Customized Preparation of Heat-Resistant Fully Flexible Sensors Based on Coaxial 3D Printing.

The conventional behavior recognition strategy for wearable sensors used in high-temperature environments typically requires an external power supply, and the manufacturing process is cumbersome. Herein, we present a rational design strategy based on fully flexible printable materials and a customized device-manufacturing process for skin-conformable triboelectric nanogenerator sensors. In detail, using high temperature-resistant ink and 3D printing technology to manufacture a coaxial triboelectric nanogenerator (C-TENG) sensor, the C-TENG exhibits high stretchability (>400%), a wide working range (>250 °C), and high output voltage (>100 V). The C-TENG can be worn on various parts of the human body, providing a robust skin-device interface that recognizes diverse human behaviors. Using machine learning algorithms, behaviors such as walking, running, sitting, squatting, climbing stairs, and falling can be identified, achieving 100% behavior recognition accuracy through the selective input and optimization of an appropriate dataset. This paper provides a research perspective for the customization, extension, and rapid fabrication of heat-resistant, fully flexible TENGs.

Discovery and Enzyme Kinetic Characterization of Novel CYP2D6 Variants.

Cytochrome P450 2D6 (CYP2D6) exhibits rich genetic polymorphism, and functional changes caused by variations are the key reasons for differences in substrate drug systemic exposure. Discovering novel variants and defining their enzymatic kinetic characteristics can contribute to the personalized application of drugs. In this study, a data chain of variant-function-structure was established through population-based sequencing, baculovirus insect cell expression, in vitro enzymatic incubation, and ultrahigh performance liquid chromatography tandem mass spectrometry. Results revealed nine novel missense mutations in the exonic regions. After the corresponding microsomes were obtained, the kinetics of the variants were investigated using dextromethorphan as a probe substrate. It was found that the activities of CYP2D6.2, 10, 17, 35, 65, R28G, T76M, and E215K were significantly reduced, while D301V almost led to loss of enzyme function. Additionally, the relative clearance rate of R25Q was significantly increased. From the molecular structure perspective, the mutation sites are distributed outside the dextromethorphan binding pocket, suggesting that they primarily influence CYP2D6 activity via allosteric modulation. These research findings provide fundamental data for the precise application of CYP2D6 substrate drugs.

Etiological stratification and prognostic assessment of haemophagocytic lymphohistiocytosis by machine learning on onco-mNGS data and clinical data.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, complicated and life threatening hyperinflammatory syndrome that maybe triggered by various infectious agents, malignancies and rheumatologic disorders. Early diagnosis and identification of the cause is essential to initiate appropriate treatment and improve the quality of life and survival of patients. The recently developed Onco-mNGS technology can be successfully used for simultaneous detection of infections and tumors. Methods: In the present study, 92 patients with clinically confirmed HLH were etiologically subtyped for infection, tumor and autoimmunity based on CNV and microbial data generated by Onco-mNGS technology, and a predictive model was developed and validated for the differential diagnosis of the underlying disease leading to secondary HLH. Furthermore, the treatment outcomes of patients with HLH triggered by EBV infection and non-EBV infection were evaluated, respectively. Results: The current study demonstrated that the novel Onco-mNGS can identify the infection and malignancy- related triggers among patients with secondary HLH. A random forest classification model based on CNV profile, infectious pathogen spectrum and blood microbial community was developed to better identify the different HLH subtypes and determine the underlying triggers. The prognosis for treatment of HLH patients is not only associated with CNV, but also with the presence of pathogens and non- pathogens in peripheral blood. Higher CNV burden along with frequent deletions on chromosome 19, higher pathogen burden and lower non-pathogenic microbes were prognosis factors that significantly related with unfavorable treatment outcomes. Discussion: Our study provided comprehensive knowledge in the triggers and prognostic predictors of patients with secondary HLH, which may help early diagnosis and appropriate targeted therapy, thus improving the survival and prognosis of the patients.

