Publications by authors named "Chang Liu"

3,630 Publications

  • Page 1 of 1

Nanotechnology-based Delivery of CRISPR/Cas9 for Cancer Treatment.

Adv Drug Deliv Rev 2021 Jul 26:113891. Epub 2021 Jul 26.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku 20520, Finland. Electronic address:

CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9) is a potent technology for gene-editing. Owing to its high specificity and efficiency, CRISPR/Cas9 is extensity used for human diseases treatment, especially for cancer, which involves multiple genetic alterations. Different concepts of cancer treatment by CRISPR/Cas9 are established. However, significant challenges remain for its clinical applications. The greatest challenge for CRISPR/Cas9 therapy is how to safely and efficiently deliver it to target sites in vivo. Nanotechnology has greatly contributed to cancer drug delivery. Here, we present the action mechanisms of CRISPR/Cas9, its application in cancer therapy and especially focus on the nanotechnology-based delivery of CRISPR/Cas9 for cancer gene editing and immunotherapy to pave the way for its clinical translation. We detail the difficult barriers for CRISIR/Cas9 delivery in vivo and discuss the relative solutions for encapsulation, target delivery, controlled release, cellular internalization, and endosomal escape.
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http://dx.doi.org/10.1016/j.addr.2021.113891DOI Listing
July 2021

Knowledge, Attitude, and Practice of Metformin Extended-Release Tablets Among Clinicians in China: A Cross-Sectional Survey.

Front Pharmacol 2021 12;12:634561. Epub 2021 Jul 12.

Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.

Metformin extended-release (XR) is a once-daily alternative conventional immediate-release (IR) tablet for adults with type 2 diabetes. This study aimed to investigate the knowledge, attitude, and practice of the use of metformin XR tablets among clinicians. We conducted a cross-sectional online survey among endocrinologists, general practitioners, and internists, who are taking routine care of adults with type 2 diabetes in health institutes at all levels in Sichuan Province, China. We designed an online questionnaire including the demographic information, knowledge, attitude, and practice about metformin XR tablets. We included 158 clinicians, 67.7% of whom were females and 63.9% were from tertiary hospitals. The median age was 39.6 years (ranging between 22 and 62 years). Only 8.2% of the clinicians correctly answered the knowledge questions, 82.3% and 62.0% of the responders assumed that metformin XR had superior efficacy and tolerability to the metformin IR, respectively. Only 46.8% of the clinicians prescribed the metformin XR based on the patient's preference for once daily frequency. The knowledge, attitude, and practice of metformin XR among Chinese clinicians need improving. Clinicians need credible information to support their clinical decision-making regarding metformin XR.
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http://dx.doi.org/10.3389/fphar.2021.634561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312381PMC
July 2021

Acoustic Ejection Mass Spectrometry for High-Throughput Analysis.

Anal Chem 2021 Jul 28. Epub 2021 Jul 28.

Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States.

We describe a mass spectrometry (MS) analytical platform resulting from the novel integration of acoustic droplet ejection (ADE) technology, an open-port interface (OPI), and electrospray ionization (ESI)-MS that creates a transformative system enabling high-speed sampling and label-free analysis. The ADE technology delivers nanoliter droplets in a touchless manner with high speed, precision, and accuracy. Subsequent sample dilution within the OPI, in concert with the capabilities of modern ESI-MS, eliminates the laborious sample preparation and method development required in current approaches. This platform is applied to a variety of experiments, including high-throughput (HT) pharmacology screening, label-free in situ enzyme kinetics, in vitro absorption, distribution, metabolism, elimination, pharmacokinetic and biomarker analysis, and HT parallel medicinal chemistry.
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http://dx.doi.org/10.1021/acs.analchem.1c01137DOI Listing
July 2021

Ketogenic Diet Prevents Paclitaxel-Induced Neuropathic Nociception through Activation of PPARγ Signaling Pathway and Inhibition of Neuroinflammation in Rat Dorsal Root Ganglion.

Eur J Neurosci 2021 Jul 27. Epub 2021 Jul 27.

Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning, PR China.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect during the course of cancer treatment, which is mainly manifested as a series of sensory abnormalities. At present, there are no recommended prevention or treatment strategies, and the underlying mechanisms are unclear. The ketogenic diet (KD), a special diet that is high in fat and low in carbohydrate intake, shows good therapeutic potential in children with epilepsy. In this study, it was found that KD significantly prevented paclitaxel-induced neuropathic nociception. Using the GSE113941 database, 281 differentially expressed genes (DEGs) were found in an animal model of CIPN and controls. The DEGs were mainly enriched in peroxisome proliferator activated receptor (PPAR) and oxidative phosphorylation signaling pathways. As a main regulatory pathway of lipid metabolism, the PPARγ signaling pathway was significantly upregulated in the KD model. In addition, KD also inhibited the expression of pro-inflammatory cytokines and the TLR4/NF-κB signaling pathway in the dorsal root ganglion (DRG) in paclitaxel-treated rats. In vitro, rat primary DRG neurons were used to investigate the role of PPARγ in paclitaxel-induced neurotoxicity. It was found that PPARγ agonist rosiglitazone significantly protected DRG neurons against cell apoptosis and reactive oxygen species generation induced by paclitaxel administration. Therefore, KD is a prospective treatment option when applied as a dietary intervention in the prevention and treatment of paclitaxel-induced neuropathic nociception, possibly through the activation of PPARγ and its neuroprotective functions.
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http://dx.doi.org/10.1111/ejn.15397DOI Listing
July 2021

Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme.

Science 2021 Jul 27. Epub 2021 Jul 27.

Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA.

