miRNAs Influence m6A RNA Methylation through FTO and IGF2BP2 in Pressure Overload-Induced Heart Failure.

BACKGROUND: N6-adenosine methylation (m6A) is a prevalent RNA modification associated with heart failure, alongside aberrant miRNA expression. Despite indications of miRNAs regulating m6A modification, their specific influence on m6A in heart failure remains unclear. METHODS: The initial analysis utilized transcriptome and methylation sequencing data from GSE131296 in mice to identify key m6A methylation enzymes in heart failure and construct an associated network. Integration of miRNA sequencing data from GSE231700 revealed miRNAs influencing m6A methylation enzymes, contributing to the formation of a comprehensive network. Furthermore, differential miRNA levels in human serum were assessed via qPCR, and the expression of m6A methyltransferases in the heart was confirmed using proteomic databases. RESULTS: In pressure overload-induced heart failure mice, 217 mRNAs showed differential expression, with FTO and IGF2BP2 identified as m6A methylation enzymes. Subsequent methylation sequencing revealed 884 highly-methylated and 178 lowly-methylated peaks, establishing a network linking Fto and Igf2bp2 with these peaks. Additionally, miRNA sequencing identified 156 differentially expressed miRNAs, including let-7b-5p and miR-23b-3p, predicted as m6Aregulating miRNAs, both elevated in heart failure patients. CONCLUSION: miR-23b-3p and let-7b-5p are identified as potential regulators of RNA methylation in heart failure, acting via FTO and IGF2BP2, offering new insights into the role of miRNA-mediated RNA methylation and its potential therapeutic avenues for heart failure.

The association between O2-pulse slope ratio and functional severity of coronary stenosis: A combined cardiopulmonary exercise testing and quantitative flow ratio study.

Background: The role of cardiopulmonary exercise testing (CPET) parameters in evaluating the functional severity of coronary disease remains unclear. The aim of this study was to quantify the O2-pulse morphology and investigate its relevance in predicting the functional severity of coronary stenosis, using Murray law-based quantitative flow ratio (µQFR) as the reference. Methods: CPET and µQFR were analyzed in 138 patients with stable coronary artery disease (CAD). The O2-pulse morphology was quantified through calculating the O2-pulse slope ratio. The presence of O2-pulse plateau was defined according to the best cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8. Results: The optimal cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8 was 0.4, with area under the curve (AUC) of 0.632 (95 % CI: 0.505-0.759, p = 0.032). The total discordance rate between O2-pulse slope ratio and µQFR was 27.5 %, with 13 patients (9.4 %) being classified as mismatch (O2-pulse slope ratio > 0.4 and µQFR ≤ 0.8) and 25 patients being classified as reverse-mismatch (O2-pulse slope ratio ≤ 0.4 and µQFR > 0.8). Angiography-derived microvascular resistance was independently associated with mismatch (OR 0.07; 95 % CI: 0.01-0.38, p = 0.002) and reverse-mismatch (OR 9.76; 95 % CI: 1.47-64.82, p = 0.018). Conclusion: Our findings demonstrate the potential of the CPET-derived O2-pulse slope ratio for assessing myocardial ischemia in stable CAD patients.

Axitinib targets cardiac fibrosis in pressure overload-induced heart failure through VEGFA-KDR pathway.

