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"Han, Dong"
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Individual variation of the SARS‐CoV‐2 receptor ACE2 gene expression and regulation
The COVID‐19 coronavirus is now spreading worldwide. Its pathogen, SARS‐CoV‐2, has been shown to use angiotensin‐converting enzyme 2 (ACE2) as its host cell receptor, same as the severe acute respiratory syndrome coronavirus (SARS‐CoV) in 2003. Epidemiology studies found males although only slightly more likely to be infected than females account for the majority of the severely ill and fatality, which also bias for people older than 60 years or with metabolic and cardiovascular diseases. Here by analyzing GTEx and other public data in 30 tissues across thousands of individuals, we found a significantly higher level in Asian females, an age‐dependent decrease in all ethnic groups, and a highly significant decrease in type II diabetic patients of ACE2 expression. Consistently, the most significant expression quantitative loci (eQTLs) contributing to high ACE2 expression are close to 100% in East Asians, >30% higher than other ethnic groups. A shockingly common enrichment of viral infection pathways was found among ACE2 anti‐expressed genes, and multiple binding sites of virus infection related transcription factors and sex hormone receptors locate at ACE2 regulatory regions. Human and mice data analysis further revealed ACE2 expression is reduced in T2D patients and with inflammatory cytokine treatment and upregulated by estrogen and androgen (both decrease with age). Our findings revealed a negative correlation between ACE2 expression and COVID‐19 fatality at both population and molecular levels. These results will be instrumental when designing potential prevention and treatment strategies for ACE2 binding coronaviruses in general. This study revealed the negative correlation of high basal ACE2 level with CoVID‐19 severity/fatality at the population level and its anticorrelation with virus infection pathway expression levels, upregulation by sex hormones and suppression by inflammatory cytokine at the molecular level.
Journal Article
A Survey on Deep Reinforcement Learning Algorithms for Robotic Manipulation
Robotic manipulation challenges, such as grasping and object manipulation, have been tackled successfully with the help of deep reinforcement learning systems. We give an overview of the recent advances in deep reinforcement learning algorithms for robotic manipulation tasks in this review. We begin by outlining the fundamental ideas of reinforcement learning and the parts of a reinforcement learning system. The many deep reinforcement learning algorithms, such as value-based methods, policy-based methods, and actor–critic approaches, that have been suggested for robotic manipulation tasks are then covered. We also examine the numerous issues that have arisen when applying these algorithms to robotics tasks, as well as the various solutions that have been put forth to deal with these issues. Finally, we highlight several unsolved research issues and talk about possible future directions for the subject.
Journal Article
Transformer for one stop interpretable cell type annotation
Consistent annotation transfer from reference dataset to query dataset is fundamental to the development and reproducibility of single-cell research. Compared with traditional annotation methods, deep learning based methods are faster and more automated. A series of useful single cell analysis tools based on autoencoder architecture have been developed but these struggle to strike a balance between depth and interpretability. Here, we present TOSICA, a multi-head self-attention deep learning model based on Transformer that enables interpretable cell type annotation using biologically understandable entities, such as pathways or regulons. We show that TOSICA achieves fast and accurate one-stop annotation and batch-insensitive integration while providing biologically interpretable insights for understanding cellular behavior during development and disease progressions. We demonstrate TOSICA’s advantages by applying it to scRNA-seq data of tumor-infiltrating immune cells, and CD14+ monocytes in COVID-19 to reveal rare cell types, heterogeneity and dynamic trajectories associated with disease progression and severity.
Developing computational tools for interpretable cell type annotation in scRNA-seq data remains challenging. Here the authors propose a Transformer-based model for interpretable annotation transfer using biologically understandable entities, and demonstrate its performance on large or atlas datasets.
Journal Article
Treatment with astragaloside IV reduced blood glucose, regulated blood lipids, and protected liver function in diabetic rats
Objectives
To investigate the effects of astragaloside IV on blood glucose, blood lipids, and liver function in diabetic rats.
