The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been ...systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.
Sleep deprivation (SD) is increasingly common in modern society, which can lead to the dysregulation of inflammatory responses and cognitive impairment, but the mechanisms remain unclear. Emerging ...evidence suggests that gut microbiota plays a critical role in the pathogenesis and development of inflammatory and psychiatric diseases, possibly via gut microbiota-brain interactions and neuroinflammation. The present study investigated the impact of SD on gut microbiota composition and explored whether alterations of the gut microbiota play a causal role in chronic inflammatory states and cognitive impairment that are induced by SD. We found that SD-induced gut dysbiosis, inflammatory responses, and cognitive impairment in humans. Moreover, the absence of the gut microbiota suppressed inflammatory response and cognitive impairment induced by SD in germ-free (GF) mice. Transplantation of the "SD microbiota" into GF mice activated the Toll-like receptor 4/nuclear factor-κB signaling pathway and impaired cognitive function in the recipient mice. Mice that harbored "SD microbiota" also exhibited increases in neuroinflammation and microglial activity in the hippocampus and medial prefrontal cortex. These findings indicate that gut dysbiosis contributes to both peripheral and central inflammatory processes and cognitive deficits that are induced by SD, which may open avenues for potential interventions that can relieve the detrimental consequences of sleep loss.
Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral ...entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.
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•Statin treatment among 13,981 patients with COVID-19 was retrospectively studied•Statin use in this cohort was associated with a lower risk of all-cause mortality•Adding an ACE inhibitor or an ARB did not affect statin-associated outcome in the cohort•The benefit of statins among this cohort may be due to immunomodulatory benefits
Statins have anti-inflammatory benefits and were suggested as an adjunct therapy for COVID-19. But statins may increase the expression of ACE2, the receptor for SARS-CoV-2. Here, Zhang et al. retrospectively analyzed 13,981 COVID-19 cases and found that in-hospital statin use is associated with a lower risk of all-cause mortality.
The remaining useful life (RUL) prediction plays a pivotal role in the predictive maintenance of industrial manufacturing systems. However, one major problem with the existing RUL estimation ...algorithms is the assumption of a single health degradation trend for different machine health stages. To improve the RUL prediction accuracy with various degradation trends, this article proposes an algorithm dubbed degradation-aware long short-term memory (LSTM) autoencoder (AE) (DELTA). First, the Hilbert transform is adopted to evaluate the degradation stage and factor with the real-time sensory signal. Second, we adopt LSTM AE to predict RUL based on multisensor time-series data and the degradation factor. Distinct from the existing studies, the proposed framework is able to dynamically model the degradation factor and explore latent variables to improve RUL prediction accuracy. The performance of DELTA is evaluated with the open-source FEMTO bearing data set. Compared with the existing algorithms, DELTA achieves appreciable improvements in the RUL prediction accuracy.
Microorganisms have been extensively applied as active biotherapeutic agents or drug delivery vehicles for antitumor treatment because of their unparalleled bio-functionalities. Taking advantage of ...the living attributes of microorganisms, a new avenue has been opened in anticancer research. The integration of customized functional materials with living microorganisms has demonstrated unprecedented potential in solving existing questions and even conferring microorganisms with updated antitumor abilities and has also provided an innovative train of thought for enhancing the efficacy of microorganism-based tumor therapy. In this review, we have summarized the emerging development of customized materials-assisted microorganisms (MAMO) (including bacteria, viruses, fungi, microalgae, as well as their components) in tumor therapeutics with an emphasis on the rational utilization of chosen microorganisms and tailored materials, the ingenious design of biohybrid systems, and the efficacious antitumor mechanisms. The future perspectives and challenges in this field are also discussed.
This review provides a comprehensive introduction to microorganisms-based biohybrid systems, namely MAMO, for application in tumor therapeutics.
RATIONALE:Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in ...patients with hypertension.
OBJECTIVE:To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.
METHODS AND RESULTS:This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 interquartile range, 55–68 years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 interquartile range 57–69; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 95% CI, 0.19–0.92; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 95% CI, 0.15–0.89; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 95% CI, 0.12–0.70; P=0.01) in patients with COVID-19 and coexisting hypertension.
CONCLUSIONS:Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.
This paper considers the parameter estimation problem of a two-input single-output Hammerstein finite impulse response system with autoregressive moving average noise. Applying the data filtering ...technique, the input-output data is filtered and the original system with autoregressive moving average noise is changed into the system with moving average noise. Then, based on the key term separation technique, the filtered system is decomposed into two subsystems: one subsystem contains the unknown parameters in the nonlinear block, the other contains the unknown parameters in the linear dynamic block and the noise model. A filtering based multi-innovation stochastic gradient algorithm is presented for Hammerstein finite impulse response systems. The simulation results confirm that the proposed algorithm is effective in estimating the parameters of two-input single-output Hammerstein finite impulse response systems.
