Publications by authors named "Hongbo Gao"

77 Publications

Early Prediction of Refractory Epilepsy in Children Under Artificial Intelligence Neural Network.

Front Neurorobot 2021 17;15:690220. Epub 2021 Jun 17.

Department of Pediatrics, Affiliated Hospital of Youjiang Medical College for Nationalities, Baise, China.

In order to realize the early prediction of refractory epilepsy in children, data preprocessing technology was used to improve the data quality, and the detection model of refractory epilepsy in children based on convolutional neural network (CNN) was established. Then, the data in the epilepsy electroencephalography (EEG) signal public data set was used for model training and the diagnosis of refractory epilepsy in children. Moreover, back propagation neural network (BPNN), support vector machine (SVM), XGBoost, gradient boosting decision tree (GBDT), AdaBoost algorithm were introduced for comparison. The results showed that the early prediction accuracy of BP, SVM, XGBoost, GBDT, AdaBoost, and the algorithm in this study for refractory epilepsy in children were 0.745, 0.778, 0.885, 0.846, 0.874, and 0.941, respectively. The sensitivities were 0.81, 0.826, 0.822, 0.84, 0.859, and 0.918, respectively. The specificities were 0.683, 0.696, 0.743, 0.792, 0.84, and 0.905, respectively. The accuracy was 0.707, 0.732, 0.765, 0.802, 0.839, and 0.881, respectively. The recall rates were 0.69, 0.716, 0.753, 0.784, 0.813, and 0.877, respectively. F1 scores were 0.698, 0.724, 0.759, 0.793, 0.826, and 0.879, respectively. Through the comparisons of the above six indicators, the algorithm proposed in this study was significantly higher than other algorithms, suggesting that the proposed algorithm was more accurate in early prediction of refractory epilepsy in children. Analysis of the EEG characteristics and magnetic resonance imaging (MRI) images of refractory epilepsy in children suggested that the MRI images of patients' brains under this algorithm had obvious characteristics. The reason for the prediction error of the algorithm was that the duration of epilepsy was too short or the EEG of the patient didn't change notably during the epileptic seizure. In summary, the prediction method of refractory epilepsy in children based on CNN was accurate, which had broad adoption prospects in assisting clinicians in the examination and diagnosis of refractory epilepsy in children.
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http://dx.doi.org/10.3389/fnbot.2021.690220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245758PMC
June 2021

Nurse cell--derived small RNAs define paternal epigenetic inheritance in .

Science 2021 07;373(6550)

Department of Cell and Developmental Biology, John Innes Centre, Norwich NR4 7UH, UK.

The plant male germline undergoes DNA methylation reprogramming, which methylates genes de novo and thereby alters gene expression and regulates meiosis. Here, we reveal the molecular mechanism underlying this reprogramming. We demonstrate that genic methylation in the male germline, from meiocytes to sperm, is established by 24-nucleotide small interfering RNAs (siRNAs) transcribed from transposons with imperfect sequence homology. These siRNAs are synthesized by meiocyte nurse cells (tapetum) through activity of CLSY3, a chromatin remodeler absent in other anther cells. Tapetal siRNAs govern germline methylation throughout the genome, including the inherited methylation patterns in sperm. Tapetum-derived siRNAs also silence germline transposons, safeguarding genome integrity. Our results reveal that tapetal siRNAs are sufficient to reconstitute germline methylation patterns and drive functional methylation reprogramming throughout the male germline.
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http://dx.doi.org/10.1126/science.abh0556DOI Listing
July 2021

Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy.

Aliment Pharmacol Ther 2021 Aug 22;54(3):329-338. Epub 2021 Jun 22.

Guangzhou, China.

Background: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB).

Aim: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy.

Methods: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body-mass index (BMI). Central obesity was evaluated by waist circumference, waist-to-hip ratio and waist-to-height ratio.

Results: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5-year cumulative incidence of HCC was 2.9%. Waist-to-height ratio performed better in predicting HCC development than BMI, waist circumference or waist-to-hip ratio. Patients with central obesity (defined as waist-to-height ratio >0.5) had significantly higher 5-year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist-to-height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12-3.13, P = 0.017).

Conclusions: Central obesity, evaluated by the waist-to-height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.
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http://dx.doi.org/10.1111/apt.16469DOI Listing
August 2021

Visualizing the Integrity of Chloroplast Envelope by Rhodamine and Nile Red Staining.

Front Plant Sci 2021 26;12:668414. Epub 2021 Apr 26.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, China.

Chloroplasts are essential organelles in plant cells with many important functions. Chloroplasts isolated by Percoll density gradient centrifugation are widely used in the study of chloroplasts. The intactness of isolated chloroplasts is necessary for many of the experiments. In the past, those isolated chloroplasts were either simply believed to be intact or had to be analyzed by indirect biochemical methods. Here we show a new method to check the intactness of isolated chloroplasts by staining their envelope with fluorescent dyes, Rhodamine or Nile red, and then observing them with a fluorescence microscope. With this method, broken chloroplasts and intact chloroplasts can be distinguished easily and their integrity can be checked in a few minutes. Results of this method agreed well with those of biochemical methods. Moreover, we have also found that sometimes the middle layer chloroplasts from the Percoll gradient centrifugation could be mostly broken, which could cause mistakes in the experiment. With our method, this problem can be easily found. This chloroplast envelope staining method can be used in the preparation of isolated chloroplasts to ensure the intactness.
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http://dx.doi.org/10.3389/fpls.2021.668414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107281PMC
April 2021

Synthesis, characterization and theoretical investigation of a new chalcohalide, BaGaSF.

Dalton Trans 2021 May;50(18):6315-6320

Key Laboratory of Functional Materials and Devices for Special Environments of CAS, Xinjiang Key Laboratory of Electronic Information Materials and Devices, Xinjiang Technical Institute of Physics & Chemistry of CAS, Urumqi, Xinjiang 830011, China.

