Publications by authors named "Lei Xu"

2,096 Publications

  • Page 1 of 1

Chondroitin Sulfate/Polycaprolactone/Gelatin Electrospun Nanofibers with Antithrombogenicity and Enhanced Endothelial Cell Affinity as a Potential Scaffold for Blood Vessel Tissue Engineering.

Nanoscale Res Lett 2021 Apr 17;16(1):62. Epub 2021 Apr 17.

Vascular Surgury, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.

Electrospun polymer nanofibers have gained much attention in blood vessel tissue engineering. However, conventional nanofiber materials with the deficiencies of slow endothelialization and thrombosis are not effective in promoting blood vessel tissue repair and regeneration. Herein, biomimetic gelatin (Gt)/polycaprolactone (PCL) composite nanofibers incorporating a different amount of chondroitin sulfate (CS) were developed via electrospinning technology to investigate their effects on antithrombogenicity and endothelial cell affinity. Varying CS concentrations in PG nanofibers affects fiber morphology and diameter. The CS/Gt/PCL nanofibers have suitable porosity (~ 80%) and PBS solution absorption (up to 650%). The introduction of CS in Gt/PCL nanofibers greatly enhances their anticoagulant properties, prolongs their coagulation time, and facilitates cell responses. Particularly, 10%CS/Gt/PCL nanofibers display favorable cell attachment, elongation, and proliferation. Thus, the Gt/PCL nanofibers containing a certain amount of CS could be excellent candidates as a promising tissue-engineering scaffold in blood vessel repair and regeneration.
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http://dx.doi.org/10.1186/s11671-021-03518-xDOI Listing
April 2021

Lactobacillus casei alleviated the abnormal increase of cholestasis-related liver indices during tuberculosis treatment: a post hoc analysis of randomized controlled trial.

Mol Nutr Food Res 2021 Apr 17:e2100108. Epub 2021 Apr 17.

Institute of Nutrition and Health, School of Public Health, Qingdao University, Qingdao, Shandong, 266021, China.

Scope: Probiotics are promising in mitigating drug-induced liver injury in animal experiments. However, the clinical evidence is absent. The objective is to investigate the effect of adjunctive Lactobacillus casei on tuberculosis-drug-induced liver injury.

Methods And Results: A post hoc analysis was conducted for a previous randomized controlled trial. The trial was registered at the Chinese Clinical Trial Registry (No. ChiCTR-IOR-17013210). 429 patients were allocated to receive standard tuberculosis therapy alone (control group), or together with 1 × 10 colony-forming units (CFU) per day (low-dose group), or 2 × 10 CFU per day of L. casei (high-dose group) during tuberculosis treatment. The L. casei supplementation significantly reduced the incidence of the abnormal increase of cholestasis-related liver indices including alkaline phosphatase (p = 0.024) and bilirubin (p = 0.013). Plasma lipopolysaccharide (p = 0.02), intestinal permeability biomarkers including zonula occludens-1 (p = 0.001) and intestinal fatty acid binding protein (p = 0.002) were significantly reduced. The gut microbiota composition was dramatically altered with a reduction of Bacteroidetes (p<0.001) and a corresponding increase of Actinobacteria (p<0.001) and Firmicutes (p = 0.003).

Conclusions: L. casei supplementation is beneficial for suppressing abnormally elevated cholestasis-related liver indices during tuberculosis treatment, which may be related to its modification on blood lipopolysaccharide, intestinal barrier function and gut microbiota. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/mnfr.202100108DOI Listing
April 2021

Bmal1 inhibits phenotypic transformation of hepatic stellate cells in liver fibrosis via IDH1/α-KG-mediated glycolysis.

Acta Pharmacol Sin 2021 Apr 13. Epub 2021 Apr 13.

School of Pharmacy, Anhui Medical University, Hefei, 230032, China.

Hepatic stellate cells (HSCs) play an important role in the initiation and development of liver fibrogenesis, and abnormal glucose metabolism is increasingly being considered a crucial factor controlling phenotypic transformation in HSCs. However, the role of the factors affecting glycolysis in HSCs in the experimental models of liver fibrosis has not been completely elucidated. In this study, we showed that glycolysis was significantly enhanced, while the expression of brain and muscle arnt-like protein-1 (Bmal1) was downregulated in fibrotic liver tissues of mice, primary HSCs, and transforming growth factor-β1 (TGF-β1)-induced LX2 cells. Overexpression of Bmal1 in TGF-β1-induced LX2 cells blocked glycolysis and inhibited the proliferation and phenotypic transformation of activated HSCs. We further confirmed the protective effect of Bmal1 in liver fibrosis by overexpressing Bmal1 from hepatic adeno-associated virus 8 in mice. In addition, we also showed that the regulation of glycolysis by Bmal1 is mediated by the isocitrate dehydrogenase 1/α-ketoglutarate (IDH1/α-KG) pathway. Collectively, our results indicated that a novel Bmal1-IDH1/α-KG axis may be involved in regulating glycolysis of activated HSCs and might hence be used as a therapeutic target for alleviating liver fibrosis.
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http://dx.doi.org/10.1038/s41401-021-00658-9DOI Listing
April 2021

Wearable Mixed-Reality Holographic Navigation Guiding the Management of Penetrating Intracranial Injury Caused by a Nail.

J Digit Imaging 2021 Apr 12. Epub 2021 Apr 12.

Department of Neurosurgery, Chongqing Emergency Medical Center, Chongqing, China.