Background: There are no specific clinical medications that target cardiac fibrosis in heart failure (HF). Recent studies have shown that tyrosine kinase inhibitors (TKIs) may benefit fibrosis in various organs. However, there is limited research on their application in cardiac fibrosis. Axitinib, an FDA-approved tyrosine kinase inhibitor, was used to evaluate its effects on cardiac fibrosis and function in pressure overload-induced heart failure. Methods: To build a pharmacological network, the pharmacological targets of axitinib were first retrieved from databases and coupled with key heart failure gene molecules for analysis and prediction. To validate the results outlined above, 8-week-old male C57BL/6 J mice were orally administrated of axitinib (30 mg/kg) daily for 8 weeks after Transverse Aortic Constriction (TAC) surgery. Mouse cardiomyocytes and cardiac fibroblasts were used as cell lines to test the function and mechanism of axitinib. Results: We found that the pharmacological targets of axitinib could form a pharmacological network with key genes involved in heart failure. The VEGFA-KDR pathway was found to be closely related to the differential gene expression of human heart-derived primary cardiomyocyte cell lines treated with axitinib, based on analysis of the publicly available dataset. The outcomes of animal experiments demonstrated that axitinib therapy greatly reduced cardiac fibrosis and improved TAC-induced cardiac dysfunction. Further research has shown that the expression of transforming growth factor-ß(TGF-ß) and other fibrosis genes was significantly reduced in vivo and in vitro. Conclusion: Our study provides evidence for the repurposing of axitinib to combat cardiac fibrosis, and offers new insights into the treatment of patients with HF.

Reduced nitrogen fertilization from pre-flowering to pre-veraison alters phenolic profiles of Vitis vinifera L. Cv. Cabernet Gernischt wine of Yantai, China.

Nitrogen (N) fertilization is important for grape growth and wine quality. Unreasonable N fertilizer application affects wine growth and has a negative impact on wine quality. Therefore, it is essential to address the mismatch between N application and wine composition. To regulate vine growth and improve grape and wine quality, Cabernet Gernischt (Vitis vinifera L.) grapevines were subjected to lower levels of N, compared to normal N supply treatments, during the grape growing seasons of 2019 and 2020 in the wine region of Yantai, China. The effects of reduced N application from pre-boom to pre-veraison on vine growth, yield and composition of grapes, and dry red wine anthocyanin and non-anthocyanin phenolic compound content were studied. We found that reduced N application significantly decreased dormant shoot fresh mass and yield. However, the effect of N application on fruit ripening depended on the season. Nitrogen-reduction treatment significantly improved wine phenolic parameters, including total phenolics, tannins, and anthocyanins, and enhanced most of the individual anthocyanins and some non-anthocyanin phenolics, especially stilbenes, including piceatannol, trans-resveratrol, and polydatin, regardless of the season. Overall, our findings highlight the importance of reducing N application during the grape growing season in order to modify the wine phenolic profiles.

Chinese stroke patients with atrial fibrillation used Robert's age-adjusted warfarin loading protocol obtained good INR results within therapeutic range.

To assess whether Roberts' age-adjusted warfarin loading protocol is effective in Chinese patients and whether the SAMeTT2R2 score can predict international normalized ratio (INR) control. Roberts' protocol for warfarin titration was applied to patients with non-valvular atrial fibrillation (NVAF) complicated with ischemic stroke at the Department of Neurology between 2014 and 2019. Clinical and sociodemographic variables were recorded. A minimum of 1-year follow-up was used to calculate the time in therapeutic range (TTR) of the INR. A total of 94 acute ischemic stroke patients with NVAF were included in the study. Seventy-seven (81.9%) of the patients had attained stable INR (2.0-3.0) at the fifth dose, and 90.0% of the patients had achieved stable INR on the ninth day. Seventeen (18.1%) of the patients had an INR > 4 during dose-adjustment period. Patients with INR > 4 had significantly lower body weight (53.8 vs. 63.1 kg, P = 0.014), lower rate of achievement of stable INR (35.3% vs. 92.2%, P = 0.000), and lower rate of TTR ≥ 65% (23.5% vs. 70.1%, P = 0.001), but with no significant increase in bleeding risk. A total of 89 patients underwent long-term INR follow-up, of which 58 (65.2%) patients achieved TTR ≥ 65%. Patients with poor TTR had significantly lower body weight (56.3 vs. 63.7 kg, P = 0.020) and lower rate of stable INR achievement (64.5% vs. 89.7%, P = 0.002). All 94 patients had SAMeTT2R2 score ≥ 2. There was no linear association between SAMeTT2R2 score and the rate of TTR ≥ 65% (Ptrend = 0.095). Chinese ischemic stroke patients with NVAF on warfarin can safely and quickly achieve therapeutic INR using Roberts' age-adjusted protocol and can obtain a good TTR. Lower body weight may be a predictor of poor TTR and INR > 4. Patients who have not attained stable INR after adjusting the dose five times are at high risk for poor TTR. SAMeTT2R2 score may not predict TTR in Chinese ischemic stroke patients with NVAF.