The transcriptome of MHV-infected RAW264.7 cells offers an alternative model for macrophage innate immunity research.

BACKGROUND: Macrophages are the primary innate immune cells encountered by the invading coronaviruses, and their abilities to initiate inflammatory reactions, to maintain the immunity homeostasis by differential polarization, to train the innate immune system by epigenic modification have been reported in laboratory animal research. METHODS: In the current in vitro research, murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus, a coronavirus existed in mouse. At 3-, 6-, 12-, 24-, and 48-h post infection (hpi.), the attached cells were washed with PBS and harvested in Trizol reagent. Then The harvest is subjected to transcriptome sequencing. RESULTS: The transcriptome analysis showed the immediate (3 hpi.) up regulation of DEGs related to inflammation, like Il1b and Il6. DEGs related to M2 differential polarization, like Irf4 showed up regulation at 24 hpi., the late term after viral infection. In addition, DEGs related to metabolism and histone modification, like Ezh2 were detected, which might correlate with the trained immunity of macrophages. CONCLUSIONS: The current in vitro viral infection study showed the key innated immunity character of macrophages, which suggested the replacement value of viral infection cells model, to reduce the animal usage in preclinical research.

Lymphocytes in Patients with Chronic Active Epstein-Barr Virus Disease Exhibited Elevated PD-1/PD-L1 Expression and a Prevailing Th2 Immune Response.

Background And Objectives: Chronic active Epstein-Barr virus disease (CAEBV) is a proliferative disease of EBV+ T or natural killer (NK) cells with an unclear pathogenesis. This study aimed to examine the frequency and exhaustion levels of lymphocyte subsets in patients with CAEBV to further investigate the pathogenesis. Methods: Using flow cytometry, we detected the frequency, expression levels of programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1), and EBV infection status of peripheral T subsets and NK cells in patients with CAEBV and healthy individuals. Results: 24 patients and 15 healthy individuals were enrolled in this study. Patients showed notably higher expression levels of PD-1 and PD-L1 in peripheral T subsets and NK cells compared to healthy individuals (P < 0.05). EBV+ lymphocytes exhibited significantly higher PD-L1 expression levels than EBV- lymphocytes. Additionally, the frequency of effector memory T (Tem) cells was significantly increased in patients, and the PD-L1 expression level was positively correlated with the EBV load. Besides, helper T cell 2 (Th2) immune bias, also favoring EBV amplification, was found in patients, including increased Th2 cell frequency, enhanced response capacity, and elevated serum levels of associated cytokines. The distribution and PD-1 expression levels of peripheral T subsets returned to normal in patients who responded to PD-1 blockade therapy. Conclusions: The up-regulation of the PD-1/PD-L1 pathway of peripheral T and NK cells and Th2 immune predominance jointly promoted EBV replication and the development of CAEBV. PD-1 blockade therapy reduced the PD-1 expression level of lymphocytes and helped normalize the distribution of the T subsets.

The effect of acupuncture on gastrointestinal recovery after abdominal surgery: a narrative review from clinical trials.

Abdominal surgery is a critical surgery, with more and more attention being paid to postoperative life quality and associated complications in recent years. Among these complications, postoperative gastrointestinal dysfunction is the most common complication of abdominal surgery. Acupuncture therapy is a treatment approach based on the Traditional Chinese Medicine theory, and its feasibility in aiding gastrointestinal recovery after abdominal surgery is supported by both Traditional Chinese Medicine theory and animal experiments. A lot of clinical research has been conducted to evaluate its efficacy, albeit with limitations, and at preliminary stages. Moreover, intervention timing, acupoint selection, and patient benefits should also be considered in clinical practices. This article summarizes the progress of clinical research on acupuncture therapy in gastrointestinal recovery after abdominal surgery and discusses related issues and operations, with the aim to provide new insights and prospects for the incorporation of acupuncture into the Enhanced Recovery After Surgery protocol.

