Small non-coding RNA signatures in atrial appendages of patients with atrial fibrillation.

The development of high-throughput technologies has enhanced our understanding of small non-coding RNAs (sncRNAs) and their crucial roles in various diseases, including atrial fibrillation (AF). This study aimed to systematically delineate sncRNA profiles in AF patients. PANDORA-sequencing was used to examine the sncRNA profiles of atrial appendage tissues from AF and non-AF patients. Differentially expressed sncRNAs were identified using the R package DEGseq 2 with a fold change >2 and p < 0.05. The target genes of the differentially expressed sncRNAs were predicted using MiRanda and RNAhybrid. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. In AF patients, the most abundant sncRNAs were ribosomal RNA-derived small RNAs (rsRNAs), followed by transfer RNA-derived small RNAs (tsRNAs), and microRNAs (miRNAs). Compared with non-AF patients, 656 rsRNAs, 45 miRNAs, 191 tsRNAs and 51 small nucleolar RNAs (snoRNAs) were differentially expressed in AF patients, whereas no significantly differentially expressed piwi-interacting RNAs were identified. Two out of three tsRNAs were confirmed to be upregulated in AF patients by quantitative reverse transcriptase polymerase chain reaction, and higher plasma levels of tsRNA 5006c-LysCTT were associated with a 2.55-fold increased risk of all-cause death in AF patients (hazard ratio: 2.55; 95% confidence interval, 1.56-4.17; p < 0.001). Combined with our previous transcriptome sequencing results, 32 miRNA, 31 snoRNA, 110 nucleus-encoded tsRNA, and 33 mitochondria-encoded tsRNA target genes were dysregulated in AF patients. GO and KEGG analyses revealed enrichment of differentially expressed sncRNA target genes in AF-related pathways, including the 'calcium signaling pathway' and 'adrenergic signaling in cardiomyocytes.' The dysregulated sncRNA profiles in AF patients suggest their potential regulatory roles in AF pathogenesis. Further research is needed to investigate the specific mechanisms of sncRNAs in the development of AF and to explore potential biomarkers for AF treatment and prognosis.

Actin-depolymerizing factors 8 and 11 promote root hair elongation at high pH.

A root hair is a polarly elongated single-celled structure that derives from a root epidermal cell and functions in uptake of water and nutrients from the surrounding environment. Previous reports have demonstrated that short periods of high pH inhibit root hair extension; but the effects of long-term high-pH treatment on root hair growth are still unclear. Here, we report that the duration of root hair elongation is significantly prolonged with increasing external pH, which counteracts the effect of decreasing root hair elongation rate and ultimately produces longer root hairs, whereas loss of actin-depolymerizing factor 8 and 11 (ADF8/11) function causes shortening of root hair length at high pH (pH 7.4). Accumulation of ADF8/11 at the tips of root hairs is inhibited by high pH, and increasing environmental pH affects the actin filament (F-actin) meshwork at the root hair tip. At high pH, the tip-focused F-actin meshwork is absent in root hairs of the adf8/11 mutant, actin filaments are disordered at the adf8/11 root hair tips, and actin turnover is attenuated. Secretory and recycling vesicles do not aggregate in the apical region of adf8/11 root hairs at high pH. Together, our results suggest that, under long-term exposure to high extracellular pH, ADF8/11 may establish and maintain the tip-focused F-actin meshwork to regulate polar trafficking of secretory/recycling vesicles at the root hair tips, thereby promoting root hair elongation.

Construction of an EMT-related lncRNA prognostic signature for lung adenocarcinoma and functional verification of its hub gene LINC01615.