Hypersensitive C-reactive protein as a potential indicator for predicting left ventricular hypertrophy in elderly community-dwelling patients with hypertension.

BACKGROUND: The aim of this study was to investigate the relationship between Hypersensitive C-reactive protein (hs-CRP) and left ventricular hypertrophy (LVH) in elderly community-dwelling patients with hypertension. METHODS: A cross-sectional study was conducted, involving the recruitment of 365 elderly hypertensive residents ≥ 65 years of age from five communities. The participants were divided into two groups: an LVH group (n = 134) and a non-LVH group (n = 231), based on the left ventricular mass index (LVMI) determined by echocardiography. Spearman correlation analysis was used to assess the relationship between hs-CRP and LVH. Univariate and Multivariate analysis was performed to detect variables associated with LVH. The diagnostic value of hs-CRP for LVH was expressed as the area under the receiver operating characteristic (ROC) curve. RESULTS: The incidence of LVH in elderly hypertension patients in the community was 36.7%. The hs-CRP levels were significantly higher in subjects with LVH compared to those without LVH (1.9 [0.8, 2.9] vs. 0.7 [0.4, 1.4], P = 0.002). Spearman correlation analysis demonstrated a positive correlation between hs-CRP and LVMI (r = 0.246, P < 0.001), as well as with IVST (r = 0.225, P < 0.001) and LVPWT (r = 0.172, P = 0.001). Among elderly hypertensive residents in the community, the cut-off value of hs-CRP for diagnosing LVH was 1.25 mg/L (sensitivity: 57.5%; specificity: 78.4%), and the area under the ROC curve for hs-CRP to predict LVH was 0.710 (95%CI: 0.654-0.766; P < 0.001). In the final model, hs-CRP ≥ 1.25 mg/L (OR = 3.569; 95%CI, 2.153-5.916; P<0.001) emerged as an independent risk factor for LVH. This association remained significant even after adjusting for various confounding factors (adjusted OR = 3.964; 95%CI, 2.323-6.765; P < 0.001). CONCLUSIONS: This community-based cohort of elderly hypertensive individuals demonstrates a strong association between hs-CRP levels and the presence of LVH. The hs-CRP ≥ 1.25 mg/L may serve as an independent predictor for LVH in hypertensive subjects and exhibit good diagnostic efficacy for LVH.

Genetically Determined Rheumatoid Arthritis May Not Affect Heart Failure: Insights from Mendelian Randomization Study.

Background: Evidence from observational epidemiological studies indicated that rheumatoid arthritis (RA) increased the risk of heart failure (HF). However, there is a possibility that the correlation is not explained as a causative role for RA in the pathogenesis of HF. A two-sample Mendelian randomization (MR) framework was designed to explore the potential etiological role of RA in HF to identify the target to improve the burden of HF disease. Methods: To assess the causal association between RA and HF, we analyzed summary statistics from genome-wide association studies (GWASs) for individuals of European descent. Genetic instruments for RA were identified at a genome-wide significance threshold (p < 5 × 10-8). Corresponding data were obtained from a GWAS meta-analysis (95,524 cases and 1,270,968 controls) to identify genetic variants underlying HF. MR estimates were pooled using the inverse variance weighted method. Complementary analyses were conducted to assess the robustness of the results. Results: There was no evidence of a causal association between genetically predicted RA and HF [odds ratio (OR), 1.00; 95% confidence interval (CI), 0.99-1.02; P = 0.60]. Various sensitivity analyses suggested no pleiotropy detected (all p > 0.05). Conclusion: Our findings did not support the causal role of RA in the etiology of HF. As such, therapeutics targeted at the control of RA may have a lower likelihood of effectively controlling the occurrence of HF.

