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PURPOSE: When performing thoracic aortic endovascular repair (TEVAR) on lesions of the aortic arch, physician-modified fenestration or in situ fenestration is often used to maintain patent branches. We designed a new adjustable prefenestration aortic stent graft that can both isolate pathologies in the aortic arch and obtain patent branches simultaneously. In this study, we use this new type of stent to perform fenestrated TEVAR in a canine’s aorta. This study aims to evaluate the safety and feasibility of the new device, which may provide preliminary data for potential human application. METHODS: Eight Labrador Retriever canines underwent fenestrated TEVAR using the new stent device. Digital subtract angiography (DSA) was performed before and after fenestrated TEVAR to evaluate the safety and feasibility of the procedure. For the device deployment, at the “large curvature” side in the endograft, there is a rectangular prefenestration area (2 × 5 cm) without the polytetrafluoroethylene membrane, and at both longer side edges of the fenestration, there are two slide rails. A moveable membrane that covers the same area as the prefenestration area is initially set at the prefenestration position. A stay line is connected from the distal site of the moveable membrane that controls it to the distal position along the slide rail, which releases the fenestration. After the positioning of the prefenestration is determined, the outer sheath of the delivery system is released, and the stay line at the end of the delivery system is pulled outside the body. The animals were divided into a 1-month group (n = 4) and a 3-month group (n = 4) after the fenestrated TEVAR. Computed tomography (CT) was performed before euthanasia, and video of the DSA during the procedures and CT angiography (CTA) images were then studied. RESULTS: The procedure success rate was 100%, but the total survival rate was only 87.5%. There were no aortic-related deaths during follow-up, and during the operation, there were no stent-graft-related accidents. In addition, no stent-graft migrations were observed in the CTA, and all branch arteries were kept patent by the adjustable fenestration. Finally, histological examination and electron microscope results showed no obvious vascular injury or inflammation. CONCLUSION: Based on the results of this study, we judge the safety and feasibility of the use of the newly designed adjustable prefenestration aortic stent graft in a fenestrated-TEVAR canine model to be acceptable. Our preliminary data may serve as an initial reference for evaluating the potential application of the new stent in humans.

Abstract As the Internet of Vehicles advances, the demand for timely data acquisition by vehicle users continues to escalate, albeit confronted with the challenge of excessive data retrieval latency. The emergence of edge computing provides technical support for the development of vehicular networks by caching data in advance to reduce data acquisition latency. Therefore, how to effectively cache and query data becomes a key issue in addressing the timeliness of data acquisition in vehicular networks. In this paper, we investigate an efficient query optimization model to minimize data acquisition latency. Firstly, based on the distribution of data query frequencies across different servers, we propose an edge collaborative caching strategy using a tabu search algorithm. This strategy prioritizes high-traffic data by finding two optimal storage nodes for each high-traffic data in descending order of data popularity, ensuring a backup within the collaborative domain for each data segment. This not only reduces data transmission latency between nodes during task execution but also prevents single-point failures. Secondly, we deploy cuckoo filters on edge nodes to enable rapid localization of cached data nodes when users query data, thus reducing data processing latency. Finally, simulation results demonstrate that the proposed query optimization model outperforms other schemes in terms of average data query latency.

In this study, three representative pears ('Yali' Pear, 'Huangguan' Pear, and 'Xuehua' Pear) peel/flesh polyphenol extracts were characterized by their antioxidant activity, polyphenol composition, and in vitro cholesterol/cholates binding capacity. 'Yali' Pear polyphenol extracts were selected to further investigate the mechanism of in vitro cholesterol/cholates lowering capacity. Lagergren adsorption kinetic and Freundlich isotherm models confirmed the occurrence of this combination. Turbidity, average particle size, transmission electron microscopy, and zeta potential combined confirmed the existence of some interaction between polyphenols and cholesterol/cholates. Cholesterol/cholates quenched the exogenous fluorescence of polyphenols by static mechanism. The thermodynamic interaction results revealed that the interaction between polyphenols and cholesterol is a spontaneous process, primarily driven by hydrogen bonding and hydrophobic interactions. Overall, this study aimed to investigate the confirmation of the binding removal properties of pear polyphenols on cholesterol/cholates to mitigate the adverse health effects of a high-fat diet.

ObjectivesBalloon dilation followed by balloon-expandable stent implantation is an effective treatment for improving hemodynamic status in patients with coarctation of the aorta (CoA). However, limited evidence exists regarding the safety and efficacy of covered balloon-expandable stents (CBSs) in a large cohort. In this meta-analysis, we aimed to evaluate the overall success rates, hemodynamic and anatomical benefits, complications, and mid-term results of CBSs in treating CoA.MethodsThe PubMed, Embase, and Cochrane Library databases were systemically searched for studies reporting outcomes of CBSs in treating CoA. Single-group rate meta-analyses were performed to calculate estimated pooled procedural success rates, the incidence of complications, and re-coarctation rates. A meta-analysis using standardized mean differences was conducted to compare pre- and postoperative trans-coarctation pressure gradients (PGs), coarctation diameter, and overall changes in systolic blood pressure (SBP). Subgroup analyses were performed to identify potential sources of heterogeneity.ResultsThe final analysis included 12 studies with a total of 411 patients. The estimated pooled procedural success rate was 100% [95% confidence interval (CI): 98%–100%, I2 = 0, P = 0.78]. Significant decreases in trans-coarctation PGs and SBP were observed. The pooled incidences of stent-related, aortic, and access site complications were 2% (95% CI: 0%–5%, I2 = 30.4%, P = 0.15), 2% (95% CI: 0%–4%, I2 = 0%, P = 0.76), and 3% (95% CI: 1%–7%, I2 = 52.9%, P = 0.02), respectively. Subgroup analyses showed that implantation of BeGraft stents was related to a significantly higher incidence of access site complications.ConclusionCovered balloon-expandable stent implantation in treating CoA is safe and effective with high procedural success rates, an acceptable incidence of complications, and a low incidence of re-coarctation.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, PROSPERO (CRD42023430356).

BackgroundMicrobial communities significantly influence the vector capacity of ticks, which, along with tick-borne diseases, pose an increasing global threat. Due to the substantial individual variability caused by various factors, it is essential to assess tick microbial communities and vectorial capacities under different environmental conditions. However, there is a relative scarcity of research on the microbial communities and pathogen transmission of ticks in different physiological states and environmental conditions, especially in Hainan Island, southern China.MethodsFrom 2021 to 2022, we collected 4,167 tick samples, grouping them by blood meal status, developmental stage, sex, time, geographical location, and tick species. We selected 128 samples for full-length 16S rRNA sequencing to describe microbial community characteristics and identify potential biomarkers. Seven hundred seventy-two samples were tested for seven tick-borne pathogens (Rickettsia, Borrelia burgdorferi, Ehrlichia, Anaplasma, Theileria, Babesia, and Hepatozoon), and sera from 208 residents of Hainan Island were tested for IgG antibodies against Rickettsia and B. burgdorferi.ResultsBlood meal status, developmental stage, sex, time, geographical location, and tick species significantly influenced the microbial communities of ticks. We observed distinct microbial community characteristics across different states. We noted the non-random replacement of stable and transient species, with functional differences between parasitic and engorged ticks mainly driven by transient species. Functionally, we observed three distinct response patterns: driven by stable species, transient species, and both together in response to the six factors. We identified 273 potential biomarkers (200 robust core species and 73 robust differential species). Six genera and eight species of pathogens were detected in ticks, with an overall positivity rate of 12.44% (96/772). Among humans, 18.27% (38/208) of serum samples were positive for at least one tick-borne pathogen IgG.ConclusionOur findings indicate that these six factors significantly influence both tick microbial communities and vectorial capacity, with varying effects on vector competence for different pathogens and inconsistent impacts on microbial communities under different conditions. This study supplemented the understanding of tick microbial communities on Hainan Island, assessed the relatively high risk of tick-borne pathogens in the region, and evaluated the impact of these factors on both microbial communities and vectorial capacity.

