Comprehensive analysis of spatial heterogeneity reveals the important role of the upper-layer fermented grains in the fermentation and flavor formation of Qingxiangxing baijiu.

Different spatial positions lead to inconsistent fermentation effects and flavors, however, the spatial heterogeneity of Qingxiangxing (QXX) Baijiu remains unknown. We investigated the microbes, flavors, and physicochemical properties of different layers in fermented grains of QXX Baijiu using Illumina HiSeq sequencing, two-dimensional gas chromatography-mass spectrometry (GC × GC-MS) and ultra-high performance liquid chromatography-mass (UHPLC-MS). A total of 79 volatiles, 1596 metabolites, 50 bacterial genera, and 52 fungal genera were identified. The contents distribution followed the order: upper layer > bottom layer > middle layer. Organic acids and derivatives were the main differential metabolites across the three layers. Starch, pH, and reducing sugar levels increased from the upper to bottom layer. Saccharomyces and Lactobacillus were dominant microbes. Pediococcus, the biomarker of upper layer, showed positive correlations with formic acid, ethyl lactate, acetic acid, ethyl linoleate, and ethyl oleate. These findings deepen our understanding of the fermentation and flavor formation mechanisms of QXX Baijiu.

Lignin Derived Ultrathin All-Solid Polymer Electrolytes with 3D Single-Ion Nanofiber Ionic Bridge Framework for High Performance Lithium Batteries.

The lignin derived ultrathin all-solid composite polymer electrolyte (CPE) with a thickness of only 13.2 µm, which possess 3D nanofiber ionic bridge networks composed of single-ion lignin-based lithium salt (L-Li) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) as the framework, and poly(ethylene oxide)/lithium bis(trifluoromethanesulfonyl)imide (PEO/LiTFSI) as the filler, is obtained through electrospinning/spraying and hot-pressing. t. The Li-symmetric cell assembled with the CPE can stably cycle more than 6000 h under 0.5 mA cm-2 with little Li dendrites growth. Moreover, the assembled Li||CPE||LiFePO4 cells can stably cycle over 700 cycles at 0.2 C with a super high initial discharge capacity of 158.5 mAh g-1 at room temperature, and a favorable capacity of 123 mAh g-1 at -20 °C for 250 cycles. The excellent electrochemical performance is mainly attributed to the reason that the nanofiber ionic bridge network can afford uniformly dispersed single-ion L-Li through electrospinning, which synergizes with the LiTFSI well dispersed in PEO to form abundant and efficient 3D Li+ transfer channels. The ultrathin CPE induces uniform deposition of Li+ at the interface, and effectively inhibit the lithium dendrites. This work provides a promising strategy to achieve ultrathin biobased electrolytes for solid-state lithium ion batteries.

Manipulating Deposition Behavior by Polymer Hydrogel Electrolyte Enables Dendrite-Free Zinc Anode for Zinc-Ion Hybrid Capacitors.

Rechargeable aqueous zinc-ion hybrid capacitors (ZHCs) have aroused unprecedented attention because of their high safety, cost effectiveness, and environmental compatibility. However, the intractable issues of dendrite growth and side reactions at the electrode-electrolyte interface deteriorate durability and reversibility of Zn anodes, deeply encumbering the large-scale application of ZHCs. Concerning these obstacles, a negatively charged carboxylated chitosan-intensified hydrogel electrolyte (CGPPHE) with cross-linked networks is reported to stabilize Zn anodes. Beyond possessing good mechanical characteristics, the CGPPHE with polar groups can reduce the desolvation energy barrier of hydrated Zn2+ , constrain the 2D Zn2+ diffusion, and uniformize electric field and Zn2+ flux distributions, assuring dendrite-free Zn deposition with high plating-stripping efficiency. Concurrently, the hydrophilic CGPPHE alleviates harmful hydrogen evolution and corrosion by abating water activity. Accordingly, Zn|CGPPHE|Zn and Zn|CGPPHE|Cu cells exhibit an extended life exceeding 350 h (1600 mAh cm-2 cumulative capacity under 20 mA cm-2 ) and a high average coulombic efficiency of 98.2%, respectively. The resultant flexible ZHCs with CGPPHE and template-regulated carbon cathode present perfect properties in capacity retention (97.7% over 10 000 cycles), energy density (91.8 Wh kg-1 ), and good mechanical adaptability. This study provides insight into developing novel hydrogel electrolytes toward highly rechargeable and stable ZHCs.