Associations between COVID-19 Vaccination and Behavioural Intention to Receive Seasonal Influenza Vaccination among Chinese Older Adults: A Population-Based Random Telephone Survey.

During the Coronavirus Disease 2019 (COVID-19) pandemic, seasonal influenza remained a significant health threat for older adults. Seasonal influenza vaccination (SIV) is highly effective and safe for older adults. This study investigated the associations of COVID-19 vaccination, perceptions related to COVID-19 and SIV, with the behavioural intention to receive SIV among older adults in Hong Kong, China. A random telephone survey was conducted among 440 community-dwelling Hong Kong residents aged 65 years or above, between November 2021 and January 2022. Among the participants, 55.7% intended to receive SIV in the next year. After adjustment for significant background characteristics, concern about whether SIV and COVID-19 vaccination would negatively affect each other was associated with a lower intention to receive SIV, while a perceived higher risk of co-infection with COVID-19 and seasonal influenza was positively associated with the dependent variable. In addition, the perceived severe consequences of seasonal influenza, perceived benefits of SIV, received cues to action from doctors and participants' family members or friends, and the perception that more older people would receive SIV was associated with a higher behavioural intention. Future programmes promoting SIV among older adults should modify perceptions related to COVID-19 vaccination and SIV at the same time.

Prevalence and risk factors of osteosarcopenia: a systematic review and meta-analysis.

BACKGROUND: Osteosarcopenia is a syndrome with a concomitant presence of both sarcopenia and osteopenia/osteoporosis. It increases the risk of frailty, falls, fractures, hospitalization, and death. Not only does it burden the lives of older adults, but it also increases the economic burden on health systems around the world. This study aimed to review the prevalence and risk factors of osteosarcopenia to generate important references for clinical work in this area. METHODS: Pubmed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, CBM, and VIP databases were searched from inception until April 24th, 2022. The quality of studies included in the review was evaluated using the NOS and AHRQ Scale. Pooled effects of the prevalence and associated factors were calculated using random or fixed effects models. Egger's test, Begg's test, and funnel plots were used to test the publication bias. Sensitivity analysis and subgroup analysis were conducted to identify the sources of heterogeneity. Statistical analysis was performed using Stata 14.0 and Review Manager 5.4. RESULTS: A total of 31 studies involving 15,062 patients were included in this meta-analysis. The prevalence of osteosarcopenia ranged from 1.5 to 65.7%, with an overall prevalence of 21% (95% CI: 0.16-0.26). The risk factors for osteosarcopenia were female (OR 5.10, 95% CI: 2.37-10.98), older age (OR 1.12, 95% CI: 1.03-1.21), and fracture (OR 2.92, 95% CI: 1.62-5.25). CONCLUSION: The prevalence of osteosarcopenia was high. Females, advanced age, and history of fracture were independently associated with osteosarcopenia. It is necessary to adopt integrated multidisciplinary management.

Reappraising the role of chronic inflammatory burden in heart failure.

BACKGROUND: Heart failure (HF) is a clinical syndrome associated with poor quality of life, substantial utilization of health care resources, and premature mortality. It is now considered to be the most urgent unmet medical need in the field of cardiovascular disease. Accumulated evidence suggested that comorbidity-driven inflammation has emerged as a critical component of HF pathogenesis. Although anti-inflammatory therapies have increased in popularity, very few effective treatments are still available. A comprehensive understanding of the interplay between chronic inflammation and its impact on HF will facilitate the identification of future therapeutic targets. METHODS: A two-sample Mendelian randomization study was conducted to assess the association between genetic liability for chronic inflammation and HF. By analyzing functional annotations and enrichment data, we were able to identify common pathophysiological mechanisms. RESULTS: The present study did not provide evidence for chronic inflammation as the cause of HF and the reliability of the results was enhanced by the other three Mendelian randomization analysis methods. Functional annotations of genes and pathway enrichment analyses have indicated that chronic inflammation and HF share a common pathophysiology. CONCLUSIONS: The associations between chronic inflammation and cardiovascular disease from observational studies may be explained by shared risk factors and comorbidities rather than direct effects.

