Publications by authors named "Juan Zhao"

671 Publications

Composition and Functional Characteristics and Influencing Factors of Bacterioplankton Community in the Huangshui River, China.

Microorganisms 2021 Oct 29;9(11). Epub 2021 Oct 29.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.

Bacterial community plays a key role in environmental and ecological processes of river ecosystems. Given the special climatic and geographical conditions, studying the compositional characteristics of microorganisms in highland rivers and the relationship between such microorganisms and water physicochemical factors is important for an in-depth understanding of microbial ecological mechanisms. In the present study, high-throughput sequencing was used to investigate and study the bacterioplankton community of the Huangshui River in the ecotone zone of the Qinghai Plateau and Loess Plateau. The results showed that the Huangshui River had significantly lower alpha diversity than the plain rivers. Despite the similarity in their environmental conditions, the main taxonomic compositions of the bacterial communities were distinct between the Huangshui River and polar regions (the Arctic and Antarctica). Proteobacteria accounted for the largest proportion (30.79-99.98%) of all the sequences, followed by Firmicutes (0-49.38%). was the most numerous genera, which accounted for 0.03-86.16% of the assigned 16S reads, followed by (0-95.9%), both belonging to Alphaproteobacteria. The diverse taxa of potential pathogens, such as Acinetobacter, Pseudomonas, and Aeromonas, were also identified. A principal coordinates analysis, coupled with a canonical correspondence analysis, showed spatial variations in the bacterial community composition. The water physical properties (e.g., Cr, total phosphorus, and COD); altitude; and land use (e.g., urban land cover and aquaculture) determined the distribution of the bacterioplankton composition. PICRUSt2 revealed that the overall functional profiles of the bacterial communities in different samples were similar, and our results suggested the potential health risks of water sources in this area. This work provided valuable insight into the composition of the plankton bacterial community and its relationship with the environmental factors in the Huangshui River in the ecotone zone of the Qinghai Plateau and Loess Plateau and a theoretical foundation for ecological health management.
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http://dx.doi.org/10.3390/microorganisms9112260DOI Listing
October 2021

Genome-Wide Identification of Reference Genes for Reverse-Transcription Quantitative PCR in Goat Rumen.

Animals (Basel) 2021 Nov 2;11(11). Epub 2021 Nov 2.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

As the largest chamber of the ruminant stomach, the rumen not only serves as the principal absorptive surface and nutrient transport pathway from the lumen into the animal, but also plays an important short-chain fatty acid (SCFA) metabolic role in addition to protective functions. Accurate characterization of the gene expression profiles of genes of interest is essential to the exploration of the intrinsic regulatory mechanisms of rumen development in goats. Thus, the selection of suitable reference genes (RGs) is an important prerequisite for real-time quantitative PCR (RT-qPCR). In the present study, 16 candidate RGs were identified from our previous transcriptome sequencing of caprine rumen tissues. The quantitative expressions of the candidate RGs were measured using the RT-qPCR method, and the expression stability of the RGs was assessed using the geNorm, NormFinder, and BestKeeper programs. GeNorm analysis showed that the M values were less than 0.5 for all the RGs except , indicating that they were stably expressed in the rumen tissues throughout development. and were the two most stable RGs. Furthermore, the expressions of two randomly selected target genes (1 and ), normalized by the selected most stable RGs ( and ), were consistent with the results of RNA sequencing, while the use of and as RGs resulted in altered profiles. Overall, and showed the highest expression stability and the lowest coefficients of variation, and could be used as the optimal reference combination for quantifying gene expression in rumen tissues via RT-qPCR analysis.
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http://dx.doi.org/10.3390/ani11113137DOI Listing
November 2021

A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome.

BMC Med Genomics 2021 Nov 22;14(1):277. Epub 2021 Nov 22.

Department of Otolaryngology, The PLA Rocket Force Characteristic Medical Center, 16# XinWai Da Jie, Beijing, 100088, People's Republic of China.