Coronavirus 3'-5' exoribonuclease (ExoN), residing in the nonstructural protein (nsp) 10-nsp14 complex, boosts replication fidelity by proofreading RNA synthesis and is critical for the virus life cycle. ExoN also recognizes and excises nucleotide analog inhibitors incorporated into the nascent RNA, undermining the effectiveness of nucleotide analog-based antivirals. Here, we present cryo-electron microscopy structures of both wild-type and mutant SARS-CoV-2 nsp10-nsp14 in complex with an RNA substrate bearing a 3'-end mismatch at resolutions ranging from 2.5 Å to 3.9 Å. The structures reveal the molecular determinants of ExoN substrate specificity and give insight into the molecular mechanisms of mismatch correction during coronavirus RNA synthesis. Our findings provide guidance for rational design of improved anti-coronavirus therapies.
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http://dx.doi.org/10.1126/science.abi9310DOI Listing
July 2021

A Porous Metal-Organic Framework as an Electrochemical Sensing Platform for Highly Selective Adsorption and Detection of Bisphenols.

Inorg Chem 2021 Jul 27. Epub 2021 Jul 27.

Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, Faculty of Chemistry, Northeast Normal University, Changchun, Jilin 130024, China.

The design of artificial receptors with a specific recognition function and enhanced selectivity is highly desirable in the electrochemical sensing field, which can be used for detection of environmental pollutants. In this facet, metal-organic frameworks (MOFs) featured adjustable porosities and specific host-guest recognition properties. Especially, the large hydrophobic cavity formed in the porous MOFs may become a potential artificial receptor. We herein designed a new porous MOF [Zn(L)(IPA)(HO)]·2DMF·2MeOH·3HO () by using a functionalized sulfonylcalix[4]arene () and isophthalic acid (HIPA) (DMF = ,'-dimethylformamide). The specific pore size and pore shape of made it efficiently selective for absorption of bisphenol A (), bisphenol F (), and bisphenol S (). Therefore, a rapid, highly selective, and ultrasensitive electrochemical sensing platform was fabricated by using as a host to recognize and absorb bisphenol guests ( = graphite powder, = glassy carbon electrode). Most strikingly, the extremely low detection limits were up to 3.46 and 0.17 nM for and , respectively, using the electrode. Furthermore, the "recognition and adsorption" mechanism was uncovered by density functional theory with the B3LYP function. This work offered a prospective strategy for selective absorption and detection of harmful bisphenols with the MOF-based porous material.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01253DOI Listing
July 2021

The Expression Patterns and Roles of Lysyl Oxidases in Aortic Dissection.

Front Cardiovasc Med 2021 7;8:692856. Epub 2021 Jul 7.

Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Lysyl oxidases (LOXs), including LOX, LOXL1, LOXL2, LOXL3, and LOXL4, catalyze the formation of a cross-link between elastin (ELN) and collagen. Multiple LOX mutations have been shown to be associated with the occurrence of aortic dissection (AD) in humans, and LOX-knockout mice died during the perinatal period due to aortic aneurysm and rupture. However, the expression levels and roles of other LOX members in AD remain unknown. A total of 33 aorta samples of AD and 15 normal aorta were collected for LOXs mRNA and protein levels detection. We also analyzed the datasets of AD in GEO database through bioinformatics methods. LOXL2 and LOXL3 were knocked down in primary cultured human aortic smooth muscle cells (HASMCs) via lentivirus. Here, we show that the protein levels of LOXL2 and LOXL3 are upregulated, while LOXL4 is downregulated in AD subjects compared with non-AD subjects, but comparable protein levels of LOX and LOXL1 are detected. Knockdown of LOXL2 suppressed MMP2 expression, the phosphorylation of AKT (p-AKT) and S6 (p-S6), but increased the mono-, di-, tri-methylation of H3K4 (H3K4me1/2/3), H3K9me3, and p-P38 levels in HASMCs. These results indicate that LOXL2 is involved in regulation of the extracellular matrix (ECM) in HASMCs. In contrast, LOXL3 knockdown inhibited PCNA and cyclin D1, suppressing HASMC proliferation. Our results suggest that in addition to LOX, LOXL2 and LOXL3 are involved in the pathological process of AD by regulating ECM and the proliferation of HASMCs, respectively. Furthermore, we found that LOXL2 and LOXL4 was inhibited by metformin and losartan in HASMCs, which indicated that LOXL2 and LOXL4 are the potential targets that involved in the therapeutic effects of metformin and losartan on aortic or aneurysm expansion. Thus, differential regulation of LOXs might be a novel strategy to prevent or treat AD.
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http://dx.doi.org/10.3389/fcvm.2021.692856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292648PMC
July 2021

Ulinastatin protects against acetaminophen-induced liver injury by alleviating ferroptosis via the SIRT1/NRF2/HO-1 pathway.

Am J Transl Res 2021 15;13(6):6031-6042. Epub 2021 Jun 15.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, Shaanxi, People's Republic of China.

Acetaminophen (APAP) overdose has been considered responsible for the drug-induced liver injury for many years. Ferroptosis is defined as an iron-dependent form of cell death associated with lipid peroxide accumulation. Ferroptosis is involved in APAP-induced acute liver failure, and UTI is an effective drug treatment for acute liver failure. Thus, we aimed to determine whether UTI protects the liver against APAP-induced acute liver failure by decreasing ferroptosis-induced lipid peroxide accumulation. C57BL/6 mice and LO2 cell line were treated with UTI before and after the exposure to APAP. Liver tissues and LO2 cells were collected for biochemical assessment of molecular parameters. APAP-induced upregulation of ferroptotic events (iron content), lipid hydroperoxides (ROS production, MDA, and 4-HNE), and depletion of GSH were effectively relieved by ferrostatin-1 (Fer-1), a ferroptosis inhibitor, and UTI. UTI blocked ferroptosis-induced lipid peroxide accumulation by promoting nuclear translocation of NRF2 to activate its downstream targets (HO-1). An increased expression or knockdown of of SIRT1 influenced the UTI effect on the NRF2 pathway and had an impact on lipid accumulation. Overall, UTI plays a role in mitigation of APAP-induced acute liver injury by inhibiting ferroptosis-induced lipid peroxide accumulation, and the effect of UT1 was mediated by the NRF2/HO-1 pathway and SIRT1 expression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290678PMC
June 2021

Autophagy: A Novel Horizon for Hair Cell Protection.