A new fluorine-containing chalcohalide, Ba4GaS4F3, has been synthesized by conventional high-temperature solid-state reaction. The compound crystallizes in the centrosymmetric space group I41/a with a = b = 16.628 (5) Å, c = 17.139 (10) Å, Z = 16. Experimental and theoretical results confirm that Ba4GaS4F3 is a direct band gap compound with an experimental band gap of about 3.13 eV, and the band gap is mainly determined by the Ba-5p, F-2p and S-3p orbitals. What's more, different from the many newly discovered chalcohalides in the Ba3AM4Q (A = Ga, In; M = S, Se; Q = Cl, Br, I) family, Ba4GaS4F3 is the first reported compound in the Ba4AM4D3 (A = Ga, In; M = chalcogen; D = halogen) family. The results enrich the structural diversity of metal chalcohalides.
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http://dx.doi.org/10.1039/d1dt00800eDOI Listing
May 2021

Infection with a newly designed dual fluorescent reporter HIV-1 effectively identifies latently infected CD4 T cells.

Elife 2021 04 9;10. Epub 2021 Apr 9.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

The major barrier to curing HIV-1 infection is a small pool of latently infected cells that harbor replication-competent viruses, which are widely considered the origin of viral rebound when antiretroviral therapy (ART) is interrupted. The difficulty in distinguishing latently infected cells from the vast majority of uninfected cells has represented a significant bottleneck precluding comprehensive understandings of HIV-1 latency. Here we reported and validated a newly designed dual fluorescent reporter virus, DFV-B, infection with which primary CD4 T cells can directly label latently infected cells and generate a latency model that was highly physiological relevant. Applying DFV-B infection in Jurkat T cells, we generated a stable cell line model of HIV-1 latency with diverse viral integration sites. High-throughput compound screening with this model identified ACY-1215 as a potent latency reversing agent, which could be verified in other cell models and in primary CD4 T cells from ART-suppressed individuals ex vivo. In summary, we have generated a meaningful and feasible model to directly study latently infected cells, which could open up new avenues to explore the critical events of HIV-1 latency and become a valuable tool for the research of AIDS functional cure.
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http://dx.doi.org/10.7554/eLife.63810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041464PMC
April 2021

Evaluation of HIV-1 latency reversal and antibody-dependent viral clearance by quantification of singly spliced HIV-1 / mRNA.

J Virol 2021 Mar 24. Epub 2021 Mar 24.

Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA

The latent reservoir of HIV-1 is a major barrier for viral eradication. Potent HIV-1 broadly neutralizing antibodies (bNabs) have been used to prevent and treat HIV-1 infections in animal models and clinical trials. Combination of bNabs and latency-reversing agents (LRAs) is considered a promising approach for HIV-1 eradication. PCR-based assays that can rapidly and specifically measure singly spliced HIV-1 / mRNA are needed to evaluate the induction of the viral envelope production at the transcription level and bNab-mediated reservoir clearance. Here we reported a PCR-based method to accurately quantify the production of intracellular HIV-1 / mRNA. With the vpu/env assay, we determined the LRA combinations that could effectively induce / mRNA production in CD4 T cells from ART-treated individuals. None of the tested LRAs were effective alone. A comparison between the quantitative viral outgrowth assay (Q-VOA) and the vpu/env assay showed that / mRNA production was closely associated with the reactivation of replication-competent HIV-1, suggesting that / mRNA was mainly produced by intact viruses. Finally, antibody-mediated killing in HIV-1-infected humanized mice demonstrated that the vpu/env assay could be used to measure the reduction of infected cells in tissues and was more accurate than the commonly used -based PCR assay which measured unspliced viral genomic RNA. In conclusion, the vpu/env assay allows convenient and accurate assessment of HIV-1 latency reversal and bNab-mediated therapeutic strategies.HIV-1 persists in individuals on antiretroviral therapy (ART) due to the long-lived cellular reservoirs that contain dormant viruses. Recent discoveries of HIV-1-specific broadly neutralizing antibodies (bNabs) targeting HIV-1 Env protein rekindled the interest in antibody-mediated elimination of latent HIV-1. Latency-reversing agents (LRAs) together with HIV-1 bNabs is a possible strategy to clear residual viral reservoirs, which makes the evaluation of HIV-1 Env expression upon LRA treatment critical. We developed a PCR-based assay to quantify the production of intracellular HIV-1 / mRNA. Using patient CD4 T cells, we found that induction of HIV-1 / mRNA required a combination of different LRAs. Using , and humanized mouse models, we showed that the vpu/env assay could be used to measure antibody efficacy in clearing HIV-1 infection. These results suggest that the vpu/env assay can accurately evaluate HIV-1 reactivation and bNab-based therapeutic interventions.
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http://dx.doi.org/10.1128/JVI.02124-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139706PMC
March 2021

CARD8 is an inflammasome sensor for HIV-1 protease activity.

Science 2021 03 4;371(6535). Epub 2021 Feb 4.

Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.

HIV-1 has high mutation rates and exists as mutant swarms within the host. Rapid evolution of HIV-1 allows the virus to outpace the host immune system, leading to viral persistence. Approaches to targeting immutable components are needed to clear HIV-1 infection. Here, we report that the caspase recruitment domain-containing protein 8 (CARD8) inflammasome senses HIV-1 protease activity. HIV-1 can evade CARD8 sensing because its protease remains inactive in infected cells before viral budding. Premature intracellular activation of the viral protease triggered CARD8 inflammasome-mediated pyroptosis of HIV-1-infected cells. This strategy led to the clearance of latent HIV-1 in patient CD4 T cells after viral reactivation. Thus, our study identifies CARD8 as an inflammasome sensor of HIV-1, which holds promise as a strategy for the clearance of persistent HIV-1 infection.
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http://dx.doi.org/10.1126/science.abe1707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029496PMC
March 2021

Analysis of risk factors for perioperative death in patients undergoing aortic valve replacement using biological valves.

Medicine (Baltimore) 2020 Dec;99(52):e23909

Department of Cardiovascular Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.

