Exosomal U2AF2 derived from human bone marrow mesenchymal stem cells attenuates the intervertebral disc degeneration through circ_0036763/miR-583/ACAN axis.

Intervertebral disc degeneration (IDD) is one of the major leading causes of back pain affecting the patient's quality of life. However, the roles of circular RNA (circRNA) in IDD remains unclear. This study aimed to explore the function and underlying mechanism of circ_0036763 in IDD. In this study, expressions of circ_0036763, U2 small nuclear RNA auxiliary factor 2 (U2AF2), miR-583 and aggrecan (ACAN) in primary human nucleus pulposus cells (HNPCs) derived from IDD patients and healthy controls were detected by quantitative real-time reverse transcription-PCR (qRT-PCR) or Western blot (WB). The relationship between pre-circ_0036763 and U2AF2, circ_0036763 and miR-583, miR-583 and ACAN mRNA was determined by bioinformatic analysis, miRNA pull down or RNA immunoprecipitation (RIP) assay. The expressions of Collagen I and Collagen II were evaluated by WB. Co-culture of bone marrow mesenchymal stem cells (bMSCs) or bMSCs-derived exosomes and HNPCs were performed to identify the effect of U2AF2 on the mature of circ_0036763 and ACAN. Results indicated that circ_0036763, U2AF2 and ACAN were downregulated while miR-583 was upregulated in HNPCs derived from IDD patients compared with that in normal HNPCs. Besides, overexpression of circ_0036763 elevated the expressions of ACAN and Collagen II whereas reduced Collagen I expression in HNPCs. Moreover, U2AF2 promoted the mature of circ_0036763, and circ_0036763 positively regulated ACAN by directly sponging miR-583. Furthermore, exosomal U2AF2 derived from bMSCs could increase U2AF2 levels in HNPCs and subsequently regulate the expression of ACAN by circ_0036763/miR-583 axis. In summary, circ_0036763 modified by exosomal U2AF2 derived from bMSCs alleviated IDD through regulating miR-583/ACAN axis in HNPCs. Thus, this study might provide novel therapeutic targets for IDD.

Epidemiological Evaluation of Bacillus cereus-Induced Foodborne Outbreaks - China, 2010-2020.

Introduction: Bacillus cereus (B. cereus) is a common gram-positive bacterium that contaminates starch-rich food and can cause outbreaks of foodborne diseases. This study describes the characteristics of outbreaks caused by B. cereus in China during 2010-2020 and explore the possible reasons for changes in the number of outbreaks over time. Results of this analysis can efficiently help guide and allocate public resources to prevent B. cereus-caused foodborne diseases. Methods: Descriptive statistical methods were used to analyze the data on B. cereus outbreaks in China during this period. The data were identified and reported at all levels in China through National Foodborne Disease Outbreak Surveillance System. Results: From 2010 to 2020, a total of 419 foodborne outbreaks prompted by B. cereus were reported in China, leading to 7,892 cases, 2,786 hospital admissions, and 5 fatalities. The bulk of the outbreaks were recorded in the summer, primarily between May and September. The most recurrent food vehicle was linked with rice or flour-based products, notably those made with rice or fried rice. School canteens bore the brunt of the B. cereus outbreaks. In multifactor outbreaks, food contamination was identified as the most common culprit; while in instances where only one factor contributed, improper storage was most frequently implicated. Conclusion: The prevalence of B. cereus outbreaks remained relatively consistent throughout the studied period. Understanding the types of foods, causative factors, and contributing elements leading to B. cereus outbreaks can help inform prevention strategies for foodborne illnesses. The majority of outbreaks were associated with rice- or flour-based foods in school canteens, suggesting contamination and improper storage during food preparation. Consequently, it is essential to prioritize continuous education for canteen staff on food safety, efficacious management, and proper practices. The implementation of comprehensive guidelines, encompassing multiple critical aspects, can potentially reduce the occurrence of B. cereus outbreaks.

Comparative efficacy of oral drugs for chronic radiation proctitis - a systematic review.