Ultrasound-guided injection of botulinum toxin type A blocks cardiac sympathetic ganglion to improve cardiac remodeling in a large animal model of chronic myocardial infarction.

BACKGROUND: Strategies to improve various cardiovascular diseases by blocking cardiac sympathetic ganglion have been increasingly available currently. Botulinum toxin type A (BTA), a typical neurotoxin, has been shown to block neural transmission in a safe and long-lasting manner. OBJECTIVE: The aim of the present preclinical study was to assess the efficacy of BTA microinjection to alleviate cardiac remodeling after chronic myocardial infarction (MI) by blocking cardiac sympathetic ganglion in a canine model. METHODS: Beagles were randomly divided into a control group (saline microinjection with sham surgery), an MI group (saline microinjection with MI), and an MI + BTA group (BTA microinjection with MI). Ultrasound-guided percutaneous BTA or saline injection into the left stellate ganglion (LSG) was performed followed by MI induction via left anterior descending artery occlusion (LADO) or sham surgery. After 30 days, electrocardiography, Doppler echocardiography, LSG function, neural activity, and ventricular electrophysiological detection were performed in all experimental dogs. At the end, LSG and ventricular tissues were collected for further detection. RESULTS: BTA treatment significantly inhibited LSG function and neural activity and improved heart rate variability. Additionally, BTA application alleviated ventricular remodeling, ameliorated cardiac function, and prevented ventricular arrhythmias after 30-day chronic LADO-induced MI. CONCLUSION: Ultrasound-guided percutaneous microinjection of BTA can block cardiac sympathetic ganglion to improve cardiac remodeling in a large animal model of chronic LADO-induced MI. Ultrasound-guided BTA microinjection has potential for clinical application as a novel cardiac sympathetic ganglion blockade strategy for MI.

Metabolism regulator adiponectin prevents cardiac remodeling and ventricular arrhythmias via sympathetic modulation in a myocardial infarction model.

The stellate ganglia play an important role in cardiac remodeling after myocardial infarction (MI). This study aimed to investigate whether adiponectin (APN), an adipokine mainly secreted by adipose tissue, could modulate the left stellate ganglion (LSG) and exert cardioprotective effects through the sympathetic nervous system (SNS) in a canine model of MI. APN microinjection and APN overexpression with recombinant adeno-associated virus vector in the LSG were performed in acute and chronic MI models, respectively. The results showed that acute APN microinjection decreased LSG function and neural activity, and suppressed ischemia-induced ventricular arrhythmia. Chronic MI led to a decrease in the effective refractory period and action potential duration at 90% and deterioration in echocardiography performance, all of which was blunted by APN overexpression. Moreover, APN gene transfer resulted in favorable heart rate variability alteration, and decreased cardiac SNS activity, serum noradrenaline and neuropeptide Y, which were augmented after MI. APN overexpression also decreased the expression of nerve growth factor and growth associated protein 43 in the LSG and peri-infarct myocardium, respectively. Furthermore, RNA sequencing of LSG indicated that 4-week MI up-regulated the mRNA levels of macrophage/microglia activation marker Iba1, chemokine ligands (CXCL10, CCL20), chemokine receptor CCR5 and pro-inflammatory cytokine IL6, and downregulated IL1RN and IL10 mRNA, which were reversed by APN overexpression. Our results reveal that APN inhibits cardiac sympathetic remodeling and mitigates cardiac remodeling after MI. APN-mediated gene therapy may provide a potential therapeutic strategy for the treatment of MI.