BACKGROUND: The epithelial-mesenchymal transition (EMT) plays a vital role in the progression of lung adenocarcinoma (LUAD). Long non-coding RNAs (lncRNAs) participate in the EMT process as an important regulatory factor and have the potential to serve as prognostic biomarkers. We aimed to construct a novel lncRNA prognostic signature for LUAD based on EMT-related lncRNAs, identify EMT-related hub lncRNA, and investigate its biological functions. METHODS: RNA-seq data, clinical and survival information were obtained from The Cancer Genome Atlas database. The EMT-related lncRNA prognostic signature (EMTscore) was constructed using the Least Absolute Shrinkage and Selection Operator Cox regression analysis. The efficiency of EMTscore in predicting the prognosis of LUAD was evaluated through the area under the time-dependent receiver operating characteristic (ROC) curves. The hub lncRNA of the prognostic signature was selected using a co-expression network map, and its effects on cell proliferation and metastasis were explored by in vitro experiments. RESULTS: We constructed a prognostic signature (EMTscore) containing 8 tumor-high expressed lncRNAs. The EMTscore performed well in predicting overall survival rates with AUC values of 0.708 at 5 years in the training set. EMTscore could independently predict the survival of LUAD, with HR = 4.011 (95% CI 2.430-6.622) in the multivariate Cox regression. Importantly, we identified LINC01615 as the hub lncRNA in the EMTscore and revealed that LINC01615 enhanced the proliferation, migration, and EMT of lung cancer cells. CONCLUSIONS: A new EMT-related lncRNA prognostic signature named EMTscore was developed, and LINC01615 was identified as the hub lncRNA of EMTscore. The hub lncRNA LINC01615 had an oncogenic biological function in LUAD.

The Arabidopsis GPI-anchored protein COBL11 is necessary for regulating pollen tube integrity.

Pollen tube integrity is required for achieving double fertilization in angiosperms. The rapid alkalinization factor4/19-ANXUR1/2-Buddha's paper seal 1/2 (RALF4/19-ANX1/2-BUPS1/2)-complex-mediated signaling pathway is critical to maintain pollen tube integrity, but the underlying mechanisms regulating the polar localization and distribution of these complex members at the pollen tube tip remain unclear. Here, we find that COBRA-like protein 11 (COBL11) loss-of-function mutants display a low pollen germination ratio, premature pollen tube burst, and seed abortion in Arabidopsis. COBL11 could interact with RALF4/19, ANX1/2, and BUPS1/2, and COBL11 functional deficiency could result in the disrupted distribution of RALF4 and ANX1, altered cell wall composition, and decreased levels of reactive oxygen species in pollen tubes. In conclusion, COBL11 is a regulator of pollen tube integrity during polar growth, which is conducted by a direct interaction that ensures the correct localization and polar distribution of RALF4 and ANX1 at the pollen tube tip.

Injection administration of mangosteen, Garcinia mangostana, husk extract enhances physiological and immune-neuroendocrinological regulation of Macrobrachiumrosenbergii.

The study aimed to investigate the effects of injecting mangosteen husk hot-water extracts (MHE) on immune and physiological factors in Macrobrachium rosenbergii. Different doses of MHE (10, 20, and 40 µg prawn-1) were injected into the prawns, and various immune and physiological parameters were evaluated. The results revealed that higher doses of MHE (20 and 40 µg prawn-1) led to significant increases in immune parameters, improved phagocytic activity, and clearance efficiency. However, certain parameters, such as phenoloxidase activity per granulocyte, plasma glucose, and lactate levels were decreased after injection. Moreover, prawns injected with MHE and subjected to hypothermal stress exhibited changes in haemolymph dopamine and norepinephrine. Prawns injected with MHE for 7 days showed increased survival rates when challenged with Lactococcus garvieae. The relative survival percentages were 11.8%, 46.6%, and 47.1% for MHE doses of 10, 20, and 40 µg prawn-1 injection, respectively, indicating enhanced resistance to the pathogen. In conclusion, injecting MHE can act as an immunostimulant and physiological and neuroendocrine regulator for prawns, enhancing their resistance to L. garvieae.

Dietary administration of mangosteen, Garcinia mangostana, peel extract enhances the growth, and physiological and immunoendocrinological regulation of prawn, Macrobrachiumrosenbergii.