Neural Plast 2021 29;2021:5511010. Epub 2021 Jun 29.

ENT Institute and Otorhinolaryngology Department, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200031, China.

As a general sensory disorder, hearing loss was a major concern worldwide. Autophagy is a common cellular reaction to stress that degrades cytoplasmic waste through the lysosome pathway. Autophagy not only plays major roles in maintaining intracellular homeostasis but is also involved in the development and pathogenesis of many diseases. In the auditory system, several studies revealed the link between autophagy and hearing protection. In this review, we aimed to establish the correlation between autophagy and hair cells (HCs) from the aspects of ototoxic drugs, aging, and acoustic trauma and discussed whether autophagy could serve as a potential measure in the protection of HCs.
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http://dx.doi.org/10.1155/2021/5511010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263289PMC
June 2021

Gene Polymorphisms Were Associated with Alcohol-Induced Osteonecrosis of the Femoral Head.

Int J Gen Med 2021 17;14:3583-3591. Epub 2021 Jul 17.

Department of Orthopedics, The Hospital of Yutian County, Tangshan, Hebei Province, 063000, People's Republic of China.

Introduction: Alcohol-induced osteonecrosis of the femoral head (ONFH), a progressive disease, is caused by excessive drinking and genetic factors. Currently, it remains to represent a significant challenge. The association between alcohol-induced ONFH and gene polymorphisms may provide a direction for the mechanism of alcoholic ONFH.

Methods: A total of 201 alcohol-induced ONFH patients and 201 healthy controls were recruited in this case-control study. The polymorphisms of gene were genotyped in blood samples by Agena MassARRAY RS1000. Pearson chi-square test was used to calculate difference in allele frequencies of gene polymorphisms between the cases and controls. Alcohol-induced ONFH risk was estimated using odds ratios (ORs) and 95% confidence intervals (CIs).

Results: In the overall analysis, the allele "G" of rs62030917 was significantly increased alcohol-induced ONFH risk (OR = 1.47, 95% CI = 1.07-2.02, = 0.017) in the allele model. In the genetic analysis, rs62030917 also increased the risk of alcohol-induced ONFH in the dominant model (adjusted OR = 1.52, 95% CI=1.02-2.26, = 0.039) and the log-additive model (adjusted OR = 1.42, 95% CI=1.05-1.93, = 0.025). Age stratification analysis suggested that rs62030917 increased the risk of alcohol-induced ONFH among the individuals younger than 42 years old. Moreover, carriers of AA, GA and GG genotypes in rs2269556 had LDL-C levels that were significantly different ( = 0.047). Among them, carriers of GG genotype had the highest LDL-C levels.

Conclusion: This study revealed rs62030917 in gene might increase the risk of alcohol-induced ONFH, providing a theoretical basis for the mechanism of in alcohol-induced ONFH.
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http://dx.doi.org/10.2147/IJGM.S316481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296705PMC
July 2021

Assembly of the complete mitochondrial genome of an endemic plant, Scutellaria tsinyunensis, revealed the existence of two conformations generated by a repeat-mediated recombination.

Planta 2021 Jul 24;254(2):36. Epub 2021 Jul 24.

Key Laboratory of Horticulture Science for Southern Mountainous Regions from Ministry of Education, College of Horticulture and Landscape Architecture, Southwest University, No. 2 Tiansheng Road, Beibei District, Chongqing, 400716, China.

Main Conclusion: We assembled the complete mitochondrial genome of Scutellaria tsinyunensis in this study. Repeat-mediated recombination resulted in the formation of two conformations of the mitochondrial genome in S. tsinyunensis. Scutellaria tsinyunensis belongs to the family Lamiaceae, distributed only in the Jinyun Mountain, Chongqing, China. As a valuable endemic and small population species, it is regarded as a natural resource potentially with significant economic and ecological importance. In this study, we assembled a complete and gap-free mitochondrial genome of S. tsinyunensis. This genome had a length of 354,073 bp and the base composition of the genome was A (27.44%), T (27.30%), C (22.58%), and G (22.68%). This genome encodes 59 genes, including 32 protein-coding genes, 24 tRNA genes, and 3 rRNA genes. The Sanger sequencing and Oxford Nanopore sequencing confirmed a pair of direct repeats had mediated genome recombination, resulting in the formation of two conformations. The gene conversation between plastome and mitochondrial genome was also observed in S. tsinyunensis by detecting gene migration, including six tRNA genes (namely, trnW-CCA, trnI-CAU, trnH-UUU, trnD-GUC, trnN-GUU, and trnM-CAU), five protein-coding gene fragments, and the fragments from 2 rRNA genes. Moreover, the dN/dS analysis revealed the atp9 gene had undergone strong negative selection, and four genes (atp4, mttB, ccmFc, and ccmB) probably had undergone positive selection during evolution in Lamiales. This work reported the first mitochondrial genome of S. tsinyunensis, which could be used as a reference genome for the important medicinal plants of the genus Scutellaria, and also provide much-desired information for molecular breeding.
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http://dx.doi.org/10.1007/s00425-021-03684-3DOI Listing
July 2021

An optimized proliferation system of embryonic stem cells for generating the rat model with large fragment modification.