Penetrating brain injury caused by a nail is an extremely rare neurosurgical emergency that poses a challenge for neurosurgeons. Nail entering the brain from the orbit and lodging within the cranial cavity is even more unusual. A 53-year-old male was found unconscious at a construction site, and brain CT revealed not only the presence of a nail beneath the inner table of the parietal bone, but also traumatic intracerebral hematoma. Consequently, accurate localization of the nail and hematoma was mandatory for surgical plan. During surgical planning, computational model reconstruction and trajectory calculation were completed using preoperative CT in 3D Slicer. Under the guidance of a head-mounted mixed-reality holographic computer, the neurosurgeon was able to visualize and interact with the hologram of the surgical plan, and intraoperative findings demonstrated that our low-cost portable wearable mixed-reality holographic navigation assisted precise localization of the nail and intracerebral hematoma, assuring less injury to the already compromised brain. After the surgery, the patient could obey commands, and postoperative imaging ruled out the possibility of brain abscess during follow-up. To the best of our knowledge, this is the first report on using a low-cost wearable mixed-reality holographic navigation to guide the management of penetrating intracranial injury caused by a nail.
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http://dx.doi.org/10.1007/s10278-021-00436-3DOI Listing
April 2021

-derived peptide SJMHE1 promotes peripheral nerve repair through a macrophage-dependent mechanism.

Am J Transl Res 2021 15;13(3):1290-1306. Epub 2021 Mar 15.

State Key Lab of Reproductive Medicine, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, Center for Global Health, Nanjing Medical University Nanjing 211166, Jiangsu, P. R. China.

Peripheral nerve injury, a disease that affects 1 million people worldwide every year, occurs when peripheral nerves are destroyed by injury, systemic illness, infection, or an inherited disorder. Indeed, repair of damaged peripheral nerves is predominantly mediated by type 2 immune responses. Given that helminth parasites induce type 2 immune responses in hosts, we wondered whether helminths or helminth-derived molecules might have the potential to improve peripheral nerve repair. Here, we demonstrated that schistosome-derived SJMHE1 promoted peripheral myelin growth and functional regeneration via a macrophage-dependent mechanism and simultaneously increased the induction of M2 macrophages. Our findings highlight the therapeutic potential of schistosome-derived SJMHE1 for improving peripheral nerve repair.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014408PMC
March 2021

RNA-Associated Co-expression Network Identifies Novel Biomarkers for Digestive System Cancer.

Front Genet 2021 26;12:659788. Epub 2021 Mar 26.

School of Applied Chemistry and Biological Technology, Shenzhen Polytechnic, Shenzhen, China.

Cancers of the digestive system are malignant diseases. Our study focused on colon cancer, esophageal cancer (ESCC), rectal cancer, gastric cancer (GC), and rectosigmoid junction cancer to identify possible biomarkers for these diseases. The transcriptome data were downloaded from the TCGA database (The Cancer Genome Atlas Program), and a network was constructed using the WGCNA algorithm. Two significant modules were found, and coexpression networks were constructed. CytoHubba was used to identify hub genes of the two networks. GO analysis suggested that the network genes were involved in metabolic processes, biological regulation, and membrane and protein binding. KEGG analysis indicated that the significant pathways were the calcium signaling pathway, fatty acid biosynthesis, and pathways in cancer and insulin resistance. Some of the most significant hub genes were , , , , and and , , , , and , respectively. These genes were predicted to be associated with the tumor prognostic reference for this patient population.
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http://dx.doi.org/10.3389/fgene.2021.659788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033200PMC
March 2021

High-throughput sequencing identifies salivary microbiota in Chinese caries-free preschool children with primary dentition.

J Zhejiang Univ Sci B 2021 Apr;22(4):285-294

The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou 310006, China.

Objectives: The study aimed at identifying salivary microbiota in caries-free Chinese preschool children using high-throughput sequencing.

Methods: Saliva samples were obtained from 35 caries-free preschool children (18 boys and 17 girls) with primary dentition, and 16S ribosomal DNA (rDNA) V3-V4 hypervariable regions of the microorganisms were analyzed using Illumina MiSeq.

Results: At 97% similarity level, all of these reads were clustered into 334 operational taxonomic units (OTUs). Among these, five phyla (Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Candidate division TM7) and 13 genera (, , , , , , , , , , , , and ) were the most dominant, constituting 99.4% and 89.9% of the salivary microbiota, respectively. The core salivary microbiome comprised nine genera (, , , , , , , ,and ). Analysis of microbial diversity and community structure revealed a similar pattern between male and female subjects. The difference in microbial community composition between them was mainly attributed to (=0.023). Furthermore, functional prediction revealed that the most abundant genes were related to amino acid transport and metabolism.

Conclusions: Our results revealed the diversity and composition of salivary microbiota in caries-free preschool children, with little difference between male and female subjects. Identity of the core microbiome, coupled with prediction of gene function, deepens our understanding of oral microbiota in caries-free populations and provides basic information for associating salivary microecology and oral health.
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http://dx.doi.org/10.1631/jzus.B2000554DOI Listing
April 2021

"Olfactory three-needle" acupuncture enhances synaptic function in Aβ-induced Alzheimer's disease via activating PI3K/AKT/GSK-3β signaling pathway.

J Integr Neurosci 2021 Mar;20(1):55-65

College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, 712046 Xianyang, P. R. China.