High expression of SULF1 is associated with adverse prognosis in breast cancer brain metastasis.

BACKGROUND: Breast cancer is the most common cancer in women, and in advanced stages, it often metastasizes to the brain. However, research on the biological mechanisms of breast cancer brain metastasis and potential therapeutic targets are limited. METHODS: Differential gene expression analysis (DEGs) for the datasets GSE43837 and GSE125989 from the GEO database was performed using online analysis tools such as GEO2R and Sangerbox. Further investigation related to SULF1 was conducted using online databases such as Kaplan-Meier Plotter and cBioPortal. Thus, expression levels, variations, associations with HER2, biological processes, and pathways involving SULF1 could be analyzed using UALCAN, cBioPortal, GEPIA2, and LinkedOmics databases. Moreover, the sensitivity of SULF1 to existing drugs was explored using drug databases such as RNAactDrug and CADSP. RESULTS: High expression of SULF1 was associated with poor prognosis in advanced breast cancer brain metastasis and was positively correlated with the expression of HER2. In the metastatic breast cancer population, SULF1 ranked top among the 16 DEGs with the highest mutation rate, reaching 11%, primarily due to amplification. KEGG and GSEA analyses revealed that the genes co-expressed with SULF1 were positively enriched in the 'ECM-receptor interaction' gene set and negatively enriched in the 'Ribosome' gene set. Currently, docetaxel and vinorelbine can act as treatment options if the expression of SULF1 is high. CONCLUSIONS: This study, through bioinformatics analysis, unveiled SULF1 as a potential target for treating breast cancer brain metastasis (BM).

The dual function of calcium ion in fruit edible coating: Regulating polymer internal crosslinking state and improving fruit postharvest quality.

The edible coating is proved to be a convenient approach for fruit preservation. Among these published explorations, naturally sourced macromolecules and green crosslinking strategies gain attention. This work centers on edible coatings containing Ca2+ as crosslinker for the first time, delving into crosslinking mechanisms, include alginate, chitosan, Aloe vera gel, gums, etc. Additionally, the crucial functions of Ca2+ in fruit's quality control are also elaborated in-depth, involving cell wall, calmodulin, antioxidant, etc. Through a comprehensive review, it becomes evident that Ca2+ plays a dual role in fruit edible coating. Specifically, Ca2+ constructs a three-dimensional dense network structure with polymers through ionic bonding. Moreover, Ca2+ acts directly with cell wall to maintain fruit firmness and serve as a second messenger to participate secondary physiological metabolism. In brief, coatings containing Ca2+ present remarkable effects in preserving fruit and this work may provide guidance for Ca2+ related fruit preservation coatings.

Predicting asymptomatic coronary artery disease in first-ever acute ischemic stroke patients: a cross-sectional study.