BACKGROUND: Chronic radiation proctitis (CRP) is a long-term complication of pelvic radiotherapy that manifests as rectal bleeding, diarrhoea, fistula formation and obstruction. Treatments such as endoscopic argon plasma coagulation, hyperbaric oxygen therapy and rectal topical formalin have imposed a significant medical burden on CRP patients. In contrast, oral therapies offer a more accessible and acceptable option for managing CRP. Here, we conducted a systematic review of the efficacy of oral treatments for CRP to assess their potential as an effective and convenient treatment option for this condition. METHODS: We searched the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, China National Knowledge Infrastructure and Chinese VIP in February 2021. We included post-radiotherapy participants with CRP that compared oral medicine alone or in combination with other treatments versus control treatments. The primary outcomes were bleeding, diarrhoea and symptom score. Heterogeneity between studies was checked using Cochrane Q test statistics and I2 test statistics. The Cochrane risk-of-bias tool was used to assess the quality of the included studies. RESULTS: We included 10 randomised controlled trials (RCTs) and 1 retrospective study with 898 participants. Three placebo-controlled trials evaluated the effects of oral sucralfate on CRP, with meta-analysis showing no significant different with placebo arm. Four trials on TCM demonstrated significant improvement of symptoms, especially for the 3 trials on oral TCM drinks. Retinyl palmitate and high-fibre diet were found to reduce rectal bleeding. The combination of oral pentoxifylline and tocopherol did not significantly change the process of CRP. CONCLUSIONS: Our study implies that oral TCM drinks, retinyl palmitate and a high-fiber diet showed significant improvement in CRP symptoms, but not with the combination of oral pentoxifylline and tocopherol. Further multicentre, larger-scale RCTs are needed to confirm the efficacy and safety of these treatments and optimize treatment strategies, ultimately improving the quality of life for patients with CRP.

Dapagliflozin ameliorates sepsis-induced heart injury by inhibiting cardiomyocyte apoptosis and electrical remodeling through the PI3K/Akt pathway.

BACKGROUND: Sepsis-induced heart injury is one of the leading causes of circulation disorders worldwide. Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor mainly used for controlling blood glucose, has been shown to exert a protective effect on cardiomyocytes. However, the protective effect of dapagliflozin against sepsis-induced cardiac injury and the underlying mechanism needs to be studied. AIM: This study aims to investigate the effect of dapagliflozin on sepsis-induced cardiomyopathy and the potential mechanisms involved. METHODS: The rat model of sepsis was constructed by intraperitoneal injection of lipopolysaccharide. Echocardiography and electrophysiological studies were performed to detect changes in cardiac function and electrical activity. Cardiac pathological alternation and cardiomyocyte apoptosis were measured by H&E staining, serological analysis, immunohistochemical, immunofluorescence, and TUNEL assays. Western blot and qRT-PCR were performed to elucidate the underlying mechanism of dapagliflozin. Additionally, corresponding experiments in H9c2 cells were performed to further validate the mechanisms in vitro. RESULTS: Dapagliflozin improved cardiac dysfunction and reduced the susceptibility to ventricular arrhythmias in sepsis rats by ameliorating cardiac inflammation, suppressing cardiomyocyte apoptosis, and alleviating ventricular electrical remodeling. The PI3K/Akt signaling pathway inhibitor inhibited the anti-apoptotic effect of dapagliflozin, indicating that the protective effect was related to the activation of the PI3K/Akt pathway. CONCLUSION: Dapagliflozin ameliorated sepsis-induced cardiac injury by suppressing electrical remodeling and cardiomyocyte apoptosis, which could be attributed to the PI3K/Akt pathway.

Attribution Analysis of Household Foodborne Disease Outbreaks in China, 2010-2020.