Biochem Biophys Res Commun 2021 Jul 20;571:8-13. Epub 2021 Jul 20.

Key Laboratory of Arrhythmias, Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China; Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai, 200092, China; Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Beijing, 100730, China. Electronic address:

Rats have long been an ideal model for disease research in the field of biomedicine, but the bottleneck of in vitro culture of rat embryonic stem (ES) cells hindered the wide application as genetic disease models. Here, we optimized a special medium which we named 5N-medium for rat embryonic stem cells, which improved the in vitro cells with better morphology and higher pluripotency. We then established a drug selection schedule harboring a prior selection of 12 h that achieved a higher positive selection ratio. These treatments induced at least 50% increase of homologous recombination efficiency compared with conventional 2i culture condition. Moreover, the ratio of euploid ES clones also increased by 50% with a higher germline transmission rate. Finally, we successfully knocked in a 175 kb human Bacterial Artificial Chromosome (BAC) fragment to rat ES genome through recombinase mediated cassette exchange (RMCE). Hence, we provide a promising system for generating sophisticated rat models which could be benefit for biomedical researches.
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http://dx.doi.org/10.1016/j.bbrc.2021.07.053DOI Listing
July 2021

Water jet as a novel technique for enamel drilling ex vivo.

PLoS One 2021 23;16(7):e0254787. Epub 2021 Jul 23.

School & Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, Peoples R China.

To investigate the usage of a water jet for enamel drilling ex vivo, 210 individual extracted molars without lesions or fillings were collected. Then, the specimens were drilled by a water jet or a high-speed dental drill. The cavities of 50 teeth were reconstructed digitally by micro-computed tomography (micro-CT) to measure the height and width. The cavities of 10 teeth were longitudinally incised and their surfaces were observed by scanning electronic microscopy (SEM). After the cavities were filled, 50 fillings were vertically incised. The bonding interface between tooth and filling was observed by SEM. 50 teeth with fillings were stained in 0.1% rhodamine B solution, and then the dye penetration between tooth and filling was observed under the stereomicroscope and confocal laser scanning microscopy (CLSM). The bonding strength between enamel and filling of 50 teeth was simulated and predicted with finite element analysis (FEA). At 140-150 MPa and for 2-3 s, cavities were made with a depth of approximately 764 μm in each tooth. SEM showed the cavity surface in the water jet group had a more irregular concave and convex structure than that in the high-speed dental drill group. There was a trend that the microleakage and bonding width was smaller in the water jet group than in the high-speed dental drill group. FEA indicated that the stress on the resin surface was greater than on the enamel surface in the water jet group. Compared with the tooth drilled by a high-speed dental drill, the tooth drilled by a water jet gained better retention of the filling material and suffered less bonding strength on the enamel surface. Water jet drilling is effective for enamel drilling.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254787PLOS
July 2021

[Q-marker prediction of Magnoliae Officinalis Cortex before and after "sweating"].

Zhongguo Zhong Yao Za Zhi 2021 Jun;46(11):2686-2690

Chengdu Diao Pharmaceutical Group Co.,Ltd. Chengdu 610000,China.

Magnoliae Officinalis Cortex, a common Chinese medicinal in clinic, should undergo "sweating" process in producing area according to Chinese Pharmacopoeia, which affects its genuineness and quality. In light of the concept and research mode of quality marker(Q-marker) for decoction pieces, the active components of Magnoliae Officinalis Cortex pieces which altered significantly before and after "sweating" were identified in this study. The main pharmacodynamic material basis was clarified by pharmacodynamic, pharmacokinetic and drug property research, followed by the prediction of Q-markers of Magnoliae Officinalis Cortex before and after "sweating", for better improving its quality standard.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210316.201DOI Listing
June 2021

management by nematicides in tomato production.

J Nematol 2021 19;53. Epub 2021 Jul 19.

Entomology and Nematology Department, University of Florida 1881 Natural Area Drive, Gainesville, FL 32611.

(southern root-knot nematode, SRKN) is a major pest in tomato () production in the Southeastern United States. Management has relied on fumigant and carbamate non-fumigant nematicides. New non-fumigant nematicides, such as fluopyram, are available and field evaluation of new nematicides is needed. The objectives of this research were to assess the efficacy of new (fluopyram) and established (oxamyl) non-fumigant nematicides as well as fumigation (1,3-dichloropropene) for (1) SRKN management, and (2) impacts on total soil abundances of non-target, free-living nematodes in field tests in Florida. Fumigation with 1,3-D consistently managed SRKN and, in two of three trials, increased yield relative to untreated. Oxamyl and fluopyram also had efficacy in managing SRKN, but were inconsistent from year to year. Oxamyl provided better root galling control than fluopyram in one of two trials, but otherwise those nematicides provided similar SRKN management and yield response. Supplementing 1,3-D fumigation with fluopyram did not improve SRKN management or yield relative to fumigation alone. Fumigation consistently reduced free-living nematode abundances relative to untreated. Oxamyl and fluopyram were more inconsistent, but always reduced total free-living nematode abundances when effective against SRKN. In summary, while non-fumigant nematicides provided some management of SRKN, fumigation continued to be the most consistent option. All nematicides had deleterious effects on free-living nematodes.
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http://dx.doi.org/10.21307/jofnem-2021-055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290502PMC
July 2021

A Novel Cognition-Guided Neurofeedback BCI Dataset on Nicotine Addiction.

Front Neurosci 2021 6;15:647844. Epub 2021 Jul 6.

Department of Radiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Science, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China.