Background: It is frequently observed that patients with first-ever acute ischemic stroke (AIS) have a common occurrence of asymptomatic coronary artery disease (CAD). This condition is associated with a poor prognosis. Early detection and recognition of asymptomatic CAD in first-ever AIS patients may optimize the clinical management and ultimately lead to improved outcomes. The aim of this study was to investigate the role of aortic arch plaque (AAP) detected through combined computed tomography angiography (CTA) as an early predictor of asymptomatic CAD in patients with first-ever AIS without prior diagnosis of CAD. Methods: A cross-sectional study was conducted at Xuanwu Hospital, Capital Medical University from January 2019 to December 2021, involving patients with first-ever AIS caused by large arterial atherosclerosis. Patients with a history of recognized cardiovascular disease, nonatherosclerotic arterial stenosis, atrial fibrillation related to cardioembolism, and complete carotid occlusions were excluded. The study utilized a combined coronary and cervicocephalic CTA to evaluate atherosclerosis in the cervicocephalic, aortic, and coronary arteries simultaneously. First-ever AIS patients without prior diagnosis of CAD were divided into 2 groups: 1 with asymptomatic CAD detected through CTA and the other without. Multivariate logistic regression was used to identify independent risk factors associated with the presence of asymptomatic CAD, including aortic arch, cervical and intracranial atherosclerotic characteristics (e.g., vascular stenosis, plaque thickness, extent, and complexity). Results: Among 182 AIS patients, 84 (46.2%) had asymptomatic CAD. Increased aortic arch plaque (AAP) thickness per millimeter [adjusted odds ratio (aOR): 1.26; 95% confidence interval (CI): 1.08-1.47], presence of severe AAP (aOR: 4.24; 95% CI: 1.59-12.03), mixed AAP (aOR: 2.65; 95% CI: 1.09-6.62), and ulcerative AAP (aOR: 11.76; 95% CI: 2.05-222.84) raised the risk of asymptomatic CAD in stroke patients, independent of other factors. The combination of ulcerative AAP, diabetes mellitus, and smoking could predict asymptomatic CAD with an area under the receiver operating characteristic curve (AUC) of 0.71 (95% CI: 0.64-0.79; P<0.001). Ulcerative AAP was found to be more valuable than cervicocephalic atherosclerotic characteristics for predicting asymptomatic CAD in first-ever AIS patients. Conclusions: The presence of ulcerative AAP was associated with asymptomatic CAD in first-ever AIS patients. As an early systemic atherosclerosis feature, ulcerative AAP is probably a more valuable indicator than cervicocephalic atherosclerotic characteristics for predicting asymptomatic CAD in AIS patients.

Flu-CED: A comparative transcriptomics database of influenza virus-infected human and animal models.

BACKGROUND: The continuing emergence of influenza virus has highlighted the value of public databases and related bioinformatic analysis tools in investigating transcriptomic change caused by different influenza virus infections in human and animal models. METHODS: We collected a large amount of transcriptome research data related to influenza virus-infected human and animal models in public databases (GEO and ArrayExpress), and extracted and integrated array and metadata. The gene expression matrix was generated through strictly quality control, balance, standardization, batch correction, and gene annotation. We then analyzed gene expression in different species, virus, cells/tissues or after antibody/vaccine treatment and imported sample metadata and gene expression datasets into the database. RESULTS: Overall, maintaining careful processing and quality control, we collected 8064 samples from 103 independent datasets, and constructed a comparative transcriptomics database of influenza virus named the Flu-CED database (Influenza comparative expression database, https://flu.com-med.org.cn/). Using integrated and processed transcriptomic data, we established a user-friendly website for realizing the integration, online retrieval, visualization, and exploration of gene expression of influenza virus infection in different species and the biological functions involved in differential genes. Flu-CED can quickly query single and multi-gene expression profiles, combining different experimental conditions for comparative transcriptome analysis, identifying differentially expressed genes (DEGs) between comparison groups, and conveniently finding DEGs. CONCLUSION: Flu-CED provides data resources and tools for analyzing gene expression in human and animal models infected with influenza virus that can deepen our understanding of the mechanisms underlying disease occurrence and development, and enable prediction of key genes or therapeutic targets that can be used for medical research.

C1ql3 knockout affects microglia activation, neuronal integrity, and spontaneous behavior in Wistar rats.