Abstract Background Human parasitic infections caused by Adenophorean nematodes encompass a range of diseases, including dioctophymiasis, trichuriasis, capillariasis, trichinellosis, and myositis. These infection can result in adverse impacts on human health and cause societal and economic concerns in tropical and subtropical regions. Methods This review conducted searches in PubMed, Embase and Google Scholar for relevant studies that published in established databases up to April 26, 2024. Studies that focused on the common morphology, life cycle, disease distribution, clinical manifestations, and prevention and control strategies for Adenophorean parasitic diseases in humans were included. Results Adenophorean nematodes exhibit shared morphological characteristics with a four-layered cuticle; uninucleate epidermal cells; pseudocoelom with six or more coelomocytes; generally three caudal glands; five esophageal glands; two testes in males with median-ventral supplementary glands in a single row; tail in males rarely possessing caudal alae; amphids always postlabial; presence of cephalic sensory organs; absence of phasmids; and a secretory-excretory system consisting of a single ventral gland cell, usually with a non-cuticularized terminal duct. Humans play two important roles in the life cycle of the nematode class, Adenophorea: 1) as a definitive host infected by ingesting undercooked paratenic hosts, embryonated eggs, infective larvae in fish tissue and meat contaminated with encysted or non-encysted larvae, and 2) as an accidental host infected by ingesting parasitic eggs in undercooked meat. Many organs are targeted by the Adenophorean nematode in humans such as the intestines, lungs, liver, kidneys, lymphatic circulation and blood vessels, resulting in gastrointestinal problems, excessive immunological responses, cell disruption, and even death. Most of these infections have significant incidence rates in the developing countries of Africa, Asia and Latin America; however, some parasitic diseases have restricted dissemination in outbreaks. To prevent these diseases, interventions together with education, sanitation, hygiene and animal control measures have been introduced in order to reduce and control parasite populations. Conclusions The common morphology, life cycle, global epidemiology and pathology of human Adenophorean nematode-borne parasitic diseases were highlighted, as well as their prevention and control. The findings of this review will contribute to improvement of monitoring and predicting human-parasitic infections, understanding the relationship between animals, humans and parasites, and preventing and controlling parasitic diseases. Graphical Abstract

Abstract Background Pedicle screw instrument surgeries can result in the development of aortic pseudoaneurysm, which is a rare yet potentially severe complication; therefore, the purpose of this work is to describe the case of pseudoaneurysm of the thoracic aorta caused by the severe migration of a pedicle screw after surgery. Case presentation We herein report a patient who underwent endovascular repair for the pseudoaneurysm of the descending thoracic aorta following thoracic vertebral fixation surgery. A 28–80 mm covered stent was initially inserted through the right femoral artery, and intraoperative aortography revealed a minor extravasation of contrast material. Subsequently, an additional 28–140 mm covered stent was implanted. The patient recovered well during the 8-year follow-up period. Conclusions Vascular complications resulting from spinal surgery are severe and rare, necessitating early diagnosis and intervention.

Abstract Background Ticks are blood-feeding significant arthropods that can harbour various microorganisms, including pathogens that pose health risks to humans and animals. Tick-symbiont microorganisms are believed to influence tick development, but the intricate interactions between these microbes and the relationships between different tick-borne microorganisms remain largely unexplored. Results Based on 111 tick pool samples presenting questing and engorged statuses including 752 questing tick and 1083 engorged tick from cattle and goats, which were collected in two types of geographic landscape (semi-desert and alpine meadow). We observed significant variations in the composition of tick-borne microorganisms across different environments and blood-engorgement statuses, with a pronounced divergence in symbionts compared to environmental bacteria. Metabolic predictions revealed over 90 differential pathways for tick-borne microorganisms in distinct environments and more than 80 metabolic variations in response to varying blood engorgement statuses. Interestingly, nine pathways were identified, particularly related to chorismate synthesis and carbohydrate metabolism. Moreover, microbial network relationships within tick-borne microorganism groups were highly distinct across different environments and blood-engorgement statuses. The microbial network relationships of symbionts involve some pathogenic and environmental microorganisms. Regression modelling highlighted positive correlations between the Coxiella symbiont and related pathogens, while some environmental bacteria showed strong negative correlations with Coxiella abundance. We also identified commensal bacteria/pathogens in bacterial cooccurrence patterns. Furthermore, we tested pathogenic microorganisms of each tick sample analysis revealed that 86.36% (1601/1855) of the tick samples carried one or more pathogenic microorganisms, The total carrier rate of bacterial pathogens was 43.77% ((812/1855). Most blood samples carried at least one pathogenic microorganism. The pathogens carried by the ticks have both genus and species diversity, and Rickettsia species are the most abundant pathogens among all pathogens. Conclusion Our findings underscore that the bacterial pattern of ticks is dynamic and unstable, which is influenced by the environment factors and tick developmental characteristics.

The peel of pitaya fruit is a promising source of pectin, and non- or low-methylesterified pectin has multiple bioactivities and application scenarios. In this study, non-methylated pectin was prepared from pitaya peel and the structure was characterized. Single factor experiment and response surface methodology were conducted to optimize the procedure of ultrasonic-assisted extraction for pectin. Under the optimal conditions (solid-liquid ratio of 1:40 g·mL−1, extraction temperature at 56 °C, extraction time of 25 min and ultrasonic power of 200 W), the pectin yield was up to 9.93% ± 0.97%. Degree of methylesterification and FTIR analysis confirmed that the extracted pectin was almost non-methylesterified. The pectin possessed less linear homogalacturonan (HG) but more rhamnogalacturonan (RG) regions according to the molar ratios of monosaccharides. Meanwhile, the molecular weight of the pectin was 33.52 kDa and the crystalline index was only 0.60%. Furthermore, the nanoscale structure observed by atomic force microscopy showed that the pectin was rich in highly branched polymers. Generally, pitaya peel pectin extracted by ultrasonic-assisted extraction showed a wide range of potential use as a non-or low- methylesterified pectic substance to reach the efficient utilization of fruit waste.

Abstract Background Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. Methods In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3’ untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P

Triclosan (TCS) is an environmental pollutant. In recent years, there has been increasing level of concern regarding the potential toxicity of TCS in animals and humans, especially its effects on the nervous system. However, whether TCS induces ADHD-like behaviour and the mechanism by which it affects neural function are unclear. The impact of 60 days of continuous exposure to TCS on the behaviour of offspring rats was assessed in this research. According to the results of this study, TCS exposure led to ADHD-like behaviour in offspring rats and activated microglia in the prefrontal cortex (PFC), inducing inflammatory factor release. In vitro studies showed that TCS increased the levels of inflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, in HMC3 cells. More importantly, we found that TCS regulated the STAT3 pathway by upregulating PKM2 via hnRNPA1. In summary, this study suggested that TCS can induce ADHD-like behaviour in offspring rats and continuously activate HMC3 microglia through the hnRNPA1-PKM2-STAT3 feedback loop, promoting inflammatory cytokine secretion.

In recent years, exposure to triclosan (TCS) has been linked to an increase in psychiatric disorders. Nonetheless, the precise mechanisms of this occurrence remain elusive. Therefore, this study developed a long-life TCS-exposed rat model, an SH-SY5Y cell model, and an atomoxetine hydrochloride (ATX) treatment model to explore and validate the neurobehavioral mechanisms of TCS from multiple perspectives. In the long-life TCS-exposed model, pregnant rats received either 0 mg/kg (control) or 50 mg/kg TCS by oral gavage throughout pregnancy, lactation, and weaning of their offspring (up to 8 weeks old). In the ATX treatment model, weanling rats received daily injections of either 0 mg/kg (control) or 3 mg/kg ATX via intraperitoneal injection until they reached 8 weeks old. Unlike the TCS model, ATX exposure only occurred after the pups were weaned. The results indicated that long-life TCS exposure led to attention-deficit hyperactivity disorder (ADHD)-like behaviors in male offspring rats accompanied by dopamine-related mRNA and protein expression imbalances in the prefrontal cortex (PFC). Moreover, in vitro experiments also confirmed these findings. Mechanistically, TCS reduced dopamine (DA) synthesis, release, and transmission, and increased reuptake in PFC, thereby reducing synaptic gap DA levels and causing dopaminergic deficits. Additional experiments revealed that increased DA concentration in PFC by ATX effectively alleviated TCS-induced ADHD-like behavior in male offspring rats. These findings suggest that long-life TCS exposure causes ADHD-like behavior in male offspring rats through dopaminergic deficits. Furthermore, ATX treatment not only reduce symptoms in the rats, but also reveals valuable insights into the neurotoxic mechanisms induced by TCS.