In this study, we investigated the potential immunostimulatory effects of mangosteen (Garcinia mangostana) peel extract on Macrobrachium rosenbergii, specifically in enhancing immunity and resistance against Lactococcus garvieae. We employed a dietary administration approach to assess the impact of different extract preparations from mangosteen peel, namely mangosteen peel powder (MPP), boiled mangosteen peel powder (MPB), and mangosteen peel extract (MPE). Following the administration of mangosteen peel extract, we evaluated growth performance, innate immune parameters, and disease resistance in the prawns. The results revealed a significant increase in total haemocyte count (THC), differential haemocyte count (DHC), phenoloxidase (PO) activity, respiratory bursts (RBs), as well as phagocytic activity and clearance efficiency against L. garvieae. Based on these findings, we suggest that mangosteen peel extract can be utilized as an immunostimulant for prawns through dietary administration, regulating immune responses and enhancing resistance against pathogens by modulating carbohydrate metabolism.

Prediction Model of New Onset Atrial Fibrillation in Patients with Acute Coronary Syndrome.

Objective: Atrial fibrillation (AF) is one of the most common complications of acute coronary syndrome (ACS) patients. Possible risk factors related to new-onset AF (NOAF) in ACS patients have been reported in some studies, and several prediction models have been established. However, the predictive power of these models was modest and lacked independent validation. The aim of this study is to define risk factors of NOAF in patients with ACS during hospitalization and to develop a prediction model and nomogram for individual risk prediction. Methods: Retrospective cohort studies were conducted. A total of 1535 eligible ACS patients from one hospital were recruited for model development. External validation was performed using an external cohort of 1635 ACS patients from another hospital. The prediction model was created using multivariable logistic regression and validated in an external cohort. The discrimination, calibration, and clinical utility of the model were evaluated, and a nomogram was constructed. A subgroup analysis was performed for unstable angina (UA) patients. Results: During hospitalization, the incidence of NOAF was 8.21% and 6.12% in the training and validation cohorts, respectively. Age, admission heart rate, left atrial diameter, right atrial diameter, heart failure, brain natriuretic peptide (BNP) level, less statin use, and no percutaneous coronary intervention (PCI) were independent predictors of NOAF. The AUC was 0.891 (95% CI: 0.863-0.920) and 0.839 (95% CI: 0.796-0.883) for the training and validation cohort, respectively, and the model passed the calibration test (P > 0.05). The clinical utility evaluation shows that the model has a clinical net benefit within a certain range of the threshold probability. Conclusion: A model with strong predictive power was constructed for predicting the risk of NOAF in patients with ACS during hospitalization. It might help with the identification of ACS patients at risk and early intervention of NOAF during hospitalization.

City Health Examination and Evaluation of Territory Spatial Planning for SDG11 in China: A Case Study of Xining City in Qinghai Province.

City health examination and evaluation of territorial spatial planning is a new policy tool in China. However, research on city health examination and evaluation of territorial spatial planning is still in the exploratory stage in China. Guided by sustainable cities and communities (SDG11), a reasonable city health examination and evaluation index system for Xining City in Qinghai Province is constructed in this paper. The improved technique for order preference by similarity to ideal solution (TOPSIS) was used to quantify the evaluation results, and the city health index was visualized using the city health examination signals and warning panel. The results show that the city health index of Xining City continuously rose from 35.76 in 2018 to 69.76 in 2020. However, it is still necessary to address the shortcomings in innovation, coordination, openness and sharing and to improve the level of city space governance in a holistic way. This study is an exploration of the methodology used in city health examination and the evaluation of territorial spatial planning in China, which can provide a foundation for the sustainable development of Xining City and also provide a case reference for other cities seeking to carry out city health examinations and evaluations of territorial spatial planning in China.

First Order Rate Law Analysis for Reset State in Vanadium Oxide Thin Film Resistive Random Access Memory Devices.