Enrichment of the Postdischarge GRACE Score With Deceleration Capacity Enhances the Prediction Accuracy of the Long-Term Prognosis After Acute Coronary Syndrome.

Background: Cardiac autonomic nerve imbalance has been well documented to provide a critical foundation for the development of acute coronary syndrome (ACS) but is not included in the postdischarge GRACE score. We investigated whether capturing cardiac autonomic nervous system (ANS)-related modulations by 24-h deceleration capacity (DC) could improve the capability of existing prognostic models, including the postdischarge Global Registry of Acute Coronary Events (GRACE) score, to predict prognosis after ACS. Method: Patients with ACS were assessed with 24-h Holter monitoring in our department from June 2017 through June 2019. The GRACE score was calculated for postdischarge 6-month mortality. The patients were followed longitudinally for the incidence of major adverse cardiac events (MACEs), set as a composite of non-fatal myocardial infarction and death. To evaluate the improvement in its discriminative and reclassification capabilities, the GRACE score with DC model was compared with a model using the GRACE score only, using area under the receiver-operator characteristic curve (AUC), Akaike's information criteria, the likelihood ratio test, category-free integrated discrimination index (IDI) and continuous net reclassification improvement (NRI). Results: Overall, 323 patients were enrolled consecutively. After the follow-up period (mean, 43.78 months), 41 patients were found to have developed MACEs, which were more frequent among patients with DC <2.5 ms. DC adjusted for the GRACE score independently predicted the occurrence of MACEs with an adjusted hazard ratio (HR) of 0.885 and 95% CI of 0.831-0.943 (p < 0.001). Moreover, adding DC to the GRACE score only model increased the discriminatory ability for MACEs, as indicated by the likelihood ratio test (χ2 = 9.277, 1 df; p < 0.001). The model including the GRACE score combined with DC yielded a lower corrected Akaike's information criterion compared to that with the GRACE score alone. Incorporation of the DC into the existing model that uses the GRACE score enriched the net reclassification indices (NRIe>0 7.3%, NRIne>0 12.8%, NRI>0 0.200; p = 0.003). Entering the DC into the GRACE score model enhanced discrimination (IDI of 1.04%, p < 0.001). Conclusion: DC serves as an independent and effective predictor of long-term adverse outcomes after ACS. Integration of DC and the postdischarge GRACE score significantly enhanced the discriminatory capability and precision in the prediction of poor long-term follow-up prognosis.

Novel Insight Into Long-Term Risk of Major Adverse Cardiovascular and Cerebrovascular Events Following Lower Extremity Arteriosclerosis Obliterans.

Background: Patients with lower extremity arteriosclerosis obliterans (LEASO) are more likely to appear to be associated with adverse cardiovascular outcomes. Currently, few studies have reported the sex-specific characteristics and risk of major cardiovascular and cerebrovascular adverse events (MACCEs) in LEASO. Our study was conducted to determine the characteristics and contributions of LEASO to MACCEs in males and females. Methods: We conducted a single-center retrospective study of consecutively enrolled patients with first-diagnosed LEASO at Renmin Hospital of Wuhan University from November 2017 to November 2019. The ratio of patients between the LEASO and control groups was 1 to 1 and based on age, sex, comorbid diabetes mellitus and hypertension, current smoking and medications. The occurrence of MACCEs was used as the primary endpoint of this observational study. Results: A LEASO group (n = 430) and control group (n = 430) were enrolled in this study. A total of 183 patients experienced MACCEs during an average of 38.83 ± 14.28 months of follow-up. Multivariate Cox regression analysis indicated that LEASO was an independent predictor of the occurrence of MACCEs in all patients (HR: 2.448, 95% CI: 1.730-3.464, P < 0.001). Subgroup analysis by sex subgroup was conducted for sex, and LEASO was also an independent predictor of the occurrence of MACCEs in both male cases (HR: 2.919, 95% CI: 1.776-4.797, P < 0.001) and female cases (HR: 1.788, 95% CI: 1.110-2.880, P = 0.017). Moreover, Kaplan-Meier analysis indicated no significant difference in event-free survival between patients of different sexes with LEASO (χ2 = 0.742, P = 0.389). Conclusion: LEASO tended to a useful risk stratified indicator for MACCEs in both male and female patients in our study. Notably, attention should be given to patients with LEASO who should undergo comprehensive cardiovascular evaluation and intervention, even if there is a lack of traditional cardiovascular risk factors.