BACKGROUND: C1QL3 is widely expressed in the brain and is specifically produced by a subset of excitatory neurons. However, its function is still not clear. We established C1ql3-deficient rats to investigate the role of C1QL3 in the brain. METHODS: C1ql3 knockout (KO) rats were generated using CRISPR/Cas9. C1ql3 KO was determined by polymerase chain reaction (PCR), DNA sequencing, and western blotting. Microglia morphology and cytokine expression with or without lipopolysaccharide (LPS) stimulus were analyzed using immunohistochemistry and real-time PCR. The brain structure changes in KO rats were examined using magnetic resonance imaging. Neuronal architecture alteration was analyzed by performing Golgi staining. Behavior was evaluated using the open field test, Morris water maze test, and Y maze test. RESULTS: C1ql3 KO significantly increased the number of ramified microglia and decreased the number of hypertrophic microglia, whereas C1ql3 KO did not influence the expression of pro-inflammatory factors and anti-inflammatory factors except IL-10. C1ql3 KO brains had more amoeboid microglia types and higher Arg-1 expression compared with the WT rats after LPS stimulation. The brain weights and HPC sizes of C1ql3 KO rats did not differ from WT rats. C1ql3 KO damaged neuronal integrity including neuron dendritic arbors and spine density. C1ql3 KO rats demonstrated an increase in spontaneous activity and an impairment in short working memory. CONCLUSIONS: C1ql3 KO not only interrupts the neuronal integrity but also affects the microglial activation, resulting in hyperactive behavior and impaired short memory in rats, which highlights the role of C1QL3 in the regulation of structure and function of both neuronal and microglial cells.

Predicting materials properties with generative models: applying generative adversarial networks for heat flux generation.

In the realm of materials science, the integration of machine learning techniques has ushered in a transformative era. This study delves into the innovative application of generative adversarial networks (GANs) for generating heat flux data, a pivotal step in predicting lattice thermal conductivity within metallic materials. Leveraging GANs, this research explores the generation of meaningful heat flux data, which has a high degree of similarity with that calculated by molecular dynamics simulations. This study demonstrates the potential of artificial intelligence (AI) in understanding the complex physical meaning of data in materials science. By harnessing the power of such AI to generate data that is previously attainable only through experiments or simulations, new opportunities arise for exploring and predicting properties of materials.

Empagliflozin Induces Vascular Relaxation in Rat Coronary Artery Due to Activation of BK Channels.

Purpose: The aim of this study was to investigate the effects and mechanisms of SGLT2 inhibitor empagliflozin on diabetic coronary function. Methods: A rat diabetic model was established by injection of streptozotocin. Rats in the treated group were administered empagliflozin by gavage and rat coronary vascular tensions were measured after eight weeks. Large conductance calcium activated K+ channel currents were recorded using a patch clamp technique, while human coronary artery smooth muscle cells were used to explore the underlying mechanisms. Results: After incubation with empagliflozin (10, 30, 100, 300, 1000 µmol/L), the Δ relaxation % of rat coronary arteries were 2.459 ± 1.304, 3.251 ± 1.119, 6.946 ± 3.407, 28.36 ± 11.47, 86.90 ± 3.868, respectively. Without and with empagliflozin in the bath solution, BK channel opening probabilities at a membrane potential of +60 mV were 0.0458 ± 0.0517 and 0.3413 ± 0.2047, respectively (p < 0.05, n = 4 cells). After incubation with iberiotoxin, the Δ tensions of rat coronary arteries in the control (Ctrl), untreated (DM), low empagliflozin (10 mg/kg/d)-treated (DM+L-EMPA) and high empagliflozin (30mg/kg/d)-treated (DM+H-EMPA) group were 103.20 ± 5.85, 40.37 ± 22.12, 99.47 ± 28.51, 78.06 ± 40.98, respectively (p < 0.01 vs Ctrl, n = 3-7; p < 0.001 vs DM+L-EMPA, n = 5-7). Empagliflozin restored high glucose-induced downregulation of Sirt1, Nrf2, and BK-ß1, while the effect of empagliflozin disappeared in the presence of EX-527, a Sirt1 selective inhibitor. Conclusion: Empagliflozin has a vasodilation effect on the coronary arteries in a concentration-dependent manner and can activate BK channels via the Sirt1-Nrf2 mechanism.

Evaluating Total Atherosclerosis Burden of Baroreceptor-Resident Arteries after Ischemic Cerebrovascular Disease for Identifying Patients with Heavy Coronary Atherosclerosis Burden.

