Tamoxifen upregulates the peroxisomal ß-oxidation enzyme Enoyl CoA hydratase and 3-hydroxyacyl CoA hydratase ameliorating hepatic lipid accumulation in mice.

Tamoxifen is an estrogen receptor modulator that has been reported to alleviate hepatic lipid accumulation in mice, but the mechanism is still unclear. Peroxisome fatty acid ß-oxidation is the main metabolic pathway for the overload of long-chain fatty acids. As long-chain fatty acids are a cause of hepatic lipid accumulation, the activation of peroxisome fatty acid ß-oxidation might be a novel therapeutic strategy for metabolic associated fatty liver disease. In this study, we investigated the mechanism of tamoxifen against hepatic lipid accumulation based on the activation of peroxisome fatty acid ß-oxidation. Tamoxifen reduced liver long-chain fatty acids and relieved hepatic lipid accumulation in high fat diet mice without sex difference. In vitro, tamoxifen protected primary hepatocytes against palmitic acid-induced lipotoxicity. Mechanistically, the RNA-sequence of hepatocytes isolated from the liver revealed that peroxisome fatty acid ß-oxidation was activated by tamoxifen. Protein and mRNA expression of enoyl CoA hydratase and 3-hydroxyacyl CoA hydratase were significantly increased in vivo and in vitro. Small interfering RNA enoyl CoA hydratase and 3-hydroxyacyl CoA hydratase in primary hepatocytes abolished the therapeutic effects of tamoxifen in lipid accumulation. In conclusion, our results indicated that tamoxifen could relieve hepatic lipid accumulation in high fat diet mice based on the activation of enoyl CoA hydratase and 3-hydroxyacyl CoA hydratase-mediated peroxisome fatty acids ß-oxidation.

Food-Borne Biotoxin Neutralization in Vivo by Nanobodies: Current Status and Prospects.

Food-borne biotoxins from microbes, plants, or animals contaminate unclean, spoiled, and rotten foods, posing significant health risks. Neutralizing such toxins is vital for human health, especially after food poisoning. Nanobodies (Nbs), a type of single-domain antibodies derived from the genetic cloning of a variable domain of heavy chain antibodies (VHHs) in camels, offer unique advantages in toxin neutralization. Their small size, high stability, and precise binding enable effective neutralization. The use of Nbs in neutralizing food-borne biotoxins offers numerous benefits, and their genetic malleability allows tailored optimization for diverse toxins. As nanotechnology continues to evolve and improve, Nbs are poised to become increasingly efficient and safer tools for toxin neutralization, playing a pivotal role in safeguarding human health and environmental safety. This review not only highlights the efficacy of these agents in neutralizing toxins but also proposes innovative solutions to address their current challenges. It lays a solid foundation for their further development in this crucial field and propels their commercial application, thereby contributing significantly to advancements in this domain.

A Membrane-Free Rechargeable Seawater Battery Unlocked by Lattice Engineering.

Seawater batteries that directly utilize natural seawater as electrolytes are ideal sustainable aqueous devices with high safety, exceedingly low cost, and environmental friendliness. However, the present seawater batteries are either primary batteries or rechargeable half-seawater/half-nonaqueous batteries because of the lack of suitable anode working in seawater. Here, a unique lattice engineering to unlock the electrochemically inert anatase TiO2 anode to be highly active for the reversible uptake of multiple cations (Na+, Mg2+, and Ca2+) in aqueous electrolytes is demonstrated. Density functional theory calculations further reveal the origin of the unprecedented charge storage behaviors, which can be attributed to the significant reduction of the cations diffusion barrier within the lattice, i.e., from 1.5 to 0.4 eV. As a result, the capacities of anatase TiO2 with 2.4% lattice expansion are ≈100 times higher than the routine one in natural seawater, and ≈200 times higher in aqueous Na+ electrolyte. The finding will significantly advance aqueous seawater energy storage devices closer to practical applications.

