Research on the ditching resistance reduction of self-excited vibrations ditching device based on MBD-DEM coupling simulation.

In plant horticulture, furrow fertilizing is a common method to promote plant nutrient absorption and to effectively avoid fertilizer waste. Considering the high resistance caused by soil compaction in southern orchards, an energy-saving ditching device was proposed. A standard ditching blade with self-excited vibration device was designed, and operated in sandy clay with a tillage depth of 30cm. To conduct self-excited vibration ditching experiments, a simulation model of the interaction between soil and the ditching mechanism was established by coupling the ADAMS and EDEM software. To begin with, the ditching device model was first set up, taking into account its motion and morphological characteristics. Then, the MBD-DEM coupling method was employed to investigate the interaction mechanism and the effect of ditching between the soil particles and the ditching blade. Afterwards, the time-domain and frequency-domain characteristics of vibration signals during the ditching process were analyzed using the fast fourier transform (FFT) method, and the energy distribution characteristics were extracted using power spectral density (PSD). The experimental results revealed that the vibrations ditching device has reciprocating displacement in the Dx direction and torsional displacements in the θy and θz directions during operation, verifying the correctness of the coupling simulation and the effectiveness of vibrations ditching resistance reduction. Also, a load vibrations ditching bench test was conducted, and the results demonstrated that the self-excited vibrations ditching device, compared with common ditching device, achieved a reduction in ditching resistance of up to 12.3%. The reasonable parameters of spring stiffness, spring damping, and spring quality in self-excited vibrations ditching device can achieve a satisfied ditching performance with relatively low torque consumption at an appropriate speed.

Liquid crystalline inverted lipid phases encapsulating siRNA enhance lipid nanoparticle mediated transfection.

Efficient cytosolic delivery of RNA molecules remains a formidable barrier for RNA therapeutic strategies. Lipid nanoparticles (LNPs) serve as state-of-the-art carriers that can deliver RNA molecules intracellularly, as exemplified by the recent implementation of several vaccines against SARS-CoV-2. Using a bottom-up rational design approach, we assemble LNPs that contain programmable lipid phases encapsulating small interfering RNA (siRNA). A combination of cryogenic transmission electron microscopy, cryogenic electron tomography and small-angle X-ray scattering reveals that we can form inverse hexagonal structures, which are present in a liquid crystalline nature within the LNP core. Comparison with lamellar LNPs reveals that the presence of inverse hexagonal phases enhances the intracellular silencing efficiency over lamellar structures. We then demonstrate that lamellar LNPs exhibit an in situ transition from a lamellar to inverse hexagonal phase upon interaction with anionic membranes, whereas LNPs containing pre-programmed liquid crystalline hexagonal phases bypass this transition for a more efficient one-step delivery mechanism, explaining the increased silencing effect. This rational design of LNPs with defined lipid structures aids in the understanding of the nano-bio interface and adds substantial value for LNP design, optimization and use.

Granzyme B+ B cells detected by single-cell sequencing are associated with prognosis in patients with intrahepatic cholangiocarcinoma following liver transplantation.

B cells possess anti-tumor functions mediated by granzyme B, in addition to their role in antigen presentation and antibody production. However, the variations in granzyme B+ B cells between tumor and non-tumor tissues have been largely unexplored. Therefore, we integrated 25 samples from the Gene Expression Omnibus database and analyzed the tumor immune microenvironment. The findings uncovered significant inter- and intra-tumoral heterogeneity. Notably, single-cell data showed higher proportions of granzyme B+ B cells in tumor samples compared to control samples, and these levels were positively associated with disease-free survival. The elevated levels of granzyme B+ B cells in tumor samples resulted from tumor cell chemotaxis through the MIF- (CD74 + CXCR4) signaling pathway. Furthermore, the anti-tumor function of granzyme B+ B cells in tumor samples was adversely affected, potentially providing an explanation for tumor progression. These findings regarding granzyme B+ B cells were further validated in an independent clinic cohort of 40 liver transplant recipients with intrahepatic cholangiocarcinoma. Our study unveils an interaction between granzyme B+ B cells and intrahepatic cholangiocarcinoma, opening up potential avenues for the development of novel therapeutic strategies against this disease.