AIM: The carotid sinuses and aortic arch are baroreceptor-resident arteries (BRAs) and atherosclerosis-susceptible sites of brain-supplying arteries, which would impair baroreflex-mediated blood pressure (BP) regulation and prompt coronary atherosclerosis. We sought to determine the relationship between total atherosclerosis burden (TAB) of BRAs and coronary atherosclerosis burden (AB) in patients with ischemic cerebrovascular disease (ICVD) and explore the potential contribution of BP profiles to this relationship. METHODS: In this cross-sectional analysis of patients with ICVD who simultaneously undertook computed tomography angiography and 24-hour ambulatory BP monitoring, TAB of BRAs was scored based on the atherosclerotic vessel circumference ratio of the carotid sinuses and aortic arch, while the ABs of the intracranial, cervical, aortic, and coronary arteries were scored based on stenosis severity and plaque complexity as routine. RESULTS: Among the 230 patients analyzed, coronary AB was significantly correlated with TAB of BRAs, independently of, and more tightly than the ABs of the intracranial, cervical, and aortic arteries, and the stenosis- and complexity-based AB of BRA-located arteries (bilateral common and extracranial internal carotid arteries and aortic arch). Both coronary AB and TAB of BRAs were negatively associated with the night-to-day BP dipping ratios, which was quite different from the relationship between intracranial AB and 24-hour BP characteristics. These findings were also true for patients with ICVD without a history of coronary artery disease. CONCLUSION: Evaluating TAB of BRAs might provide a new link between atherosclerosis of brain- and heart-supplying arteries, connected partially by BP circadian rhythm. It might facilitate identifying patients with ICVD with heavy coronary AB and comprehensively managing vascular risk.

Prognostic scoring system for pediatric Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis based on baseline characteristics: A multicenter retrospective study.

BACKGROUND: The prognosis of pediatric Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) varies. This study aimed to identify high-risk children early. PROCEDURE: Data from 264 children (0-14 years of age), diagnosed with EBV-HLH at six centers in China between January 2016 and December 2021, were analyzed. Patients were randomly divided into derivation (n = 185) and verification (n = 79) cohorts. A Cox regression model was used to explore risk predictors and establish a prognostic scoring system for death events that occurred during the follow-up period. RESULTS: Chronic active EBV infection (CAEBV) history (hazard ratio [HR] 1.82 [95% confidence interval, CI: 1.02-3.26]; p = .0441), plasma EBV-DNA more than 104  copies/mL (HR 2.89 [95% CI: 1.62-5.16]; p = .0003), pulmonary infection (HR 2.24 [95% CI: 1.06-4.75]; p = .0353), digestive tract hemorrhage (HR 2.55 [95% CI: 1.35-4.82]; p = .0041), and hypoxemia (HR 3.95 [95% CI: 2.15-7.26]; p < .0001) were independent risk factors. Accordingly, the CAEBV history, plasma EBV-DNA copy number, pulmonary infection hemorrhage of digestive tract, hypoxemia prognostic scoring system (CEPHO-PSS) were developed, which separated patients into low- (0-1 points), middle- (2-3 points), and high- (4-8 points) risk groups. Survival curves for the three groups exhibited statistically significant differences (p < .0001). Internal and external verification of CEPHO-PSS was performed using receiver operating characteristic (ROC) and calibration curves in the derivation and verification cohorts, respectively, confirming good accuracy and applicability. CONCLUSIONS: The CEPHO-PSS identified three risk groups with statistically significant differences in survival curves. It was based on the baseline characteristics, and can give clinicians a convenient check for risk prediction.

Advanced Glycation End Products Downregulate Connexin 43 and Connexin 40 in Diabetic Atrial Myocytes via the AMPK Pathway.