Compared with the traditional neurofeedback paradigm, the cognition-guided neurofeedback brain-computer interface (BCI) is a novel paradigm with significant effect on nicotine addiction. However, the cognition-guided neurofeedback BCI dataset is extremely lacking at present. This paper provides a BCI dataset based on a novel cognition-guided neurofeedback on nicotine addiction. Twenty-eight participants are recruited and involved in two visits of neurofeedback training. This cognition-guided neurofeedback includes two phases: an offline classifier construction and a real-time neurofeedback training. The original electroencephalogram (EEG) raw data of two phases are provided and evaluated in this paper. The event-related potential (ERP) amplitude and channel waveform suggest that our BCI dataset is of good quality and consistency. During neurofeedback training, the participants' smoking cue reactivity patterns have a significant reduction. The mean accuracy of the multivariate pattern analysis (MVPA) classifier can reach approximately 70%. This novel cognition-guided neurofeedback BCI dataset can be used to develop comparisons with other neurofeedback systems and provide a reference for the development of other BCI algorithms and neurofeedback paradigms on addiction.
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http://dx.doi.org/10.3389/fnins.2021.647844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290081PMC
July 2021

Echinacea purpurea polysaccharide prepared by fractional precipitation prevents alcoholic liver injury in mice by protecting the intestinal barrier and regulating liver-related pathways.

Int J Biol Macromol 2021 Jul 20;187:143-156. Epub 2021 Jul 20.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; Synergetic Innovation Center for Food Safety and Nutrition, Jiangnan University, Wuxi 214122, China. Electronic address:

Oxidative damage and intestinal dysbiosis are regarded as crucial culprits in alcoholic liver disease (ALD). This study aimed to examine the protective effects of Echinacea purpurea polysaccharides (EPPs) against ALD and explore the underlying mechanisms based on hepatic oxidative stress, inflammation, and intestinal barrier function. Three polysaccharide fractions, namely, EPP40, EPP60, and EPP80, were obtained by stepwise ethanol precipitation, and their antioxidant activity in vitro was investigated. The results showed that EPP80 with Mw 11.82 kDa had the strongest radical-scavenging capacity against DPPH, ABTS, and •OH radicals. Besides, EPP80 comprised arabinose, galactose, glucose, mannose, galacturonic acid, and glucuronic acid in molar ratios of 13.42:25.12:10.92:8.59:2.07:0.82. The in vivo results showed that EPP80 increased the activities of antioxidant enzymes and reduced the levels of inflammatory cytokines both in mouse serum and liver. Moreover, EPP80 upregulated the expression of Occludin and ZO-1, revealing its protective effect against intestinal barrier dysfunction. Furthermore, EPP80 inhibited alcohol-induced oxidative damage by promoting the expression of Nrf2, HO-1, and NQO1 in the liver. In summary, EPP80 markedly scavenged free radicals in vitro and ameliorated alcohol-induced liver injury via Nrf2/HO-1 pathways in vivo. These findings suggested that EPP80 could provide effective supplementary support in preventing and treating ALD.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.095DOI Listing
July 2021

A cell-based FcRn-dependent recycling assay for predictive pharmacokinetic assessment of therapeutic antibodies.

Bioanalysis 2021 Jul 22. Epub 2021 Jul 22.

Department of BioAnalytical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Evaluation of suitable pharmacokinetic properties is critical for successful development of IgG-based biotherapeutics. The prolonged half-lives of IgGs depend on the intracellular trafficking function of neonatal Fc receptor, which rescues internalized IgGs from lysosomal degradation and recycles them back to circulation. Here, we developed a novel cell-based assay to quantify recycling of monoclonal antibodies in a transwell culture system that uses a cell line that stably expresses human neonatal Fc receptor. We tested seven therapeutic antibodies and showed that the recycling output of the assay strongly correlated with the clearance in humans. This recycling assay has potential application as a pharmacokinetic prescreening tool to facilitate development and selection of IgG-based candidate therapeutic monoclonal antibodies.
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http://dx.doi.org/10.4155/bio-2021-0099DOI Listing
July 2021

In Vitro Reconstitution of Yeast Translation System Capable of Synthesizing Long Polypeptide and Recapitulating Programmed Ribosome Stalling.

Methods Protoc 2021 Jul 4;4(3). Epub 2021 Jul 4.

Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa-shi, Chiba 277-8562, Japan.

The rates of translation elongation or termination in eukaryotes are modulated through cooperative molecular interactions involving mRNA, the ribosome, aminoacyl- and nascent polypeptidyl-tRNAs, and translation factors. To investigate the molecular mechanisms underlying these processes, we developed an in vitro translation system from yeast, reconstituted with purified translation elongation and termination factors, utilizing CrPV IGR IRES-containing mRNA, which functions in the absence of initiation factors. The system is capable of synthesizing not only short oligopeptides but also long reporter proteins such as nanoluciferase. By setting appropriate translation reaction conditions, such as the Mg/polyamine concentration, the arrest of translation elongation by known ribosome-stalling sequences (e.g., polyproline and CGA codon repeats) is properly recapitulated in this system. We describe protocols for the preparation of the system components, manipulation of the system, and detection of the translation products. We also mention critical parameters for setting up the translation reaction conditions. This reconstituted translation system not only facilitates biochemical analyses of translation but is also useful for various applications, such as structural and functional studies with the aim of designing drugs that act on eukaryotic ribosomes, and the development of systems for producing novel functional proteins by incorporating unnatural amino acids by eukaryotic ribosomes.
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http://dx.doi.org/10.3390/mps4030045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293373PMC
July 2021

Softness, Elasticity, and Toughness of Polymer Networks with Slide-Ring Cross-Links.

Gels 2021 Jul 13;7(3). Epub 2021 Jul 13.