Foodborne diseases have become a serious public health problem worldwide, and foodborne disease outbreaks have placed a heavy disease burden on China. Foodborne disease outbreaks occur most frequently among families in China. The objectives of this study were to analyze the cause of household foodborne disease outbreaks in China from 2010 to 2020 and to identify where preventive measures could be targeted. All data were obtained from the China Foodborne Disease Surveillance System Report. A total of 17,985 outbreaks, which resulted in 73,252 illnesses, 38,829 hospitalizations, and 1269 deaths, were reported in this period. Most household outbreaks of foodborne diseases occurred in May-October, and the highest number occurred in July (3620 outbreaks, 20%). The province with the highest number of outbreaks was Yunnan Province (4829 outbreaks), followed by Hunan Province (2264 outbreaks). The attribution analysis revealed that fungi (mainly poisonous mushrooms) were the most implicated food category, with 8873 (49.3%) cases. The second was poisonous plants and their products, with 1552 (8.6%) cases. Fungi were the primary etiologic agent, with 31,125 illnesses, accounting for 42.5% of the incidents. Inedibility and misuse (9423 outbreaks), unknown origin (2505 outbreaks), and improper processing (2365 outbreaks) were the main contributing factors causing outbreaks of foodborne diseases. The results show that southwest China was a high-risk area for household foodborne diseases. Therefore, public health institutions should strengthen supervision and food safety education of residents to reduce the outbreaks of household foodborne diseases.

UV-C Promotes the Accumulation of Flavane-3-ols in Juvenile Fruit of Grape through Positive Regulating VvMYBPA1.

Flavane-3-ol monomers are the precursors of proanthocyanidins (PAs), which play a crucial role in grape resistance. Previous studies showed that UV-C positively regulated leucoanthocyanidin reductase (LAR) enzyme activity to promote the accumulation of total flavane-3-ols in juvenile grape fruit, but its molecular mechanism was still unclear. In this paper, we found that the contents of flavane-3-ol monomers increased dramatically at the early development stage grape fruit after UV-C treatment, and the expression of its related transcription factor VvMYBPA1 was also enhanced significantly. The contents of (-)-epicatechin and (+)-catechin, the expression level of VvLAR1 and VvANR, and the activities of LAR and anthocyanidin reductase (ANR) were improved significantly in the VvMYBPA1 overexpressed grape leaves compared to the empty vector. Both VvMYBPA1 and VvMYC2 could interact with VvWDR1 using bimolecular fluorescence complementation (BiFC) and yeast two hybrid (Y2H). Finally, VvMYBPA1 was proven to bind with the promoters of VvLAR1 and VvANR by yeast one hybrid (Y1H). To sum up, we found that the expression of VvMYBPA1 increased in the young stage of grape fruit after UV-C treatment. VvMYBPA1 formed a trimer complex with VvMYC2 and VvWDR1 to regulate the expression of VvLAR1 and VvANR, thus positively promoting the activities of LAR and ANR enzyme, and eventually improved the accumulation of flavane-3-ols in grape fruit.

Left Atrial Thrombus in Patients With Non-valvular Atrial Fibrillation: A Cross-Sectional Study in China.

Background: Stroke is predominately attributed to left atrial thrombus (LAT) in patients with non-valvular atrial fibrillation (NVAF), however, its detection rate in real clinical practice has been few reported in China. Objective: This study aimed to investigate the prevalence and associated factors of LAT in patients with NVAF in China. Methods: All adult NVAF patients undergoing transesophageal echocardiography (TEE) in the China Atrial Fibrillation Center database from January 2017 to January 2022 were enrolled in this study. The prevalence of LAT was calculated, and associated factors were identified. Results: A total of 36,007 NVAF inpatients from 602 hospitals in 30 provinces/autonomous regions/municipalities were included in the final analysis, with a median age of 66 years and 39.4% were female. LAT was present in 1,467 (4.1%) patients overall, 2.7, 5.7, and 6.8% in patients with paroxysmal, persistent, and long-standing persistent AF, respectively. In subgroup analysis, including age ≥ 65 years, CHA2DS2-VASC score ≥ 2, left atrial diameter (LAD) ≥ 50 mm, left ventricular ejection fraction (LVEF) < 50%, and anticoagulation, patients with paroxysmal AF always had the lowest LAT prevalence, followed by patients with persistent and long-standing persistent AF. Patients treated with anticoagulants had less prevalent LAT than those without anticoagulation (2.1 vs. 5.0%, p < 0.001). In multivariate analysis, AF pattern (both persistent AF and long-standing persistent AF), hypertension, chronic heart failure, coronary heart disease, transient ischemic attack/stroke, diabetes mellitus, and LAD (per 5 mm) were associated with an increased prevalence of LAT. However, LVEF (per 5%) and anticoagulation were associated with a reduced prevalence of LAT. Conclusion: LAT was found in 4.1% of Chinese adult NVAF inpatients underwent TEE in real-world experience. The prevalence of LAT mainly associated with non-paroxysmal AF, cardiovascular diseases, diabetes mellitus, enlarged left atrium, lower LVEF, and lack of anticoagulation therapy.