Deceleration Capacity Improves Prognostic Accuracy of Relative Increase and Final Coronary Physiology in Patients With Non-ST-Elevation Acute Coronary Syndrome.

Background: Both coronary physiology and deceleration capacity (DC) showed prognostic efficacy for patients with acute coronary syndrome (ACS). This retrospective cohort study was performed to evaluate the prognostic implication of DC combined with the relative increase and final coronary physiology as detected by quantitative flow ratio (QFR) for patients with non-ST-elevation ACS (NSTE-ACS) who underwent complete and successful percutaneous coronary intervention (PCI). Methods: Patients with NSTE-ACS who underwent PCI with pre- and post-procedural QFR in our department between January 2018 and November 2019 were included. The 24-hour deceleration capacity (DC 24h) was obtained via Holter monitoring. The incidence of major adverse cardiac and cerebrovascular events (MACCEs) during follow up was defined as the primary outcome. The optimal cutoffs of the relative increase, final QFR, and DC 24h for prediction of MACCEs were determined via receiver operating characteristic (ROC) analysis and the predictive efficacies were evaluated with multivariate Cox regression analysis. Results: Overall, 240 patients were included. During a mean follow up of 21.3 months, 31 patients had MACCEs. Results of multivariate Cox regression analyses showed that a higher post-PCI QFR [adjusted hazard ratio (HR): 0.318; 95% confidence interval (CI): 0.129-0.780], a higher relative QFR increase (HR: 0.161; 95% CI: 0.066-0.391], and a higher DC (HR: 0.306; 95% CI: 0.134-0.701) were all independent predictors of lower risk of MACCEs. Subsequently, incorporating low DC (≤2.42) into the risk predicting model with clinical variables, the predictive efficacies of low relative QRS increase (≤23%) and low post-PCI QFR (≤0.88) for MACCEs were both significantly improved. Conclusions: The DC combined with relative increase and final coronary physiology may improve the predictive efficacy of existing models based on clinical variables for MACCEs in NSTE-ACS patients who underwent complete and successful PCI.

Relationship Between Immunoinflammation and Coronary Physiology Evaluated by Quantitative Flow Ratio in Patients With Coronary Artery Disease.

Background: The association between coronary physiology and immunoinflammation has not been investigated. We performed a retrospective study using quantitative flow ratio (QFR) to evaluate the interaction between immunoinflammatory biomarkers and coronary physiology. Methods: A total of 172 patients with CAD who underwent coronary arteriography (CAG) and QFR were continuously enrolled from May 2020 to February 2021. As a quantitative indicator of coronary physiology, QFR can reflect the functional severity of coronary artery stenosis. The target vessel measured by QFR was defined as that with the most severe lesions. Significant coronary anatomical stenosis was defined as 70% stenosis in the target vessel. Results: Compared with the QFR > 0.8 group, interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were increased and CD3+ and CD4+ T lymphocyte counts were decreased in the QFR ≤ 0.8 group. In addition, patients with DS ≤ 70% had higher IL-6, IL-10, and TNF-α levels and decreased CD3+ and CD4+ T lymphocyte counts than those with DS > 70%. Logistic regression analysis indicated IL-6 to be an independent predictor of significant coronary functional and anatomic stenosis (odds ratio, 1.125; 95% CI, 1.059-1.196; P < 0.001). Receiver operating characteristic (ROC) analyses showed that IL-6 > 6.36 was predictive of QFR ≤ 0.8 of the target vessel. The combination of IL-6, IL-10 and CD4 improved the value for predicting QFR ≤ 0.8 of the target vessel (AUC, 0.737; 95% CI, 0.661-0.810). Conclusion: Among immunoinflammatory biomarkers, IL-6 was independently associated with a higher risk of QFR ≤ 0.8 of the target vessel. The combination of immunoinflammatory biomarkers was highly predictive of significant coronary functional and anatomic stenosis.