Autoimmune glial fibrillary acidic protein astrocytopathy: clinical analysis and review of 15 cases.

BACKGROUND: To review clinical characteristics, auxiliary examination results, treatment effects, and outcomes of patients with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). METHODS: We collated and retrospectively analyzed clinical data of 15 patients admitted with clinical characteristics of an autoimmune GFAP-A acute encephalitis or meningitis phenotype. RESULTS: All patients were diagnosed with acute-onset meningoencephalitis and meningoencephalomyelitis. Initial presentations included pyrexia and headache at onset; dual symptoms of prominent tremor with urinary and bowel dysfunction; ataxia, psychiatric and behavioral abnormalities, and impaired consciousness; neck resistance; reduced extremity muscle strength; blurred vision; epileptic seizures; and reduced basic blood pressure. Cerebrospinal fluid (CSF) examination showed that the degree of protein elevation was significantly higher than the degree of increase in white blood cells. Moreover, in the absence of obvious low chloride and glucose levels, CSF chloride levels decreased in 13 patients, accompanied by a CSF glucose level decrease in four. Brain abnormalities were found in magnetic resonance imaging of ten patients, with a linear radial perivascular enhancement present in the lateral ventricles of two patients and symmetric abnormalities in the splenium of the corpus callosum in three patients. CONCLUSIONS: Autoimmune GFAP-A may be a spectrum disorder, with acute- or subacute-onset meningitis, encephalitis, and myelitis being the main phenotypes. When used for acute stage treatment, combined hormone and immunoglobulin therapy was superior to hormone pulse therapy or immunoglobulin pulse therapy alone. However, hormone pulse therapy alone without immunoglobulin pulse therapy was associated with a greater number of remaining neurological deficits.

Upper Limb Movement Decoding Scheme Based on Surface Electromyography Using Attention-Based Kalman Filter Scheme.

Convolutional neural network (CNN)-based models are widely used in human movement decoding based on surface electromyography. However, they capture only the spatial information of the surface electromyography and lack prior knowledge of the system, resulting in unsatisfactory decoding accuracy. To address these issues, we propose an attention-based Kalman filter scheme (AKFS), which uses an attention-based CNN model to better extract temporal information and a KF to add prior knowledge of the system. We further solve the problem of insufficient data due to the short training time of new subjects by using a transfer learning method based on a fine-tuning strategy. The proposed scheme was tested in four scenarios: intra-session, intra-session long-time use, inter-subject, and inter-subject with a fine-tuning strategy. The proposed attention-based CNN model outperformed the vanilla CNN model and a hybrid CNN-long short-term memory (LSTM) model in intra-session and intra-session long-time use. After fine-tuning with a small amount of data on a new subject, the attention-based CNN model achieved higher decoding accuracy than the vanilla CNN model and lower response time than CNN-LSTM model. Furthermore, the schemes with KF outperformed the schemes without KF in all scenarios. Our proposed scheme improves the decoding accuracy of the traditional CNN model for a single subject by better capturing the temporal information of the surface electromyography signal and increasing the prior knowledge of the system. Additionally, the proposed scheme can be easily transferred to a new subject using only a small amount of data.