Abstract Elderly hypertensive patients diagnosed with transient ischemic attack (TIA) are at a heightened risk for developing acute ischemic stroke (AIS). This underscores the critical need for effective risk prediction and identification of predictive factors. In our study, we utilized patient data from peripheral blood tests and clinical profiles within hospital information systems. These patients were followed for a three-year period to document incident AIS. Our cohort of 11,056 individuals was randomly divided into training, validation, and testing sets in a 5:2:3 ratio. We developed an XGBoost model, developed using selected indicators, provides an effective and non-invasive method for predicting the risk of AIS in elderly hypertensive patients diagnosed with TIA. Impressively, this model achieved a balanced accuracy of 0.9022, a recall of 0.8688, and a PR-AUC of 0.9315. Notably, our model effectively encapsulates essential data variations involving mixed nonlinear interactions, providing competitive performance against more complex models that incorporate a wider range of variables. Further, we conducted an in-depth analysis of the importance and sensitivity of each selected indicator and their interactions. This research equips clinicians with the necessary tools for more precise identification of high-risk individuals, thereby paving the way for more effective stroke prevention and management strategies.

Abstract Artificial intelligence and blockchain technology have become indispensable in the era of the digital economy, particularly in the field of financial financing. However, when it comes to supply chain finance (SCF), existing models primarily focus on risk identification and credit evaluation, neglecting the critical aspects of trust transfer continuity and reliability within the chain. To address this issue, this paper proposes a blockchain-based transitive trust model for SCF, which ensures seamless trust transfer from core enterprises to bottom suppliers during financing enterprise credit evaluation. The model utilizes multi-layer metrics to calculate the comprehensive trust value of underlying suppliers, serving as the basis for credit delivery. Additionally, the model stores transitive signature receivable warrants on the blockchain and utilizes splittable delivery of warrants to underlying suppliers. The model’s rationality and correctness are verified through experimental analysis, with results demonstrating that the transitive trust model enhances Small and Medium-Sized Enterprises’ (SMEs) trust at the bottom of the supply chain, thus alleviating financing difficulties for SMEs.

Infrared and visible image fusion (IVIF) aims to generate a fused image with both salient target and rich textures from two different complementary modality images. To better integrate valuable edge information into the fused image, we first propose a novel two-stream network based on Auto-Encoder (AE) framework, which extracts deep hierarchical detail information at coarse scale from base stream by multi-level wavelet decomposition progressively and incorporates them into detail stream for information compensation. The aggregation of edge information ranging from coarse to fine facilitates a more comprehensive representation of contours and textures. Then, we propose a new feature fusion strategy, termed as Structural Feature Map Decomposition (SFMD). The first step is to decompose local patches of feature map with each modality into three independent components by Structural Patch Decomposition (SPD). In the second step, appropriate fusion rules are carefully designed for each component and the fused patch can be derived by inverse SPD. Our extensive experiments on several benchmark datasets show that our method outperforms seven compared state-of-the-art methods, especially in human visual perception.

Abstract The aim of this study is to research the expression of the transient receptor potential canonical channel 3 (TRPC3) in a neonatal hyperoxic lung injury model of bronchopulmonary dysplasia (BPD), and to further investigate the role of the TRPC3/nuclear factor‐κB (NF‐κB) signaling pathway in hyperoxia‐induced BPD by a TRPC3 agonist (GSK1702934A). The hyperoxic lung injury model of BPD was established in Sprague–Dawley neonatal rats. Hematoxylin and eosin (HE) staining and radial alveolar count (RAC) values showed that the hyperoxic lung injury model of BPD was successfully established in the neonatal rats, and pulmonary edema was found in the neonatal rats with BPD. The results of reference transcriptome sequencing, Quantitative real‐time PCR (qPCR), and western blot showed lower pulmonary expression of TRPC3 in the BPD group than in the control group. Immunofluorescence showed predominant expression of TRPC3 in airways and pulmonary vessels, and the fluorescence intensity of the BPD group was lower than that of the control group. Lung dry‐to‐wet weight ratio, HE staining, and RAC value showed that the lung histomorphology significantly improved in the BPD + TRPC3 agonist group compared with the BPD group on day 14 but did not revert to the level of the control group. According to qPCR results, compared with the control group, the expression of NF‐κB1 decreased and the expression of NF‐κBiz increased in the BPD group, whereas the expression of NF‐κBiz decreased in the BPD + TRPC3 agonist group. Therefore, we draw the conclusion that TRPC3 may activate NF‐κB by inhibiting NF‐κBiz to promote cell proliferation and lung growth and development.

Abstract Aortic root aneurysm is a potentially life‐threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, this understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete. This knowledge gap has impeded the development of effective targeted therapies. Here, this study performs the first integrative analysis of single‐nucleus multiomic (gene expression and chromatin accessibility) and spatial transcriptomic sequencing data of human aortic root tissue under healthy and MFS conditions. Cell‐type‐specific transcriptomic and cis‐regulatory profiles in the human aortic root are identified. Regulatory and spatial dynamics during phenotypic modulation of vascular smooth muscle cells (VSMCs), the cardinal cell type, are delineated. Moreover, candidate key regulators driving the phenotypic modulation of VSMC, such as FOXN3, TEAD1, BACH2, and BACH1, are identified. In vitro experiments demonstrate that FOXN3 functions as a novel key regulator for maintaining the contractile phenotype of human aortic VSMCs through targeting ACTA2. These findings provide novel insights into the regulatory and spatial dynamics during phenotypic modulation in the aneurysmal aortic root of humans.

Background The aim of this study is to investigate the expression levels of ephrinB2 in patients with lower extremity peripheral arterial disease (PAD) and explore its association with the severity of the disease and the risk of amputation after endovascular revascularization. Methods During the period from March 2021 to March 2023, this study collected blood samples and clinical data from 133 patients diagnosed with lower extremity PAD and 51 healthy volunteer donors. The severity of lower extremity PAD patients was classified using the Rutherford categories. The expression of ephrin-B2 in plasma samples was detected using the Western Blotting. Results Compared to the control group, the levels of serum ephrinB2 in patients were significantly elevated (p < 0.001). Moreover, the plasma EphrinB2 levels were positively correlated with white blood cell counts (r = 0.204, p = 0.018), neutrophil counts (r = 0.174, p = 0.045), and neutrophil-to-lymphocyte ratio (NLR) (r = 0.223, p = 0.009). Furthermore, the AUCs of plasma ephrinB2 level, NLR, and their combination as predictors for amputation events within 30 months after lower extremity PAD endovascular revascularization were 0.659, 0.730 and 0.811. In the high-ephrinB2 group, the incidence of amputation events within 30 months after endovascular revascularization was higher. Conclusions Plasma EphrinB2 levels may be linked to lower extremity PAD development, inflammation, and postoperative amputation. Combining EphrinB2 and NLR can improve amputation prediction accuracy after endovascular revascularization in lower extremity PAD patients.