In the reset state, the decay reaction mechanism and bipolar switching properties of vanadium oxide thin film RRAM devices for LRS/HRS are investigated and discussed here. To discover the properties of I-V switching curves, the first order rate law behaviors of the reset state between the resistant variety properties and the reaction time were observed. To verify the decay reaction mechanism in the reset state, vanadium oxide thin films from RRAM devices were measured by different constant voltage sampling and exhibited the same decay reaction rate constant. Finally, the electrical conduction transfer mechanism and metallic filament forming model described by I-V switching properties of the RRAM devices were proven and investigated.

The immunostimulatory effects of Theobroma cacao L. pod husk extract via injection and dietary administrations on Macrobrachium rosenbergii and its resistance against Lactococcus garvieae.

The extract from Theobroma cacao L, pod husk served as the immunostimulant to enhance the immunity and resistance against Lactococcus garvieae of Macrobrachium rosenbergii. In this study, we employed the injection method and dietary administration method to determine the effect of cocoa pod husk (CPH) on M. rosenbergii. The non-specific immune parameters and disease resistance were evaluated after the prawn injected with 1 µg prawn-1 CPH extract (C1), 3 µg prawn-1 CPH extract (C3), and 5 µg prawn-1 CPH extract (C5) for 1, 3, and 7 days. The results showed a significant increase of total haemocyte count (THC), differential haemocyte count (DHC), phenoloxidase (PO) activity, respiratory bursts (RBs), and phagocytic activity and clearance efficiency to L. garvieae. The non-specific immune parameters, physiological parameters, and disease resistance and growth performance were evaluated after the prawn fed with 1 g kg-1 CPH extract diet (CD1), 3 g kg-1 CPH extract diet (CD3) and 5 g kg-1 CPH extract diet (CD5). The results showed a significant increase in all immune parameters and showed a significant decrease in physiological parameters. No significant difference was observed in growth performance of prawn fed with the CPH containing diet. Both injection and dietary method showed a significant increase in disease resistance against to L. garvieae. We therefore recommend that CPH extract can be used as a immunostimulant for prawn by dietary administration to regulate immune responses, and carbohydrate metabolism lead to enhance resistance against pathogen.

Role of circulating long non-coding RNA for the improvement of the predictive ability of the CHA 2 DS 2 -VASc score in patients with atrial fibrillation.

BACKGROUND: The CHA 2 DS 2 -VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation (AF) and was found to be effective in predicting all-cause mortality outcomes. To date, it is still unclear whether circulating long non-coding RNAs (lncRNAs) as emerging biomarkers, can improve the predictive power of the CHA 2 DS 2 -VASc score in stroke and all-cause mortality. METHODS: Candidate lncRNAs were screened by searching the literature and analyzing previous RNA sequencing results. After preliminary verification in 29 patients with AF, the final selected lncRNAs were evaluated by Cox proportional hazards regression in 192 patients to determine whether their relative expression levels were associated with stroke and all-cause mortality. The c-statistic, net reclassification improvement (NRI), and integrated discrimination improvement of the patients were calculated to evaluate the discrimination and reclassification power for stroke and all-cause mortality when adding lncRNA expression levels to the CHA 2 DS 2 -VASc score model. RESULTS: Five plasma lncRNAs associated with stroke and all-cause mortality in AF patients were selected in our screening process. Patients with elevated H19 levels were found to have a higher risk of stroke (hazard ratio [HR] 3.264, 95% confidence interval [CI]: 1.364-7.813, P  = 0.008). Adding the H19 expression level to the CHA 2 DS 2 -VASc score significantly improved the discrimination and reclassification power of the CHA 2 DS 2 -VASc score for stroke in AF patients. In addition, the H19 level showed a marginally significant association with all-cause mortality (HR 2.263, 95% CI: 0.889-5.760, P  = 0.087), although it appeared to have no significant improvement for the CHA 2 DS 2 -VASc model for predicting all-cause mortality. CONCLUSIONS: Plasma expression of H19 was associated with stroke risk in AF patients and improved the discriminatory power of the CHA 2 DS 2 -VASc score. Therefore, lncRNA H19 served as an emerging non-invasive biomarker for stroke risk prediction in patients with AF.