Synaptic dysfunction and neuronal loss are related to cognitive impairment of Alzheimer's disease. Recent evidence indicates that regulating the phosphatidylinositol 3-Kinase (PI3K)/AKT/GSK-3β pathway is a therapeutic strategy for improving synaptic plasticity in Alzheimer's disease. Here, we investigated "olfactory three-needle" effects on synaptic function and the PI3K/AKT/GSK-3β signaling pathway in β-amyloid (Aβ)-induced Alzheimer's disease rats. A three-needle olfactory bulb insertion for 28 days alleviated Aβ-induced Alzheimer's disease rats' cognitive impairment as assessed by performance in the Morris water maze test. Furthermore, the three-needle electrode inhibited neuro-apoptosis and neuro-inflammation. It significantly upregulated the protein expression of postsynaptic density protein 95, synaptophysin, and GAP43, indicating a protective effect on hippocampal synaptic plasticity. Additionally, the activation level of PI3K/AKT signaling and the phosphorylation inactivation of GSK-3β were significantly enhanced by the "olfactory three-needle". Our findings suggested that the three-needle acupuncture is a potential alternative to improve synaptic plasticity and neuronal survival of Alzheimer's disease brain in rodents.
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http://dx.doi.org/10.31083/j.jin.2021.01.224DOI Listing
March 2021

A comprehensive review of the imbalance classification of protein post-translational modifications.

Brief Bioinform 2021 Apr 8. Epub 2021 Apr 8.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, China.

Post-translational modifications (PTMs) play significant roles in regulating protein structure, activity and function, and they are closely involved in various pathologies. Therefore, the identification of associated PTMs is the foundation of in-depth research on related biological mechanisms, disease treatments and drug design. Due to the high cost and time consumption of high-throughput sequencing techniques, developing machine learning-based predictors has been considered an effective approach to rapidly recognize potential modified sites. However, the imbalanced distribution of true and false PTM sites, namely, the data imbalance problem, largely effects the reliability and application of prediction tools. In this article, we conduct a systematic survey of the research progress in the imbalanced PTMs classification. First, we describe the modeling process in detail and outline useful data imbalance solutions. Then, we summarize the recently proposed bioinformatics tools based on imbalanced PTM data and simultaneously build a convenient website, ImClassi_PTMs (available at lab.malab.cn/∼dlj/ImbClassi_PTMs/), to facilitate the researchers to view. Moreover, we analyze the challenges of current computational predictors and propose some suggestions to improve the efficiency of imbalance learning. We hope that this work will provide comprehensive knowledge of imbalanced PTM recognition and contribute to advanced predictors in the future.
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http://dx.doi.org/10.1093/bib/bbab089DOI Listing
April 2021

Comparison of Clinical Features and Outcomes of Medically Attended COVID-19 and Influenza Patients in a Defined Population in the 2020 Respiratory Virus Season.

Front Public Health 2021 23;9:587425. Epub 2021 Mar 23.

Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), which is causing the coronavirus disease-2019 (COVID-19) pandemic, poses a global health threat. However, it is easy to confuse COVID-19 with seasonal influenza in preliminary clinical diagnosis. In this study, the differences between influenza and COVID-19 in epidemiological features, clinical manifestations, comorbidities and pathogen biology were comprehensively compared and analyzed. SARS-CoV-2 causes a higher proportion of pneumonia (90.67 vs. 17.07%) and acute respiratory distress syndrome (12.00 vs. 0%) than influenza A virus. The proportion of leukopenia for influenza patients was 31.71% compared with 12.00% for COVID-19 patients ( = 0.0096). The creatinine and creatine kinase were significantly elevated when there were COVID-19 patients. The basic reproductive number (R) for SARS-CoV-2 is 2.38 compared with 1.28 for seasonal influenza A virus. The mutation rate of SARS-CoV-2 ranges from 1.12 × 10 to 6.25 × 10, while seasonal influenza virus has a lower evolutionary rate (0.60-2.00 × 10). Overall, this study compared the clinical features and outcomes of medically attended COVID-19 and influenza patients. In addition, the S477N and N439K mutations on spike may affect the affinity with receptor ACE2. This study will contribute to COVID-19 control and epidemic surveillance in the future.
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http://dx.doi.org/10.3389/fpubh.2021.587425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021703PMC
March 2021

Novel ginsenoside derivatives have shown their effects on PC-3 cells by inducing G1-phase arrest and reactive oxygen species-mediate cell apoptosis.

Bioorg Chem 2021 Mar 26;112:104864. Epub 2021 Mar 26.

School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China; Key Laboratory of Structure-based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

In this study, piperazine groups were introduced into ginsenoside to enhance its ability to induce Reactive Oxygen Species (ROS) production and apoptosis in cancer cells. In total, 27 ginsenoside piperazine derivatives were synthesized and tested for their anti-proliferative activity in cancer cell lines by MTT assay. The results showed that compounds 4a, 4g, 4f, 4i, 5g, 5i, 6a, 6g, 6f and 6i had significant inhibitory effects on cancer cell growth. Compound 6g showed the strongest anti-proliferative effect on PC-3 cells with an IC of 1.98 ± 0.34 μM. Compound 6g could also induce G1-phase arrest and apoptosis in PC-3 cells, with apoptosis rates of 8.1%, 41% and 56.1% observed at 5, 10 and 20 μM, respectively. Compound 6g also significantly enhanced the intracellular fluorescence of ROS sensitive substrates, with a fluorescence intensity ratio of 23.1% observed in treated cells, indicative of ROS production. Following N-acetylcysteine treatment, apoptotic rates of the cancer cell lines decreased from 38.9% to 7.3%, and the expression of Cl-PARP, Cl-Caspase-3 and Cl-Caspase-9 also decreased, confirming that compound 6g induced apoptosis through ROS induction. Compound 6g also stimulated the translocation of Bax from the cytoplasm to the mitochondria, which enhanced Cytochrome C (Cyt C) release, and increased the expression of the apoptotic markers Cl-PARP, Cl-Caspase-3, and Cl-Caspase-9 in PC-3 cells. Taken together, these data reveal the anti-cancer effects of compound 6g that enhance ROS production, and then induce apoptosis through mitochondrial pathway.
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http://dx.doi.org/10.1016/j.bioorg.2021.104864DOI Listing
March 2021

Prediction of neoadjuvant chemotherapy response in high-grade osteosarcoma: added value of non-tumorous bone radiomics using CT images.