Chemical Structures, Biological Activities, and Biosynthetic Analysis of Secondary Metabolites from Agaricus Mushrooms: A Review.

Agaricus mushrooms are an important genus in the Agaricaceae family, belonging to the order Agaricales of the class Basidiomycota. Among them, Agaricus bisporus is a common mushroom for mass consumption, which is not only nutritious but also possesses significant medicinal properties such as anticancer, antibacterial, antioxidant, and immunomodulatory properties. The rare edible mushroom, Agaricus blazei, contains unique agaricol compounds with significant anticancer activity against liver cancer. Agaricus blazei is believed to expel wind and cold, i.e., the pathogenic factors of wind and cold from the body, and is an important formula in traditional Chinese medicine. Despite its nutritional richness and outstanding medicinal value, Agaricus mushrooms have not been systematically compiled and summarized. Therefore, the present review compiles and classifies 70 natural products extracted from Agaricus mushrooms over the past six decades. These compounds exhibit diverse biological and pharmacological activities, with particular emphasis on antitumor and antioxidant properties. While A. blazei and A. bisporus are the primary producers of these compounds, studies on secondary metabolites from other Agaricus species remain limited. Further research is needed to explore and understand the anticancer and nutritional properties of Agaricus mushrooms. This review contributes to the understanding of the structure, bioactivity, and biosynthetic pathways of Agaricus compounds and provides insights for the development of functional foods using these mushrooms.

Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice.

Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.

Infrared laser moxibustion for cancer-related fatigue in breast cancer survivors: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors. METHODS: A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population. RESULTS: Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported. CONCLUSION: While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.

The prognostic value of serum α-klotho in age-related diseases among the US population: A prospective population-based cohort study.

Objective: α-Klotho is a potential biological marker of aging with satisfactory clinical applicability. However, its prognostic significance in age-related diseases has largely been undermined. Therefore, we aimed to report the prognostic value of serum α-klotho levels in age-related diseases. Methods: Participants with available serum α-klotho data from the National Health and Nutrition Examination Survey (2007-2016) were included. Their survival status was collected at 7.62 ± 2.99 years after serum α-klotho data was collected, and the endpoint was all-cause and cardiovascular mortality. A Cox regression model was established to examine the association between serum α-klotho levels and all-cause and cardiovascular mortality. Results: The present study included 13,746 U.S. adults with a survey-weighted mean age of 56.19 ± 10.42 years old. Of these, 52.2 % were female and 72.9 % were non-Hispanic whites. The optimal cutoff value of serum α-klotho for predicting all-cause mortality risk in the general population was 603.5 pg/ml. Individuals with low serum α-klotho (<603.5 pg/ml) had a significantly higher risk of all-cause (adjusted HR: 1.34(1.18-1.52), P < 0.001) and cardiovascular mortality (adjusted HR: 1.63(1.27-2.10), P < 0.001). Subgroup analysis showed that low serum α-klotho level was an independent risk factor for all-cause and cardiovascular mortality in people with hypertension, congestive heart failure, diabetes mellitus, and emphysema, while it was an independent risk factor for all-cause mortality in patients with renal insufficiency. Conclusion: A low serum α-klotho concentration (<603.5 pg/ml) could serve as a marker of all-cause and cardiovascular mortality in the general population and in people with age-related diseases, including hypertension, congestive heart failure, diabetes mellitus, and emphysema.

Towards complex dynamic physics system simulation with graph neural ordinary equations.