Mutations in the Forkhead Box C1 (FOXC1) are known to cause autosomal dominant hereditary Axenfeld-Rieger syndrome, which is a genetic disorder characterized by ocular and systemic features including glaucoma, variable dental defects, craniofacial dysmorphism and hearing loss. Due to late-onset of ocular disorders and lack of typical presentation, clinical diagnosis presents a huge challenge. In this study, we described a pathogenic in-frame variant in FOXC1 in one 5-year-old boy who is presented with hypertelorism, pupil deformation in both eyes, conductive hearing loss, and dental defects. By whole exome sequencing, we identified a 3 bp deletion in FOXC1, c.516_518delGCG (p.Arg173del) as the disease-causing variant, which was de novo and not detected in the parents, and could be classified as a "pathogenic variant" according to the American College of Medical Genetics and Genomics guidelines. After confirmation of this FOXC1 variant, clinical data on Axenfeld-Rieger syndrome-associated clinical features were collected and analyzed. Furthermore, Although the affected individual present hearing loss, however, the hearing loss is conductive and is reversible during the follow-up, which might not linke to the FOXC1 variant and is coincidental. Routine examination of FOXC1 is necessary for the genetic diagnosis of hypertelorism-associated syndrome. These findings may assist clinicians in reaching correct clinical and molecular diagnoses, and providing appropriate genetic counseling.
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http://dx.doi.org/10.1186/s12920-021-01130-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609746PMC
November 2021

LINC00665 Targets miR-214-3p/MAPK1 Axis to Accelerate Hepatocellular Carcinoma Growth and Warburg Effect.

J Oncol 2021 10;2021:9046798. Epub 2021 Nov 10.

Department of Gastroenterrology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201100, China.

Inhibition of aerobic glycolysis is a hopeful method for cancer treatment. In this study, we aimed to explore LINC00665/miR-214-3p/MAPK1 role in regulating cell viability and aerobic glycolysis in hepatocellular carcinoma (HCC). The expressions of LINC00665 in 50 paired HCC tissues and normal tissues were determined by qRT-PCR. Pearson analysis was applied to evaluate the association between the expression levels of miR-214-3p, LINC00665, and MAPK1 in HCC tissues. The interactions between miR-214-3p and LINC00665 or MAPK1 were determined by luciferase reporter assay and RNA immunoprecipitation. CCK-8 and colony formation assays were used for cell viability evaluation. Lactate production, glucose consumption, and ATP levels were measured to assess Warburg effect. The results showed that LINC00665 was overexpressed in HCC, which positively associated with MAPK1 level and negatively associated with miR-214-3p level in HCC tissues. Overexpression of LINC00665 led to significant enhancements in cell viability and colony formation, whereas this effect was weakened when miR-214-3p was overexpressed or MAPK1 was downregulated. In addition, deletion of LINC00665 expression repressed tumor formation . Mechanically, LINC00665 increased MAPK1 expression through binding to miR-214-3p. Collectively, this study revealed that LINC00665 accelerated cell growth and Warburg effect through sponging miR-214-3p to increase MAPK1 expression in HCC.
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http://dx.doi.org/10.1155/2021/9046798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8598336PMC
November 2021

Gene Pathogenic Variants in Chinese Twin Boys With Epidermolysis Bullosa Simplex.

Front Genet 2021 5;12:729628. Epub 2021 Nov 5.

Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China.

The aim of this study was to determine the molecular etiology and clinical manifestations of a pair of Chinese twins affected with epidermolysis bullosa simplex. Pediatricians should pay attention to the early genetic diagnosis of this disease. Histopathological examination of HE-stained skin, electron microscopy of biopsied normal skin, and whole-exome sequencing was performed to assess pathogenicity and conservation of detected mutations. Two years later, the cutaneous and extracutaneous manifestations of the twins were comprehensively evaluated. pathogenic variant c.2T>C (p.M1T) in (NM_017,644) was identified in both twins. The characteristics of extensive skin defects on the extremities at birth and the tendency to lesson with increasing age were confirmed. No positive sensitive markers, such as B-type natriuretic peptide, cardiac troponin I, for cardiac dysfunction were detected. The pathogenic variants c.2T>C (p.M1T) in (NM_017,644) contributes to the development of epidermolysis bullosa. Genetic diagnosis at birth or early infancy can better predict the disease prognosis and guide the treatment.
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http://dx.doi.org/10.3389/fgene.2021.729628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602111PMC
November 2021

Modification of the effect of maturity variation on nondestructive detection of apple quality based on the compensation model.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 11:120598. Epub 2021 Nov 11.