Background: Aortic valve disease has become one of the important factors affecting human health. Aortic valve disease is a progressive disease, if not actively treated, the prognosis is poor. Aortic valve replacement (AVR) surgery is an important treatment for aortic valve disease. At present, the AVR surgery using biological valve accounts for about 40% of the total number of AVR surgery. There are still more perioperative deaths in China due to the large number of AVR patients using biological valves. The objective of this study is to explore measures to reduce perioperative mortality of patients after AVR surgery with biological valves.

Methods: The clinical data of patients undergoing AVR surgery with biological valves in Affiliated Hospital of Qingdao University from November 15, 2020 to December 31, 2022 were reviewed and analyzed. Patients were divided into death group and survival group according to their perioperative survival. Risk factors that may influence perioperative mortality were analyzed and compared between the 2 groups.

Discussion: This study was a retrospective analysis of risk factors that may influence perioperative mortality in patients undergoing AVR surgery using biological valves. The conclusions of this study can be used to guide clinical decisions-making and relevant guidelines-developing for perioperative treatment of patients undergoing AVR surgery using biological valves.
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http://dx.doi.org/10.1097/MD.0000000000023909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769375PMC
December 2020

Editorial: Structure and Function of Chloroplasts - Volume II.

Front Plant Sci 2020 25;11:620152. Epub 2020 Nov 25.

College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing, China.

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http://dx.doi.org/10.3389/fpls.2020.620152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723994PMC
November 2020

Forkhead-box A3 (FOXA3) represses cancer stemness and partially potentiates chemosensitivity by targeting metastasis-associated in colon cancer 1 (MACC1) signaling pathway in colorectal cancer cells.

Curr Cancer Drug Targets 2020 Dec 7. Epub 2020 Dec 7.

Department of Radiology, Suining Central Hospital, Suining 629000. China.

Background: The major challenge to the treatment of advanced colorectal cancer (CRC) is persistent occurrence of chemoresistance. One of the established etiologies is the existence of cancerstem-like cells (CSCs) using which tumors resist to external therapeutic challenges.

Objective: The forkhead-box A3 (FOXA3) is a potent transcription factor that potentiates the acquisition and maintenance of stemness fate in many physiological systems. However, its effect on cancer stemness, particularly treatment, has not been explored in CRC, forming the basis of the current study.

Methods: FOXA3 expression in oxaliplatin-resistant CRC tissues and cells was evaluated using RT-qPCR. Effects of FOXA3 manipulation on sensitivity to oxaliplatin were assessed using WST-1, apoptotic ELISA, colony formation and xenograft model. Effects of FOXA3 alteration on CSCs were determined using tumor sphere assay and CD44 staining. Transcriptional regulation of MACC1 by FOXA3 was studied using ChIP, Co-IP and luciferase reporter assay.

Results: FOXA3 expression was significantly reduced in tumor samples from oxaliplatin-non-responsive patients compared with that in tumor samples from oxaliplatin-sensitive patients. This downregulation of FOXA3 expression predicted a poor post-chemotherapy overall- or disease-free survival in our 117-patient cohort. FOXA3 down-regulation significantly enhanced cell survival and stem-like properties, thus rendering the CRC cells unresponsiveness to oxaliplatin-induced cell death. Mechanistically, the anti-neoplasic effect of FOXA3 was mediated mainly through transcriptional repression of metastasis-associated in colon cancer 1 (MACC1) in oxaliplatin-resistant CRC cells.

Conclusion: Our findings establish FOXA3 as a potent tumor suppressor in CRC, which may disrupt the maintenance of stemness and modulate sensitivity to oxaliplatin by inhibiting the transcription of MACC1 within CRC cells.
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http://dx.doi.org/10.2174/1568009620666201207150632DOI Listing
December 2020

UCHL1 regulates oxidative activity in skeletal muscle.

PLoS One 2020 2;15(11):e0241716. Epub 2020 Nov 2.

Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States of America.

Ubiquitin C-terminal Hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally identified in neurons. Our recent study showed that UCHL1 was expressed in C2C12 myoblast cells and mouse skeletal muscle. Here we report that in mouse skeletal muscle, UCHL1 is primarily expressed in oxidative muscle fibers. Skeletal muscle specific gene knockout (smKO) of UCHL1 in mice reduced oxidative activity in skeletal muscle measured by SDH staining. The in situ muscle contraction test revealed that gastrocnemius muscle from UCHL1 smKO mice was more prone to fatigue in response to the repetitive stimulation. This data suggests that UCHL1 plays a role in maintenance of muscle oxidative metabolism. Moreover, UCHL1 smKO caused a significant reduction in key proteins that are involved in mitochondrial oxidative phosphorylation in soleus muscles, suggesting that UCHL1 may be involved in regulation of mitochondrial content and function. Immunostaining showed the co-localization of UCHL1 and mitochondrial marker VDAC in skeletal muscle. Mitochondrial fractionation assay revealed that, although UCHL1 was primarily present in the cytosolic fraction, a low level of UCHL1 protein was present in mitochondrial fraction. The level of phosphorylation of AMPKα, a master regulator of mitochondrial biogenesis, were unchanged in UCHL1 smKO muscle. On the other hand, immunoprecipitation from soleus muscle sample indicated the interaction between UCHL1 and HSP60, a chaperon protein that is involved in mitochondrial protein transport. There was a trend of downregulation of HSP60 in UCHL1 smKO muscle. Overall, our data suggests UCHL1 is a novel regulator of mitochondrial function and oxidative activity in skeletal muscle.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241716PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605647PMC
December 2020

The clock regulator Bmal1 protects against muscular dystrophy.

Exp Cell Res 2020 12 29;397(1):112348. Epub 2020 Oct 29.