The great learning ability of deep learning facilitates us to comprehend the real physical world, making learning to simulate complicated particle systems a promising endeavour both in academia and industry. However, the complex laws of the physical world pose significant challenges to the learning based simulations, such as the varying spatial dependencies between interacting particles and varying temporal dependencies between particle system states in different time stamps, which dominate particles' interacting behavior and the physical systems' evolution patterns. Existing learning based methods fail to fully account for the complexities, making them unable to yield satisfactory simulations. To better comprehend the complex physical laws, we propose a novel model - Graph Networks with Spatial-Temporal neural Ordinary Differential Equations (GNSTODE) - that characterizes the varying spatial and temporal dependencies in particle systems using a united end-to-end framework. Through training with real-world particle-particle interaction observations, GNSTODE can simulate any possible particle systems with high precisions. We empirically evaluate GNSTODE's simulation performance on two real-world particle systems, Gravity and Coulomb, with varying levels of spatial and temporal dependencies. The results show that GNSTODE yields better simulations than state-of-the-art methods, showing that GNSTODE can serve as an effective tool for particle simulation in real-world applications. Our code is made available at https://github.com/Guangsi-Shi/AI-for-physics-GNSTODE.

In vitro simulated digestion and fermentation characteristics of pectic polysaccharides from fresh passion fruit (Passiflora edulis f. flavicarpa L.) peel.

In this study, two pectic polysaccharides (PFP-T and PFP-UM) were extracted from fresh passion fruit peels using three-phase partitioning (TPP) and sequential ultrasound-microwave-assisted TPP methods, respectively, and their effects on the in vitro gastrointestinal digestion and fecal fermentation characteristics were examined. The results indicate that gastrointestinal digestion has a minimal effect on the physicochemical and structural characteristics of PFP-T and PFP-UM. However, during in vitro fecal fermentation, both undigested PFP-T and PFP-UM are significantly degraded and utilized by intestinal microorganisms, showing increased the total relative abundance of Firmicutes and Bacteroidota in the intestinal flora. Notably, compared with PFP-UM, PFP-T better promoted the reproduction of beneficial bacteria such as Prevotella, Megasphaera and Dialister, while suppressed the growth of harmful genera including Escherichia-Shigella, producing higher content of short-chain fatty acids. Therefore, our findings suggest that PFP-T derived from passion fruit peel has potential as a dietary supplement for promoting intestinal health.

A biosensor method based on surfactant-mediated surface droplet evaporation for the detection of Aflatoxin B1.

Aflatoxin B1 (AFB1) is a common mycotoxin that is of significant global concern due to its impact on food safety. Herein, we innovatively develop a sensing platform to detect AFB1 based on evaporation of surfactant solutions on the hydrophobic surface, resulting in dried patterns with varied sizes. The surfactant CTAB solution produces a relatively large dried pattern due to the surface wetting. However, the reduction in the dried pattern size is found when the mixture of CTAB and AFB1 aptamer is tested, because the formation of CTAB/aptamer complex. Moreover, the dried pattern size of the mixture of CTAB, aptamer, and AFB1 increases due to the specific binding of AFB1 to its aptamer. Using this innovative strategy, the AFB1 detection can be fulfilled with a detection limit of 0.77 pg/mL. As a simple, convenient, inexpensive, and label-free method, the surfactant-mediated surface droplet evaporation-based biosensor is very promising for various potential applications.

CT radiomics based on the peritumoral adipose region of gastric adenocarcinoma for preoperative prediction of lymph node metastasis.

PURPOSE: To construct and validate CT radiomics model based on the peritumoral adipose region of gastric adenocarcinoma to preoperatively predict lymph node metastasis (LNM). METHODS AND METHODS: 293 consecutive gastric adenocarcinoma patients receiving radical gastrectomy with lymph node dissection in two medical institutions were stratified into a development set (from Institution A, n = 237), and an external validation set (from Institution B, n = 56). Volume of interest of peritumoral adipose region was segmented on preoperative portal-phase CT images. The least absolute shrinkage and selection operator method and stepwise logistic regression were used to select features and build radiomics models. Manual classification was performed according to routine CT characteristics. A classifier incorporating the radiomics score and CT characteristics was developed for predicting LNM. Area under the receiver operating characteristic curve (AUC) was used to show discrimination between tumors with and without LNM, and the calibration curves and Brier score were used to evaluate the predictive accuracy. Violin plots were used to show the distribution of radiomics score. RESULTS: AUC values of radiomics model to predict LNM were 0.938, 0.905, and 0.872 in the training, internal test, and external validation sets, respectively, higher than that of manual classification (0.674, all P values < 0.01). The radiomics score of the positive LNM group were higher than that of the negative group in all sets (both P-values < 0.001). The classifier showed no improved predictive power compared with the radiomics signature alone with AUC values of 0.916 and 0.872 in the development and external validation sets, respectively. Multivariate analysis showed that radiomics score was an independent predictor. CONCLUSIONS: Radiomics model based on peritumoral adipose region could be a useful approach for preoperative LNM prediction in gastric adenocarcinoma.