Material Innovation Research Center (MIRC), Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan.

Slide-ring (SR) gels cross-linked by ring molecules are characterized by softness (low Young's modulus), elasticity (low hysteresis loss), and toughness (large fracture energy). In this article, the mechanical and fracture properties of SR gels are reviewed to clarify the physical understanding of the relationship between the molecular-level sliding dynamics of the slide-ring cross-links and macroscopic properties of SR gels. The low Young's modulus and large fracture energy of SR gels are expressed by simple equations as a function of the degree of sliding movement. The dynamic fracture behaviors of SR gels gives us the time scale of the sliding dynamics of the cross-links, which is at the micro-sec scale. The fast sliding motion of the cross-links leads to the elasticity of the SR gels. The SR concept can be applied to solvent-free elastomers and composite materials.
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http://dx.doi.org/10.3390/gels7030091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293080PMC
July 2021

Managing Patient Bias: Teaching Residents to Navigate Racism and Bias in the Workplace.

J Surg Educ 2021 Jul 17. Epub 2021 Jul 17.

Department of Surgery, Inova Fairfax Medical Campus, Falls Church, Virginia.

Background: Racial inequities are infused within American society and healthcare systems; notable events in 2020 highlighted an urgent need for change. Many organizations were inspired to examine the impacts of systemic racism. The impact of physician bias on patient experiences and outcomes has been well documented; biased patient behavior is now becoming more openly discussed. In response to the current climate and painful effects of discrimination on healthcare and providers, we aimed to provide training for our surgical residents to more comfortably respond to bias in the workplace.

Methods: We designed and piloted a simulation-based communication module focused on managing bias with medical students. We incorporated feedback received from students, facilitators, faculty, and simulated patients (SPs) to create an anti-bias workshop for surgical residents. Additionally, we worked with the pediatric and emergency departments to develop training videos depicting bias incidents, standardize debriefing processes, and implement anti-bias workshops for their residencies.

Results: Twenty students participated in the medical student pilot session. Student confidence increased in target skills; many noted this was their first exposure to the topic in a medical school course, and first opportunity to practice these skills. Sixteen surgical residents participated in an in-person module; learners self-identifying as "completely confident" increased in number significantly for "determining whether to respond" (p = 0.023), "knowing how to ensure follow up" (p = 0.041), and "self-care following an event" (p = 0.023).

Conclusion: Our low-cost, high-impact anti-bias module provided learners with tools and practice, suggesting that such an effort is feasible, affordable, and effective. Our interdepartmental trainings have inspired our institution to develop approved statements clinicians may use when responding to race-based discrimination; offering a uniform approach to race-based microaggression or abuse can create a shared mental model for all team members, especially for those vulnerable to biased comments.
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http://dx.doi.org/10.1016/j.jsurg.2021.06.007DOI Listing
July 2021

Aging Effect on Mandarin Chinese Vowel and Tone Identification in Six-Talker Babble.

Am J Audiol 2021 Jul 20:1-15. Epub 2021 Jul 20.

School of Foreign Languages, Tongji University, Shanghai, China.

Purpose The purpose of this study was to measure Mandarin Chinese vowel-plus-tone identification in quiet and noise for younger and older listeners. Method Two types of noise served as the masker, namely, six-talker babble and babble-modulated noise, at two signal-to-noise ratios (SNRs) of -4 and -8 dB. Fourteen listeners from both age groups were recruited, and three sets of data analyses were conducted: the identification of vowel plus tone, the identification of vowel, and the identification of tone. Results Younger listeners outperformed older listeners in all listening conditions, whereas the younger-older listener difference became greater in noise than in quiet, indicating a more detrimental effect of noise for older listeners than for younger listeners. In addition, vowel identification showed slightly better scores than tone identification in noise, suggesting that noise appeared to affect tone perception more negatively than vowel perception in Mandarin Chinese. At -4 dB SNR, there was a significantly greater amount of informational masking (IM) and a greater amount of energetic masking (EM) for older listeners than for younger listeners. At -8 dB SNR, there was a greater amount of EM for older listeners than for younger listeners but with no group difference in the amount of IM. Conclusion These results suggest that older listeners received a more negative impact of noise for Mandarin Chinese phonemic and tone recognition and had a larger amount of IM or EM from competing speech noise than younger listeners, depending on the SNR.
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http://dx.doi.org/10.1044/2021_AJA-20-00139DOI Listing
July 2021

Effects of general versus subarachnoid anaesthesia on circadian melatonin rhythm and postoperative delirium in elderly patients undergoing hip fracture surgery: A prospective cohort clinical trial.

EBioMedicine 2021 Jul 16;70:103490. Epub 2021 Jul 16.

Department of Anesthesiology, Peking University Third Hospital, No. 49, North Garden Street, Haidian District, Beijing 100191, China. Electronic address:

Background: Circadian rhythm disturbance is common postoperatively in older patients with hip fractures, which may contribute to the development of postoperative delirium (POD). As a reliable biomarker of endogenous circadian rhythms, melatonin regulates the sleep-wake cycle and environmental adaptation, and its secretory rhythm may be modified by anaesthesia and surgery. This study compared the impact of subarachnoid anaesthesia (SA) and general anaesthesia (GA), on the peak of melatonin secretion (primary outcome), the circadian rhythm of melatonin, cortisol and sleep, and the POD incidence (secondary outcome).

Methods: In this prospective cohort observational study, hip fracture surgery patients were enrolled and assigned to receive either SA or GA. Postoperative plasma melatonin and cortisol levels were dynamically measured every six hours on seven time-points, and the circadian rhythm parameters including mesor, amplitude, and acrophase were calculated. Subjective and objective sleep assessments were performed by sleep diaries and sleep trackers, respectively. The Confusion Assessment Method was used twice daily by a specific geriatrician to screen for POD occurrence.