BackgroundThe relationship between vitamin D levels, depressive symptoms, and cognitive function has yet to be definitively understood in the elderly, particularly when considering the impact of chronic diseases. This study focuses on how depression mediates the impact of 25-hydroxyvitamin D3 (25(OH)D3) on cognitive performance in older U.S. adults.MethodsWe analyzed data from 2,745 elderly individuals extracted from the NHANES 2011–2014 cycles, applying weighted processing to account for the complex multi-stage sampling design characteristic of NHANES data. Utilizing weighted data for covariate and model selection, we conducted mediation analyses on both the overall population and subgroup data. Significant mediation pathways were validated using a stratified weighted bootstrap approach. For significant subgroup pathways, we explored interactive mechanisms through interactive mediation analysis.ResultsMediation analyses, thoroughly accounting for the impact of chronic conditions, revealed significant pathways in both the weighted overall population and the weighted diabetes subgroup. After 1,000 stratified weighted bootstrap replications, the proportion of mediation effects were 10.6% [0.040, 0.268] and 20.9% [0.075, 0.663], respectively. Interactive mediation analysis for diabetes indicated that the interaction between diabetes and depression was not significant in the direct pathway (estimates = 0.050, p = 0.113) but was significant in the mediation pathway, yielding the largest effect size compared to other covariates (estimates = 0.981, p

Depression is the most common psychiatric disorder that burdens modern society heavily. Numerous studies have shown that adverse childhood experiences can increase susceptibility to depression, and depression with adverse childhood experiences has specific clinical-biological features. However, the specific neurobiological mechanisms are not yet precise. Recent studies suggest that the gut microbiota can influence brain function and behavior associated with depression through the “microbe-gut-brain axis” and that the composition and function of the gut microbiota are influenced by early stress. These studies offer a possibility that gut microbiota mediates the relationship between adverse childhood experiences and depression. However, few studies directly link adverse childhood experiences, gut microbiota, and depression. This article reviews recent studies on the relationship among adverse childhood experiences, gut microbiota, and depression, intending to provide insights for new research.

IN738LC alloy has broad application potential in modern aerospace and energy industries due to its excellent high-temperature durability, excellent corrosion and fatigue resistance, however, its application has been greatly limited due to its high crack sensitivity. To address this challenge, this research proposes a method of incorporating TiC nanoparticles to mitigate cracks and enhance the strength of the nickel-based materials. The crack-free TiC-IN738LC materials were successfully fabricated using laser-powder bed fusion. The relationship between the processing parameters and processed quality was studied. The fracture morphology and mechanical properties of samples were analyzed and the strengthening mechanisms of nano-TiC particles were clarified. The results showed that volume energy density (VED) = 111.1J/mm3 is the optimal processing parameter with the laser energy 225W, scanning speed 750 mm/s, and 0.09 mm hatch distance. The effects of processing parameters were discussed in depth. Compared with the virgin IN738LC, the microhardness of TiC-IN738LC is improved by 20 %–40 %, and the tensile strength of TiC-IN738LC is enhanced by 5%–30 %, respectively, which indicates the significant strengthening effect of nano-TiC on IN738LC. The synergistic effect of fine grain strengthening, load-bearing strengthening and Orowan strengthening mechanisms was accounted for the performance enhancement. The research results provide an experimental reference for selecting the processing parameters of TiC-IN738LC.

Abstract Objective Thoracic aortic pseudoaneurysm (TAP) is an uncommon but life-threatening condition. The present study aimed to investigate the early and midterm clinical outcome of TAP patients following TEVAR and identify potential mortality predictors. Methods We retrospectively reviewed a series of 37 eligible patients with TAP admitted to our hospital from July 2010 to July 2020. We explored their baseline, perioperative and follow-up data. Fisher exact test and Kaplan–Meier method were applied for comparing difference between groups. Results There were 29 men and 12 women, with the mean age as 59.5 ± 13.0 years (range 30–82). The mean follow-up period was 30.7 ± 28.3 months (range 1–89). For early outcome (≤ 30 days), mortality happened in 3 (8.1%) zone 3 TAP patients versus 0 in zone 4 (p = 0.028); postoperative acute arterial embolism of lower extremity and type II endoleak respectively occurred in 1(2.7%) case. For midterm outcome, survival at 3 months, 1 year and 5 years was 88.8%, 75.9% and 68.3%, which showed significant difference between zone 2/3 versus zone 4 group (56.3% vs. 72.9%, p = 0.013) and emergent versus elective TEVAR group (0.0% versus 80.1%, p = 0.049). Previous stent grafting or esophageal foreign body with Aortoesophageal fistula (AEF), and systemic vasculitis, as etiologies, resulted in encouraging immediate outcome but worse midterm prognosis. Conclusion TAP lesions at zone 2/3 and emergent TEVAR predict worse midterm outcomes compared to zone 4 lesions and elective TEVAR. The outcomes are also mainly restricted by the etiology of the TAP.

Against the background of smart city construction and the increasing application of big data in the field of planning, a method is proposed to effectively improve the objectivity, scientificity, and global nature of urban park siting, taking Guangzhou and its current urban park layout as an example. The proposed approach entails integrating POI data and innovatively applying machine learning algorithms to construct a decision tree model to make predictions for urban park siting. The results show that (1) the current layout of urban parks in Guangzhou is significantly imbalanced and has blind zones, and with an expansion of the search radius, the distribution becomes more concentrated; high-density areas decrease from the center outward in a circle, which manifests as a pattern of high aggregation at the core and low dispersion at the edge. (2) Urban park areas with a service pressure of level 3 have the largest coverage and should be prioritized for construction as much as possible; there are fewer areas at levels 4 and 5, which are mainly concentrated in the central city, and unreasonable resource allocation is a problem that needs to be solved urgently. (3) There was a preliminary prediction of 6825 sites suitable for planning, and the fit with existing city parks was 93.7%. The prediction results were reasonable, and the method was feasible. After further screening through the coupling and superposition of the service pressure and the layout status quo, 1537 locations for priority planning were finally obtained. (4) Using the ID3 machine learning algorithm to predict urban park sites is conducive to the development of an overall optimal layout, and subjectivity in site selection can be avoided, providing a methodological reference for the planning and construction of other infrastructure or the optimization of layouts.

Immunotherapies have shown significant promise as an impactful strategy in cancer treatment. However, in glioblastoma multiforme (GBM), the most prevalent primary brain tumor in adults, these therapies have demonstrated lower efficacy than initially anticipated. Consequently, there is an urgent need for strategies to enhance the effectiveness of immune treatments. AURKA has been identified as a potential drug target for GBM treatment. An analysis of the GBM cell transcriptome following AURKA inhibition revealed a potential influence on the immune system. Our research revealed that AURKA influenced PD-L1 levels in various GBM model systems in vitro and in vivo. Disrupting AURKA function genetically led to reduced PD-L1 levels and increased MHC-I expression in both established and patient-derived xenograft GBM cultures. This process involved both transcriptional and non-transcriptional pathways, partly implicating GSK3β. Interfering with AURKA also enhanced NK-cell-mediated elimination of GBM by reducing PD-L1 expression, as evidenced in rescue experiments. Furthermore, using a mouse model that mimics GBM with patient-derived cells demonstrated that Alisertib decreased PD-L1 expression in living organisms. Combination therapy involving anti-PD-1 treatment and Alisertib significantly prolonged overall survival compared to vehicle treatment. These findings suggest that targeting AURKA could have therapeutic implications for modulating the immune environment within GBM cells.

Background: Endovascular abdominal aortic aneurysm repair (EVAR) is the most frequently used treatment for aneurysm in abdominal aorta. The endoleak after EVAR causes the aneurysm sac to remain enlarged and risk for rupture. Aims: The purpose of the study was to assess the efficacy of strategies and techniques for endoleak treatment. Methods: This study was a single center retrospective study of 30 patients who had kinds of endoleak. The 30 patients were from a cohort of 597 patients who received EVAR from the Secondary Xiangya Hospital, Central South University between Jan 2014 to Dec 2021, what is follow-up well and diagnosed as endoleak. Data included basic clinical information, aspects of the endoleak treatment techniques, and follow-up findings. Results: The 30 patients with endoleak were diagnosed by computed tomography angiography or digital subtraction angiography. Age is 69 ± 7.9 yrs. 26 patients are male with only 4 female patients. Immediate endoleak after EVAR is 46.7%and delayed endoleak is 53.3%. The classification of endoleak is type Ⅰ:76.6%; type Ⅱ 26.7%; type Ⅲ:6.7%; type Ⅳ:6.7%; type Ⅴ:13.3%. Different treatment of endoleak includes: screening, endovascular re-intervention and open surgery. There are 3 patients (10.0%) underwent emergency EVAR due to their rupture condition of aneurysm. All the endoleak patients’ CTA image characteristics has been reviewed. The follow-up rate is 93.3%. There are 6 patients (21.4%) died during follow-up. No aneurysm sac rupture death has been recorded. Conclusions: Endoleak after EVAR is the most frequent complication that directly affects survival and re-intervention rates. Our findings suggested that different treatment strategies based on the individual patient's situation is important for their endoleak treating result.