Toxic effects of nanoplastics on biological nitrogen removal in constructed wetlands: Evidence from iron utilization and metabolism.

Nanoplastics (NPs) in wastewaters may present a potential threat to biological nitrogen removal in constructed wetlands (CWs). Iron ions are pivotal in microbially mediated nitrogen metabolism, however, explicit evidence demonstrating the impact of NPs on nitrogen removal regulated by iron utilization and metabolism remains unclear. Here, we investigated how NPs disturb intracellular iron homeostasis, consequently interfering with the coupling mechanism between iron utilization and nitrogen metabolism in CWs. Results indicated that microorganisms affected by NPs developed a siderophore-mediated iron acquisition mechanism to compensate for iron loss. This deficiency resulted from NPs internalization limited the activity of the electron transport system and key enzymes involved in nitrogen metabolism. Microbial network analysis further suggested that NPs exposure could potentially trigger destabilization in microbial networks and impair effective microbial communication, and ultimately inhibit nitrogen metabolism. These adverse effects, accompanied by the dominance of Fe3+ over certain electron acceptors engaged in nitrogen metabolism under NPs exposure, were potentially responsible for the observed significant deterioration in nitrogen removal (decreased by 30 %). This study sheds light on the potential impact of NPs on intracellular iron utilization and offers a substantial understanding of the iron-nitrogen coupling mechanisms in CWs.

Assembly and succession of the phyllosphere microbiome and nutrient-cycling genes during plant community development in a glacier foreland.

The phyllosphere, particularly the leaf surface of plants, harbors a diverse range of microbiomes that play a vital role in the functioning of terrestrial ecosystems. However, our understanding of microbial successions and their impact on functional genes during plant community development is limited. In this study, considering core and satellite microbial taxa, we characterized the phyllosphere microbiome and functional genes in various microhabitats (i.e., leaf litter, moss and plant leaves) across the succession of a plant community in a low-altitude glacier foreland. Our findings indicate that phyllosphere microbiomes and associated ecosystem stability increase during the succession of the plant community. The abundance of core taxa increased with plant community succession and was primarily governed by deterministic processes. In contrast, satellite taxa abundance decreased during plant community succession and was mainly governed by stochastic processes. The abundance of microbial functional genes (such as C, N, and P hydrolysis and fixation) in plant leaves generally increased during the plant community succession. However, in leaf litter and moss leaves, only a subset of functional genes (e.g., C fixation and degradation, and P mineralization) showed a tendency to increase with plant community succession. Ultimately, the community of both core and satellite taxa collaboratively influenced the characteristics of phyllosphere nutrient-cycling genes, leading to the diverse profiles and fluctuating abundance of various functional genes during plant community succession. These findings offer valuable insights into the phyllosphere microbiome and plant-microbe interactions during plant community development, advancing our understanding of the succession and functional significance of the phyllosphere microbial community.

Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

Correction of human nonsense mutation via adenine base editing for Duchenne muscular dystrophy treatment in mouse.