Elder people can be more susceptible to the association between short-term ambient air pollution and sleep disorder outpatient visits: a time-series study.

Sleep disorders attract increasing concerns. However, the evidence of the association between ambient air pollution and sleep disorders is limited. Therefore, our aim was to determine the association between short-term air pollution exposure and outpatient visits for sleep disorders in Xi'an, the largest city in Northwest China. Baseline outpatient data of daily sleep disorders between 2011 and 2013 were collected. Quasi-Poisson distribution was applied by adjusting the day of the week and weather conditions. A total of 49,282 sleep disorder outpatient visits were recorded. The most significant association between air pollutants and outpatient visits was observed on concurrent day: per 10 µg/m3 increase of NO2, SO2, and PM10 at lag 0 corresponded to increased outpatient sleep disorder visits at 0.22% (95% CI: 0.03%, 0.42%), 1.53% (95% CI: 0.53, 2.53%), and 2.57% (95% CI: 1.33%, 3.82%), respectively. As for gender-specific analysis, there was no statistically significant difference between males and females. The result of season-specific analysis showed no statistically significant difference between warm seasons and cool seasons, either. As for age-specific analysis, obvious associations were observed in 20-40 age group (NO2) and > 40 age group (PM10 and SO2), while no evident association was found for the young age group (< 20 years old). Conclusively, short-term exposure to air pollutants, especially gaseous air pollutants, might increase the risk of sleep disorders, and such association appears to be more obvious in elder people. We provide novel data that there may be age differences in the relationship between short-term air pollution exposure and sleep disorders.

Prognostic value of interleukin-34 and interleukin-38 in patients with newly diagnosed atrial fibrillation.

Background: Interleukin (IL)-34 and IL-38 are associated with cardiovascular disease (CVD). However, their involvement in atrial fibrillation (AF) and AF-associated adverse events remains uncertain. Therefore, we aimed to investigate their association with various AF prognostic factors in a cohort study and assessed their predictive value for the prognosis of patients with AF. Methods: Patients with new-onset non-valvular AF were consecutively enrolled between 2013 and 2015 at the Department of Cardiovascular Medicine of the Southwest Hospital of the Army Medical University (Third Military Medical University) in Chongqing, China. The endpoints included stroke and all-cause mortality. The baseline levels of plasma IL-34, IL-38, NT-proBNP, high-sensitivity cardiac troponin T (hs-cTnT), and GDF-15 were measured and their correlation with AF-related adverse events were analyzed in a Cox proportional-hazards regression model. The C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the performance of the AF prognostic models. Decision curve analysis (DCA) was used to evaluate the clinical net benefit of the original and modified models. Results: A total of 299 patients with new-onset AF were enrolled. During the median follow-up time of 28 (IQR: 27, 29) months, the higher levels of IL-34 were associated with a lower risk of stroke, and the higher levels of IL-38 were associated with an increased risk of all-cause death (all adjusted P < 0.05). In addition, elevated hs-cTnT and NT-proBNP concentrations were associated with a higher risk of stroke and all-cause mortality (all adjusted P < 0.05). Furthermore, the CHA2DS2-VASc score combined with IL-38 and NT-proBNP significantly improved the C-statistic, IDI, and NRI (all P < 0.01). There was no statistically significant difference (all P > 0.05) in the discrimination power between the preference models and the ABC (age, biomarkers, and clinical history) score for the two prognostic outcomes. Conclusion: Our results suggested that IL-34 and IL-38 were independently associated with stroke and all-cause mortality in patients with AF. Moreover, adding IL-38 and NT-proBNP to the CHA2DS2-VASc score significantly improved its predictive ability of AF-related all-cause death. Finally, the preference model performed equally well as the ABC score in predicting AF prognosis.