Triclosan (TCS) is a widely used synthetic, with broad-spectrum antibacterial properties found in both pharmaceuticals and personal care products. More specifically, it is hepatotoxic in rodents and exhibits differential effects in mice and humans. However, the mechanisms underlying TCS-induced liver toxicity have not been elucidated. This study examined the role of the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB)/ nod-like receptor protein 3 (NLRP3) pathway in TCS-exposed liver toxicity by established a long-life TCS-exposed mice liver injury model. The 24 C57BL/6 pregnant mice exposed to TCS (0, 50 and 100 mg/kg) every day during the gestation and nursing period. After weaning, the male mice were left to continue administrate with TCS until 8 weeks of age. Then, mice in each group were sacrificed for investigation. Long-life exposure to TCS resulted in a reduction of body weight in growth mice. TCS exposure caused the increase of serum ALT, AST and ALP. The situation of inflammatory cell infiltration, macrophage recruitment and collagen fiber deposition in TCS-exposed mice liver tissues were performed by histological analysis including hematoxylin-eosin, Masson, Sirius red, and immunohistochemistry staining. Protein expression levels in TLR4/NF-κB/NLRP3 pathway was measured through Western blot, and the NLRP3 inflammasome activation was measured using real-time quantitative PCR (RT-qPCR). The results showed that exposure to TCS elevated TLR4, myeloid differentiation factor 88 (Myd88), TNF receptor associated factor 6 (TRAF6), enhanced NF-κB activation, and affected NLRP3 inflammasome activation in mice liver. Collectively, these findings indicate that long-life exposure to TCS-induced mice by upregulating the TLR4-Myd88-TRAF6 pathway, activating the NF-κB signaling cascade, initiating the NLRP3 inflammasome pathway, and ultimately leading to liver injury, including inflammation, hepatocyte pyroptosis and hepatofibrosis. Henceforth, the TLR4/NF-κB/NLRP3 pathway may now provide a theoretical basis and valuable therapeutic targets for overcoming TCS-induced liver toxicity.

The investigation of peptide drugs has become essential in the development of innovative medications for hypertension. In this study, a sensitive high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to determine the plasma concentration and stability of the antihypertensive peptide FR-6 in rats. An isotopically labeled peptide (with an unchanged sequence) was utilized as an internal standard (IS) for validation purposes. Subsequently, this assay was employed to examine the pharmacokinetics of different administration methods (tail vein and gavage) in Sprague Dawley (SD) rats. Extracted plasma samples underwent sample preparation through methanol protein precipitation, followed by elution of FR-6 on Wondasil C18 Superb column (4.6 × 150 mm, 5 μm), using a mobile phase consisting of formic acid (0.1%) in water (A) and formic acid (0.125%)-ammonium formate (2 mM) in methanol (B). Ion pairs corresponding to FR-6 and IS were monitored via multiple reaction monitoring (MRM) under positive ion mode: m/z 400.7 → 285.1 for FR-6 and m/z 406.1 → 295.1 for IS detection respectively. The method exhibited excellent linearity with respect to FR-6 concentrations. In addition, the inter-day and intra-day precision were 0.61–6.85% and 1.76–11.75%; the inter-day and intra-day accuracy were −7.28–0.13% and −7.20–2.28%, respectively. In conclusion, the matrix effect, extraction recovery, and stability data were validated according to FDA recommended acceptance criteria for bioanalytical methods. This validated method serves as a reliable tool for determining the concentration of antihypertensive peptide FR-6, and has been successfully applied in pharmacokinetic studies involving rats.

Thrombin plays a pivotal role in blood coagulation, wound healing, and tumor metastasis. In this study, we developed a fluorescent probe (Apt15@QDs) by functionalizing quantum dots (QDs) with an aptamer 15 to specifically recognize thrombin. The aptamer Apt15 binds specifically to thrombin by adopting a G-quadruplex conformation, resulting in the formation of a binary complex that quenches the fluorescence of the probe. Analysis using the classical fluorescence quenching equations Stem-Volmer and Lineweaver-Burk revealed that the mechanism of quenching is static in nature. The established method was successfully applied for detecting thrombin in human serum samples. As shown from the results, the established method exhibited high sensitivity, with a limit of detection (LOD) of 8 nM, and possessed a wide linear range within the concentration span of 20 to 200 nM. Additionally, this method circumvented the need for intricate experimental procedures. Furthermore, it offered a short analysis time, obviated the requirement for additional reagents, and proved suitable for high-throughput analysis of biological samples. This study presents a sensitive, straightforward, and rapid approach for detecting thrombin in complex biological matrices.

ObjectiveWe introduce the comprehensive inflammatory prognostic index (CIPI), a novel prognostic tool for critically ill cerebral infarction patients, designed to meet the urgent need for timely and convenient clinical decision-making in this high-risk patient group.MethodsUsing exploratory factor analysis on selected indices—neutrophil to lymphocyte ratio (NLR), systemic inflammation response index (SIRI), and systemic immune inflammation index (SIII)—we derived CIPI, a latent variable capturing their combined predictive power. Data from 1,022 patients in the Medical Information Mart for Intensive Care (MIMIC)-IV database were used to develop CIPI-based survival models, with the robustness and area under the receiver operating characteristic curve (AUC) performance of CIPI validated against an independent dataset of 326 patients from the MIMIC-III CareVue subset. The CIPI’s predictive power for in-hospital and intensive care unit (ICU) mortality was assessed through Kaplan–Meier analysis, univariate and multivariate Cox regression models, and time-dependent AUC analysis. Linearity, subgroup sensitivity analyses and interaction effects with CIPI were also evaluated.ResultsCIPI was an independent prognostic factor, demonstrating a statistically significant association with in-hospital and ICU mortality, when assessed as a continuous and a categorical variable. It showed a linear relationship with mortality rates and demonstrated stability across most subgroups, with no significant interactions observed. Its predictive capabilities for in-hospital and ICU mortality among critically ill cerebral infarction patients matched those of established prognostic indices in the MIMIC database.ConclusionOur study indicates that CIPI is a reliable and effective prognostic tool for critically ill cerebral infarction patients in predicting in-hospital and ICU mortality. Its straightforward calculation, rooted in routine blood tests, enhances its practicality, promising significant utility in clinical settings.

Organic acids play critical roles in fruit physiological metabolism and sensory quality. However, the conventional storage of apple fruit at 0 ± 0.1 °C cannot maintain fruit acidity efficiently. This study investigated near-freezing temperature (NFT) storage for ‘Golden Delicious’ apples, and the quality parameters, organic acid content, and malate metabolism were studied. The results indicate that NFT storage at −1.7 ± 0.1 °C effectively maintained the postharvest quality of apple fruit when compared to traditional storage at 0 ± 0.1 °C. Fruit that underwent NFT storage showed a better appearance and lower respiratory rate, ethylene production, weight loss, and malondialdehyde (MDA) content but higher firmness and soluble solids content. Further, fruit after NFT storage contained higher titratable acid (18.75%), malate (51.61%), citrate (36.59%), and succinate (2.12%) content when compared to the control after 250 days. This was achieved by maintaining higher cytosolic NAD-dependent malate dehydrogenase (cyNAD-MDH), phosphoenolpyruvate carboxylase (PEPC), vacuolar H+-ATPase (V-ATPase), and vacuolar inorganic pyrophosphatase (V-PPase) activities that promote malate biosynthesis and accumulation while inhibiting enzyme activity that is responsible for malate decomposition, including phosphoenolpyruvate carboxylase kinase (PEPCK) as well as the cytosolic NAD phosphate-dependent malic enzyme (cyNADP-ME). Further, storage at NFTs maintained a higher expression of malate biosynthesis-related genes (MdcyNAD-MDH and MdPEPC) and transport-related genes (MdVHA and MdVHP) while suppressing malate consumption-related genes (MdcyME and MdPEPCK). The results demonstrate that NFT storage could be an effective application for apple fruit, which maintains postharvest quality and alleviates organic acid degradation.