Corrigendum: The Reversal Effect of Sigma-1 Receptor (S1R) Agonist, SA4503, on Atrial Fibrillation After Depression and Its Underlying Mechanism.

[This corrects the article DOI: 10.3389/fphys.2019.01346.].

Psychosocial Intervention on the Dual-Process Model for a Group of COVID-19 Bereaved Individuals in Wuhan: A Pilot Study.

Wuhan was the first large city where the initial breakout of COVID-19 took numerous lives. A group of social workers and mental health specialists coordinated the "Be Together Program" (BTP), a psychosocial grief intervention program to help a group of Wuhan COVID-19 bereaved people. Under the Dual-process model framework, BTP used the internet and social media as the main tools, combined with group and individual intervention. Additionally, it employed a "Supermarket Mode" with abundant intervention themes and approaches for BTP participants to choose according to their special needs. Additionally, Chinese cultural elements are integrated into the program. At the end of the program, the grief scores of participants in the qualified sample reduced significantly, and the prevalence of the potential Prolonged Grief Disorder diagnosis reduced from 75% to 12%. The study also found that the BTP was especially effective for those who had high levels of grief reaction.

Altered Gut Microbiota Associated With Hemorrhage in Chronic Radiation Proctitis.

Pelvic cancer radiotherapy may cause chronic radiation proctitis (CRP) that adversely affects patient's quality of life, especially in patients with prolonged hematochezia. However, previous studies of radiation enteropathy mainly focused on acute irradiation hazards, and the detailed pathogenesis process and mechanism of prolonged hematochezia associated with radiation-induced toxicity remain unclear. In this study, we characterized the gut microbiota of 32 female CRP patients with or without hematochezia. Differential patterns of dysbiosis were observed. The abundance of Peptostreptococcaceae, Eubacterium, and Allisonella was significantly higher in CRP patients with hematochezia, while the compositions of the Lachnospiraceae, Megasphera, Megamonas, and Ruminococcaceae were lower in the microbiota of non-hematochezia patients. Functional prediction suggested significant difference in the expression of mineral absorption and the arachidonic acid metabolism proteins between hematochezia and non-hematochezia patients, possibly interdependent on radiation-induced inflammation. This study provides new insight into the altered composition and function of gut microbiota in patients with hematochezia, implying the potential use of probiotics and prebiotics for assessment and treatment of CRP.

Mushroom Poisoning Outbreaks - China, 2010-2020.

Introduction: Mushroom poisoning was the leading cause of foodborne disease outbreaks and outbreak-associated deaths in China. Mushroom poisoning outbreak surveillance can provide insight into the epidemiological characteristics of mushroom poisonings and guide policymaking and health education to reduce illnesses and deaths.Methods: Foodborne Disease Outbreak Surveillance System was upgraded in 2011 to collect foodborne disease outbreaks in China. Mushroom poisoning outbreaks during 2010-2020 were selected to analyze geographical distribution, seasonal distribution, and setting of food preparation.Results: A total of 10,036 outbreaks, which resulted in 38,676 illnesses and 788 deaths, were reported in this period. Mushroom poisonings occurred all over the country, but with highest incidence in the southwest and central China. Overall, 84.6% outbreaks were associated with food prepared in households, followed by 8.7% in street stalls, and 2.5% in canteens. Mushroom poisoning outbreaks clearly exhibited seasonality, and the peak season was summer through autumn. Outbreaks occurring between May and October accounted for 94.1% of total outbreaks, 92.4% illnesses, and 97.2% deaths.Conclusions: Mushroom poisoning is a food safety issue of higher concern in China. Targeted health education is essential to reduce mushroom poisoning, especially in southwest China. Citizens are advised to not collect or eat wild mushrooms.

