate using scRNA sequencing that cGAS‒STING signalling is involved in BAS, which is accompanied by increased dsDNA, expression and activation of STING. STING inhibition or deficiency effectively alleviates tracheal fibrosis of BAS mice by decreasing both acute and chronic inflammation. Macrophage depletion also effectively ameliorates BAS. Mechanistically, dsDNA from damaged epithelial cells activates the cGAS-STING pathway of macrophages and induces IL-6 to activate STAT3 and promote fibrosis. In summary, the present results suggest that cGAS-STING signalling induces acute inflammation and amplifies the chronic inflammation and tracheal fibrosis associated with benign airway stenosis, highlighting the mechanism and potential drug target of BAS., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: Apricot (Prunus armeniaca L.) fruits are highly perishable and prone to quality deterioration during storage and transportation., Objectives: To investigate the effects of LED white light treatment on postharvest ripening of fruits using metabolomics, transcriptomics, and ATAC-Seq analysis., Methods: Fruits were exposed to 5 μmol m -2 s -1 LED white light for 12 h followed by 12 h of darkness at 20 °C daily for 12 days. The effects of the treatments on the physiological and nutritional quality of the fruits were evaluated. These data were combined with transcriptomic, metabolomic, and ATAC-Seq data from fruits taken on 8 d of treatment to provide insight into the potential mechanism by which LED treatment delays ripening., Results: LED treatment activated pathways involved in ascorbate and aldarate metabolism and flavonoid and phenylpropanoid biosynthesis. Specifically, LED treatment increased the expression of UDP-sugar pyrophosphorylase (USP), L-ascorbate peroxidase (AO), dihydroflavonol 4-reductase (DFR), chalcone synthase (CHS), and caffeoyl-CoA O-methyltransferase (CCOAOMT1), leading to the accumulation of caffeoyl quinic acid, epigallocatechin, and dihydroquercetin and the activation of anthocyanin biosynthesis. LED treatment also affected the expression of genes associated with plant hormone signal transduction, fruit texture and color transformation, and antioxidant activity. The notable genes affected by LED treatment included 1-aminocyclopropane-1-carboxylate synthase (ACS), 1-aminocyclopropane-1-carboxylate oxidase (ACO), hexokinase (HK), lipoxygenase (LOX), malate dehydrogenase (MDH), endoglucanase (CEL), various transcription factors (TCP, MYB, EFR), and peroxidase (POD). ATAC-Seq analysis further revealed that LED treatment primarily regulated phenylpropanoid biosynthesis., Conclusion: The results obtained in this study provide insights into the effects of LED light exposure on apricot fruits ripening. LEDs offer a promising approach for extending the shelf life of other fruits and vegetables., 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.)

Biodosimetry is a key diagnostic tool for radiation exposure, risk assessment and treatment planning of acute radiation sickness. To effectively respond to a large-scale radiological incident, there is a need for the development of biodosimetric methods with fast, portable, and convenient operating advantages. We employed the recombinase polymerase amplification specific high-sensitivity enzymatic reporter unlocking (RPA-SHERLOCK) technology to establish a method for fast radiation dose assessment by measuring the expression level of radiation-inducible genes. Moreover, we proposed for the first time the principle of quantitative detection of curve slopes based on this method. Using this new method, changes in mRNA expression were confirmed in a number of radiation-sensitive genes (XPC, CDKN1A, and ATM) in human lymphocytes after irradiation. The standard curve of the dose-effect relationship was established, which can be used to quickly determine the exposed dose of the irradiated samples. Compared with traditional detection methods such as RT-qPCR, this method was found to be more convenient, fast and easy to operate. With the same amount of template input as RT-qPCR, the detection time of this method can be shortened to less than 20 min. The detection instrument required by this method is also more portable than a qPCR system., (© 2025 by Radiation Research Society. All rights of reproduction in any form reserved.)

With the popularization of intelligence, the necessity of cooperation between intelligent machines makes the research of collaborative multi-agent reinforcement learning (MARL) more extensive. Existing approaches typically address this challenge through task decomposition of the environment or role classification of agents. However, these studies may rely on the sharing of parameters between agents, resulting in the homogeneity of agent behavior, which is not effective for complex tasks. Or training that relies on external rewards is difficult to adapt to scenarios with sparse rewards. Based on the above challenges, in this paper we propose a novel dynamic skill learning (DSL) framework for agents to learn more diverse abilities motivated by internal rewards. Specifically, the DSL has two components: (i) Dynamic skill discovery, which encourages the production of meaningful skills by exploring the environment in an unsupervised manner, using the inner product between a skill vector and a trajectory representation to generate intrinsic rewards. Meanwhile, the Lipschitz constraint of the state representation function is used to ensure the proper trajectory of the learned skills. (ii) Dynamic skill assignment, which utilizes a policy controller to assign skills to each agent based on its different trajectory latent variables. In addition, in order to avoid training instability caused by frequent changes in skill selection, we introduce a regularization term to limit skill switching between adjacent time steps. We thoroughly tested the DSL approach on two challenging benchmarks, StarCraft II and Google Research Football. Experimental results show that compared with strong benchmarks such as QMIX and RODE, DSL effectively improves performance and is more adaptable to difficult collaborative scenarios., 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.)