Objective: To explore the potential imaging biomarkers for predicting Traditional Chinese medicine (TCM) deficiency and excess syndrome in prostate cancer (PCa) patients by radiomics approach based on MR imaging. Methods: A total of 121 PCa patients from 2 centers were divided into 1 training cohort with 84 PCa patients and 1 validation cohort with 37 PCa patients. The PCa patients were divided into deficiency and excess syndrome group according to TCM syndrome differentiation. Radiomic features were extracted from T2-weighted imaging (T2WI), diffusion-weighted imaging and apparent diffusion coefficient images originated from diffusion-weighted imaging. A radiomic signature was constructed after reduction of dimension in training group by the minimum redundancy maximum relevance and the least absolute shrinkage and selection operator. The performance of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve. Results: The radiomic scores of PCa with TCM excess syndrome group were statistically higher than those of PCa with TCM deficiency syndrome group among T2WI, diffusion-weighted imaging and apparent diffusion coefficient imaging models. The area under ROC curves for T2WI, diffusion-weighted imaging and apparent diffusion coefficient imaging models were 0.824, 0.824, 0.847 in the training cohort and 0.759, 0.750, 0.809 in the validation cohort, respectively. The apparent diffusion coefficient imaging model had the best discrimination in separating patients with TCM excess syndrome and deficiency syndrome, and its accuracy was 0.788, 0.778 in the training and validation cohort, respectively. The calibration curve demonstrated that there was a high consistency between the prediction of radiomic scores and the actual classification of TCM's deficiency and excess syndrome in PCa. Conclusion: The radiomic signature based on MR imaging can be performed as a non-invasive, potential approach to discriminate TCM deficiency syndrome from excess syndrome in PCa, in which apparent diffusion coefficient imaging model has the best diagnostic efficiency.

Abstract Background Aortic pseudoaneurysm is a life-threatening clinical condition, and thoracic endovascular aortic repair (TEVAR) has been reported to have a relatively satisfactory effect in aortic pathologies. We summarized our single-centre experience using chimney TEVAR for aortic arch pseudoaneurysms with inadequate landing zones. Methods A retrospective study was conducted from October 2015 to August 2020, 32 patients with aortic arch pseudoaneurysms underwent chimney TEVAR to exclude an aortic lesion and reconstruct the supra-aortic branches, including 3 innominate artery, 12 left common carotid arteries and 29 left subclavian arteries. Follow-up computed tomography was suggested before discharge; at 3, 6, 12 months and yearly thereafter. Results The median age of 32 patients was 68.0 years (range, 28–81) with the mean max diameter of aneurysm of 47.9 ± 12.0 mm. Forty-four related supra-aortic branches were well preserved, and the technical success rate was 100%. The Type Ia endoleaks occurred in 3 (9%) patients. Two patients were lost to follow-up and 4 patients died during the follow-up period. The mean follow-up times was 46.5 ± 14.3 months. One patient died due to acute myocardial infarction just 10 days after chimney TEVAR and the other 3 patients passed away at 1.5 months, 20 months, and 31 months with non-aortic reasons. The 4.5-year survival estimate was 84.4%. The primary patency rate of the target supra-arch branch vessels was 97.7% (43/44), and no other aorta-related reinterventions and severe complications occurred. Conclusion For aortic arch pseudoaneurysms with inadequate landing zones for TEVAR, the chimney technique seems to be feasible, with acceptable mid-term outcomes, and it could serve as an alternative minimally invasive approach to extend the landing zone. Slow flow type Ia endoleak could be treated conservatively after chimney TEVAR. Additional experience is needed, and the long-term durability of chimney TEVAR requires further follow-up.

Fistula caused by iliac aneurysm rupture into the inferior vena cava is a kind of extremely rare pathologic condition. In case of this, heart failure and lower extremity edema are the most often seeing symptoms. We report this patient has even rare symptoms of severe hepatic dysfunction. The hepatic function deteriorates from the beginning of the administration to the endovascular repair procedure. The bilateral iliac aneurysm and left iliac aneurysm-inferior vena cava fistula have been repaired by endovascular aortic repair (EVAR) and patients were discharged safely. Learn from this case and we treated before (1) hepatic function in this condition needs to be considering more and (2) EVAR is the mini-invasive and effective method to treat this rare situation.

Open domain response generation is the task of creating a response given a user query in any topics/domain. Limited by context and reference information, responses generated by current systems are often “bland” or generic. In this paper, we combine a response generation model with a retrieval system that searches for relevant utterances and responses. The generation model has two main components: a keyword extraction module and a two-stage transformer. The keyword extraction module aims to extract two types of keywords in an unsupervised fashion from the retrieved results: (1) keywords in the query not found in the retrieved utterances (DiffKey), and (2) overlapping keywords among the retrieved responses (SimKey). Given these keywords, the two-stage transformer first decides where to insert the keywords in the response, and the second generates the full response given the location of the keywords. The keyword extraction module and the two-stage transformer are connected in a single network, and so our system is trained end-to-end. Experimental results on Cornell Movie-Dialog corpus, Douban and Weibo demonstrate that our model outperforms state-of-the-art systems in terms of ROUGE, relevance scores and human evaluation.

Treatment of aortic arch (AA) diseases is challenging for surgeons. Conventional open surgery remains the “gold standard” but is associated with significant morbidity and mortality despite improvements in techniques. In the last 2 decades, thoracic endovascular aortic repair (TEVAR) has become the first-line treatment for diseases of the descending aorta, and its indications have expanded gradually. Various strategies have been proposed to preserve supra-aortic branches in TEVAR: hybrid technique, chimney technique, fenestration technique (including custom-made fenestrated or “scalloped” stent grafts, in situ fenestration, and physician-modified fenestration), and branched stent grafts. Though acceptable outcomes of endovascular aortic repair have been documented, the evidence regarding its long-term safety and efficacy is lacking, and concerns remain about the risk of cerebrovascular events, retrograde type-A dissection, endoleaks, and branch occlusion. This review discusses the current status and progress of endovascular repair of the AA, and looks toward future trends. We believe that multidisciplinary collaboration of a “HENDO” team (professionals in hybrid repair, endovascular repair, open surgery, cardiovascular anesthesia, and genetics) is essential for future repair of the AA to provide the optimal treatment.