Effects of Childhood Maltreatment on Self-Compassion: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review aims to estimate the extent to which childhood maltreatment influences self-compassion in later life. METHOD: Four English databases (Web of Science, PsycINFO, PubMed, and PsycARTICLES) and three Chinese databases (China National Knowledge Infrastructure, Wanfang, and Weipu) were systematically searched. We extracted data related to the associations between child maltreatment and self-compassion and pooled them using random effect models. FINDINGS: A total of 20 eligible studies were included involving 6,877 participants in the analyses. Overall child maltreatment was negatively related to self-compassion (r = -.28, p < .001); emotional abuse and neglect were negatively related to self-compassion (r = -.28, p < .01; r = -.31, p < .01, respectively) at a moderate level; and physical abuse, sexual abuse, and physical neglect were negatively related to self-compassion (r = -.12, p < .01; r = -.10, p < .01; and r = -.22, p < .001, respectively) at a small level. CONCLUSION: The results indicate that overall and subtypes of maltreatment are associated with decreased self-compassion, and child intervention programs focused on self-compassion should be designed to protect the well-being of individuals with a history of childhood maltreatment.

Modification of wine phenolic profiles by gibberellic acid application in 'Cabernet Gernischt' grapevines before anthesis.

BACKGROUND: Vitis vinifera L. 'Cabernet Gernischt' grapes from the Yantai wine region of China usually form dense clusters and contain low phenolic content. We applied five concentrations (ranged from 5 to 25 mg L-1 ) of gibberellic acid (GA3 ) to 'Cabernet Gernischt' before anthesis to decrease cluster compactness in two consecutive vintages. Yield indices, grape maturity, and wine phenolic compounds were determined. RESULTS: GA3 application significantly reduced cluster compactness, bunch weight, and yield per vine, but it did not significantly improve fruit ripening. The levels of total phenolics, total tannins, and total anthocyanins in wine were enhanced by GA3 application, with 10 and 15 mg L-1 GA3 treatments consistently producing a significant increase in the concentrations of mavidin, cyanidin, and their derivatives. Specifically, trans-resveratrol was consistently significantly increased by 15 mg L-1 GA3 application. Principal component analysis of phenolic compounds demonstrated the differences among wines produced from GA3 treatment groups and the control. CONCLUSION: Overall, wine phenolic profiles could be significantly modified by application of low concentrations of GA3 before anthesis. Application of high levels of GA3 is not recommended due to significant yield decrease. © 2022 Society of Chemical Industry.

Anatomical and Functional Discrepancy in Diabetic Patients With Intermediate Coronary Lesions　- An Intravascular Ultrasound and Quantitative Flow Ratio Study.

BACKGROUND: Data regarding the performance of computational fractional flow reserve in patients with diabetes mellitus (DM) remain scarce. This study sought to explore the impact of DM on quantitative flow ratio (QFR) and its association with intravascular ultrasound (IVUS)-derived anatomical references.Methods and Results: IVUS and QFR were retrospectively analyzed in 237 non-diabetic and 93 diabetic patients with 250 and 102 intermediate lesions, respectively. Diabetics were further categorized based on adequate (HbA1c <7.0%: 47 patients with 53 lesions) or poor (HbA1c ≥7.0%: 46 patients with 49 lesions) glycemic control. Lesions with QFR ≤0.8 or minimum lumen area (MLA) ≤4.0 mm2and plaque burden (PB, %) ≥70 were considered functionally or anatomically significant, respectively. PB increased, and MLA decreased stepwise across non-diabetics, diabetics with adequate glycemic control and those with poor glycemic control. In contrast, QFR was similar among the 3 groups. PB correlated significantly with the QFR for lesions in non-diabetics, but not for lesions in diabetics. DM was independently correlated with the functionally non-significant lesions (QFR >0.8) with high-risk IVUS features (MLA ≤4.0 mm2and PB ≥70; OR 2.053, 95% CI: 1.137-3.707, P=0.017). When considering the effect of glycemic control, HbA1c was an independent predictor of anatomical-functional discordance (OR 1.347, 95% CI: 1.089-1.667, P=0.006). CONCLUSIONS: Anatomical-functional discordance of intermediate coronary lesions assessed by IVUS and QFR is exacerbated in patients with diabetes, especially when glycemia is poorly controlled.

Comparative mitogenomes provide new insights into phylogeny and taxonomy of the subfamily Xenocyprinae (Cypriniformes: Cyprinidae).