Clinical characteristics, risk factors, and cardiac manifestations of cancer patients with COVID-19.

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features, which may be deteriorated in patients with cancer. However, cardiac outcomes of cancer patients with COVID-19 have not been closely examined. We retrospectively assessed 1,244 patients with COVID-19 from February 1 to August 31, 2020 (140 cancer and 1,104 noncancer patients). Demographic and clinical data were obtained and compared between cancer and noncancer groups. Including the cardiac biomarkers, we also analyzed laboratory findings between these two groups. Risk factors for in-hospital mortality were identified by multivariable Cox regression models. For cancer group, 56% were in severe and critical status with more diabetes and immune deficiency, whereas the proportion was 10% for noncancer group. Patients with cancer had increased levels of leukocyte, neutrophil count, and blood urea nitrogen (BUN) (all P < 0.01), whereas lymphocyte count was significantly lower (P < 0.001). The most common solid tumor types were gastrointestinal cancer (26%), lung cancer (21%), and breast and reproductive cancer (both 19%). There is a rising for cardiac biomarkers, including pro-B-type natriuretic peptide (Pro-BNP), sensitive troponin I (cTnI), myoglobin (MYO), creatine kinase-MB (CK-MB), as well as D-Dimer in COVID-19 cancer population, especially in deceased subjects with cancer. The 30-day in-hospital mortality in cancer group was dramatically raised than that in noncancer group (12.9% vs. 4.0%, P < 0.01). In multivariable Cox regression models, fever, disease severity status, and underlying diseases were risk factors for mortality. COVID-19 patients with cancer relate to deteriorating conditions and poor cardiac outcomes accompanied by a high in-hospital mortality, which warrants more aggressive treatment.NEW & NOTEWORTHY Our study indicates that the 30-day mortality is higher in COVID-19 patients with cancer; more COVID-19 patients with cancer are in severe and critical status; age, respiratory rate, neutrophil count, AST, BUN, MYO, Pro-BNP, disease severity status, underlying diseases, and fever are risk factors for in-hospital mortality among COVID-19 cancer cases; COVID-19 patients with cancer display severely impaired myocardium, damaged heart function, and imbalanced homeostasis of coagulation; what is more, those with both cancer and CVD have more significantly increased Pro-BNP and D-Dimer level.

Decreased Low-Density Lipoprotein Cholesterol Level Indicates Poor Prognosis of Severe and Critical COVID-19 Patients: A Retrospective, Single-Center Study.

Coronavirus disease 2019 (COVID-19) has become a global public health crisis. Reduced low-density lipoprotein cholesterol (LDL-C) levels were observed in COVID-19 patients. The present study aimed to explore the relationship between LDL-C levels and the prognosis of severe and critical COVID-19 patients. A total of 211 severe and critical COVID-19 patients were enrolled and divided into four groups according to the LDL-C levels, including 53 patients in Group A (LDL-C ≥ 2.71 mmol/L), 53 patients in Group B (2.28 ≤ LDL-C < 2.71 mmol/L), 53 patients in Group C (1.83 ≤ LDL-C < 2.28 mmol/L) and 52 patients in Group D (LDL-C < 1.83 mmol/L). LDL-C levels were lower in critically ill patients than in severe patients. The main symptoms before admission, characteristics on admission and comorbidities of enrolled patients did not differ among the four groups. Compared with patients with high LDL-C levels, patients with low LDL-C levels were more likely to have immune and inflammation dysfunction, renal dysfunction, liver dysfunction and cardiac dysfunction on admission. The proportions of patients with shock and acute cardiac injury, of those admitted to intensive care unit (ICU) and of those treated with mechanical ventilation were inversely related to LDL-C level. The mortality of COVID-19 patients increased with LDL-C reduction. Serum LDL-C levels of COVID-19 patients was negatively correlated with CRP level, but positively correlated with lymphocyte count, as shown by Pearson correlation analysis. Proportional hazard models showed that low LDL-C levels were associated with increased risk of hospitalization death, cardiac injury and admission to the ICU. Taken together, these results suggest that decreased LDL-C levels indicate poor prognosis of severe and critical COVID-19 patients.