Prognostic value of interleukin-6 in atrial fibrillation: A cohort study and meta-analysis.

OBJECTIVE: The prognostic value of interleukin-6 (IL-6) in patients with atrial fibrillation (AF) has not been fully elucidated. Therefore, we conducted a cohort study and a meta-analysis to assess the predictive value of IL-6 for stroke and mortality in patients with AF. METHODS: A cohort study was performed in newly diagnosed non-valvular patients with AF. A total of 217 patients with AF were followed up for a mean of 27 months. A multivariate Cox regression analysis was used to evaluate the association between IL-6 and stroke/all-cause mortality. The incremental value was also assessed by adding IL-6 to the CHA2DS2-VASc score. Besides, a meta-analysis of all reported cohort studies and our cohort study was conducted to validate the association of circulating IL-6 and stroke/mortality in patients with AF. RESULTS: Our cohort study showed that elevated plasma level of IL-6 was an independent risk factor for predicting stroke [hazard ratio (HR)=3.81; 95% confidence interval (CI), 1.11-13.05; p=0.033] and all-cause mortality (HR=3.11; 95% CI, 1.25-7.72; p=0.015) in patients with AF. Adding IL-6 levels to CHA2DS2-VASc score showed limited improvement of the predictive power for stroke [area under curve (AUC) from 0.81 to 0.88, p=0.006]. Meta-analysis confirmed that increased circulating level of IL-6 was significantly associated with increased risk of stroke (pooled HR=1.97; 95% CI, 1.22-3.17; p=0.006) and all-cause mortality (pooled HR=2.73; 95% CI, 2.29-3.25; p<0.001). CONCLUSION: Increased circulating level of IL-6 was significantly associated with greater risk of stroke and all-cause mortality in patients with AF. Adding IL-6 biomarker to the CHA2DS2-VASc score may help to determine the management of AF treatment.

Early kidney injury predicts disease progression in patients with COVID-19: a cohort study.

BACKGROUND: The receptor of severe respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2, is more abundant in kidney than in lung tissue, suggesting that kidney might be another important target organ for SARS-CoV-2. However, our understanding of kidney injury caused by Coronavirus Disease 2019 (COVID-19) is limited. This study aimed to explore the association between kidney injury and disease progression in patients with COVID-19. METHODS: A retrospective cohort study was designed by including 2630 patients with confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China) from 1 February to 13 April 2020. Kidney function indexes and other clinical information were extracted from the electronic medical record system. Associations between kidney function indexes and disease progression were analyzed using Cox proportional-hazards regression and generalized linear mixed model. RESULTS: We found that estimated glomerular filtration rate (eGFR) and creatinine clearance (Ccr) decreased in 22.0% and 24.0% of patients with COVID-19, respectively. Proteinuria was detected in 15.0% patients and hematuria was detected in 8.1% of patients. Hematuria (HR 2.38, 95% CI 1.50-3.78), proteinuria (HR 2.16, 95% CI 1.33-3.51), elevated baseline serum creatinine (HR 2.84, 95% CI 1.92-4.21) and blood urea nitrogen (HR 3.54, 95% CI 2.36-5.31), and decrease baseline eGFR (HR 1.58, 95% CI 1.07-2.34) were found to be independent risk factors for disease progression after adjusted confounders. Generalized linear mixed model analysis showed that the dynamic trajectories of uric acid was significantly related to disease progression. CONCLUSION: There was a high proportion of early kidney function injury in COVID-19 patients on admission. Early kidney injury could help clinicians to identify patients with poor prognosis at an early stage.

Fasting plasma glucose and glucose fluctuation are associated with COVID-19 prognosis regardless of pre-existing diabetes.