Xenocyprinae is a cyprinid subfamily that not only has a discrete geographic distribution but also has a long history dating to the Early Miocene. However, it is controversial whether systematic classification and some species validity of Xenocyprinae exist, as well as its phylogenetic relationships and evolutionary history. In the present study, we first reviewed the description and taxonomic history of Xenocyprinae, and then the complete mitochondrial genome of Distoechodon compressus, an endemic and locally distributed species belonging to Xenocyprinae, was sequenced and annotated. Finally, all the mitogenomes of Xenocyprinae were compared to reconstruct the phylogenetic relationship and estimate the divergence time. The results showed that the mitogenomes are similar in organization and structure with 16618-16630 bp length from 12 mitogenomes of eight species. Phylogenetic analysis confirmed the monology of Xenocyprinae and illustrated three clades within the Xenocyprinae to consist of ambiguous generic classification. Plagiognathops is a valid genus located at the base of the phylogenetic tree. The genus Xenocypris was originally monophyletic, but X. fangi was excluded. Divergence time estimation revealed that the earliest divergence within Xenocyprinae occurred approximately 12.1 Mya when Plagiognathops separated from the primitive Xenocypris. The main two clades (Xenocypris and (Distoechodon + Pseudobrama + X. fangi)) diverged 10.0 Mya. The major divergence of Xenocyprinae species possibly occurred in the Middle to Late Miocene and Late Pliocene, suggesting that speciation and diversifications could be attributed to the Asian monsoon climate. This study clarifies some controversial issues of systematics and provides essential information on the taxonomy and phylogeny of the subfamily Xenocyprinae.

Influence of Oxygen Management during the Post-Fermentation Stage on Acetaldehyde, Color, and Phenolics of Vitis vinifera L. Cv. Cabernet Sauvignon Wine.

Oxygen exposure is unavoidable and the impact of its management during the post-fermentation stage (PFS) on dry red wine is poorly investigated. This study was dedicated to the variation of acetaldehyde, color and phenolics of Cabernet Sauvignon dry red wine during five discontinuous oxidation cycles of four levels of controlled oxygen supply, which were carried out to simulate probable oxidation during the PFS. Free SO2 disappeared after the first, second and third oxidation cycles in wines with high, medium and low levels of oxygen exposure severally, but subsequent oxygen exposure below or equal to 2 mg O2/L per cycle had little effect while 3-3.9 mg O2/L per cycle dramatically facilitated acetaldehyde accumulation, which was accompanied by an enormous variation in color and pigments, especially when total oxygen consumption was above 10 mg/L. The utilization of clustered heatmap and partial least square regression demonstrated the feasibility of characterization of wine oxidation degree using the chemical parameters measured by UV-spectrophotometry. Oxygen exposure during the PFS should be emphatically controlled, and chemical indexes determined by the UV-spectrophotometric method can be used for a scientific and effective description of wine oxidation degree.

Development and validation of a predictive model for new-onset atrial fibrillation in sepsis based on clinical risk factors.

Objective: New-onset atrial fibrillation (NOAF) is a common complication and one of the primary causes of increased mortality in critically ill adults. Since early assessment of the risk of developing NOAF is difficult, it is critical to establish predictive tools to identify the risk of NOAF. Methods: We retrospectively enrolled 1,568 septic patients treated at Wuhan Union Hospital (Wuhan, China) as a training cohort. For external validation of the model, 924 patients with sepsis were recruited as a validation cohort at the First Affiliated Hospital of Xinjiang Medical University (Urumqi, China). Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analyses were used to screen predictors. The area under the ROC curve (AUC), calibration curve, and decision curve were used to assess the value of the predictive model in NOAF. Results: A total of 2,492 patients with sepsis (1,592 (63.88%) male; mean [SD] age, 59.47 [16.42] years) were enrolled in this study. Age (OR: 1.022, 1.009-1.035), international normalized ratio (OR: 1.837, 1.270-2.656), fibrinogen (OR: 1.535, 1.232-1.914), C-reaction protein (OR: 1.011, 1.008-1.014), sequential organ failure assessment score (OR: 1.306, 1.247-1.368), congestive heart failure (OR: 1.714, 1.126-2.608), and dopamine use (OR: 1.876, 1.227-2.874) were used as risk variables to develop the nomogram model. The AUCs of the nomogram model were 0.861 (95% CI, 0.830-0.892) and 0.845 (95% CI, 0.804-0.886) in the internal and external validation, respectively. The clinical prediction model showed excellent calibration and higher net clinical benefit. Moreover, the predictive performance of the model correlated with the severity of sepsis, with higher predictive performance for patients in septic shock than for other patients. Conclusion: The nomogram model can be used as a reliable and simple predictive tool for the early identification of NOAF in patients with sepsis, which will provide practical information for individualized treatment decisions.