Northwest A&F University, College of Mechanical and Electronic Engineering, Yangling, Shaanxi 712100, China; Key Laboratory of Agricultural Internet of Things, Ministry of Agriculture and Rural Affairs, Yangling, Shaanxi 712100, China; Shaanxi Key Laboratory of Agricultural Information Perception and Intelligent Service, Yangling, Shaanxi 712100, China. Electronic address:

In this study, the effect of maturity variation on the prediction of the soluble solids content (SSC) and firmness of apples was determined using visible and near-infrared spectroscopy. In 2018, 520 apples from six ripening stages were collected. The single maturity model and multi-maturity model of SSC and firmness were established using partial least-squares regression. Apples at the same and different maturity stages were used to verify the developed model. Whereas the single maturity model was affected by maturity variation, the multi-maturity model could accurately predict the SSC and firmness of apples at different maturity stages. The multi-maturity model developed based on six maturity calibration sets had the best predictive performance. The root mean square error of prediction (RMSEP) of SSC and firmness was 0.614-0.802 °Brix and 0.402-0.650 kg/cm, respectively. The long-term performance of the optimal multi-maturity model was evaluated using validation sets. The predictive performance was decreased and the RMSEP increased when the model was used to predict the SSC and firmness of apples in different seasons. The predictive performance of the model was improved after slope/bias (S/B) correction, and the RMSEP of SSC and firmness decreased to 0.405-0.587°Brix and 0.518-0.628 kg/cm respectively. Overall, the multi-maturity model eliminated the effect of maturity variation, and the multi-maturity model coupled with S/B correction permitted the rapid and accurate detection of the SSC and firmness of apples at different maturity stages and in different seasons.
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http://dx.doi.org/10.1016/j.saa.2021.120598DOI Listing
November 2021

Developing a scale measuring the doctor-patient relationship in China from the perspective of doctors.

Fam Pract 2021 Nov 13. Epub 2021 Nov 13.

Department of Social Medicine, School of Health Management, Harbin Medical University, Nangang District, Harbin, Heilongjiang, China.

Objectives: The doctor-patient relationship is usually measured in line with patient needs and demands. This study aimed to develop a scale measuring such a relationship from the perspective of doctors.

Methods: A draft scale was developed and adapted to the hospital context of China based on several existing scales, with an intention to measure how medical doctors view and manage their relationship with patients beyond episodic clinical encounters. Two rounds of Delphi consultations involving 14 experts were conducted to seek their consensus on the inclusion and descriptions of items. This resulted in a 19-item scale measuring four domains of the relationship. The scale was validated through a survey of 1,712 medical doctors selected from 27 public hospitals in Heilongjiang province of China. The internal consistency of the scale was assessed using Cronbach's α coefficients of the four domains. Confirmatory factor analyses were performed to test the construct validity of the scale. Linear regression analyses were performed to assess the known-group validity of the scale.

Results: The scale measures four domains. The Cronbach's α of the scale reached an acceptable level, ranging from 0.61 to 0.78 for its four domains. Good fitness of data into the four-domain structure of the scale was confirmed by the confirmatory factor analysis. Known-group differences were demonstrated in the regression analyses.

Conclusion: The doctor-patient relationship scale developed in this study is a psychometrically valid tool assessing how medical doctors view and manage their relationship with patients in the hospital setting in China.
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http://dx.doi.org/10.1093/fampra/cmab142DOI Listing
November 2021

Application of topical gentamicin-a new era in the treatment of genodermatosis.

World J Pediatr 2021 Nov 17. Epub 2021 Nov 17.

China National Clinical Research Center for Respiratory Diseases, Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 South Li Shi Road, Xi Cheng District, Beijing, 100045, China.

Background: The clinical use of gentamicin always lies in its antimicrobial activity in the past as an aminoglycoside antibiotic. However, in the past decade, there were considerable interests in therapeutic approaches in treating hereditary diseases. Some of the genodermatosis is caused by nonsense mutations that create premature termination codons and lead to the production of truncated or non-functional proteins. Gentamicin could induce readthrough of nonsense mutations and enable the synthesis of full-length proteins. We focus on previous publications on topical application of gentamicin and review its utility in genetic skin diseases.

Data Sources: We search the MEDLINE through PubMed, EMBASE databases, and the Clinical Trials Registry Platform from January 1960 to July 2020 using the key search terms "gentamicin, topical gentamicin, genodermatosis, genetic skin diseases".

Results: The application of gentamicin in genodermatosis yielded promising results, both in vivo and in vitro, including Nagashima-type palmoplantar keratosis, epidermolysis bullosa, Hailey-Hailey disease, hereditary hypotrichosis simplex of the scalp, etc. CONCLUSIONS: Topical gentamicin is a potential treatment option for genodermatosis caused by nonsense mutation.
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http://dx.doi.org/10.1007/s12519-021-00469-2DOI Listing
November 2021

Microencapsulation of Osmanthus essential oil by interfacial polymerization: Optimization, characterization, release kinetics, and storage stability of essential oil from microcapsules.