Pinocembrin ameliorates arrhythmias in rats with chronic ischaemic heart failure.

OBJECTIVE: Ventricular arrhythmias (VAs) are a common complication of chronic ischaemic heart failure (CIHF). The purpose of this study is to investigate the efficacy of pinocembrin in a rat model of VAs induced by CIHF and further examine the possible mechanism. METHODS: Rats were subjected to ligation of left anterior descending coronary artery to mimic CIHF and then received pinocembrin treatment daily for 2 months. The vivo electrophysiology were performed to determine the effect of pinocembrin on ventricular electrical activity. The expression of Cav1.2, Kv4.2, and NGF was determined by Western blot. The structural change of ventricle was tested by the Echocardiography, Masson staining, and HE staining. The effect of pinocembrin on sympathetic nerve-related markers was detected by the immunostaining and the ELISA was used to test for biomarkers associated with heart failure. RESULTS: Pinocembrin increased the expression of ion channel protein Cav1.2 and Kv4.3, ameliorated the shortening of action potential duration (APD) and reduced the incidence and duration of ventricular fibrillation (VF). Pinocembrin also reduced the expression of nerve growth factor (NGF) and improved the autonomic nerve remodelling. In addition, pinocembrin reduced the area of infarct area and myocardial fibrosis, accompanied by increasing the expression of connexin protein 43 (CX43). CONCLUSION: We demonstrate that pinocembrin reduces cardiac nerve remodelling and protects against Vas induced by CIHF. The findings suggest that pinocembrin can be a promising candidate for the treatment of VAs.

Corrigendum: Pinocembrin Decreases Ventricular Fibrillation Susceptibility in a Rat Model of Depression.

[This corrects the article DOI: 10.3389/fphar.2020.547966.].

4-CPA (4-Chlorophenoxyacetic Acid) Induces the Formation and Development of Defective "Fenghou" (Vitis vinifera × V. labrusca) Grape Seeds.

For some horticultural plants, auxins can not only induce normal fruit setting but also form fake seeds in the induced fruits. This phenomenon is relatively rare, and, so far, the underlying mechanism remains unclear. In this study, "Fenghou" (Vitis vinifera × V. labrusca) grapes were artificially emasculated before flowering and then sprayed with 4-CPA (4-chlorophenoxyacetic acid) to analyze its effect on seed formation. The results show that 4-CPA can induce normal fruit setting in "Fenghou" grapes. Although more seeds were detected in the fruits of the 4-CPA-treated grapevine, most seeds were immature. There was no significant difference in the seed shape; namely, both fruit seeds of the grapevines with and without 4-CPA treatment contained a hard seed coat. However, the immature seeds lacked embryo and endosperm tissue and could not germinate successfully; these were considered defective seeds. Tissue structure observation of defective seeds revealed that a lot of tissue redifferentiation occurred at the top of the ovule, which increased the number of cell layers of the outer integument; some even differentiated into new ovule primordia. The qRT-PCR results demonstrated that 4-CPA application regulated the expression of the genes VvARF2 and VvAP2, which are associated with integument development in "Fenghou" grape ovules. Together, this study evokes the regulatory role of 4-CPA in the division and continuous redifferentiation of integument cells, which eventually develop into defective seeds with thick seed coats in grapes.

MADS-Box Protein Complex VvAG2, VvSEP3 and VvAGL11 Regulates the Formation of Ovules in Vitis vinifera L. cv. 'Xiangfei'.