Duchenne muscular dystrophy (DMD) is the most prevalent herediatry disease in men, characterized by dystrophin deficiency, progressive muscle wasting, cardiac insufficiency, and premature mortality, with no effective therapeutic options. Here, we investigated whether adenine base editing can correct pathological nonsense point mutations leading to premature stop codons in the dystrophin gene. We identified 27 causative nonsense mutations in our DMD patient cohort. Treatment with adenine base editor (ABE) could restore dystrophin expression by direct A-to-G editing of pathological nonsense mutations in cardiomyocytes generated from DMD patient-derived induced pluripotent stem cells. We also generated two humanized mouse models of DMD expressing mutation-bearing exons 23 or 30 of human dystrophin gene. Intramuscular administration of ABE, driven by ubiquitous or muscle-specific promoters could correct these nonsense mutations in vivo, albeit with higher efficiency in exon 30, restoring dystrophin expression in skeletal fibers of humanized DMD mice. Moreover, a single systemic delivery of ABE with human single guide RNA (sgRNA) could induce body-wide dystrophin expression and improve muscle function in rotarod tests of humanized DMD mice. These findings demonstrate that ABE with human sgRNAs can confer therapeutic alleviation of DMD in mice, providing a basis for development of adenine base editing therapies in monogenic diseases.

Self-Supervised Learning for Time Series Analysis: Taxonomy, Progress, and Prospects.

Self-supervised learning (SSL) has recently achieved impressive performance on various time series tasks. The most prominent advantage of SSL is that it reduces the dependence on labeled data. Based on the pre-training and fine-tuning strategy, even a small amount of labeled data can achieve high performance. Compared with many published self-supervised surveys on computer vision and natural language processing, a comprehensive survey for time series SSL is still missing. To fill this gap, we review current state-of-the-art SSL methods for time series data in this article. To this end, we first comprehensively review existing surveys related to SSL and time series, and then provide a new taxonomy of existing time series SSL methods by summarizing them from three perspectives: generative-based, contrastive-based, and adversarial-based. These methods are further divided into ten subcategories with detailed reviews and discussions about their key intuitions, main frameworks, advantages and disadvantages. To facilitate the experiments and validation of time series SSL methods, we also summarize datasets commonly used in time series forecasting, classification, anomaly detection, and clustering tasks. Finally, we present the future directions of SSL for time series analysis.

Biocompatible Electronic Skins for Cardiovascular Health Monitoring.

Cardiovascular diseases represent a significant threat to the overall well-being of the global population. Continuous monitoring of vital signs related to cardiovascular health is essential for improving daily health management. Currently, there has been remarkable proliferation of technology focused on collecting data related to cardiovascular diseases through daily electronic skin monitoring. However, concerns have arisen regarding potential skin irritation and inflammation due to the necessity for prolonged wear of wearable devices. To ensure comfortable and uninterrupted cardiovascular health monitoring, the concept of biocompatible electronic skin has gained substantial attention. In this review, biocompatible electronic skins for cardiovascular health monitoring are comprehensively summarized and discussed. The recent achievements of biocompatible electronic skin in cardiovascular health monitoring are introduced. Their working principles, fabrication processes, and performances in sensing technologies, materials, and integration systems are highlighted, and comparisons are made with other electronic skins used for cardiovascular monitoring. In addition, the significance of integrating sensing systems and the updating wireless communication for the development of the smart medical field is explored. Finally, the opportunities and challenges for wearable electronic skin are also examined.

Parametric analysis of craniocerebral injury mechanism in pedestrian traffic accidents based on finite element methods.

PURPOSE: The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners. METHODS: Based on the Total Human Model for Safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities was conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized. RESULTS: There is a significant correlation observed between each criterion of skull and brain injury (p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. CONCLUSION: The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.

Evaluation of aconitine cardiotoxicity with a heart-on-a-particle prepared by a microfluidic device.

A heart-on-a-particle model based on multicompartmental microgel is proposed to simulate the heart microenvironment and study the cardiotoxicity of drugs. The relevant microgel was fabricated by a biocompatible microfluidic-based approach, where heart function-related HL-1 and HUVEC cells were arranged in separate compartments. Finally, the mechanism of aconitine-induced heart toxicity was elucidated using mass spectrometry and molecular biotechnology.