J Food Sci 2021 Nov 10. Epub 2021 Nov 10.

Key Laboratory of Food Nutrition and Safety, Ministry of Education, Tianjin University of Science and Technology, Tianjin, P. R. China.

In this paper, the interface polymerization method was used to prepare Osmanthus essential oil microcapsules. The optimal preparation process of Osmanthus essential oil microcapsules was explored as follows: the dosage ratio of Osmanthus essential oil to N100 was 6:1, the reaction temperature was 70°C, and the reaction time was 2 h. The encapsulation efficiency of Osmanthus essential oil microcapsules could reach 80.31%. The particle size distribution, morphology, chemical structure, and thermal stability of the obtained microcapsules were characterized by laser particle size analyzer, scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The release kinetics and storage stability experiments of the microcapsules were studied. The results showed that the average volume diameter of the microcapsules was 101.2 µm. The microcapsules were in the shape of full spheres, with a smooth surface, low viscosity, and high elasticity. Microencapsulation improved the thermal stability of Osmanthus essential oil and promoted the slow release of essential oil. The synthesized microcapsules showed good storage stability under refrigerated and dark conditions, which indicated that microcapsules had broad application prospects in food, medicine, and other fields. PRACTICAL APPLICATION: In this study, we prepared a polyurea membrane to encapsulate Osmanthus essential oil microcapsules by interfacial polymerization. The encapsulation conditions of the microcapsules were optimized and the structure of the microcapsules was characterized in this study. The results showed that microcapsules had a full spherical shape with a smooth surface, high elasticity, good sustained-release ability, good thermal stability, and storage stability. These properties indicated that microcapsules have good application prospects and can be used as a high-quality flavor with a long residual effect and high thermal stability for food and cosmetic scope.
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http://dx.doi.org/10.1111/1750-3841.15943DOI Listing
November 2021

Adipose tissue spexin in physical exercise and age-associated diseases.

Ageing Res Rev 2021 Nov 6;73:101509. Epub 2021 Nov 6.

Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, China. Electronic address:

It is known that a strong association exists between a suboptimal lifestyle (physical inactivity and sedentary behavior and/or high calorie diet) and increased propensity of developing age-associated diseases, such as obesity and T2DM. Physical exercise can alleviate obesity-induced insulin resistance and T2DM, however, the precise mechanism for this outcome is not fully understood. The endocrine disorder of adipose tissue in obesity plays a critical role in the development of insulin resistance. In this regard, spexin has been recently described as an adipokine that plays an important role in the pathophysiology of obesity-induced insulin resistance and T2DM. In obese states, expression of adipose tissue spexin is reduced, inducing the adipose tissue and skeletal muscle more susceptible to insulin resistance. Emerging evidences point out that exercise can increase spexin expression. In return, spexin could exert the exercise-protective roles to ameliorate insulin resistance, suggesting that spexin is a potential mediator for exercise to ameliorate obesity-induced insulin resistance and T2DM, namely, the beneficial effect of exercise on insulin sensitivity is at least partly mediated by spexin. This review summarizes our and others' recent studies regarding the effects of obesity on adipose tissue spexin induction, along with the potential effect of exercise on this response in obese context, and provides a new insight into the multivariate relationship among exercise, spexin and T2DM. It should be therefore taken into account that a combination of spexin and exercise training is an effective therapeutic strategy for age-associated diseases.
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http://dx.doi.org/10.1016/j.arr.2021.101509DOI Listing
November 2021

Selective oxidative stress induces dual damage to telomeres and mitochondria in human T cells.

Aging Cell 2021 Nov 9:e13513. Epub 2021 Nov 9.

Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA.