The phenomenon of multi-carpel and multi-ovule exists in the grapevine cultivar 'Xiangfei', but the mechanism of ovule formation is seldom reported. In this study, we observed the ovule formation process by using 'Xiangfei' grapes. The role of the VvAG2 (VvAGAMOUS) gene in ovule formation was identified, and we explored the relationship between VvAG2, VvSEP3(VvMADS4) and VvAGL11(VvMADS5) proteins. The results showed that the ovule primordium appeared when the inflorescence length of 'Xiangfei' grapes were 4-5 cm long; the relative expression levels of VvAG2, VvAGL11 and VvSEP3 genes were higher during ovule formation, and the expression levels of VvAG2 gene was the highest. Transgenic tomato (Solanum lycopersicum) plants expressing VvAG2 produced higher numbers of ovules and carpels than the wild type. Moreover, yeast two-hybrid and yeast three-hybrid experiments demonstrated that VvSEP3 acts as a bridge and interacts with VvAG2 and VvAGL11 proteins, respectively. Meanwhile, a homodimer can be formed between VvSEP3 and VvSEP3, but there was no interaction between VvAG2 and VvAGL11. These findings suggest that the VvAG2 gene is involved in the formation of ovules, and VvAG2/VvSEP3 together with VvAGL11/VvSEP3 can form a tetrameric complex. In summary, our data showed that VvAG2 along with VvSEP3 and VvAGL11 jointly regulate the ovule formation of 'Xiangfei' grapes.

Sigma-1 receptor ligands improves ventricular repolarization-related ion remodeling in rats with major depression disorder.

RATIONALE: It has been reported that patients with major depressive disorder (MDD) are prone to developing ventricular arrhythmias. Moreover, the Sigma-1 receptor not only plays a crucial role in MDD but has also been shown to have antiarrhythmic properties. The Sigma-1 receptor is a common receptor related to depression and ventricular arrhythmias. OBJECTIVE: We analyzed the effects of the Sigma-1 receptor on depression and ventricular repolarization-related ion remodeling in MDD rats. METHODS: MDD was induced in rats by chronic unpredictable mild stress (CUMS), and 28 days later, the rats were subjected to behavior tests. Protein expression was measured by western blotting, and cardiac morphological changes were observed by Masson staining. Electrophysiological measurement of the myocardium was performed with the whole-cell patch-clamp technique. RESULTS: Compared with the control rats, the MDD rats exhibited lower transient outward potassium current (Ito) and L-type calcium current (ICa-L) amplitudes. On the other hand, a trend of depolarization of Ito and hyperpolarization of ICa-L was observed in the MDD rats. Thus, we investigated the effect of fluvoxamine, a Sigma-1 receptor agonist, on Ito and ICa-L. Fluvoxamine enhanced Ito and altered its current kinetics, as shown by acceleration of activation and recovery from inactivation. In contrast, fluvoxamine inhibited the Ca2+ by hyperpolarizing the steady-state activation of ICa-L. All these effects were blocked by BD1047. CONCLUSION: Taken together, our results indicate that Sigma-1 receptor modulates the functions of Ito and ICa-L to possibly exert antiarrhythmic effects.

Outcomes of Cardiac Resynchronization Therapy in Patients with Hypothyroidism and Heart Failure.

BACKGROUND: Hypothyroidism is known to be associated with adverse clinical outcomes in heart failure. The association between hypothyroidism and cardiac resynchronization therapy outcomes in patients with severe heart failure is not clear. METHODS: The study included 1316 patients who received cardiac resynchronization therapy between 2002 and 2015. Baseline demographics and cardiac resynchronization therapy outcomes, including left ventricular ejection fraction, New York Heart Association class, appropriate implantable cardioverter-defibrillator therapy, and all-cause mortality, were collected from the electronic health record. RESULTS: Of the study cohort, 350 patients (26.6%) were classified as the hypothyroidism group. The median duration of follow-up was 3.6 years (interquartile range, 1.7-6.2 years). Hypothyroidism was not associated with a higher risk of all-cause mortality in patients receiving CRT for heart failure. The risk of appropriate implantable cardioverter-defibrillator therapy significantly increased in association with increased baseline thyroid-stimulating hormone level in the entire cohort (hazard ratio, 1.23 per 5mIU/L increase; 95% CI, 1.01-1.5; P = 0.04) as well as in the hypothyroid group (hazard ratio, 1.44 per 5mIU/L increase; 95% CI, 1.13-1.84; P = 0.004). CONCLUSIONS: CRT improves cardiac function in hypothyroid patients. The ventricular arrhythmic events requiring ICD therapies are associated with baseline TSH level, which might be considered as an important biomarker to stratify the risk of sudden death for patients with heart failure and hypothyroidism.