[Spatial Constraints of Rectangular Hydrogel Microgrooves Regulate the Morphology and Arrangement of Human Umbilical Vein Endothelial Cells]. / çŸ©å½¢æ°´å‡èƒ¶å¾®å‡¹æ§½çš„ç©ºé—´çº¦æŸè°ƒæŽ§äººè„é™è„‰å† çš®ç»†èƒžçš„å½¢æ€å’ŒæŽ’åˆ—.

Objective: To construct microscale rectangular hydrogel grooves and to investigate the morphology and alignment of human umbilical vein endothelial cells (HUVECs) under spatial constraints. Vascular endothelial cell morphology and alignment are important factors in vascular development and the maintenance of homeostasis. Methods: A 4-arm polyethylene glycol-acrylate (PEG-acrylate) hydrogel was used to fabricate rectangular microgrooves of the widths of 60 µm, 100 µm, and 140 µm. The sizes and the fibronectin (FN) adhesion of these hydrogel microgrooves were measured. HUVECs were seeded onto the FN-coated microgrooves, while the flat surface without micropatterns was used as the control. After 48 hours of incubation, the morphology and orientation of the cells were examined. The cytoskeleton was labelled with phalloidine and the orientation of the cytoskeleton in the hydrogel microgrooves was observed by laser confocal microscopy. Results: The hydrogel microgrooves constructed exhibited uniform and well-defined morphology, a complete structure, and clear edges, with the width deviation being less than 3.5%. The depth differences between the hydrogel microgrooves of different widths were small and the FN adhesion is uniform, providing a micro-patterned growth interface for cells. In the control group, the cells were arranged haphazardly in random orientations and the cell orientation angle was (46.9±1.8)°. In contrast, the cell orientation angle in the hydrogel microgrooves was significantly reduced (P<0.001). However, the cell orientation angles increased with the increase in hydrogel microgroove width. For the 60 µm, 100 µm, and 140 µm hydrogel microgrooves, the cell orientation angles were (16.4±2.8)°, (24.5±3.2)°, and (30.3±3.5)°, respectively. Compared to that of the control group (35.7%), the number of cells with orientation angles <30° increased significantly in the hydrogel microgrooves of different widths (P<0.001). However, as the width of the hydrogel microgrooves increased, the number of cells with orientation angles <30° gradually decreased (79.9%, 62.3%, 54.7%, respectively), while the number of cells with orientation angles between 60°-90° increased (P<0.001). The cell bodies in the microgrooves were smaller and more rounded in shape. The cells were aligned along the direction of the microgrooves and corresponding changes occurred in the arrangement of the cell cytoskeleton. In the control group, cytoskeletal filaments were aligned in random directions, presenting an orientation angle of (45.5±3.7)°. Cytoskeletal filaments were distributed evenly within various orientation angles. However, in the 60 µm, 100 µm, and 140 µm hydrogel microgrooves, the orientation angles of the cytoskeletal filaments were significantly decreased, measuring (14.4±3.1)°, (24.7±3.5)°, and (31.9±3.3)°, respectively. The number of cytoskeletal filaments with orientation angles <30° significantly increased in hydrogel microgrooves of different widths (P<0.001). However, as the width of the hydrogel microgrooves increased, the number of cytoskeletal filaments with orientation angles <30° gradually decreased, while the number of cytoskeletal filaments with orientation angles between 60°-90° gradually increased (P<0.001). Conclusion: Hydrogel microgrooves can regulate the morphology and orientation of HUVECs and mimic to a certain extent the in vivo microenvironment of vascular endothelial cells, providing an experimental model that bears better resemblance to human physiology for the study of the unique physiological functions of vascular endothelial cells. Nonetheless, the molecular mechanism of spatial constraints on the morphology and the assembly of vascular endothelial cell needs to be further investigated.

Noncovalent Conjugation of OVA323 to ELP Micelles Increases Immune Response.