Findings: In a cohort of 138 patients who underwent hip fracture surgery, the circadian rhythm disruption of the patients in the GA group (n=69) was greater than the SA group (n=69). Compared with SA, GA provided the lower peak concentration, mesor, and amplitude of melatonin secretion on postoperative day 1 (p < 0.05). Patients in the GA group experienced higher awakenings, more sleep deprivation, and poor sleep quality on surgery day (p < 0.05). A proportion of 12 patients in the SA group (17.4%) and 24 patients in the GA group (34.8%) experienced POD (p = 0.020).

Interpretation: These results suggest that SA may be superior to GA in elderly patients undergoing hip fracture surgery as SA is associated with less impairment of the melatonin rhythm and sleep patterns, and fewer POD occurrences.
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http://dx.doi.org/10.1016/j.ebiom.2021.103490DOI Listing
July 2021

Phosphine Sulfide-Based Bipolar Host Materials for Blue Phosphorescent Organic Light-Emitting Diodes.

Molecules 2021 Jul 3;26(13). Epub 2021 Jul 3.

State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China.

Three phosphine sulfide-based bipolar host materials, , , and , were facilely prepared through a one-pot synthesis in excellent yields. The developed hosts exhibit superior thermal stabilities with the decomposition temperatures () all exceeding 350 °C and the melting temperatures () over 200 °C. In addition, their triplet energy () levels are estimated to be higher than 3.0 eV, illustrating that they are applicable to serve as hosts for blue phosphorescent organic light-emitting diodes (PhOLEDs). The maxima luminance, current efficiency (CE), power efficiency (PE), and external quantum efficiency (EQE) of 17,223 cd m, 36.7 cd A, 37.5 lm W, and 17.5% are achieved for the blue PhOLEDs hosted by . The PhOLEDs based on and show inferior device performance than that of , which might be ascribed to the deteriorated charge transporting balance as the increased number of the constructed carbazole units in and molecules would enhance the hole-transporting ability of the devices to a large extent. Our study demonstrates that the bipolar hosts derived from phosphine sulfide have enormous potential applications in blue PhOLEDs, and the quantity of donors should be well controlled to exploit highly efficient phosphine sulfide-based hosts.
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http://dx.doi.org/10.3390/molecules26134079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271492PMC
July 2021

Machine Learning to Predict Quasicrystals from Chemical Compositions.

Adv Mater 2021 Jul 19:e2102507. Epub 2021 Jul 19.

The Institute of Statistical Mathematics, Research Organization of Information and Systems, Tachikawa, 190-8562, Japan.

Quasicrystals have emerged as the third class of solid-state materials, distinguished from periodic crystals and amorphous solids, which have long-range order without periodicity exhibiting rotational symmetries that are disallowed for periodic crystals in most cases. To date, more than one hundred stable quasicrystals have been reported, leading to the discovery of many new and exciting phenomena. However, the pace of the discovery of new quasicrystals has lowered in recent years, largely owing to the lack of clear guiding principles for the synthesis of new quasicrystals. Here, it is shown that the discovery of new quasicrystals can be accelerated with a simple machine-learning workflow. With a list of the chemical compositions of known stable quasicrystals, approximant crystals, and ordinary crystals, a prediction model is trained to solve the three-class classification task and its predictability compared to the observed phase diagrams of ternary aluminum systems is evaluated. The validation experiments strongly support the superior predictive power of machine learning, with the overall prediction accuracy of the phase prediction task reaching ≈0.728. Furthermore, analyzing the input-output relationships black-boxed into the model, nontrivial empirical equations interpretable by humans that describe conditions necessary for stable quasicrystal formation are identified.
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http://dx.doi.org/10.1002/adma.202102507DOI Listing
July 2021

Racial differences in anxiety, depression, and quality of life in women with polycystic ovary syndrome.

F S Rep 2021 Jun 13;2(2):230-237. Epub 2021 Mar 13.

Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Objective: To evaluate racial differences in the anxiety and depression prevalence and scores in women with polycystic ovary syndrome (PCOS).

Design: Cross-sectional.

Setting: Academic institution.

Patients: Reproductive-aged women with PCOS (n = 272) and controls (n = 295).

Interventions: Hospital anxiety and depression scale and modified PCOS quality-of-life survey (MPCOS-Q).

Main Outcome Measures: Differences in depression and anxiety scores and quality-of-life score measured using the hospital anxiety and depression scale and MPCOS-Q were determined between White and Black women with PCOS. Multivariable correlation regressions assessed the association of the Ferriman-Gallwey score, total testosterone, body mass index (BMI), and homeostatic model assessment of insulin resistance with anxiety, depression, and quality-of-life scores.

Results: Multivariable regression controlling for age, BMI, and socioeconomic status showed that White women with PCOS had a significantly higher prevalence of anxiety than Black women with PCOS (75.9% vs. 61.3%) and significantly higher anxiety scores (mean ± SD, 10.3 ± 4.1 vs. 8.7 ± 4.6). The prevalence of depression (24.4% vs. 29%) and depression scores (4.8 ± 3.6 vs. 5.1 ± 4.0) was not significantly different. In multivariable correlation regressions, the interaction between BMI and race in its association with anxiety scores was significant. The association of race with Ferriman-Gallwey score, total testosterone, or homeostatic model assessment of insulin resistance was not significant. In multivariable models, although the total MPCOS-Q scores were similar, the infertility domain was significantly lower in Black women with PCOS (mean ± SD, 12.6 ± 7.8 vs. 17.5 ± 6.8) indicating a lower quality of life related to infertility.