Quant Imaging Med Surg 2021 Apr;11(4):1184-1195

Nuclear & Radiological Engineering and Medical Physics Programs, Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.

Background: This study aimed to determine the impact of including radiomics analysis of non-tumorous bone region of interest in improving the performance of pathological response prediction to chemotherapy in high-grade osteosarcomas (HOS), compared to radiomics analysis of tumor region alone.

Methods: This retrospective study included 157 patients diagnosed with HOS between November 2013 and November 2017 (age range, 5-44 years; mean age, 16.99 ±7.42 years), in which 69 and 88 patients were diagnosed as pathological good response (pGR) and non-pGR, respectively. Radiomics features were extracted from tumor and non-tumorous bone regions based on diagnostic CT images. Pathological response classifiers were developed and validated via leave-one-out cross validation (LOOCV) and independent validation methods by using the area under the receiver operating characteristic curve (AUC) value as the figure of merit.

Results: Using the LOOCV, the classifiers combining features from tumor and non-tumorous regions showed better prediction performance than those from tumor region alone (AUC, 0.8207±0.0043 0.7799±0.0044). The combined classifier also showed better performance than the tumor feature-based classifier in both training and validation datasets [training dataset: 0.791, 95% confidence interval (CI), 0.706-0.860 0.766, 95% CI, 0.679-0.840; validation dataset: 0.816, 95% CI, 0.662-0.920 0.766, 95% CI, 0.606-0.885].

Conclusions: Radiomics analysis of combined tumor and non-tumorous bone features showed improved performance of pathological response prediction to chemotherapy in HOS compared to that of tumor features alone. Moreover, the proposed classifier had the potential to predict pathological response to chemotherapy for HOS patients.
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http://dx.doi.org/10.21037/qims-20-681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930704PMC
April 2021

EEG-Based Sleep Staging Analysis with Functional Connectivity.

Sensors (Basel) 2021 Mar 11;21(6). Epub 2021 Mar 11.

School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China.

Sleep staging is important in sleep research since it is the basis for sleep evaluation and disease diagnosis. Related works have acquired many desirable outcomes. However, most of current studies focus on time-domain or frequency-domain measures as classification features using single or very few channels, which only obtain the local features but ignore the global information exchanging between different brain regions. Meanwhile, brain functional connectivity is considered to be closely related to brain activity and can be used to study the interaction relationship between brain areas. To explore the electroencephalography (EEG)-based brain mechanisms of sleep stages through functional connectivity, especially from different frequency bands, we applied phase-locked value (PLV) to build the functional connectivity network and analyze the brain interaction during sleep stages for different frequency bands. Then, we performed the feature-level, decision-level and hybrid fusion methods to discuss the performance of different frequency bands for sleep stages. The results show that (1) PLV increases in the lower frequency band (delta and alpha bands) and vice versa during different stages of non-rapid eye movement (NREM); (2) alpha band shows a better discriminative ability for sleeping stages; (3) the classification accuracy of feature-level fusion (six frequency bands) reaches 96.91% and 96.14% for intra-subject and inter-subjects respectively, which outperforms decision-level and hybrid fusion methods.
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http://dx.doi.org/10.3390/s21061988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999974PMC
March 2021

The Boundary of Lithium Plating in Graphite Electrode for Safe Lithium-Ion Batteries.

Angew Chem Int Ed Engl 2021 Apr 1. Epub 2021 Apr 1.

Tsinghua University, Department of Chemical Engineering, Gongwu Building 308B, 100084, Beijing, CHINA.

Graphite has been the dominant anode material for practical lithium-ion batteries. However, uncontrolled Li plating in graphite electrodes remains the main bottleneck that endangers battery life and safety, which have driven tremendous efforts aiming to eliminate Li plating. Herein we systematically investigate the boundary of Li plating in graphite electrodes for safe lithium-ion batteries. On one hand, the cell exhibits superior safety performance than that with Li dendrites by defining the endurable amount of uniform Li plating in graphite anode. On the other hand, the presence of "dead Li" can be eliminated owing to the uniform distribution of Li plating, and the average Coulombic efficiency for deposited Li during the reversible plating/stripping process is decoupled as high as ~99.5%. Attributing to the limited Li plating with superior Coulombic efficiency, the LiNi0.5Mn0.3Co0.2O2 | graphite cell achieves a high capacity retention of 80.2% over 500 cycles. This work sheds a different light on further improving the fast-charging capability, low-temperature performance, and energy density of practical lithium-ion batteries.
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http://dx.doi.org/10.1002/anie.202102593DOI Listing
April 2021

Acquiring high expression of suilysin enable non-epidemic to cause Streptococcal toxic shock-like syndrome (STSLS) through NLRP3 inflammasome hyperactivation.

Emerg Microbes Infect 2021 Apr 1:1-26. Epub 2021 Apr 1.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University. Wuhan, Hubei, 430070, China.