Department of Diabetes Complications & Metabolism, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. Electronic address:

The muscle-intrinsic clock machinery is required for the maintenance of muscle growth, remodeling and function. Our previous studies demonstrated that the essential transcription activator of the molecular clock feed-back loop, Brain and Muscle Arnt-Like 1(Bmal1), plays a critical role in myogenic progenitor behavior to promote and regenerative myogenesis. Using genetic approaches targeting Bmal1 in the DMD (mdx) dystrophic mouse model, here we report that the loss of Bmal1 function significantly accelerated dystrophic disease progression. In contrast to the mild dystrophic changes in mdx mice, the genetic loss-of-function of Bmal1 aggravated muscle damage in this dystrophic disease background, as indicated by persistently elevated creatine kinase levels, increased injury area and reduced muscle grip strength. Mechanistic studies revealed that markedly impaired myogenic progenitor proliferation and myogenic response underlie the defective new myofiber formation in the chronic dystrophic milieu. Taken together, our study identified the function of pro-myogenic clock gene Bmal1 in protecting against dystrophic damage, suggesting the potential for augmenting Bmal1 function to ameliorate dystrophic or degenerative muscle diseases.
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http://dx.doi.org/10.1016/j.yexcr.2020.112348DOI Listing
December 2020

Gamma-aminobutyric acid (GABA) alleviates salt damage in tomato by modulating Na uptake, the GAD gene, amino acid synthesis and reactive oxygen species metabolism.

BMC Plant Biol 2020 Oct 9;20(1):465. Epub 2020 Oct 9.

College of Horticulture, Hebei Agricultural University, Baoding, 071001, China.

Background: Salt stress is a serious abiotic stress that caused crop growth inhibition and yield decline. Previous studies have reported on the the synthesis of gamma-aminobutyric acid (GABA) and its relationship with plant resistance under various abiotic stress. However, the relationship between exogenous GABA alleviating plant salt stress damage and ion flux, amino acid synthesis, and key enzyme expression remains largely unclear. We investigated plant growth, Na transportation and accumulation, reactive oxygen species (ROS) metabolism and evaluated the effect of GABA on amino acids, especially SlGADs gene expression and the endogenous GABA content of tomato (Solanum lycopersicum L.) seedlings treated with or without 5 mmol·L GABA under 175 mmol·L NaCl stress.

Results: Exogenous application of GABA significantly reduced the salt damage index and increased plant height, chlorophyll content and the dry and fresh weights of tomato plants exposed to NaCl stress. GABA significantly reduced Na accumulation in leaves and roots by preventing Na influx in roots and transportation to leaves. The transcriptional expression of SlGAD1-3 genes were induced by NaCl stress especially with GABA application. Among them, SlGAD1 expression was the most sensitive and contributed the most to the increase in glutamate decarboxylase (GAD) activity induced by NaCl and GABA application; Exogenous GABA increased GAD activity and amino acid contents in tomato leaves compared with the levels under NaCl stress alone, especially the levels of endogenous GABA, proline, glutamate and eight other amino acids. These results indicated that SlGADs transcriptional expression played an important role in tomato plant resistance to NaCl stress with GABA application by enhancing GAD activity and amino acid contents. GABA significantly alleviated the active oxygen-related injury of leaves under NaCl stress by increasing the activities of antioxidant enzymes and decreasing the contents of active oxygen species and malondialdehyde.

Conclusion: Exogenous GABA had a positive effect on the resistance of tomato seedlings to salt stress, which was closely associated with reducing Na flux from root to leaves, increasing amino acid content and strengthening antioxidant metabolism. Endogenous GABA content was induced by salt and exogenous GABA at both the transcriptional and metabolic levels.
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http://dx.doi.org/10.1186/s12870-020-02669-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547442PMC
October 2020

Deep Learning Method for Grasping Novel Objects Using Dexterous Hands.

IEEE Trans Cybern 2020 Oct 1;PP. Epub 2020 Oct 1.

Robotic grasping ability lags far behind human skills and poses a significant challenge in the robotics research area. According to the grasping part of an object, humans can select the appropriate grasping postures of their fingers. When humans grasp the same part of an object, different poses of the palm will cause them to select different grasping postures. Inspired by these human skills, in this article, we propose new grasping posture prediction networks (GPPNs) with multiple inputs, which acquire information from the object image and the palm pose of the dexterous hand to predict appropriate grasping postures. The GPPNs are further combined with grasping rectangle detection networks (GRDNs) to construct multilevel convolutional neural networks (ML-CNNs). In this study, a force-closure index was designed to analyze the grasping quality, and force-closure grasping postures were generated in the GraspIt! environment. Depth images of objects were captured in the Gazebo environment to construct the dataset for the GPPNs. Herein, we describe simulation experiments conducted in the GraspIt! environment, and present our study of the influences of the image input and the palm pose input on the GPPNs using a variable-controlling approach. In addition, the ML-CNNs were compared with the existing grasp detection methods. The simulation results verify that the ML-CNNs have a high grasping quality. The grasping experiments were implemented on the Shadow hand platform, and the results show that the ML-CNNs can accurately complete grasping of novel objects with good performance.
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http://dx.doi.org/10.1109/TCYB.2020.3022175DOI Listing
October 2020

WITHDRAWN: Analysis of Risk Factors for Prognosis and Infection of Child with Refractory Epilepsy Via Artificial Intelligence Neural Network Image Information.

Neurosci Lett 2020 Jun 22. Epub 2020 Jun 22.

Department of Pediatrics, Affiliated Hospital of Youjiang Medical College for Nationalities, Baise, 533000, Guangxi, China.

This article has been withdrawn at the request of the Editor-in-Chief. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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http://dx.doi.org/10.1016/j.neulet.2020.135198DOI Listing
June 2020

Survey of mineral oil hydrocarbons in infant formula from the Chinese market.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2020 Jun 16;37(6):1040-1048. Epub 2020 Apr 16.

Division III of Risk Assessment, China National Center for Food Safety Risk Assessment , Beijing, China.