Inhibition of apoptosis signal‐regulating kinase 1 (ASK1) activation has emerged as a promising target for the treatment of nonalcoholic steatohepatitis (NASH). Multiple forms of posttranslational ...modifications determine the activity of ASK1. In addition to phosphorylation, recent studies revealed that ubiquitination is essential for ASK1 activation. However, the endogenous factor that regulates ASK1 ubiquitination and activation remains poorly defined. In this study, we identified the E3 ligase Skp1‐Cul1‐F‐box (SCF) protein F‐box/WD repeat‐containing protein 5 (FBXW5) as a key endogenous activator of ASK1 ubiquitination. FBXW5 is the central component of the SCF complex (SCFFbxw5) that directly interacts with and ubiquitinates ASK1 in hepatocytes during NASH development. An in vivo study showed that hepatocyte‐specific overexpression of FBXW5 exacerbated diet‐induced systemic and hepatic metabolic disorders, as well as the activation of ASK1‐related mitogen‐activated protein kinase (MAPK) signaling in the liver. Conversely, hepatocyte‐specific deletion of FBXW5 significantly prevented the progression of these abnormalities. Mechanically, FBXW5 facilitated the addition of Lys63‐linked ubiquitin to ASK1 and thus exacerbated ASK1‐c‐Jun N‐terminal kinase/p38 MAPK signaling, inflammation, and lipid accumulation. Furthermore, we demonstrated that the N‐terminus (S1) and C‐terminus (S3) of FBXW5 respectively and competitively ablate the function of FBXW5 on ASK1 activation and served as effective inhibitors of NASH progression. Conclusion: This evidence strongly suggests that SCFFbxw5 is an important activator of ASK1 ubiquitination in the context of NASH. The development of FBXW5(S1) or FBXW5(S3)‐mimicking drugs and screening of small‐molecular inhibitors specifically abrogating ASK1 ubiquitination‐dependent activation are viable approaches for NASH treatment.
Heart failure (HF) is the end stage of many cardiovascular diseases and seriously threatens people’s health. This article aimed to explore the biological role of fat-mass and obesity-associated gene ...(FTO) in HF. We constructed HF mouse model by transverse aortic constriction or intraperitoneal injection of doxorubicin. Mouse myocardial cells were exposed to hypoxia/reoxygenation (H/R). FTO and Mhrt were downregulated in heart tissues of HF mice. HF mice exhibited an increase in the total levels of N
6
methyladenosine (m
6
A) and the m
6
A levels of Mhrt. Moreover, FTO overexpression caused an upregulation of Mhrt and reduced m
6
A modification of Mhrt in the H/R-treated myocardial cells. FTO upregulation repressed apoptosis of H/R-treated myocardial cells. FTO knockdown had the opposite results. Mhrt overexpression reduced apoptosis of H/R-treated myocardial cells. Moreover, the influence conferred by FTO upregulation was abolished by Mhrt knockdown. In conclusion, our data demonstrate that FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt. Thus, FTO may be a target gene for HF treatment.
Epigenetic reprogramming is a critical process of pathological gene induction during cardiac hypertrophy and remodeling, but the underlying regulatory mechanisms remain to be elucidated. Here we ...identified a heart-enriched long noncoding (lnc)RNA, named cardiac-hypertrophy-associated epigenetic regulator (Chaer), which is necessary for the development of cardiac hypertrophy. Mechanistically, Chaer directly interacts with the catalytic subunit of polycomb repressor complex 2 (PRC2). This interaction, which is mediated by a 66-mer motif in Chaer, interferes with PRC2 targeting to genomic loci, thereby inhibiting histone H3 lysine 27 methylation at the promoter regions of genes involved in cardiac hypertrophy. The interaction between Chaer and PRC2 is transiently induced after hormone or stress stimulation in a process involving mammalian target of rapamycin complex 1, and this interaction is a prerequisite for epigenetic reprogramming and induction of genes involved in hypertrophy. Inhibition of Chaer expression in the heart before, but not after, the onset of pressure overload substantially attenuates cardiac hypertrophy and dysfunction. Our study reveals that stress-induced pathological gene activation in the heart requires a previously uncharacterized lncRNA-dependent epigenetic checkpoint.
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