Subunit vaccines would benefit from a safe particle-based adjuvant. Elastin-like polypeptide (ELP)-based micelles are interesting candidate adjuvants due to their well-defined size and easy modification with protein-based cargo. Coiled coils can facilitate noncovalent modifications, while potentially enhancing antigen delivery through interaction with cell membranes. ELP micelles comprise ELP diblock copolymers that self-assemble above a critical micelle temperature. In this study, an amphiphilic ELP was conjugated to peptide "K", which forms a heterodimeric coiled-coil complex with peptide "E". Self-assembled "covalent" micelles containing ELP-OVA323 (i.e., model antigen OVA323 conjugated to ELP), "coiled-coil" micelles containing ELP-K/E-OVA323 and "hybrid" micelles containing ELP-K and ELP-OVA323 were shown to be monodisperse and spherical. Dendritic cells (DCs) were exposed to all micelle compositions, and T-cell proliferation was investigated. The presence of ELP-K enhanced micelle uptake and subsequent DC maturation, resulting in enhanced CD4+ T-cell proliferation, which makes ELPs with coiled coil-associated antigens a promising vaccine platform.

Organic Semiconductor Based on N, S-Containing Crown Ether Enabling Efficient and Stable Perovskite Solar Cells.

The uncoordinated lead cations are ubiquitous in perovskite films and severely affect the efficiency and stability of perovskite solar cells (PSCs). In this work, 15-crown-5 with various heteroatoms are connected to the organic semiconductor carbazole diphenylamine, and two new compounds, CDT-S and CDT-N, are developed to modify the Pb2+ defects in perovskite films through the anti-solvent method. Apart from the oxygen atoms, there are also N atoms on crown ether ring in CDT-N, and both S and N heteroatoms in CDT-S. The heteroatoms enhance the interaction between the crown ether-based semiconductors and the undercoordinated Pb2+ defect in perovskite. Particularly, the stronger interaction between S atoms and Pb2+ further enhances the defect passivation effect of CDT-S than CDT-N, thereby more effectively suppressing the non-radiative recombination of charge carriers. Finally, the efficiency of the device treated with CDT-S is up to 23.05 %. Moreover, the unencapsulated device based on CDT-S maintained 90.5 % of the initial efficiency after being stored under dark conditions for 1000 hours, demonstrating good long-term stability. Our work demonstrates that crown ethers are promising in perovskite solar cells, and the crown ether containing multiple heteroatoms could effectively improve both efficiency and stability of devices.

Targeting FoxO1 in traditional Chinese medicine for the treatment of diabetes.

Traditional Chinese medicine (TCM) encompasses treatment strategies for diabetes, which is referred to as "Consumptive Thirsty" syndrome. Recently, there has been discovery regarding the mapping between TCM and signaling molecules, which has revealed a remarkable consistency between TCM and modern medicine from a molecular perspective. In this manuscript, we have summarized the etiology and treatment strategies for diabetes in TCM and have examined these strategies in the context of molecular mechanisms. Our review demonstrates that the targeting molecule of TCM for the treatment of diabetes is FoxO1, a transcription factor that plays a pivotal role in regulating gluconeogenesis and glycogenolysis. TCM ranks the development of diabetes into three stages and utilizes different herbal formulas to control FoxO1 accordingly. At Stage 1, TCM inhibits FoxO1 by lowering its expression in the lung. At Stage 2, TCM increases the expression of FoxO1 by suppressing its activity in the stomach. At Stage 3, TCM utilizes the famous herbal formula Liuwei Dihuang Pill to amplify the expression of FoxO1, and to enhance the concentrations of potassium, phosphorus, and Wnt, but to reduce the concentration of calcium. These TCM treatment strategies are in accordance with corresponding mechanisms in modern medicine.

Epidemiological and clinical profile of pediatric hepatitis B virus infections in Wuhan: a retrospective cohort study.