Mineral oil hydrocarbon (MOH) contamination of various foods in the past few decades has raised much concern due to its potential adverse health effects. Since infant formulas (IF) is the major food source for infants, it is necessary to understand MOH contamination level in IF and consequent potential food safety risks. Data on the contamination of IF by mineral oil are lacking in China. On the other hand, the analysis of MOH in food is difficult. There is no harmonised standard analytical method for testing MOHs in IF. GC-FID/MS was chosen as the analytical tool being more convenient for surveys at a national level. Fifty-one IFs comprising dairy milk-based IFs (n = 39) and goat milk-based IFs (n = 12), including different stages (Stage 1, 2 and 3), package type (metal cans and paper boxes) were collected in China market in 2018 for this survey. 17 of 51 IFs were found positive, but trace levels MOAH were found (≤0.7 mg/kg). For the positive samples, all the MOSH and MOAH hump fell into the C16-C25 fraction. MOH humps were found in all the 12 goat milk-based IFs, even 4 samples are reported with quantifiable values which are higher than the method defined LOQ. The highest quantifiable MOH contamination level of goat milk-based IFs were MOSH = 3.5 mg/kg and MOAH = 0.7 mg/kg. Further root cause analysis of contamination is highly recommended to control the MOH contamination for goat milk-based IFs.
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http://dx.doi.org/10.1080/19440049.2020.1748234DOI Listing
June 2020

Effect of Hemodialysis on Efficacy and Pharmacokinetics of Sofosbuvir Coformulated with Either Daclatasvir or Ledipasvir in Patients with End-Stage Renal Disease.

Blood Purif 2020 14;49(6):692-699. Epub 2020 Apr 14.

Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China,

Background/aims: Direct-acting antivirals (DAAs) play a key role in the eradication of hepatitis C virus (HCV) infection. However, limited data are available on DAA for treating HCV infection in hemodialysis (HD) patients. This study was to evaluate the pharmacokinetic characteristics and effectiveness of daclatasvir/sofosbuvir (DAC/SOF) and ledipasvir/SOF (LDV/SOF) in HD patients.

Methods: Seven patients were given SOF coadministered with DAC or LDV once daily for 12 weeks. The plasma concentrations of SOF007, DAC, and LDV were determined by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

Results: A sustained virologic response in week 12 (SVR12) was achieved in 6 (100%) patients, except for 1 patient dying due to severe cerebral hemorrhage not related to antiviral therapy. The extraction ratio of SOF007 was 66.67%, and the estimated HD clearance of SOF007 was 5.65 L/h.

Conclusion: The combination of SOF with either DAC or LDV is well tolerated and offers high SVR12 in HD patients.
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http://dx.doi.org/10.1159/000499161DOI Listing
June 2021

Full-Process Radiosensitization Based on Nanoscale Metal-Organic Frameworks.

ACS Nano 2020 03 12;14(3):3032-3040. Epub 2020 Mar 12.

Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

Full-process radiosensitization, that is, pre-increasing radiation sensitivity of cancer cells, magnifying •OH formation during ionizing irradiation, and intervention on the resultant DNA repair for final cells death, could enhance the overall radiotherapeutic effects, but has not yet been achieved. Herein, Hf-nMOFs with Fe ions uniformly dispersed () were constructed to integratedly improve radiotherapeutic effects a multifaceted mechanism. The experiments demonstrated that persistent reactive oxygen species stress from -activated Fenton reaction reassorted cell cycle distribution, consequently contributing to increased tumoral radiosensitivity to photon radiation. Upon irradiation during the course of radiation therapy, Hf in gave substantial amounts of high-energy electrons, which partially converted HO to •OH and, meanwhile, relaxed to a low-energy state in nMOF pores, leading to an electron-rich environment. These aggregated electrons facilitated the reduction from Fe to Fe and further promoted the production of •OH in the Fenton process to attack DNA. The postponed the DNA damage response process by interfering with certain proteins involved in the DNA repair signaling pathway. The experiments showed improved radiotherapeutic effects from integrated contributions from Fe-based Fenton reaction and Hf-induced X-ray energy conversion in tumors. This work provides a nMOFs-based full-process radiosensitizing approach for better radiotherapeutic efficacy.
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http://dx.doi.org/10.1021/acsnano.9b07898DOI Listing
March 2020

Thiostrepton Reactivates Latent HIV-1 through the p-TEFb and NF-κB Pathways Mediated by Heat Shock Response.

Antimicrob Agents Chemother 2020 04 21;64(5). Epub 2020 Apr 21.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

Antiretroviral therapy (ART) suppresses HIV-1 replication but fails to cure the infection. The presence of an extremely stable viral latent reservoir, primarily in resting memory CD4 T cells, remains a major obstacle to viral eradication. The "shock and kill" strategy targets these latently infected cells and boosts immune recognition and clearance, and thus, it is a promising approach for an HIV-1 functional cure. Although some latency-reversing agents (LRAs) have been reported, no apparent clinical progress has been made, so it is still vital to seek novel and effective LRAs. Here, we report that thiostrepton (TSR), a proteasome inhibitor, reactivates latent HIV-1 effectively in cellular models and in primary CD4 T cells from ART-suppressed individuals TSR does not induce global T cell activation, severe cytotoxicity, or CD8 T cell dysfunction, making it a prospective LRA candidate. We also observed a significant synergistic effect of reactivation when TSR was combined with JQ1, prostratin, or bryostatin-1. Interestingly, six TSR analogues also show reactivation abilities that are similar to or more effective than that of TSR. We further verified that TSR upregulated expression of heat shock proteins (HSPs) in CD4 T cells, which subsequently activated positive transcriptional elongation factor b (p-TEFb) and NF-κB signals, leading to viral reactivation. In summary, we identify TSR as a novel LRA which could have important significance for applications to an HIV-1 functional cure in the future.
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http://dx.doi.org/10.1128/AAC.02328-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179580PMC
April 2020

Fractionating of Calcium in Tuber and Leaf Tissues Explains the Calcium Deficiency Symptoms in Potato Plant Overexpressing .

Front Plant Sci 2019 31;10:1793. Epub 2020 Jan 31.