AIMS: We aimed to investigate the role of Fasting Plasma Glucose (FPG) and glucose fluctuation in the prognosis of COVID-19 patients stratified by pre-existing diabetes. METHODS: The associations of FPG and glucose fluctuation indexes with prognosis of COVID-19 in 2,642 patients were investigated by multivariate Cox regression analysis. The primary outcome was in-hospital mortality; the secondary outcome was disease progression. The longitudinal changes of FPG over time were analyzed by the latent growth curve model in COVID-19 patients stratified by diabetes and severity of COVID-19. RESULTS: We found FPG as an independent prognostic factor of overall survival after adjustment for age, sex, diabetes and severity of COVID-19 at admission (HR: 1.15, 95% CI: 1.06-1.25, P = 1.02 × 10-3). Multivariate logistic regression analysis indicated that the standard deviation of blood glucose (SDBG) and largest amplitude of glycemic excursions (LAGE) were also independent risk factors of COVID-19 progression (P = 0.03 and 0.04, respectively). The growth trajectory of FPG over the first 3 days of hospitalization was steeper in patients with critical COVID-19 in comparison to moderate patients. CONCLUSIONS: Hyperglycemia and glucose fluctuation were adverse prognostic factors of COVID-19 regardless of pre-existing diabetes. This stresses the importance of glycemic control in addition to other therapeutic management.

Circular RNA mmu_circ_0005019 inhibits fibrosis of cardiac fibroblasts and reverses electrical remodeling of cardiomyocytes.

BACKGROUND: Circular RNA (circRNA) have been reported to play important roles in cardiovascular diseases including myocardial infarction and heart failure. However, the role of circRNA in atrial fibrillation (AF) has rarely been investigated. We recently found a circRNA hsa_circ_0099734 was significantly differentially expressed in the AF patients atrial tissues compared to paired control. We aim to investigate the functional role and molecular mechanisms of mmu_circ_0005019 which is the homologous circRNA in mice of hsa_circ_0099734 in AF. METHODS: In order to investigate the effect of mmu_circ_0005019 on the proliferation, migration, differentiation into myofibroblasts and expression of collagen of cardiac fibroblasts, and the effect of mmu_circ_0005019 on the apoptosis and expression of Ito, INA and SK3 of cardiomyocytes, gain- and loss-of-function of cell models were established in mice cardiac fibroblasts and HL-1 atrial myocytes. Dual-luciferase reporter assays and RIP were performed to verify the binding effects between mmu_circ_0005019 and its target microRNA (miRNA). RESULTS: In cardiac fibroblasts, mmu_circ_0005019 showed inhibitory effects on cell proliferation and migration. In cardiomyocytes, overexpression of mmu_circ_0005019 promoted Kcnd1, Scn5a and Kcnn3 expression. Knockdown of mmu_circ_0005019 inhibited the expression of Kcnd1, Kcnd3, Scn5a and Kcnn3. Mechanistically, mmu_circ_0005019 exerted biological functions by acting as a miR-499-5p sponge to regulate the expression of its target gene Kcnn3. CONCLUSIONS: Our findings highlight mmu_circ_0005019 played a protective role in AF development and might serve as an attractive candidate target for AF treatment.

Inflammation characteristics and anti-inflammation treatment with tocilizumab of severe/critical COVID-19 patients: A retrospective cohort study.

The efficacy of tocilizumab on the prognosis of severe/critical COVID-19 patients is still controversial so far. We aimed to delineate the inflammation characteristics of severe/critical COVID-19 patients and determine the impact of tocilizumab on hospital mortality. Here, we performed a retrospective cohort study which enrolled 727 severe or critical inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China), among which 50 patients received tocilizumab. This study confirmed that most recovered patients manifested relatively normal inflammation levels at admission, whereas most of the deceased cases presented visibly severe inflammation at admission and even progressed into extremely aggravated inflammation before their deaths, proved by some extremely high concentrations of interleukin-6, procalcitonin, C-reactive protein and neutrophil count. Moreover, based on the Cox proportional-hazards models before or after propensity score matching, we demonstrated that tocilizumab treatment could lessen mortality by gradually alleviating excessive inflammation and meanwhile continuously enhancing the levels of lymphocytes within 14 days for severe/critical COVID-19 patients, indicating potential effectiveness for treating COVID-19.