BACKGROUND: Hepatitis B virus (HBV) remains a substantial public health safety concern drawing considerable attention in China and globally. The detection of HBV serological markers can enable the assessment of HBV infection and replication status in vivo and evaluate the body's protection against HBV. Therefore, this study aims to identify the epidemiological and clinical characteristics of HBV infection in children to prevent and control HBV infection in Wuhan areas. METHODS: We conducted an extensive retrospective cohort analysis of 115,029 individuals aged 0-18 years who underwent HBV serological markers detection for HBV infection in hospital between 2018 and 2021 using Electrochemiluminescence immunoassay. We generated descriptive statistics and analysed HBV infection's epidemiological and clinical characteristics between different sex and age groups. RESULTS: The overall positive detection rates of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb in all participants were 0.13%, 79.09%, 0.17%, 2.81%, and 5.82%, respectively. The positive rate of HBeAb and HBcAb in males was significantly lower than that in females (2.64% vs. 3.13%, 5.56% vs. 6.29%) (P < 0.05). Twenty-two distinct HBV serological expression patterns were revealed. Among them, 8 common expression patterns accounted for 99.63%, while the remaining 14 uncommon expression patterns were primarily observed in neonatal patients with HBV infection. There are no significant differences in serological patterns based on sex (P < 0.05). The overall HBV infection detection rate was 5.82% [range 5.68-5.95] and showed a declining yearly trend. The rate in females was higher than that in males 6.29% [6.05, 6.35] vs. 5.56% [5.39, 5.59]. The overall HBV diagnostic rate over 4 years was 0.20% [0.17, 0.22], and the rate declined yearly. The prevalence of acute infection was higher than that of other infection types before 2019, but the incidence of unclassified infection showed a significant upward trend after 2019. CONCLUSIONS: While the overall HBV infection detection rate in children has decreased year by year, the infection rate remains high in children under one year and between 4 and 18 years. This continued prevalence warrants heightened attention and vigilance.

Modulation of muscarinic receptors by anisodine hydrobromide in cerebral ischemia.

Ischemic cerebrovascular diseases pose significant challenges due to their high mortality, disability rates, and recurrence risk, imposing substantial societal and healthcare burdens. Current treatment modalities, including medication and surgical interventions, have limitations. This study explores the therapeutic potential of anisodine hydrobromide, a neuroprotective compound, with a focus on its interaction with muscarinic receptors (M1-M5) in cerebral ischemic diseases, employing a middle cerebral artery occlusion (MCAO) rat model, and microglial HM cells and astrocytes SVG12 as models. Immunohistochemistry comprehensively assessed M1-M5 receptor expression in cerebral arteries, hippocampus, and parenchymal tissues in MCAO rats before and after anisodine hydrobromide administration. Additionally, a hypoxia/reoxygenation (H/R) model validated our findings using SVG12 and HM cells. M receptor mechanisms under hypoxia, including calcium ion influx, reactive oxygen species (ROS) levels, and aspartate expression were explored. Anisodine hydrobromide effectively reduced exacerbated M1, M2, M4, and M5 receptor expression in hypoxia/reoxygenation (H/R)-treated brain tissues and M2 receptors in H/R-treated cells. Concentration-dependent inhibition of calcium ion influx and ROS levels was observed, elucidating its neuroprotective mechanisms. Under H/R conditions, HM cells exhibited decreased aspartate levels by anisodine hydrobromide, Atropine, and M2 inhibitor treatments. These findings shed light on the modulation of muscarinic receptors, particularly the M2 subtype, by anisodine hydrobromide in cerebral ischemia. The neuroprotective effects observed in this study highlight the promising clinical prospects of anisodine hydrobromide as a potential therapeutic agent for ischemic brain diseases, warranting further investigation into its mechanisms of action.

Fusogenic Coiled-Coil Peptides Enhance Lipid Nanoparticle-Mediated mRNA Delivery upon Intramyocardial Administration.

Heart failure is a serious condition that results from the extensive loss of specialized cardiac muscle cells called cardiomyocytes (CMs), typically caused by myocardial infarction (MI). Messenger RNA (mRNA) therapeutics are emerging as a very promising gene medicine for regenerative cardiac therapy. To date, lipid nanoparticles (LNPs) represent the most clinically advanced mRNA delivery platform. Yet, their delivery efficiency has been limited by their endosomal entrapment after endocytosis. Previously, we demonstrated that a pair of complementary coiled-coil peptides (CPE4/CPK4) triggered efficient fusion between liposomes and cells, bypassing endosomal entrapment and resulting in efficient drug delivery. Here, we modified mRNA-LNPs with the fusogenic coiled-coil peptides and demonstrated efficient mRNA delivery to difficult-to-transfect induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs). As proof of in vivo applicability of these fusogenic LNPs, local administration via intramyocardial injection led to significantly enhanced mRNA delivery and concomitant protein expression. This represents the successful application of the fusogenic coiled-coil peptides to improve mRNA-LNPs transfection in the heart and provides the potential for the advanced development of effective regenerative therapies for heart failure.