Co-winemaking with Vitis amurensis Rupr. "Beibinghong" enhances the quality of Vitis vinifera L. cv. Cabernet Gernischt wine.

In some wine regions of China, Cabernet Gernischt (CG; Vitis vinifera L.) grape berries usually exhibit low pigment content and titratable acidity, and low sensory quality of the resulting wine. The aim of this study was to evaluate co-winemaking of CG wines using the red grape cultivar Beibinghong (BBH; Vitis amurensis Rupr.) at different proportions in terms of alcohols, phenolic compounds, and sensory properties of the wines. The results showed that the co-winemaking wines contained a similar content of higher alcohols, whereas the methanol content increased with an increase in BBH proportion, although this was still corresponded with the national standard. Significantly higher levels of titratable acidity were observed in co-winemaking wines at the ratio of 6:4 and 5:5, compared with monocultivar CG wines. All co-winemaking wines, except CG:BBH (9:1) wine, showed significantly higher levels of total anthocyanins, total phenolics, total tannins, and total flavan-3-ols. Further, individual phenolics, primarily diglucoside anthocyanins and non-anthocyanins (trans-ferulic acid, myricetin, viniferin, trans-caffeic acid, 3,4-dihydroxybenzoic acid), as important contributors to wine color intensity, permitted the differentiation of the wines via principal component analysis. In most cases, co-winemaking wines exhibited higher scores of the 10 sensory attributes on color, aroma, mouthfeel, and overall quality compared with monocultivar wines. Co-winemaking CG wines with BBH at 7:3 ratio demonstrated the highest scores of color intensity, aroma intensity, aroma quality, and overall quality. The results indicate that co-winemaking with V. amurensis grape variety may be useful to enhance V. vinifera wine quality by modifying wine composition. PRACTICAL APPLICATION: Cabernet Gernischt (CG) is the predominant grape cultivar used to prepare premium-quality wine in China; however, in some wine regions, CG wines have low levels of pigment and titratable acidity, and low sensory quality. Co-winemaking with another native grape cultivar, Beibinghong (BBH), which is characterized by a higher content of anthocyanins and acidity, provided sufficient experimental evidence of adjustments in the Vitis vinifera wine composition leading to improved wine sensory quality.

The single-cell stereo-seq reveals region-specific cell subtypes and transcriptome profiling in Arabidopsis leaves.

Understanding the complex functions of plant leaves requires a thorough characterization of discrete cell features. Although single-cell gene expression profiling technologies have been developed, their application in characterizing cell subtypes has not been achieved yet. Here, we present scStereo-seq (single-cell spatial enhanced resolution omics sequencing) that enabled us to show the bona fide single-cell spatial transcriptome profiles of Arabidopsis leaves. Subtle but significant transcriptomic differences between upper and lower epidermal cells have been successfully distinguished. Furthermore, we discovered cell-type-specific gene expression gradients from the main vein to the leaf edge, which led to the finding of distinct spatial developmental trajectories of vascular cells and guard cells. Our study showcases the importance of physical locations of individual cells for exerting complex biological functions in plants and demonstrates that scStereo-seq is a powerful tool to integrate single-cell location and transcriptome information for plant biology study.