The epidemic () strain [Sequence type (ST) 7] was gradually evolving from the non-epidemic ST1 strain, and got the ability for high expressing of suilysin (SLY). And the high expression of SLY was required for the epidemic strain to cause NLRP3 hyperactivation, which is essential for the induction of cytokines storm, dysfunction of multiple organs and a high incidence of mortality, the characters of Streptococcal toxic shock-like syndrome (STSLS). However, it remains to be elucidated whether acquiring high SLY expression due to genome evolution was sufficient for the non-epidemic strain to cause STSLS. Here, we found that overexpression of SLY in ST1 strain (P1/7-SLY) could obviously increase the inflammasome activation, which was dependent on NLRP3 signaling. In contrast, the strain (P1/7-mSLY) overexpressing the mutant SLY (protein without hemolytic activity) could not significantly increase the inflammasome activation. Furthermore, similar to the epidemic strain, P1/7-SLY could cause STSLS in mice but not in mice. In contrast, P1/7-mSLY could not cause STSLS in both mice and mice. In summary, we demonstrate that genetic evolution enabling strain to express high level of SLY may be an essential and sufficient condition for NLRP3 inflammasome hyperactivation, which could further cause cytokines storm and STSLS.
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http://dx.doi.org/10.1080/22221751.2021.1908098DOI Listing
April 2021

Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease.

Front Pharmacol 2021 10;12:640521. Epub 2021 Mar 10.

School of Pharmacy, Anhui Medical University, Hefei, China.

Hepatic macrophages play a critical role in inflammation caused by alcohol feeding. During this process, variation of macrophage phenotypes triggers inflammatory responses in a variety of ways. Moreover, there is increasing evidence that Brain and Muscle Arnt-Like Protein-1 (Bmal1) is regarded as a key regulator of macrophage transformation. In our study, Bmal1 was detected to be low expressed in EtOH-fed mice tissue samples and ethanol-induced RAW264.7 cells. After hepatic specific overexpression of Bmal1, M1 macrophage markers were evidently down-regulated, while M2 markers were on the contrary, showing an upward trend. Furthermore, alcoholic liver lesions were also improved in alcohol feeding mice with overexpressed Bmal1. On this basis, we also found that the glycolytic pathway can regulate macrophage polarization. , blocking of glycolytic pathway can significantly inhibit M1-type polarization. Importantly, glycolysis levels were also restrained after Bmal1 overexpression. What's more, Bmal1 exerts a negative regulatory effect on glycolysis by interacting with S100A9 protein. Further studies showed that the alleviation of alcoholic liver disease (ALD) by Bmal1 was associated with glycolytic pathway suppression and M1 macrophage polarization. In summary, we demonstrated that Bmal1 is a gene capable of relieving ALD, and this effect may provide new insights for altering macrophage phenotypes to regulate inflammatory responses in ALD.
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http://dx.doi.org/10.3389/fphar.2021.640521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006279PMC
March 2021

Machine learning for phytopathology: from the molecular scale towards the network scale.

Brief Bioinform 2021 Mar 31. Epub 2021 Mar 31.

Shenzhen Polytechnic, China.

With the increasing volume of high-throughput sequencing data from a variety of omics techniques in the field of plant-pathogen interactions, sorting, retrieving, processing and visualizing biological information have become a great challenge. Within the explosion of data, machine learning offers powerful tools to process these complex omics data by various algorithms, such as Bayesian reasoning, support vector machine and random forest. Here, we introduce the basic frameworks of machine learning in dissecting plant-pathogen interactions and discuss the applications and advances of machine learning in plant-pathogen interactions from molecular to network biology, including the prediction of pathogen effectors, plant disease resistance protein monitoring and the discovery of protein-protein networks. The aim of this review is to provide a summary of advances in plant defense and pathogen infection and to indicate the important developments of machine learning in phytopathology.
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http://dx.doi.org/10.1093/bib/bbab037DOI Listing
March 2021

Unraveling the Orbital Physics in a Canonical Orbital System KCuF_{3}.

Phys Rev Lett 2021 Mar;126(10):106401

Diamond Light Source, Harwell Campus, Didcot OX11 0DE, United Kingdom.

We explore the existence of the collective orbital excitations, orbitons, in the canonical orbital system KCuF_{3} using the Cu L_{3}-edge resonant inelastic x-ray scattering. We show that the nondispersive high-energy peaks result from the Cu^{2+}  dd orbital excitations. These high-energy modes display good agreement with the ab initio quantum chemistry calculation, indicating that the dd excitations are highly localized. At the same time, the low-energy excitations present clear dispersion. They match extremely well with the two-spinon continuum following the comparison with Müller ansatz calculations. The localized dd excitations and the observation of the strongly dispersive magnetic excitations suggest that the orbiton dispersion is below the resolution detection limit. Our results can reconcile with the strong local Jahn-Teller effect in KCuF_{3}, which predominantly drives orbital ordering.
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http://dx.doi.org/10.1103/PhysRevLett.126.106401DOI Listing
March 2021

Control of Triplet Blinking Using Cyclooctatetraene to Access the Dynamics of Biomolecules at the Single-Molecule Level.

Angew Chem Int Ed Engl 2021 Mar 30. Epub 2021 Mar 30.

Osaka University, The Institute of Scientific and Industrial Research, Mihogaoka 8-1, Ibaraki, 567-0047, Osaka, JAPAN.

To explore the dynamics of biomolecules, tracing the kinetics of photo-induced chemical reactions via the triplet excited state (T1) of probe molecules offers a timescale that is ~10^6   times wider than via the singlet excited state (S1). Here, using cyclooctatetraene (COT) as a triplet energy acceptor and at the same time as a photostabilizer, the triplet-triplet energy transfer (TTET) kinetics governed by oligonucleotide (oligo) dynamics were studied at the single-molecule level by measuring fluorescence blinking. TTET kinetics measurement allowed us to access the length- and sequence-dependent dynamics of oligos, and realize the single-molecule detection of a model microRNA biomarker. In sharp contrast to the singlet-singlet Förster resonance energy transfer (FRET) that occurs in the 1-10 nm range, TTET requires a Van der Waals contact. Thus, the present method serves as a complementary method to FRET and provides direct information on biomolecular dynamics on the μs to ms timescale.
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http://dx.doi.org/10.1002/anie.202101606DOI Listing
March 2021

Salivary microbial community alterations due to probiotic yogurt in preschool children with healthy deciduous teeth.