Novel Insights Into the Interaction Between the Autonomic Nervous System and Inflammation on Coronary Physiology: A Quantitative Flow Ratio Study.

Background: Heart rate variability (HRV) was proposed as a noninvasive biomarker to stratify the risk of cardiovascular disease. However, it remains to be determined if HRV can be used as a surrogate for coronary artery physiology as analyzed by quantitative flow ratio (QFR) in patients with new-onset unstable angina pectoris (UAP). Methods: A total of 129 consecutive patients with new-onset UAP who underwent 24-h long-range 12-channel electrocardiography from June 2020 to December 2020 were included in this study. HRV, coronary angiography, and QFR information was retrieved from patient medical records, the severity of coronary lesions was evaluated using the Gensini score (GS), and total atherosclerotic burden was assessed using the three-vessel contrast QFR (3V-cQFR) calculated as the sum of cQFR in three vessels. Results: Multivariate logistic analysis showed that low-frequency power (LF) and high-sensitivity C-reactive protein (hs-CRP) were directly correlated with functional ischemia of target vessel, which were inversely correlated with total atherosclerotic burden as assessed by 3V-cQFR. Moreover, incorporation of the increase in LF into the existing model that uses clinical risk factors, GS, and hs-CRP significantly increased the discriminatory ability for evaluating coronary artery physiology of target vessel. Conclusions: LF and hs-CRP are independently associated with functional ischemia in patients with new-onset UAP. The relative increase of LF and hs-CRP could add value to the use of classical cardiovascular risk factors to predict the functional severity of coronary artery stenosis. Our results suggest a potential association between the autonomic nervous system, inflammation, and coronary artery physiology.

Vagal Stimulation and Arrhythmias.

I mbalance of the sympathetic and parasympathetic nervous systems is probably the most prevalent autonomic mechanism underlying many a rrhythmias . Recently, vagus nerve stimulation ( VNS has emerged as a novel therapeutic modality to treat arrhythmias through its anti adrenergic and anti inflammatory actions . C linical trials applying VNS to the cervical vagus nerve in heart failure pati en ts yielded conflicting results, possibly due to limited understanding of the optimal stimulation parameters for the targeted cardiovascular diseases. Transcutaneous VNS by stimulating the auricular branch of the vagus nerve, has attracted great attention d ue to its noninvasiveness. In this r eview, we summarize current knowledge about the complex relationship between VNS and cardiac arrhythmias and discuss recent advances in using VNS , particularly transcutaneous VNS , to treat arrhythmias.

Using shadow page cache to improve isolated drivers performance.

With the advantage of the reusability property of the virtualization technology, users can reuse various types and versions of existing operating systems and drivers in a virtual machine, so as to customize their application environment. In order to prevent users' virtualization environments being impacted by driver faults in virtual machine, Chariot examines the correctness of driver's write operations by the method of combining a driver's write operation capture and a driver's private access control table. However, this method needs to keep the write permission of shadow page table as read-only, so as to capture isolated driver's write operations through page faults, which adversely affect the performance of the driver. Based on delaying setting frequently used shadow pages' write permissions to read-only, this paper proposes an algorithm using shadow page cache to improve the performance of isolated drivers and carefully study the relationship between the performance of drivers and the size of shadow page cache. Experimental results show that, through the shadow page cache, the performance of isolated drivers can be greatly improved without impacting Chariot's reliability too much.