Methods
Fifty diabetic rats were randomly placed into five groups (n = 10 each): the diabetes mellitus (DM) group received intragastric saline, the metformin hydrochloride group received intragastric metformin hydrochloride, and the astragaloside-30, -60, and -120 groups received intragastric astragaloside 30 mg/kg, 60 mg/kg, and 120 mg/kg for 28 days, respectively. Ten non-diabetic rats received intragastric saline as controls.
Results
Relative to the DM group, fasting blood glucose, triglyceride, total cholesterol, serum alanine transaminase, and serum aspartate aminotransferase levels decreased in the astragaloside-60 and astragaloside-120 groups; serum alkaline phosphatase decreased solely in the astragaloside-120 group. Serum superoxide dismutase (SOD), glutathione (GSH-Px), and catalase (CAT) levels were elevated, while maleic dialdehyde (MDA) decreased in the astragaloside-120 group, relative to the DM group. Relative to the DM group, the liver index and liver cell apoptosis rate were reduced, while histopathological changes in liver tissue were ameliorated in the astragaloside groups; moreover, liver tissue SOD, GSH-Px, and CAT levels were increased, while liver tissue MDA was reduced.
Conclusions
Astragaloside IV can lower blood glucose, regulate blood lipids, and protect liver function in diabetic rats.
Journal Article
Improved Side-Channel Attack on CTR DRBG Using a Clustering Algorithm
Deterministic random bit generators (DRBG) play a crucial role in device security because they generate secret information cryptographic systems, e.g., secret keys and parameters. Thus, attacks on DRBGs can result in the exposure of important secret values, which can threaten the entire cryptographic system of the target Internet of Things (IoT) equipment and smart devices. In 2020, Meyer proposed a side-channel attack (SCA) method that recovers the output random bits by analyzing the power consumption traces of the NIST standard AES CTR DRBG. In addition, most algorithmic countermeasures against SCAs also utilize random numbers; thus, such vulnerabilities are more critical than other SCAs on cryptographic modules. Meyer’s attack recovers the secret random number in four stages of the attack using only the power traces, which the CTR DRBG processes in 256 blocks. We present an approach that employs a clustering algorithm to enhance Meyer’s attack. The proposed attack increases the attack success rate and recovers more information using a clustering attack in the first step. In addition, it improves the attack accuracy in the third and fourth steps using the information obtained from the clustering process. These results lead to the possibility of attacks at higher noise levels and increase the diversity of target devices for attacking the CTR DRBG. Experiments were conducted on an Atmel XMEGA128D4 processor to evaluate the effectiveness of the proposed attack method. We also introduced artificial noise into the power traces to compare the proposed attack’s performance at different noise levels. Our results demonstrate that the first step of the proposed attack achieves a higher success rate than Meyer’s attack at all noise levels. For example, at high noise levels, the difference in the success rates is up to 50%. In steps 3 and 4, an average performance improvement of 18.5% greater than Meyer’s proposed method is obtained. The proposed attack effectively extends the target to more noisy environments than previous attacks, thereby increasing the threat of SCA on CTR DRBGs.
Journal Article
Targeting skeletal endothelium to ameliorate bone loss
Recent studies have identified a specialized subset of CD31
hi
endomucin
hi
(CD31
hi
EMCN
hi
) vascular endothelium that positively regulates bone formation. However, it remains unclear how CD31
hi
EMCN
hi
endothelium levels are coupled to anabolic bone formation. Mice with an osteoblast-specific deletion of
Shn3
, which have markedly elevated bone formation, demonstrated an increase in CD31
hi
EMCN
hi
endothelium. Transcriptomic analysis identified SLIT3 as an osteoblast-derived, SHN3-regulated proangiogenic factor. Genetic deletion of
Slit3
reduced skeletal CD31
hi
EMCN
hi
endothelium, resulted in low bone mass because of impaired bone formation and partially reversed the high bone mass phenotype of
Shn3
−/−
mice. This coupling between osteoblasts and CD31
hi
EMCN
hi
endothelium is essential for bone healing, as shown by defective fracture repair in SLIT3-mutant mice and enhanced fracture repair in SHN3-mutant mice. Finally, administration of recombinant SLIT3 both enhanced bone fracture healing and counteracted bone loss in a mouse model of postmenopausal osteoporosis. Thus, drugs that target the SLIT3 pathway may represent a new approach for vascular-targeted osteoanabolic therapy to treat bone loss.