Abstract Objectives Peri-implantitis was an inflammatory progress on the tissue around the implant. The Osteoprotegerin G1181C (rs2073618) polymorphism was reported to be related to the increased risk of the peri-implantitis, whereas another found no relationship. The present study was conducted to research the relationship between Osteoprotegerin rs2073618 polymorphism and peri-implantitis susceptibility. Materials and methods The meta-analysis was performed according to the Preferred Reporting Items for Systematic reviews. Electronic databases including PubMed, Web of science, Springer Link and Embase (updated to April 15, 2022) were retrieved. The cohort study, case-control study or cross-sectional study focusing on the Osteoprotegerin rs2073618 polymorphism and peri-implantitis were retrieved. The data included basic information of each study and the genotype and allele frequencies of the cases and controls. Results Three studies were finally included, including 160 cases and 271 controls. Allelic model, homozygote model, recessive model, dominant model, and heterozygous model were established to assess the relationship between OPG rs2073618 polymorphism and peri-implantitis susceptibility. The Osteoprotegerin rs2073618 polymorphism was significantly associated with peri-implantitis in Recessive model and Homozygote model. Conclusion OPG rs2073618 polymorphism in Recessive model and Homozygote model was highly likely related to the risk of peri-implantitis. PROSPERO registration number: CRD42022320812

Abstract Tumor-derived exosomes participate in omental metastatic colonization of ovarian cancer by inducing an adaptive response in the tumor microenvironment. However, cell–cell communication via exosomes between primary tumor cells and the microenvironment of distant omentum and the mechanism of pre-metastatic niche formation are poorly understood. Here, we demonstrated that ETS1-overexpressing ovarian cancer cells secreted larger exosomes with higher laminin levels. In addition, ovarian cancer exosomes could be taken up by omental macrophages through integrin and laminin interaction. Compared with control exosomes, exosomes derived from ETS1-overexpressing ovarian cancer cells (LV-ETS1 Exos) stimulated the polarization of more macrophages toward the M2 phenotype (CD163 marker), as well as the production of more CXCL5 and CCL2 in macrophages, via integrin αvβ5/AKT/Sp1 signaling. In vivo experiments showed that LV-ETS1 Exos promoted omental metastasis of ovarian cancer by mediating the tumor-promoting effect of macrophages, which could be neutralized by integrin ανβ5 inhibitor cilengitide. These results indicated that ETS1 could drive ovarian cancer cells to release exosomes with higher laminin levels, thereby accelerating the exosome-mediated pro-metastatic effects of omental macrophages via the integrin αvβ5/AKT/Sp1 signaling pathway, and the integrin ανβ5 inhibitor cilengitide could inhibit omental metastasis of ovarian cancer driven by tumor-derived exosomes.

Abstract Background 2019 Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has already had a serious influence on human existence, causing a huge public health concern for countries all around the world. Because SARS-CoV-2 infection can be spread by contact with the oral cavity, the link between oral illness and COVID-19 is gaining traction. Through bioinformatics approaches, we explored the possible molecular mechanisms linking the COVID-19 and periodontitis to provide the basis and direction for future research. Methods Transcriptomic data from blood samples of patients with COVID-19 and periodontitis was downloaded from the Gene Expression Omnibus database. The shared differentially expressed genes were identified. The analysis of Gene Ontology, Kyoto Encyclopedia of Genesand Genomes pathway, and protein–protein interaction network was conducted for the shared differentially expressed genes. Top 5 hub genes were selected through Maximal Clique Centrality algorithm. Then mRNA-miRNA network of the hub genes was established based on miRDB database, miRTarbase database and Targetscan database. The Least absolute shrinkage and selection operator regression analysis was used to discover possible biomarkers, which were then investigated in relation to immune-related genes. Results Fifty-six shared genes were identified through differential expression analysis in COVID-19 and periodontitis. The function of these genes was enriched in regulation of hormone secretion, regulation of secretion by cell. Myozenin 2 was identified through Least absolute shrinkage and selection operator regression Analysis, which was down-regulated in both COVID-19 and periodontitis. There was a positive correlation between Myozenin 2 and the biomarker of activated B cell, memory B cell, effector memory CD4 T cell, Type 17 helper cell, T follicular helper cell and Type 2 helper cell. Conclusion By bioinformatics analysis, Myozenin 2 is predicted to correlate to the pathogenesis and immune infiltrating of COVID-19 and periodontitis. However, more clinical and experimental researches are needed to validate the function of Myozenin 2.

Abstract Objectives To quantitatively assess periodontal soft tissue changes, including gingival thickness and keratinized gingiva width after periodontally accelerated osteogenic orthodontics (PAOO) surgery by digital measurements. Methods This study enrolled 15 maxillaries with 89 anterior teeth and 16 mandibles with 94 anterior teeth from Chinese adult patients with skeletal Angle Class III malocclusion for whom PAOO surgery was proposed during orthodontic treatment. Intraoral scanning and cone beam computed tomography (CBCT) examinations were performed before PAOO surgery and 6 months after the surgery. Keratinized gingiva width was measured on the digital model acquired by intraoral scanning. The gingival thickness was measured using a digital three-dimensional (3D) model based on the combination of digital intraoral scanning and CBCT data. Results The mean gingival thickness before surgery was 0.91 ± 0.32 mm and 1.21 ± 0.38 mm at 6-month after PAOO. Patients showed periodontal soft tissue increase with a mean gingival tissue gain of 0.30 ± 0.33 mm. At 1 mm, 2 and 3 mm apical to cemento-enamel junction (CEJ) levels, the gingival thickness increase of the mandible was higher than that of the maxilla (0.38 ± 0.30 mm vs. 0.24 ± 0.31 mm, 0.43 ± 0.35 mm vs. 0.26 ± 0.41 mm, 0.36 ± 0.27 vs. 0.25 ± 0.32 mm, respectively, all P 1 mm (0.36 ± 0.32 mm vs. 0.18 ± 0.31 mm, P

Synthetic 4-Chloroethcathinone (4-CEC) is a derivative of cathinone that belongs to one of the more severe abused substances among new psychoactive substances (NPS). Current researches on 4-CEC mainly focus on metabolite identification studies, and there is a lack of researches on pharmacokinetic, tissue distribution and metabolomics studies in vivo. A sensitive and reliable LC-MS/MS assay was developed and validated for the determination of 4-CEC concentrations in plasma and tissue homogenates. According to the pharmacokinetic results, the absorption and elimination of 4-CEC were faster after administration. The Cmax was 1896 ± 876 ng/ml, the peak time Tmax was 10.1 ± 9.2 min, and the elimination half-life t1/2 was 100.4 min. Metabolomics studies showed that the highest concentrations of 4-CEC were found in brain, lung, kidney and liver. The results of tissue biopsy showed that the liver, kidney and brain tissue had a certain degree of damage. After 4-CEC administration, amino acid-related metabolism and biosynthesis, lipid metabolism, niacin and niacinamide metabolism in mice were interfered, suggesting that 4-CEC could cause energy metabolism disorder in mice. The metabolic pathways and toxicity mechanisms related to 4-CEC entry into the body were explained at the overall metabolic level by multivariate data analysis, screening and identification of differential metabolites and metabolic pathway analysis.

We investigate an active dual-control metamaterial leveraging electromagnetically induced transparency (EIT), exploiting near-field interactions between electric and magnetic dipole resonances. Our hybrid strip element, combining metal and vanadium dioxide, generates electric dipole resonance, while split-ring resonators integrating metal and photosensitive silicon induce magnetic dipole resonance. Simulations confirm coupling validity and demonstrate dynamic adjustability of EIT via temperature and light intensity changes. EIT modulation transitions between transparent and non-resonant states due to temperature fluctuations, or resonant states with varying light intensity. Temperature adjustments dominate when both factors are altered. Analysis via a coupled oscillator model reveals modulation of damping rates as the origin of disappearance curve variations. This innovative design enhances tunable EIT metamaterial versatility, with implications for high transmission ratios and adaptable slow-light effects in terahertz applications.

We investigate a thermally controlled electromagnetically induced transparency terahertz metamaterial through the near-field coupling of electric and toroidal resonances. The fundamental unit consists of a composite design incorporating both metal and vanadium dioxide components aimed at inducing toroidal resonance, along with a pair of metal strips generating electric resonance. Simulation results authenticate the coupling mechanism and illustrate that the envisioned EIT phenomenon can be dynamically adjusted by temperature. In a coupled oscillator model analysis, the control over coupling strength primarily emerges from the fluctuating damping rate of the bright-mode oscillator. Moreover, the displacement of the EIT peak is linked to alterations in the inherent resonant frequency of the bright-mode oscillator. This study not only broadens the potential applications for toroidal terahertz metamaterials but also enhances the range of EIT methodologies available, providing practical approaches for the utilization of terahertz slow-light devices, sensors, and switch devices.