Purpose: Diabetes mellitus is an independent risk factor for atrial fibrillation (AF), which may be related to accumulation of advanced glycation end products (AGEs). However, the mechanisms involved are not completely clear. Abnormality of gap junction proteins, especially connexin 43 (Cx43) and connexin 40 (Cx40) in atrial myocytes, is an important cause of increased susceptibility of AF. The aim of our work is to investigate the mechanism of dysregulated Cx43 and Cx40 in atrial myocytes of diabetic rats. Methods: We established a type 1 diabetic rat model by intraperitoneal injection of streptozotocin. HL-1 cells and primary rat atrial myocytes were treated with AGEs in vitro. Using Western blotting, immunofluorescence staining, immunohistochemistry, and lucifer yellow diffusion measurements, we investigated dysregulation of Cx43 and Cx40 and its mechanism in atrial myocytes of diabetic rats. Results: Accumulation of AGEs was found in diabetic rats. The expression of Cx43 and Cx40 was reduced in the atrium of diabetic rats, accompanied by the decrease of phosphorylated Adenosine 5'-monophosphate-activated protein kinase (p-AMPK). Similar results were found in cultured HL-1 cells and primary rat atrial myocytes, suggesting a role of AGEs on gap junction proteins. An AMPK agonist, 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), reversed the down-regulated Cx43 expression induced by AGEs stimulation. More importantly, lucifer yellow diffusion assay showed that AGEs significantly affected gap junctional function, and these changes were reversed by AICAR. Conclusion: Thus, we conclude that AGEs cause dysregulation of Cx43 and Cx40 in diabetic atria via the AMPK pathway, thereby leading to gap junction dysfunction, which may contribute to the increased AF susceptibility in diabetes.

Atherosclerosis Burden of Brain- and Heart-Supplying Arteries and the Relationship With Vascular Risk in Patients With Ischemic Stroke.

Background Atherosclerosis of brain- and heart-supplying arteries (BHAs) are risk indicators for patients with ischemic stroke, but the atherosclerosis burden (AB) of intracranial, cervical, aortic, and coronary arteries in each and in total have not been simultaneously evaluated, and the associations with vascular risk remain unknown. Methods and Results With computed tomography angiography, single-territory AB was triple ranked on the basis of the number of arterial segments with a significant atherosclerotic lesion. The total AB (TAB) of BHAs was triple ranked on the basis of the number of arterial territories with a significant atherosclerotic lesion, or according to the sum of 4 single-territory AB rank-scores. After a 12-month follow-up of 395 patients with ischemic stroke, a composite outcome of ischemic stroke, myocardial infarction, and vascular death occurred in 10.9%. The single-territory AB of intracranial, cervical, aortic, and coronary arteries showed distinct strata patterns and different associations with vascular risk. The score-based TAB of BHAs predicted vascular risk (crude hazard ratios [95% CIs]: per level increase, 2.35 [1.54-3.58]; median versus low, 3.37 [1.45-7.82]; high versus low, 6.00 [2.36-15.24]) independently of vascular risk factors and single-territory AB, providing more prognostic information than the TAB of BHAs measured by the number of significantly atherosclerotic territories. Vascular events occurred in 3.0%, 13.6%, and 22.6% of patients in the low (41.8%), median (44.8%), and high (13.4%) strata of the score-based TAB of BHAs, respectively. Conclusions The single-territory AB of intracranial, cervical, aortic, or coronary arteries might be not reliable for vascular risk stratification in patients with ischemic stroke, and evaluating the TAB of BHAs by quantitatively integrating the single-territory AB is advisable.

Characteristics and Mechanism of Acute Ischemic Stroke in NAVF Patients With Prior Oral Anticoagulant Therapy.