Recombinant SLIT3 represents a new mechanistic approach to treating osteoporosis by increasing skeletal CD31
hi
EMCN
hi
vascular endothelium.
Journal Article
Bioinspired Soft Robots Based on the Moisture‐Responsive Graphene Oxide
Graphene oxide (GO), which has many oxygen functional groups, is a promising candidate for use in moisture‐responsive sensors and actuators due to the strong water–GO interaction and the ultrafast transport of water molecules within the stacked GO sheets. In the last 5 years, moisture‐responsive actuators based on GO have shown distinct advantages over other stimuli‐responsive materials and devices. Particularly, inspired by nature organisms, various moisture‐enabled soft robots have been successfully developed via rational assembly of the GO‐based actuators. Herein, the milestones in the development of moisture‐responsive soft robots based on GO are summarized. In addition, the working mechanisms, design principles, current achievement, and prospects are also comprehensively reviewed. In particular, the GO‐based soft robots are at the forefront of the advancement of automatable smart devices. In recent years, moisture‐responsive actuators based on graphene oxide (GO) have revealed a series of distinct advantages over other stimuli‐responsive materials and devices. In this research news, the milestones in moisture‐responsive soft robots based on the GO, including working mechanisms, design principles, current achievement, and prospects, are comprehensively reviewed.
Journal Article
Hawking radiation as instantons
There have been various interpretations of Hawking radiation proposed based on the perturbative approach, and all have confirmed Hawking’s original finding. One major conceptual challenge of Hawking evaporation is the associated black hole information loss paradox, which remains unresolved. A key factor to the issue is the end-stage of the black hole evaporation. Unfortunately by then the evaporation process becomes non-perturbative. Aspired to provide a tool for the eventual solution to this problem, here we introduce a new interpretation of Hawking radiation as the tunneling of instantons. We study instantons of a massless scalar field in Einstein gravity. We consider a complex-valued instanton that connects an initial pure black hole state to a black hole with a scalar field that represents the Hawking radiation at future null infinity, where its action depends only on the areal entropy difference. By comparing it with several independent approaches to Hawking radiation in the perturbative limit, we conclude that Hawking radiation may indeed be described by a family of instantons. Since the instanton approach can describe non-perturbative processes, we hope that our new interpretation and holistic method may shed lights on the information loss problem.
Journal Article
The circular RNA ACR attenuates myocardial ischemia/reperfusion injury by suppressing autophagy via modulation of the Pink1/ FAM65B pathway
Dysregulated autophagy is associated with many pathological disorders such as cardiovascular diseases. Emerging evidence has suggested that circular RNAs (circRNAs) have important roles in some biological processes. However, it remains unclear whether circRNAs participate in the regulation of autophagy. Here we report that a circRNA, termed autophagy-related circular RNA (ACR), represses autophagy and myocardial infarction by targeting Pink1-mediated phosphorylation of FAM65B. ACR attenuates autophagy and cell death in cardiomyocytes. Moreover, ACR protects the heart from ischemia/reperfusion (I/R) injury and reduces myocardial infarct sizes. We identify Pink1 as an ACR target to mediate the function of ACR in cardiomyocyte autophagy. ACR activates Pink1 expression through directly binding to Dnmt3B and blocking Dnmt3B-mediated DNA methylation of Pink1 promoter. Pink1 suppresses autophagy and Pink1 transgenic mice show reduced myocardial infarction sizes. Further, we find that FAM65B is a downstream target of Pink1 and Pink1 phosphorylates FAM65B at serine 46. Phosphorylated FAM65B inhibits autophagy and cell death in the heart. Our findings reveal a novel role for the circRNA in regulating autophagy and ACR-Pink1-FAM65B axis as a regulator of autophagy in the heart will be potential therapeutic targets in treatment of cardiovascular diseases.
Journal Article