Guava (Psidium guajava L.) is an important economic crop grown widely in tropical and subtropical regions. Guava exhibits fast ripening and senescence as a climacteric fruit, causing a short shelf life and quality deterioration. Chitosan–essential oil nanoemulsions can be an edible coating used to improve postharvest quality attributes. In this study, chitosan was mixed with carvacrol to generate a nano-emulsoid solution containing 0.1 and 0.2% (v/v) carvacrol, using a sonic dismembrator. Guava fruit were coated with the above emulsion and postharvest quality parameters were measured during storage at 20 ± 1 °C and RH = 80 ± 5% for 8 days. The result illustrated that the particle size of the chitosan–carvacrol emulsions was nanoscale, and their high stability was demonstrated by the zeta potential and polydispersity index. Chitosan coating (2%, w/v, 310–375 kDa) containing 0.2% (v/v) carvacrol maintained postharvest quality compared to chitosan alone, with higher firmness, soluble solid content, total acid, and total phenol content, and lower weight loss and pericarp browning. The collective data were further verified by principal component analysis. A chitosan coating containing carvacrol can reduce postharvest losses. It can be applied as an effective strategy to improve postharvest fruit quality.

Abstract Background Early life stress (ELS) is associated with the development of schizophrenia later in life. The hippocampus develops significantly during childhood and is extremely reactive to stress. In rodent models, ELS can induce neuroinflammation, hippocampal neuronal loss, and schizophrenia-like behavior. While nicotinamide (NAM) can inhibit microglial inflammation, it is unknown whether NAM treatment during adolescence reduces hippocampal neuronal loss and abnormal behaviors induced by ELS. Methods Twenty-four hours of maternal separation (MS) of Wistar rat pups on post-natal day (PND)9 was used as an ELS. On PND35, animals received a single intraperitoneal injection of BrdU to label dividing neurons and were given NAM from PND35 to PND65. Behavioral testing was performed. Western blotting and immunofluorescence staining were used to detect nicotinamide adenine dinucleotide (NAD+)/Sirtuin3 (Sirt3)/superoxide dismutase 2 (SOD2) pathway-related proteins. Results Compared with controls, only MS animals in the adult stage (PND56–65) but not the adolescent stage (PND31–40) exhibited pre-pulse inhibition deficits and cognitive impairments mimicking schizophrenia symptoms. MS decreased the survival and activity of puberty-born neurons and hippocampal NAD+ and Sirt3 expression in adulthood. These observations were related to an increase in acetylated SOD2, microglial activation, and significant increases in pro-inflammatory IL-1β, TNF-α, and IL-6 expression. All the effects of MS at PND9 were reversed by administering NAM in adolescence (PND35–65). Conclusions MS may lead to schizophrenia-like phenotypes and persistent hippocampal abnormalities. NAM may be a safe and effective treatment in adolescence to restore normal hippocampal function and prevent or ameliorate schizophrenia-like behavior.

Abstract Ovarian aging refers to the process by which ovarian function declines until eventual failure. The pathogenesis of ovarian aging is complex and diverse; oxidative stress (OS) is considered to be a key factor. This review focuses on the fact that OS status accelerates the ovarian aging process by promoting apoptosis, inflammation, mitochondrial damage, telomere shortening and biomacromolecular damage. Current evidence suggests that aging, smoking, high-sugar diets, pressure, superovulation, chemotherapeutic agents and industrial pollutants can be factors that accelerate ovarian aging by exacerbating OS status. In addition, we review the role of nuclear factor E2-related factor 2 (Nrf2), Sirtuin (Sirt), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), Forkhead box O (FoxO) and Klotho signaling pathways during the process of ovarian aging. We also explore the role of antioxidant therapies such as melatonin, vitamins, stem cell therapies, antioxidant monomers and Traditional Chinese Medicine (TCM), and investigate the roles of these supplements with respect to the reduction of OS and the improvement of ovarian function. This review provides a rationale for antioxidant therapy to improve ovarian aging.

This study aimed to explore whether stroke prevention strategies differ for men and women. Data used were from China Kadoorie Biobank. According to the China-PAR Project model, a predicted 10-year stroke risk of ≥7% is defined as a high stroke risk. The effects of risk factor control and medication use as primary and secondary stroke prevention strategies were assessed, respectively. Logistic regression models were used to assess the sex-specific differences in the primary and secondary stroke prevention practices. Of the 512,715 participants (59.0% women), 218,972 (57.4% women) had a high risk of stroke and 8884 (44.7% women) had an established stroke. Of high-risk participants, women were considerably less likely than men to receive antiplatelets (odds ratio [OR], 0.80; [95% confidence interval, CI, 0.72–0.89]), antihypertensives (0.46[0.44–0.48]), and antidiabetics (0.65[0.60–0.70]). Meanwhile, stroke women were significantly less likely to receive antiplatelets (0.75[0.65–0.85]) but more likely to receive antidiabetics (1.56 [1.34–1.82]) than their male counterparts. Besides, differences were found in risk factor control between women and men. Sex-specific differences in stroke prevention strategies are prevalent in China. Effective prevention requires the implementation of better overall nationwide strategies and special emphasis on women.

Abstract Background The present study was conducted to determine the inflammatory response in the lungs of children with Mycoplasma pneumoniae pneumonia (MPP). Methods This study retrospectively analyzed cytokine levels, cytological findings, and M. pneumoniae (MP)‐DNA level in the bronchoalveolar lavage fluid (BALF) of 96 children with MPP. The study utilized Spearman's correlation method to evaluate the contribution of BALF and blood parameters in MPP children. Results (1) A total of 96 MPP children were classified into the Low MP‐DNA MPP group (BALF MP‐DNA ≤ 105 copies/mL) and the High MP‐DNA MPP group (BALF MP‐DNA > 105copies/mL); the Non‐fever MPP group (no fever during the entire course of pneumonia) and the Fever MPP group; the Defervescence MPP group (fever had subsided at the time of bronchoscopy) and the Fervescence MPP group; and the Mild MPP group and the Severe MPP group. (2) The High MP‐DNA MPP, Fever MPP, Fervescence MPP, and Severe MPP groups had higher levels of interleukin (IL)‐6, IL‐10, and tumor necrosis factor‐α (TNF‐α) in their BALF (all p

SHR-1222, a novel humanized monoclonal antibody targeting sclerostin, has been shown to induce bone formation and decrease bone resorption at a single dose ranging 50–400 mg in our previous phase 1 trial. This study was a randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial, which further investigated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of multiple ascending doses of SHR-1222 in women with postmenopausal osteoporosis (POP). A total of 105 women with POP were enrolled and randomly assigned. Twenty-one received placebo and eighty-four received SHR-1222 sequentially (100 mg QM, n=4; 200 or 300 mg QM, n=20; and 400 or 600 mg Q2M, n=20). The most common adverse events included increased blood parathyroid hormone, increased low-density lipoprotein, increased blood alkaline phosphatase, increased blood cholesterol, back pain, and arthralgia, the majority of which were mild in severity without noticeable safety concerns. Serum SHR-1222 exposure (Cmax,ss and AUC0-tau,ss) increased in a greater than dose-proportional manner. Following multiple doses of SHR-1222, the bone formation markers (terminal propeptide of type I procollagen, bone-specific alkaline phosphatase, and osteocalcin) increased in a dose-dependent manner, whereas the bone resorption marker (β-C-telopeptide) was downregulated. Accordingly, BMD gains in the lumbar spine, total hip, and femoral neck were observed. The maximum BMD increase from baseline at the lumbar spine was detected in the 300 mg QM cohort (14.6% vs. 0.6% in the placebo group on day 169). Six (6/83; 7.2%) subjects developed anti-SHR-1222 antibodies with no discernible effects on PKs, PDs, and safety. Thus, multiple doses of SHR-1222 showed an acceptable safety profile and dose-dependent plasma exposure in women with POP, and could improve their BMD rapidly and prominently by promoting bone formation and inhibiting bone resorption. These findings further support SHR-1222 as a potential alternative agent for the treatment of POP.