OBJECTIVES: We aimed to analyze the characteristics and mechanisms of acute ischemic stroke (AIS) in patients with nonvalvular atrial fibrillation (NVAF) who received prior anticoagulant therapy. METHODS: We retrospectively analyzed the data of patients with NVAF and AIS between January 2016 and December 2021. Patients were divided into non-anticoagulant, adequate anticoagulant, and insufficient anticoagulant groups according to their prior anticoagulant status. Patients with prior anticoagulant therapy were further divided into warfarin and direct oral anticoagulant groups. RESULTS: A total of 749 patients (661 without anticoagulants, 33 with adequate anticoagulants, and 55 with insufficient anticoagulants) were included. Patients with adequate anticoagulant had a milder National Institute of Health Stroke Scale at presentation ( P =0.001) and discharge ( P =0.003), a higher proportion of Modified Rankin Scale (mRS) ≤2 at discharge ( P =0.011), and lower rates of massive infarction ( P =0.008) than patients without anticoagulant. Compared with the non-anticoagulant group, the proportion of intravenous thrombolysis was significantly lower in the adequate anticoagulant ( P <0.001) and insufficient anticoagulant ( P =0.009) groups. Patients in the adequate anticoagulant group had higher rates of responsible cerebral atherosclerotic stenosis ( P =0.001 and 0.006, respectively) and competing large artery atherosclerotic mechanisms ( P =0.006 and 0.009, respectively) than those in the other 2 groups. Compared with warfarin, direct oral anticoagulant was associated with higher rates of Modified Rankin Scale ≤2 at discharge ( P =0.003). CONCLUSIONS: Adequate anticoagulant therapy may be associated with milder stroke severity and better outcomes at discharge in patients with NVAF. Competing large artery atherosclerotic mechanisms may be associated with anticoagulant failure in patients with NAVF with prior adequate anticoagulant therapy.

Cuticular Wax Triterpenes Maintain Storage Quality of Blueberries by Reducing Water Loss.

Cuticular wax contributes to maintaining postharvest storage quality against fruit water loss and softening. Triterpenoids, such as oleanolic acid (OA) and ursolic acid (UA), are the main components in blueberry cuticular wax, but their role in water migration during the storage of blueberries remains to be determined. Here, we examined the relationship between the content of OA and UA and the storage quality of blueberry fruit (25 °C). The results revealed that the UA content during eight-day postharvest storage ranged from 58 to 77 µg cm-2, which was negatively related to weight loss. Additionally, we investigated the effect of exogenous OA and UA on water migration in the blueberry fruit during storage at room temperature; the weight loss was significantly lower (by 22%) with UA treatment than in the control fruit. Our findings indicate that OA and UA effectively affect water migration in blueberry fruit during postharvest storage, which could contribute to improving postharvest preservation techniques.

Reductive stress induced by NRF2/G6PD through glucose metabolic reprogramming promotes malignant transformation in Arsenite-exposed human keratinocytes.

Our previous research found that the nuclear factor-E2-related factor 2 (NRF2) protein was sustained activated in malignant transformation of human keratinocyte (HaCaT cells) caused by NaAsO2, but the role of NRF2 in it remains unknown. In this study, malignant transformation of HaCaT cells and labeled HaCaT cells used to detect mitochondrial glutathione levels (Mito-Grx1-roGFP2 HaCaT cells) were induced by 1.0 µM NaAsO2. Redox levels were measured at passages 0, early stage (passages 1, 7, 14), later stage (passages 21, 28 and 35) of arsenite-treated HaCaT cells. Oxidative stress levels increased at early stage. The NRF2 pathway was sustained activated. Cells and mitochondrial reductive stress levels (GSH/GSSG and NADPH/NADP+) increased. The mitochondrial GSH/GSSG levels of Mito-Grx1-roGFP2 HaCaT cells also increased. The indicators of glucose metabolism glucose-6-phosphate, lactate and the glucose-6-phosphate dehydrogenase (G6PD) levels increased, however Acetyl-CoA level decreased. Expression levels of glucose metabolic enzymes increased. After transfection with NRF2 siRNA, the indicators of glucose metabolism were reversed. After transfection with NRF2 or G6PD siRNA, cells and mitochondrial reductive stress levels decreased and the malignant phenotype was reversed. In conclusion, oxidative stress occurred in the early stage and the NRF2 was sustained high expression. In the later stage, increased NRF2/G6PD through glucose metabolic reprogramming induced reductive stress, thereby leading to malignant transformation.