Arch Microbiol 2021 Mar 30. Epub 2021 Mar 30.

The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China.

Probiotics are considered valuable to human health since they improve intestinal microbial balance. Probiotics are orally taken and affect the oral microbiota, which is one of the most important parts of the human microbial community. However, there is little information on the effects of probiotics on the oral microbiota. Caries-free preschool children (N = 6) with complete deciduous dentition were enrolled and given 100 g probiotic yogurt daily for 1 year. Salivary samples were collected every 6 months and then sequenced by Illumina MiSeq system based on 16S rDNA V3-V4 hypervariable regions. The data were analyzed to obtain the changes in microbiota profiles before and after the probiotic yogurt consumption. The α diversity analysis showed that salivary microbial diversity and richness were similar between the groups. The β diversity analysis showed that salivary microbial community structure changed with the consumption of probiotic yogurt. The variation of the microbial community composition was mainly due to 9 genera; for 7 genera (Campylobacter, Haemophilus, Lautropia, Bacillus, Catonella, Lactococcus, and Solibacillus) increased, while 2 genera (Gemella, and Streptococcus) decreased. The variation of salivary microbiota structure and composition with the consumption of probiotic yogurt was revealed. This expands overall insights on the effects of probiotic products on oral microecology. It further provides a basis for predicting possible relations between probiotic interventions and oral health in preschool children.
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http://dx.doi.org/10.1007/s00203-021-02292-9DOI Listing
March 2021

Downregulation of c-Myc expression confers sensitivity to CHK1 inhibitors in hematologic malignancies.

Acta Pharmacol Sin 2021 Mar 29. Epub 2021 Mar 29.

National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Checkpoint kinase 1 inhibitors (CHK1i) have shown impressive single-agent efficacy in treatment of certain tumors, as monotherapy or potentiators of chemotherapy in clinical trials, but the sensitive tumor types and downstream effectors to dictate the therapeutic responses to CHK1i remains unclear. In this study we first analyzed GDSC (Genomics of Drug Sensitivity in Cancer) and DepMap database and disclosed that hematologic malignancies (HMs) were relatively sensitive to CHK1i or CHK1 knockdown. This notion was confirmed by examining PY34, a new and potent in-house selective CHK1i, which exhibited potent anti-HM effect in vitro and in vivo, as single agent. We demonstrated that the downregulation of c-Myc and its signaling pathway was the common transcriptomic profiling response of sensitive HM cell lines to PY34, whereas overexpressing c-Myc could partially rescue the anticancer effect of PY34. Strikingly, we revealed the significant correlations between downregulation of c-Myc and cell sensitivity to PY34 in 17 HM cell lines and 39 patient-derived cell (PDC) samples. Thus, our results demonstrate that HMs are more sensitive to CHK1i than solid tumors, and c-Myc downregulation could represent the CHK1i efficacy in HMs.
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http://dx.doi.org/10.1038/s41401-021-00652-1DOI Listing
March 2021

Discovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders.

Eur J Med Chem 2021 Mar 11;218:113341. Epub 2021 Mar 11.

Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing, 100049, China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China. Electronic address:

SHP2, a non-receptor tyrosine phosphatase, plays a pivotal role in numerous oncogenic cell-signaling cascades like RAS-ERK, PI3K-AKT and JAK-STAT. On the other hand, proteolysis targeting chimera (PROTAC) has emerged as a promising strategy for the degradation of disease-related protein of interest (POI). SHP2 degradation via the PROTAC strategy will provide an alternative startegy for SHP2-mediated cancer therapy. Herein we described the design, synthesis and evaluation of a series of thalidomide-based heterobifunctional molecules and identified 11(ZB-S-29) as the highly efficient SHP2 degrader with a DC of 6.02 nM. Further mechanism investigation illustrated that 11 came into function through targeted SHP2 protein degradation.
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http://dx.doi.org/10.1016/j.ejmech.2021.113341DOI Listing
March 2021

rBPDL: Predicting RNA-binding proteins using deep learning.

IEEE J Biomed Health Inform 2021 Mar 29;PP. Epub 2021 Mar 29.

RNA-binding protein (RBP) is a powerful and wide-ranging regulator that plays an important role in cell development, differentiation, metabolism, health and disease. The prediction of RBPs provides valuable guidance for biologists; although the wet test RBP has made good progress, it is time-consuming and not flexible. Therefore, we developed a network model, rBPDL, by combining a convolutional neural network and long short-term memory for multilabel classification of RBPs. Moreover, to achieve better prediction results, we used a voting algorithm for ensemble learning of the model. We compared rBPDL with state-of-the-art methods and found that rBPDL significantly improved identification performance for the RBP68 dataset, with a macro-Area Under Curve (AUC), micro-AUC, and weighted AUC of 0.936, 0.962, and 0.946, respectively. Furthermore, we analyzed the performance of rBPDL on a single RBP and found, through AUC statistical analysis of the RBP domain, that the RBP identification performance in the same domain was similar. In addition, we analyzed the performance preferences and physicochemical properties of the binding protein amino acids and explored the characteristics that affect the binding by using the RBP86 dataset. The code and datasets can be found at the link: https://github.com/nmt315320/rBPDL.git.
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http://dx.doi.org/10.1109/JBHI.2021.3069259DOI Listing
March 2021

Litter decomposes slowly on shaded steep slope and sunny gentle slope in a typical steppe ecoregion.