Department of Horticulture, University of Wisconsin-Madison, Madison, WI, United States.

Consistent with reports on other plants we recently reported that a potato transgenic line (AT010901) overexpressing show classic symptoms of calcium deficiency shoot tip injury, leaf curling, leaf margin necrosis and tuber internal defects such as hollow heart and brown spots. The present study was undertaken to quantify calcium in various fraction of leaf and tuber tissues of this transgenic and wild type potato clones to understand the development of these deficiency symptoms at normal calcium nutrition (1mM) and its mitigation at higher calcium nutrition (10mM). Plants were grown in controlled environment growth chamber and watered with balanced nutrient solution containing either 1 or 10 mM calcium. The plants overexpressing showed calcium deficiency symptoms while sequestering calcium in the vacuole as calcium oxalate crystals. Various fractions of calcium were qualified in the young and mature leaves as well as tuber tissue. A reduced concentration of water soluble fraction of calcium was most important factor related to the development of calcium deficiency symptoms in the line overexpressing . Furthermore, an increase in this fraction appear to explain the alleviation of the deficiency symptoms in these transgenic plants.Ours is the first study to document the significance of water-soluble calcium in the development of calcium-deficiency symptoms in the potato transgenic lines overexpressing . Furthermore, our result demonstrates that an increase in this fraction plays a significant role in the alleviation of calcium deficiency symptoms when calcium concentration in the nutrient media is increased. These results provide important insight on the role of in the calcium homeostasis.
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http://dx.doi.org/10.3389/fpls.2019.01793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006644PMC
January 2020

Secondary Mutation-Induced Alternative Splicing Suppresses RNA Splicing Defect of the Mutant.

Plant Physiol 2020 04 13;182(4):2025-2034. Epub 2020 Feb 13.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing 100083, China

() is a mutant of the DNA2 homolog in Arabidopsis (), which was previously identified as being involved in DNA damage repair, cell cycle regulation, and meristem maintenance. A mutation at the 3' intron splice site of the 11th intron causes alternative splicing of this intron at two other sites, which results in frame shifts and premature stop codons. Here, we screened suppressors of to further study the function and regulatory networks of Three suppressors with wild-type-like phenotypes were obtained. Sequencing analysis results showed that each of the suppressors has a second mutation in that causes further alternative splicing of the intron and corrects the shifted reading frame with small insertions. Precursor mRNA sequence analysis and intron splice site evaluation results suggested that intron splicing was disturbed in the suppressors, and this switched the splice site, resulting in small insertions in the coding regions of JHS1. Structural analysis of JHS1 suggested that the insertions are in a disordered loop region of the DNA2 domain and do not seem to have much deleterious effect on the function of the protein. This work not only has implications for the evolution of protein sequences at exon junctions but also provides a strategy to study the mechanism of precursor mRNA splicing.
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http://dx.doi.org/10.1104/pp.19.01571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140918PMC
April 2020

Clinical efficacy and safety in telbivudine- or tenofovir-treated hepatitis B e antigen-positive pregnant women.

Antivir Ther 2020 ;25(1):33-41

Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.

Background: Telbivudine (LdT) and tenofovir (TDF) are widely used in pregnant women to prevent vertical transmission; however, limited data are available on the differences in clinical efficacy and safety between the two drugs.

Methods: A total of 307 hepatitis B e antigen (HBeAg)-positive pregnant women with complete follow-up data were enrolled, the patients with alanine aminotransferase (ALT) levels <1×ULN at baseline were enrolled to cohort 1 for treatment from 28 ±4 weeks gestation to delivery, while ALT levels >1×ULN at baseline were enrolled to cohort 2 for treatment from 28 ±4 weeks gestation and continued after delivery. The clinical efficacy and safety was compared in LdT- and TDF-treated patients. In addition, 32 patients in cohort 1 were analysed for nucleoside analogue (NA)-related resistance mutations at baseline and after delivery.

Results: The results showed that HBV DNA levels were significantly lower at delivery than at baseline (P<0.001), but the decreases in HBV DNA, ALT, total bilirubin and total bile acid levels did not differ between the LdT- and TDF-treated patients at different time points (P>0.05) in the two cohorts. However, gastrointestinal adverse effects (vomiting) occurred more frequently in TDF-treated than LdT-treated patients (6.6% versus 0.0%; P=0.001). The results of NA-related resistance mutations analysis in cohort 1 revealed that short-term LdT or TDF treatment did not significantly change the NA-related resistance mutations (P>0.05).

Conclusions: This study revealed that the clinical efficacy in LdT- or TDF-treated HBeAg-positive Chinese pregnant women is similar, and gastrointestinal adverse effects occurred more frequently in TDF-treated patients.
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http://dx.doi.org/10.3851/IMP3345DOI Listing
January 2020

Long noncoding RNA CASC9 promotes the proliferation and metastasis of papillary thyroid cancer via sponging miR-488-3p.

Cancer Med 2020 03 13;9(5):1830-1841. Epub 2020 Jan 13.

Department of Radionuclide Treatment Center, Beijing Nuclear Industry Hospital, Beijing, China.