Risk stratification scores for hospitalization duration and disease progression in moderate and severe patients with COVID-19.

BACKGROUND: During outbreak of Coronavirus Disease 2019 (COVID-19), healthcare providers are facing critical clinical decisions based on the prognosis of patients. Decision support tools of risk stratification are needed to predict outcomes in patients with different clinical types of COVID-19. METHODS: This retrospective cohort study recruited 2425 patients with moderate or severe COVID-19. A logistic regression model was used to select and estimate the factors independently associated with outcomes. Simplified risk stratification score systems were constructed to predict outcomes in moderate and severe patients with COVID-19, and their performances were evaluated by discrimination and calibration. RESULTS: We constructed two risk stratification score systems, named as STPCAL (including significant factors in the prediction model: number of clinical symptoms, the maximum body temperature during hospitalization, platelet count, C-reactive protein, albumin and lactate dehydrogenase) and TRPNCLP (including maximum body temperature during hospitalization, history of respiratory diseases, platelet count, neutrophil-to-lymphocyte ratio, creatinine, lactate dehydrogenase, and prothrombin time), to predict hospitalization duration for moderate patients and disease progression for severe patients, respectively. According to STPCAL score, moderate patients were classified into three risk categories for a longer hospital duration: low (Score 0-1, median = 8 days, with less than 20.0% probabilities), intermediate (Score 2-6, median = 13 days, with 30.0-78.9% probabilities), high (Score 7-9, median = 19 days, with more than 86.5% probabilities). Severe patients were stratified into three risk categories for disease progression: low risk (Score 0-5, with less than 12.7% probabilities), intermediate risk (Score 6-11, with 18.6-69.1% probabilities), and high risk (Score 12-16, with more than 77.9% probabilities) by TRPNCLP score. The two risk scores performed well with good discrimination and calibration. CONCLUSIONS: Two easy-to-use risk stratification score systems were built to predict the outcomes in COVID-19 patients with different clinical types. Identifying high risk patients with longer stay or poor prognosis could assist healthcare providers in triaging patients when allocating limited healthcare during COVID-19 outbreak.

Arabidopsis ADF5 Acts as a Downstream Target Gene of CBFs in Response to Low-Temperature Stress.

Low temperature is a major adverse environment that affects normal plant growth. Previous reports showed that the actin cytoskeleton plays an important role in the plant response to low-temperature stress, but the regulatory mechanism of the actin cytoskeleton in this process is not clear. C-repeat binding factors (CBFs) are the key molecular switches for plants to adapt to cold stress. However, whether CBFs are involved in the regulation of the actin cytoskeleton has not been reported. We found that Arabidopsis actin depolymerizing factor 5 (ADF5), an ADF that evolved F-actin bundling function, was up-regulated at low temperatures. We also demonstrated that CBFs bound to the ADF5 promoter directly in vivo and in vitro. The cold-induced expression of ADF5 was significantly inhibited in the cbfs triple mutant. The freezing resistance of the adf5 knockout mutant was weaker than that of wild type (WT) with or without cold acclimation. After low-temperature treatment, the actin cytoskeleton of WT was relatively stable, but the actin cytoskeletons of adf5, cbfs, and adf5 cbfs were disturbed to varying degrees. Compared to WT, the endocytosis rate of the amphiphilic styryl dye FM4-64 in adf5, cbfs, and adf5 cbfs at low temperature was significantly reduced. In conclusion, CBFs directly combine with the CRT/DRE DNA regulatory element of the ADF5 promoter after low-temperature stress to transcriptionally activate the expression of ADF5; ADF5 further regulates the actin cytoskeleton dynamics to participate in the regulation of plant adaptation to a low-temperature environment.