Ecol Evol 2021 Mar 26;11(6):2461-2470. Epub 2021 Feb 26.

State Key Laboratory of Grassland Agro-Ecosystems Key Laboratory of Grassland Livestock Industry Innovation Ministry of Agriculture Lanzhou China.

Plant litter decomposition is mainly affected by litter properties and environmental factors, but the influence of terrain on litter decomposition is not well understood. We studied the effects of terrain on litter decomposition over a period of 12 months at six locations in a typical steppe ecoregion and measured the concomitant release of carbon (C), nitrogen (N), and phosphorus (P). The study site has two aspects, shaded and sunny, each aspect having three slopes: 15°, 30°, and 45°. The same mixed litter was used at each location to exclude the influence of litter quality variation. Results showed that soil temperature and moisture, solar radiation, and plant species diversity varied by terrain, which in turn, affected the -value (standardized total effects, 0.78, 0.12, 0.92, 0.23, respectively) and the release of C (0.72, -0.25, 0.83, 0.24, respectively), N (0.89, -0.45, 0.76, 0.40, respectively) and P (0.88, 0.77, 0.58, 0.57, respectively). -value and C release decreased with increasing slope on shaded aspect, while increased with increasing slope on sunny aspect. The release of N and P decreased with increasing slope on the shaded aspect. -value and C, N, and P release were significantly higher on shaded than that on sunny aspect at 15° and 30°, while at 45°, it was higher on sunny than on shaded aspect. The litter mass loss was slower on shaded 45° and sunny 15°. So moderate grazing or mowing could be used to reduce litter accumulation and accelerate litter decomposition on these terrains. Structural equation modeling indicated that soil temperature and solar radiation had the greatest influence on -value and C, N, and P release, and these two factors were directly related to soil moisture and plant species diversity. Overall, our results emphasize the need to consider terrain for litter decomposition in typical steppe ecoregions.
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http://dx.doi.org/10.1002/ece3.6933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981220PMC
March 2021

Discovery of novel antagonists targeting the DNA binding domain of androgen receptor by integrated docking-based virtual screening and bioassays.

Acta Pharmacol Sin 2021 Mar 25. Epub 2021 Mar 25.

Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

Androgen receptor (AR), a ligand-activated transcription factor, is a master regulator in the development and progress of prostate cancer (PCa). A major challenge for the clinically used AR antagonists is the rapid emergence of resistance induced by the mutations at AR ligand binding domain (LBD), and therefore the discovery of novel anti-AR therapeutics that can combat mutation-induced resistance is quite demanding. Therein, blocking the interaction between AR and DNA represents an innovative strategy. However, the hits confirmed targeting on it so far are all structurally based on a sole chemical scaffold. In this study, an integrated docking-based virtual screening (VS) strategy based on the crystal structure of the DNA binding domain (DBD) of AR was conducted to search for novel AR antagonists with new scaffolds and 2-(2-butyl-1,3-dioxoisoindoline-5-carboxamido)-4,5-dimethoxybenzoicacid (Cpd39) was identified as a potential hit, which was competent to block the binding of AR DBD to DNA and showed decent potency against AR transcriptional activity. Furthermore, Cpd39 was safe and capable of effectively inhibiting the proliferation of PCa cell lines (i.e., LNCaP, PC3, DU145, and 22RV1) and reducing the expression of the genes regulated by not only the full-length AR but also the splice variant AR-V7. The novel AR DBD-ARE blocker Cpd39 could serve as a starting point for the development of new therapeutics for castration-resistant PCa.
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http://dx.doi.org/10.1038/s41401-021-00632-5DOI Listing
March 2021

Barriers and Facilitators for Mental Health Service Use Among Racial/Ethnic Minority Adolescents: A Systematic Review of Literature.

Front Public Health 2021 8;9:641605. Epub 2021 Mar 8.

Department of Health Education and Promotion, College of Health and Human Performance, East Carolina University, Greenville, NC, United States.

Mental disorders represent serious public health concerns in the U.S. Compared with Whites, racial/ethnic minority adolescents are more likely to be affected by mental disorders but less likely to use mental health services. This systematic review aimed to summarize factors related to mental health service use among minority adolescents in the U.S. as identified in previous research. Following the PRISMA guideline, we systematically searched seven databases for peer reviewed articles related to barriers and facilitators of mental health service use among racial/ethnic minority adolescents. Thirty-two quantitative studies met our inclusion criteria, among which 12 studies (37.5%) sampled mostly Blacks or African Americans, 6 studies (18.7%) focused primarily on Hispanics or Latin/a/x, including Mexican Americans and Puerto Ricans, and 4 studies (12.5%) were mostly Asian Americans (e.g., Chinese, Vietnamese). Based on the socio-ecological framework, 21 studies (65.6%) identified adolescent-related barriers and facilitators of mental health service use, including biological (e.g., age, gender), clinical (e.g., symptom severity), behavioral (e.g., drug/alcohol use), and psychological characteristics (e.g., internal asset) of minority youth. Ten studies (31.3%) identified parents-related factors that influenced minority adolescent mental health service use, including parental perceptions and beliefs, family and parenting issues, and demographic characteristics. Primary factors at the therapist level included ethnic match between patient and practitioner, relationship with healthcare practitioners, and patient-therapist co-endorsement of etiological beliefs. Fifteen studies (46.9%) identified factors influencing minority adolescent mental health service use at the contextual/structural level, including household income, insurance status, and family structure. Lastly, acculturation and school experiences were major factors at the social/cultural level that influence minority adolescent service use. More empirical studies are needed to understand the mechanism underlying minority adolescents' unmet mental health service needs. Culturally competent interventions are warranted to engage minority adolescents with mental disorders into treatment.
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http://dx.doi.org/10.3389/fpubh.2021.641605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982679PMC
March 2021

Genetic characterization of a novel porcine reproductive and respiratory syndrome virus type I strain from southwest China.