Cancer susceptibility candidate 9 (CASC9) is a recently identified lncRNA that acted as a tumor promotor in diversified cancer types. However, its role in papillary thyroid cancer (PTC) remains unknown. The expression of CASC9 was measured in 52 human PTC tissues and PTC cell lines as well as their controls. The proliferation, migration, and invasion of PTC cells were determined after knockdown or overexpression of CASC9 to evaluate the effect of CASC9 on PTC cells. Also, the role of PTC tumorigenesis was confirmed in mice xenograft models. Additionally, the underlying mechanisms of CASC9 were further researched. We found that CASC9 expression was augmented in human PTC tissues and cells. Higher CASC9 expression was associated with large tumor size, advanced stage, or lymph node metastasis. Downregulation of CASC9 significantly attenuated the proliferative, migrative, and invasive abilities of PTC cells, and suppressed tumorigenesis in vivo. While overexpression of CASC9 elevated the proliferation, migration, and invasion of PTC cells. miR-488-3p expression was decreased, and ADAM9 level was increased in PTC tissues and cells. CASC9 expression was negatively related to miR-488-3p, but positively associated with ADAM9 expression in PTC tissues. Molecular mechanism analysis revealed that CASC9 functioned via sponging miR-488-3p to regulate ADAM9 expression, followed by activation of EGFR-Akt signaling. In conclusion, lncRNA CASC9 promoted the malignant phenotypes of PTC via modulating miR-488-3p/ADAM9 pathway. This study may provide a novel therapeutic target for the treatment of PTC.
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http://dx.doi.org/10.1002/cam4.2839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050070PMC
March 2020

Inhibition of LncRNA FOXD3-AS1 suppresses the aggressive biological behaviors of thyroid cancer via elevating miR-296-5p and inactivating TGF-β1/Smads signaling pathway.

Mol Cell Endocrinol 2020 01 31;500:110634. Epub 2019 Oct 31.

Department of Nuclear Medicine, The Mine Hospital of Xuzhou, Jiangsu, 221000, China.

Background: Thyroid cancer is the most common malignant tumor with relatively high incidence and mortality in endocrine system. Research about thyroid cancer-related targets is the basis for the diagnosis of thyroid cancer and the development of new drugs. However, the predictive value of long non-coding RNA (lncRNA) for the diagnosis and prognosis of thyroid cancer is still in the preliminary stage of exploration. Thus, we for the first time investigated the effects and associated regulatory mechanism of lncRNA Forkhead box D3 antisense RNA 1 (FOXD3-AS1) in thyroid cancer in vitro and in vivo.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of lncRNA FOXD3-AS1 and miR-296-5p. Cell proliferation was detected through colony formation assay. Cell cycle was analyzed through flow cytometry. Cell mobility was valued through transwell invasion assay and wound healing assay. Western blotting was used to examine the expression of proteins related to cell proliferation and cell migration and TGF-β1/Smads signaling pathway. Luciferase reporter assay was used to verify the targeting relationship between FOXD3-AS1 and miR-296-5p. Tumor xenograft model was established and immunohistochemistry (IHC) was used to examine the expression of Ki67 and VEGF.

Results: We found that the expression of lncRNA FOXD3-AS1was upregulated and it had negative correlation with the level of miR-296-5p in thyroid cancer tissues and cells. LncRNA FOXD3-AS1 knockdown effectively suppressed cell proliferation and cell invasion in vitro. Further study revealed that miR-296-5p was a target of lncRNA FOXD3-AS1 and FOXD3-AS1 exerted anti-tumor effect through up-regulating miR-296-5p. Moreover, we found that FOXD3-AS1 knockdown suppressed the aggressive biological behaviors of thyroid cancer through inactivating the TGF-β1/Smads signaling pathway. Subsequently, the in vivo experiments further verified that the FOXD3-AS1/miR-296-5p axis exerted obvious anti-tumor effect through inhibiting tumor growth and metastasis and the TGF-β1/Smads signaling pathway was also inactivated in vivo by the inhibition of FOXD3-AS1.

Conclusion: Inhibition of LncRNA FOXD3-AS1 suppresses the aggressive biological behaviors of thyroid cancer via elevating miR-296-5p and inactivating TGF-β1/Smads signaling pathway.
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http://dx.doi.org/10.1016/j.mce.2019.110634DOI Listing
January 2020

CD161 CD4 T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals.

mBio 2019 10 8;10(5). Epub 2019 Oct 8.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

The presence of an extremely stable latent reservoir of HIV-1 is the major obstacle to eradication, despite effective antiretroviral therapy (ART). Recent studies have shown that clonal expansion of latently infected cells without viral reactivation is an important phenomenon that maintains the long-term stability of the reservoir, yet its underlying mechanism remains unclear. Here we report that a subset of CD4 T cells, characterized by CD161 expression on the surface, is highly permissive for HIV-1 infection. These cells possess a significantly higher survival and proliferative capacity than their CD161-negative counterparts. More importantly, we found that these cells harbor HIV-1 DNA and replication-competent latent viruses at a significantly higher frequency. By using massive single-genome proviral sequencing from ART-suppressed individuals, we confirm that CD161 CD4 T cells contain remarkably more identical proviral sequences, indicating clonal expansion of the viral genome in these cells. Taking the results together, our study identifies infected CD161 CD4 T cells to be a critical force driving the clonal expansion of the HIV-1 latent reservoir, providing a novel mechanism for the long-term stability of HIV-1 latency. The latent reservoir continues to be the major obstacle to curing HIV-1 infection. The clonal expansion of latently infected cells adds another layer maintaining the long-term stability of the reservoir, but its mechanism remains unclear. Here, we report that CD161 CD4 T cells serve as an important compartment of the HIV-1 latent reservoir and contain a significant amount of clonally expanded proviruses. In our study, we describe a feasible strategy that may reduce the size of the latent reservoir to a certain extent by counterbalancing the repopulation and dissemination of latently infected cells.
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http://dx.doi.org/10.1128/mBio.02121-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786872PMC
October 2019

Reference Trajectory Reshaping Optimization and Control of Robotic Exoskeletons for Human-Robot Co-Manipulation.

IEEE Trans Cybern 2020 Aug 30;50(8):3740-3751. Epub 2019 Aug 30.