[Research progress on vascularization of organoids].

Organoids are three-dimensional structures formed by self-organizing growth of cells in vitro, which own many structures and functions similar with those of corresponding in vivo organs. Although the organoid culture technologies are rapidly developed and the original cells are abundant, the organoid cultured by current technologies are rather different with the real organs, which limits their application. The major challenges of organoid cultures are the immature tissue structure and restricted growth, both of which are caused by poor functional vasculature. Therefore, how to develop the vascularization of organoids has become an urgent problem. We presently reviewed the progresses on the original cells of organoids and the current methods to develop organoids vascularization, which provide clues to solve the above-mentioned problems.

Efficient mRNA delivery using lipid nanoparticles modified with fusogenic coiled-coil peptides.

Gene delivery has great potential in modulating protein expression in specific cells to treat diseases. Such therapeutic gene delivery demands sufficient cellular internalization and endosomal escape. Of various nonviral nucleic acid delivery systems, lipid nanoparticles (LNPs) are the most advanced, but still, are very inefficient as the majority are unable to escape from endosomes/lysosomes. Here, we develop a highly efficient gene delivery system using fusogenic coiled-coil peptides. We modified LNPs, carrying EGFP-mRNA, and cells with complementary coiled-coil lipopeptides. Coiled-coil formation between these lipopeptides induced fast nucleic acid uptake and enhanced GFP expression. The cellular uptake of coiled-coil modified LNPs is likely driven by membrane fusion thereby omitting typical endocytosis pathways. This direct cytosolic delivery circumvents the problems commonly observed with the limited endosomal escape of mRNA. Therefore fusogenic coiled-coil peptide modification of existing LNP formulations to enhance nucleic acid delivery efficiency could be beneficial for several gene therapy applications.

CT radiomics model for predicting the Ki-67 proliferation index of pure-solid non-small cell lung cancer: a multicenter study.

Purpose: This study aimed to explore the efficacy of the computed tomography (CT) radiomics model for predicting the Ki-67 proliferation index (PI) of pure-solid non-small cell lung cancer (NSCLC). Materials and methods: This retrospective study included pure-solid NSCLC patients from five centers. The radiomics features were extracted from thin-slice, non-enhanced CT images of the chest. The minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) were used to reduce and select radiomics features. Logistic regression analysis was employed to build predictive models to determine Ki-67-high and Ki-67-low expression levels. Three prediction models were established: the clinical model, the radiomics model, and the nomogram model combining the radiomics signature and clinical features. The prediction efficiency of different models was evaluated using the area under the curve (AUC). Results: A total of 211 NSCLC patients with pure-solid nodules or masses were included in the study (N=117 for the training cohort, N=49 for the internal validation cohort, and N=45 for the external validation cohort). The AUC values for the clinical models in the training, internal validation, and external validation cohorts were 0.73 (95% CI: 0.64-0.82), 0.75 (95% CI:0.62-0.89), and 0.72 (95% CI: 0.57-0.86), respectively. The radiomics models showed good predictive ability in diagnosing Ki-67 expression levels in the training cohort (AUC, 0.81 [95% CI: 0.73-0.89]), internal validation cohort (AUC, 0.81 [95% CI: 0.69-0.93]) and external validation cohort (AUC, 0.78 [95% CI: 0.64-0.91]). Compared to the clinical and radiomics models, the nomogram combining both radiomics signatures and clinical features had relatively better diagnostic performance in all three cohorts, with the AUC of 0.83 (95% CI: 0.76-0.90), 0.83 (95% CI: 0.71-0.94), and 0.81 (95% CI: 0.68-0.93), respectively. Conclusion: The nomogram combining the radiomics signature and clinical features may be a potential non-invasive method for predicting Ki-67 expression levels in patients with pure-solid NSCLC.