Conclusion: Racial differences identified in the prevalence of anxiety and MPCOS-Q domains suggest the importance of routine screening and provide an opportunity for targeted interventions based on race.
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http://dx.doi.org/10.1016/j.xfre.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267396PMC
June 2021

Protective effects of notoginsenoside R1 on acute lung injury in rats with sepsis.

Ann Transl Med 2021 Jun;9(12):996

Southwest Medical University, Luzhou, China.

Background: To clarify the mechanism of notoginsenoside R1 in the treatment of septic acute lung injury (ALI) based on network pharmacological analysis, and to verify it in the model of septic ALI in rats.

Methods: Based on database searching, the related targets of notoginsenoside R1 and ALI were identified, and the component-disease-target network was constructed. The core targets were screened by protein-protein interaction (PPI), and the functional enrichment of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was analyzed. The rat model of septic ALI was further established to investigate the pharmacological effects of notoginsenoside R1.

Results: Notoginsenoside R1 possibly affected ALI through 150 targets, of which 36 were core targets. GO semantic similarity analysis showed that notoginsenoside R1 might play a role in regulating interleukin 17 (IL-17) signal pathway, tumor necrosis factor (TNF) signal pathway and other key links by regulating MAPK1, MAPK3, IL-1β and other targets. The results of pharmacological experiments showed that notoginsenoside R1 could significantly reduce the wet:dry ratio of the lung in an animal model of ALI, improve the pathological injury of the lung, and reduce the content of IL-1β in serum and in bronchoalveolar lavage fluid (BALF) of experimental animals.

Conclusions: Notoginsenoside R1 can inhibit pulmonary edema, reduce inflammation, and improve lung lesions through multiple targets and pathways to achieve the pharmacological effects in the treatment of septic ALI.
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http://dx.doi.org/10.21037/atm-21-2496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267269PMC
June 2021

Host Gasdermin D restrains systemic endotoxemia by capturing Proteobacteria in the colon of high-fat diet-feeding mice.

Gut Microbes 2021 Jan-Dec;13(1):1946369

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Gasdermin D (GSDMD) functions as a key pyroptotic executor through its secreted N-terminal domain (GSDMD-N). However, the functional relevance and mechanistic basis of the precise roles of host colonic GSDMD in high-fat diet (HFD)-induced gut dysbiosis and systemic endotoxemia remain elusive. In this study, we demonstrate that HFD feeding triggers GSDMD-N secretion of both T-lymphocytes and enterocytes in mouse colons. GSDMD deficiency aggravates HFD-induced systemic endotoxemia, gut barrier impairment, and colonic inflammation. More importantly, active GSDMD-N kills the phylum via directly interacting with Cardiolipin. Mechanistically, we identify that the Glu236 (a known residue for GSDMD protein cleavage) is a important site for the bacterial recognition of GSDMD. Collectively, our findings explain the mechanism by which colonic GSDMD-N maintains low levels of HFD-induced metabolic endotoxemia. A GSDMD-N mimetic containing an exposed Glu236 site could be an attractive strategy for the treatment of HFD-induced metabolic endotoxemia.
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http://dx.doi.org/10.1080/19490976.2021.1946369DOI Listing
July 2021

ADAR2 increases in exercised heart and protects against myocardial infarction and doxorubicin-induced cardiotoxicity.

Mol Ther 2021 Jul 15. Epub 2021 Jul 15.

Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai 200444, China; Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, China. Electronic address:

Exercise training benefits the heart. The knowledge of post-transcription regulation, especially RNA editing, in the hearts remain rare. ADAR2 is an enzyme that edits adenosine to inosine nucleotides in double strand RNA, and RNA editing is associated with many human diseases. We found that ADAR2 was up-regulated in the hearts during exercise training. AAV9-mediated cardiac specific ADAR2 overexpression attenuated acute myocardial infarction (AMI), MI remodeling and doxorubicin-induced cardiotoxicity. In vitro, overexpression of ADAR2 inhibited doxorubicin-induced cardiomyocyte apoptosis but could also induce neonatal rat cardiomyocyte proliferation. Mechanistically, ADAR2 could regulate the abundance of mature miR-34a in cardiomyocytes. Regulations of miR-34a or its target genes (Sirt1, Cyclin D1, and Bcl2) could affect the pro-proliferation and anti-apoptosis effects of ADAR2 on cardiomyocyte. These data demonstrated that exercise-induced ADAR2 protects the heart from MI and doxorubicin-induced cardiotoxicity. Our work suggests that ADAR2 overexpression or a post-transcriptional associated RNA editing via ADAR2 might be a promising therapeutic strategy for heart diseases.
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http://dx.doi.org/10.1016/j.ymthe.2021.07.004DOI Listing
July 2021

Finite-Time Estimation for Markovian BAM Neural Networks With Asymmetrical Mode-Dependent Delays and Inconstant Measurements.

IEEE Trans Neural Netw Learn Syst 2021 Jul 16;PP. Epub 2021 Jul 16.

The issue of finite-time state estimation is studied for discrete-time Markovian bidirectional associative memory neural networks. The asymmetrical system mode-dependent (SMD) time-varying delays (TVDs) are considered, which means that the interval of TVDs is SMD. Because the sensors are inevitably influenced by the measurement environments and indirectly influenced by the system mode, a Markov chain, whose transition probability matrix is SMD, is used to describe the inconstant measurement. A nonfragile estimator is designed to improve the robustness of the estimator. The stochastically finite-time bounded stability is guaranteed under certain conditions. Finally, an example is used to clarify the effectiveness of the state estimation.
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http://dx.doi.org/10.1109/TNNLS.2021.3094551DOI Listing
July 2021
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