Arch Virol 2021 Mar 24. Epub 2021 Mar 24.

College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating viral diseases in the global pig industry. Recently, we isolated and plaque-purified porcine reproductive and respiratory syndrome virus (PRRSV) strain SC2020-1 from "aborted piglets" on a farm in Sichuan, China. To investigate the molecular biological characteristics of this strain, it was subjected to genome sequencing and analysis. The full-length genome sequence of strain SC2020-1 was 87.7% identical to that of the Lelystad strain (PRRSV type I protoype strain) and 82.2-84.8% identical to PRRSV type I isolates from China. NSP2, ORF3, and ORF4 were the most variable regions and contained discontinuous deletions or insertions when compared to other PRRSV type I strains. Phylogenetic analysis of the complete genome sequence showed that SC2020-1 clustered with PRRSV type I but outside of the three previously described branches (Lelystad virus-like, Amervac PRRS-like, and BJEU06-1-like). The Nsp2 gene was in the same branch with EUGDHD strains from China. This is the first report of PRRSV type I infection associated with abortion in sows in southwest China. Close attention should be paid to the prevention and control of this evolving virus.
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http://dx.doi.org/10.1007/s00705-021-04998-zDOI Listing
March 2021

Identification of long noncoding RNAs with machine learning methods: a review.

Brief Funct Genomics 2021 Mar 23. Epub 2021 Mar 23.

Second Affiliated Hospital, Harbin Medical University, Harbin, China.

Long noncoding RNAs (lncRNAs) are noncoding RNAs with a length greater than 200 nucleotides. Studies have shown that they play an important role in many life activities. Dozens of lncRNAs have been characterized to some extent, and they are reported to be related to the development of diseases in a variety of cells. However, the biological functions of most lncRNAs are currently still unclear. Therefore, accurately identifying and predicting lncRNAs would be helpful for research on their biological functions. Due to the disadvantages of high cost and high resource-intensiveness of experimental methods, scientists have developed numerous computational methods to identify and predict lncRNAs in recent years. In this paper, we systematically summarize the machine learning-based lncRNAs prediction tools from several perspectives, and discuss the challenges and prospects for the future work.
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http://dx.doi.org/10.1093/bfgp/elab017DOI Listing
March 2021

Cardiovascular magnetic resonance shows promise in grading cardiac tumors.

Int J Cardiol 2021 Mar 20. Epub 2021 Mar 20.

Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2021.03.038DOI Listing
March 2021

PRDX1 activates autophagy via the PTEN-AKT signaling pathway to protect against cisplatin-induced spiral ganglion neuron damage.

Autophagy 2021 Apr 12:1-23. Epub 2021 Apr 12.

Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Spiral ganglion neurons (SGNs) are auditory neurons that relay sound signals from the inner ear to the brainstem. The ototoxic drug cisplatin can damage SGNs and thus lead to sensorineural hearing loss (SNHL), and there are currently no methods for preventing or treating this. Macroautophagy/autophagy plays a critical role in SGN development, but the effect of autophagy on cisplatin-induced SGN injury is unclear. Here, we first found that autophagic flux was activated in SGNs after cisplatin damage. The SGN apoptosis and related hearing loss induced by cisplatin were alleviated after co-treatment with the autophagy activator rapamycin, whereas these were exacerbated by the autophagy inhibitor 3-methyladenine, indicating that instead of inducing SGN death, autophagy played a neuroprotective role in SGNs treated with cisplatin both and . We further demonstrated that autophagy attenuated reactive oxygen species (ROS) accumulation and alleviated cisplatin-induced oxidative stress in SGNs to mediate its protective effects. Notably, the role of the antioxidant enzyme PRDX1 (peroxiredoxin 1) in modulating autophagy in SGNs was first identified. Deficiency in PRDX1 suppressed autophagy and increased SGN loss after cisplatin exposure, while upregulating PRDX1 pharmacologically or by adeno-associated virus activated autophagy and thus inhibited ROS accumulation and apoptosis and attenuated SGN loss induced by cisplatin. Finally, we showed that the underlying mechanism through which PRDX1 triggers autophagy in SGNs was, at least partially, through activation of the PTEN-AKT signaling pathway. These findings suggest potential therapeutic targets for the amelioration of drug-induced SNHL through autophagy activation.: 3-MA: 3-methyladenine; AAV : adeno-associated virus; ABR: auditory brainstem responses; AKT/protein kinase B: thymoma viral proto-oncogene; Baf: bafilomycin A; CAP: compound action potential; COX4I1: cytochrome c oxidase subunit 4I1; Cys: cysteine; ER: endoplasmic reticulum; HO: hydrogen peroxide; HC: hair cell; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; NAC: N-acetylcysteine; PRDX1: peroxiredoxin 1; PTEN: phosphatase and tensin homolog; RAP: rapamycin; ROS: reactive oxygen species; SGNs: spiral ganglion neurons; SNHL: sensorineural hearing loss; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling; WT: wild type.
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http://dx.doi.org/10.1080/15548627.2021.1905466DOI Listing
April 2021