[Risk Analysis and Study of Post-marketing Adverse Events for Absorbable Sutures].

Objective To investigate, analyze, and evaluate the risk data associated with the clinical use of absorbable sutures by retrieving and summarizing information from the databases of the US FDA and CNKI, as well as the adverse event reports related to absorbable sutures from January 2019 to October 2022 within Zhejiang province. The adverse event reports are obtained from both incident locations and monitoring organizations affiliated with the registrant. The aim is to identify the main risk factors associated with the clinical use of absorbable sutures. The key risk factors are potential product quality defects, product design and material selection, clinical selection and application, and postoperative recovery care including patient's self-care. Risk control strategies are further proposed to reduce or minimize the risk of adverse events caused by this product.

Research on the local path planning of an orchard mowing robot based on an elliptic repulsion scope boundary constraint potential field method.

In orchard scenes, the complex terrain environment will affect the operational safety of mowing robots. For this reason, this paper proposes an improved local path planning algorithm for an artificial potential field, which introduces the scope of an elliptic repulsion potential field as the boundary potential field. The potential field function adopts an improved variable polynomial and adds a distance factor, which effectively solves the problems of unreachable targets and local minima. In addition, the scope of the repulsion potential field is changed to an ellipse, and a fruit tree boundary potential field is added, which effectively reduces the environmental potential field complexity, enables the robot to avoid obstacles in advance without crossing the fruit tree boundary, and improves the safety of the robot when working independently. The path length planned by the improved algorithm is 6.78% shorter than that of the traditional artificial potential method, The experimental results show that the path planned using the improved algorithm is shorter, smoother and has good obstacle avoidance ability.

In vitro and in vivo evaluation of clinically-approved ionizable cationic lipids shows divergent results between mRNA transfection and vaccine efficacy.

Ionizable cationic lipids (ICLs) play an essential role in the effectiveness of lipid nanoparticles (LNPs) for delivery of mRNA therapeutics and vaccines; therefore, critical evaluations of their biological performance would extend the existing knowledge in the field. In the present study, we examined the effects of the three clinically-approved ICLs, Dlin-MC3-DMA, ALC-0315 and SM-102, as well as DODAP, on the in vitro and in vivo performance of LNPs for mRNA delivery and vaccine efficacy. mRNA-LNPs containing these lipids were successfully prepared, which were all found to be very similar in their physicochemical properties and mRNA encapsulation efficiencies. Furthermore, the results of the in vitro studies indicated that these mRNA-LNPs were efficiently taken up by immortalized and primary immune cells with comparable efficiency; however, SM-102-based LNPs were superior in inducing protein expression and antigen-specific T cell proliferation. In contrast, in vivo studies revealed that LNPs containing ALC-0315 and SM-102 yielded almost identical protein expression levels in zebrafish embryos, which were significantly higher than Dlin-MC3-DMA-based LNPs. Additionally, a mouse immunization study demonstrated that a single-dose subcutaneous administration of the mRNA-LNPs resulted in a high production of intracellular cytokines by antigen-specific T cells, but no significant differences among the three clinically-approved ICLs were observed, suggesting a weak correlation between in vitro and in vivo outcomes. This study provides strong evidence that ICLs modulate the performance of mRNA-LNPs and that in vitro data does not adequately predict their behavior in vivo.

Public Surveillance of Social Media for Suicide Using Advanced Deep Learning Models in Japan: Time Series Study From 2012 to 2022.