For human-robot co-manipulation by robotic exoskeletons, the interaction forces provide a communication channel through which the human and the robot can coordinate their actions. In this article, an optimization approach for reshaping the physical interactive trajectory is presented in the co-manipulation tasks, which combines impedance control to enable the human to adjust both the desired and the actual trajectories of the robot. Different from previous studies, the proposed method significantly reshapes the desired trajectory during physical human-robot interaction (pHRI) based on force feedback, without requiring constant human guidance. The proposed scheme first formulates a quadratically constrained programming problem, which is then solved by neural dynamics optimization to obtain a smooth and minimal-energy trajectory similar to the natural human movement. Then, we propose an adaptive neural-network controller based on the barrier Lyapunov function (BLF), which enables the robot to handle the uncertain dynamics and the joint space constraints directly. To validate the proposed method, we perform experiments on the exoskeleton robot with human operators for co-manipulation tasks. The experimental results demonstrate that the proposed controller could complete the co-manipulation tasks effectively.
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http://dx.doi.org/10.1109/TCYB.2019.2933019DOI Listing
August 2020

Natural Variation in TBP-ASSOCIATED FACTOR 4b Controls Meiotic Crossover and Germline Transcription in Arabidopsis.

Curr Biol 2019 08 1;29(16):2676-2686.e3. Epub 2019 Aug 1.

Department of Plant Sciences, Downing Street, University of Cambridge, Cambridge CB2 3EA, UK. Electronic address:

Meiotic crossover frequency varies within genomes, which influences genetic diversity and adaptation. In turn, genetic variation within populations can act to modify crossover frequency in cis and trans. To identify genetic variation that controls meiotic crossover frequency, we screened Arabidopsis accessions using fluorescent recombination reporters. We mapped a genetic modifier of crossover frequency in Col × Bur populations of Arabidopsis to a premature stop codon within TBP-ASSOCIATED FACTOR 4b (TAF4b), which encodes a subunit of the RNA polymerase II general transcription factor TFIID. The Arabidopsis taf4b mutation is a rare variant found in the British Isles, originating in South-West Ireland. Using genetics, genomics, and immunocytology, we demonstrate a genome-wide decrease in taf4b crossovers, with strongest reduction in the sub-telomeric regions. Using RNA sequencing (RNA-seq) from purified meiocytes, we show that TAF4b expression is meiocyte enriched, whereas its paralog TAF4 is broadly expressed. Consistent with the role of TFIID in promoting gene expression, RNA-seq of wild-type and taf4b meiocytes identified widespread transcriptional changes, including in genes that regulate the meiotic cell cycle and recombination. Therefore, TAF4b duplication is associated with acquisition of meiocyte-specific expression and promotion of germline transcription, which act directly or indirectly to elevate crossovers. This identifies a novel mode of meiotic recombination control via a general transcription factor.
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http://dx.doi.org/10.1016/j.cub.2019.06.084DOI Listing
August 2019

UCHL1 regulates muscle fibers and mTORC1 activity in skeletal muscle.

Life Sci 2019 Sep 26;233:116699. Epub 2019 Jul 26.

Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, United States of America. Electronic address:

Aims: Skeletal muscle wasting is associated with many chronic diseases. Effective prevention and treatment of muscle wasting remain as a challenging task due to incomplete understanding of mechanisms by which muscle mass is maintained and regulated. This study investigated the functional role of Ubiquitin C-terminal hydrolase L1 (UCHL1) in skeletal muscle.

Main Methods: Mice with skeletal muscle specific gene knockout of UCHL1 and C2C12 myoblast cells with UCHL1 knockdown were used. Muscle fiber types and size were measured using tissue or cell staining. The mammalian target of rapamycin complex 1 (mTORC1) and mTORC2 activities were assessed with the phosphorylation of their downstream targets.

Key Findings: In mouse skeletal muscle, UCHL1 was primarily expressed in slow twitch muscle fibers. Mice with skeletal muscle specific knockout (skmKO) of UCHL1 exhibited enlarged muscle fiber sizes in slow twitch soleus but not fast twitch extensor digitorum longus (EDL) muscle. Meanwhile, UCHL1 skmKO enhanced mTORC1 activity and reduced mTORC2 activity in soleus but not in EDL. Consistently, in C2C12 cells, UCHL1 knockdown increased the myotube size, enhanced mTORC1 activity, and reduced mTORC2 activities as compared with control cells. UCHL1 knockdown did not change the major proteins of mTOR complex but decreased the protein turnover of PRAS40, an inhibitory factor of mTORC1.

Significance: These data revealed a novel function of UCHL1 in regulation of mTORC1 activity and skeletal muscle growth in slow twitch skeletal muscle. Given the upregulation of UCHL1 in denervation and spinal muscle atrophy, our finding advances understanding of regulators that are involved in muscle wasting.
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http://dx.doi.org/10.1016/j.lfs.2019.116699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718320PMC
September 2019

Bovine serum albumin-templated nanoplatform for magnetic resonance imaging-guided chemodynamic therapy.

J Nanobiotechnology 2019 May 20;17(1):68. Epub 2019 May 20.

Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Background: Nanotechnology in medicine has greatly expanded the therapeutic strategy that may be explored for cancer treatment by exploiting the specific tumor microenvironment such as mild acidity, high glutathione (GSH) concentration and overproduced hydrogen peroxide (HO). Among them, tumor microenvironment responsive chemodynamic therapy (CDT) utilized the Fenton or Fenton-like reaction to produce excess hydroxyl radical (·OH) for the destruction of tumor cells. However, the produced ·OH is easily depleted by the excess GSH in tumors, which would undoubtedly impair the CDT's efficiency. To overcome this obstacle and enhance the treatment efficiency, we design the nanoplatforms for magnetic resonance imaging (MRI)-guided CDT.

Results: In this study, we applied the bovine serum albumin (BSA)-templated CuS:Gd nanoparticles (CuS:Gd NPs) for MRI-guided CDT. The Cu in the CuS:Gd NPs could be reduced to Cu by GSH in tumors, which further reacted with HO and triggered Fenton-like reaction to simultaneously generate abundant ·OH and deplete GSH for tumor enhanced CDT. Besides, the Gd in CuS:Gd NPs endowed them with excellent MRI capability, which could be used to locate the tumor site and monitor the therapy process preliminarily.

Conclusions: The designed nanoplatforms offer a major step forward in CDT for effective treatment of tumors guided by MRI.
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http://dx.doi.org/10.1186/s12951-019-0501-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528315PMC
May 2019
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