BACKGROUND: Social media platforms have been increasingly used to express suicidal thoughts, feelings, and acts, raising public concerns over time. A large body of literature has explored the suicide risks identified by people's expressions on social media. However, there is not enough evidence to conclude that social media provides public surveillance for suicide without aligning suicide risks detected on social media with actual suicidal behaviors. Corroborating this alignment is a crucial foundation for suicide prevention and intervention through social media and for estimating and predicting suicide in countries with no reliable suicide statistics. OBJECTIVE: This study aimed to corroborate whether the suicide risks identified on social media align with actual suicidal behaviors. This aim was achieved by tracking suicide risks detected by 62 million tweets posted in Japan over a 10-year period and assessing the locational and temporal alignment of such suicide risks with actual suicide behaviors recorded in national suicide statistics. METHODS: This study used a human-in-the-loop approach to identify suicide-risk tweets posted in Japan from January 2013 to December 2022. This approach involved keyword-filtered data mining, data scanning by human efforts, and data refinement via an advanced natural language processing model termed Bidirectional Encoder Representations from Transformers. The tweet-identified suicide risks were then compared with actual suicide records in both temporal and spatial dimensions to validate if they were statistically correlated. RESULTS: Twitter-identified suicide risks and actual suicide records were temporally correlated by month in the 10 years from 2013 to 2022 (correlation coefficient=0.533; P<.001); this correlation coefficient is higher at 0.652 when we advanced the Twitter-identified suicide risks 1 month earlier to compare with the actual suicide records. These 2 indicators were also spatially correlated by city with a correlation coefficient of 0.699 (P<.001) for the 10-year period. Among the 267 cities with the top quintile of suicide risks identified from both tweets and actual suicide records, 73.5% (n=196) of cities overlapped. In addition, Twitter-identified suicide risks were at a relatively lower level after midnight compared to a higher level in the afternoon, as well as a higher level on Sundays and Saturdays compared to weekdays. CONCLUSIONS: Social media platforms provide an anonymous space where people express their suicidal thoughts, ideation, and acts. Such expressions can serve as an alternative source to estimating and predicting suicide in countries without reliable suicide statistics. It can also provide real-time tracking of suicide risks, serving as an early warning for suicide. The identification of areas where suicide risks are highly concentrated is crucial for location-based mental health planning, enabling suicide prevention and intervention through social media in a spatially and temporally explicit manner.

Tumour associated endothelial cells: origin, characteristics and role in metastasis and anti-angiogenic resistance.

Tumour progression and metastasis remain the leading causes of cancer-related death worldwide. Tumour angiogenesis is essential for tumour progression. The vasculature surrounding tumours is not only a transport channel for nutrients, oxygen, and metabolites, but also a pathway for metastasis. There is a close interaction between tumour cells and endothelial cells in the tumour microenvironment. Recent studies have shown that tumour-associated endothelial cells have different characteristics from normal vascular endothelial cells, play an important role in tumour progression and metastasis, and are expected to be a key target for cancer therapy. This article reviews the tissue and cellular origin of tumour-associated endothelial cells and analyses the characteristics of tumour-associated endothelial cells. Finally, it summarises the role of tumour-associated endothelial cells in tumour progression and metastasis and the prospects for their use in clinical anti-angiogenic therapy.

The cell origins of foam cell and lipid metabolism regulated by mechanical stress in atherosclerosis.

Atherosclerosis is an inflammatory disease initiated by endothelial activation, in which lipoprotein, cholesterol, extracellular matrix, and various types of immune and non-immune cells are accumulated and formed into plaques on the arterial wall suffering from disturbed flow, characterized by low and oscillating shear stress. Foam cells are a major cellular component in atherosclerotic plaques, which play an indispensable role in the occurrence, development and rupture of atherosclerotic plaques. It was previously believed that foam cells were derived from macrophages or smooth muscle cells, but recent studies have suggested that there are other sources of foam cells. Many studies have found that the distribution of atherosclerotic plaques is not random but distributed at the bend and bifurcation of the arterial tree. The development and rupture of atherosclerotic plaque are affected by mechanical stress. In this review, we reviewed the advances in foam cell formation in atherosclerosis and the regulation of atherosclerotic plaque and lipid metabolism by mechanical forces. These findings provide new clues for investigating the mechanisms of atherosclerotic plaque formation and progression.

A Novel Assay for Investigating the Role of Exosomes in Tumor Cell-Endothelial Cell Crosstalk.

Exosomes have critical role in regulating the tumor development and progression and resistance following antiangiogenesis therapies (AATs). Exosomes could be released by both tumor cells and surrounding endothelial cells (ECs). Here, we describe the methods to explore the cargo transfer between tumor cells and ECs by a novel four-compartment co-culture methods and to investigate the effect of tumor cells on angiogenic ability of ECs by Transwell co-culture methods.