Oxidative stress caused by excess reactive oxygen species (ROS) accelerates telomere erosion and mitochondrial injury, leading to impaired cellular functions and cell death. Whether oxidative stress-mediated telomere erosion induces mitochondrial injury, or vice versa, in human T cells-the major effectors of host adaptive immunity against infection and malignancy-is poorly understood due to the pleiotropic effects of ROS. Here we employed a novel chemoptogenetic tool that selectively produces a single oxygen ( O ) only at telomeres or mitochondria in Jurkat T cells. We found that targeted O production at telomeres triggered not only telomeric DNA damage but also mitochondrial dysfunction, resulting in T cell apoptotic death. Conversely, targeted O formation at mitochondria induced not only mitochondrial injury but also telomeric DNA damage, leading to cellular crisis and apoptosis. Targeted oxidative stress at either telomeres or mitochondria increased ROS production, whereas blocking ROS formation during oxidative stress reversed the telomeric injury, mitochondrial dysfunction, and cellular apoptosis. Notably, the X-ray repair cross-complementing protein 1 (XRCC1) in the base excision repair (BER) pathway and multiple mitochondrial proteins in other cellular pathways were dysregulated by the targeted oxidative stress. By confining singlet O formation to a single organelle, this study suggests that oxidative stress induces dual injury in T cells via crosstalk between telomeres and mitochondria. Further identification of these oxidation pathways may offer a novel approach to preserve mitochondrial functions, protect telomere integrity, and maintain T cell survival, which can be exploited to combat various immune aging-associated diseases.
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http://dx.doi.org/10.1111/acel.13513DOI Listing
November 2021

Arabidopsis P4 ATPase-mediated cell detoxification confers resistance to Fusarium graminearum and Verticillium dahliae.

Nat Commun 2021 11 5;12(1):6426. Epub 2021 Nov 5.

The Affiliation Biotechnology Research Center, Southwest University, No. 2 Tiansheng Rd, Beibei, Chongqing, 400716, P. R. China.

Many toxic secondary metabolites produced by phytopathogens can subvert host immunity, and some of them are recognized as pathogenicity factors. Fusarium head blight and Verticillium wilt are destructive plant diseases worldwide. Using toxins produced by the causal fungi Fusarium graminearum and Verticillium dahliae as screening agents, here we show that the Arabidopsis P4 ATPases AtALA1 and AtALA7 are responsible for cellular detoxification of mycotoxins. Through AtALA1-/AtALA7-mediated vesicle transport, toxins are sequestered in vacuoles for degradation. Overexpression of AtALA1 and AtALA7 significantly increases the resistance of transgenic plants to F. graminearum and V. dahliae, respectively. Notably, the concentration of deoxynivalenol, a mycotoxin harmful to the health of humans and animals, was decreased in transgenic Arabidopsis siliques and maize seeds. This vesicle-mediated cell detoxification process provides a strategy to increase plant resistance against different toxin-associated diseases and to reduce the mycotoxin contamination in food and feed.
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http://dx.doi.org/10.1038/s41467-021-26727-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571369PMC
November 2021

RLB (RICE LATERAL BRANCH) recruits PRC2-mediated H3K27 tri-methylation on OsCKX4 to regulate lateral branching.

Plant Physiol 2021 Nov 3. Epub 2021 Nov 3.

State Key Lab of Rice Biology, China National Rice Research Institute, Hangzhou 311400, China.

Lateral branches such as shoot and panicle are determining factors and target traits for rice (Oryza sativa L.) yield improvement. Cytokinin promotes rice lateral branching; however, the mechanism underlying the fine-tuning of cytokinin homeostasis in rice branching remains largely unknown. Here, we report the map-based cloning of RLB (RICE LATERAL BRANCH) encoding a nuclear-localized, KNOX-type homeobox protein from a rice cytokinin-deficient mutant showing more tillers, sparser panicles, defected floret morphology as well as attenuated shoot regeneration from callus. RLB directly binds to the promoter and represses the transcription of OsCKX4, a cytokinin oxidase gene with high abundance in panicle branch meristem. OsCKX4 over-expression lines phenocopied rlb which showed up-regulated OsCKX4 levels. Meanwhile, RLB physically binds to Polycomb repressive complex 2 (PRC2) component OsEMF2b and co-localized with H3K27me3, a suppressing histone modification mediated by PRC2, in the OsCKX4 promoter. We proposed that RLB recruits PRC2 to the OsCKX4 promoter to epigenetically repress its transcription, which suppresses the catabolism of cytokinin, thereby promoting rice lateral branching. Moreover, antisense inhibition of OsCKX4 under the LOG promoter successfully increased panicle size and spikelet number per plant without affecting other major agronomic traits. The current study provides insight into cytokinin homeostasis, lateral branching in plants, and also promising target genes for rice genetic improvement.
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http://dx.doi.org/10.1093/plphys/kiab494DOI Listing
November 2021

RLB (RICE LATERAL BRANCH) recruits PRC2-mediated H3K27 tri-methylation on OsCKX4 to regulate lateral branching.

Plant Physiol 2021 Nov 3. Epub 2021 Nov 3.

State Key Lab of Rice Biology, China National Rice Research Institute, Hangzhou 311400, China.

Lateral branches such as shoot and panicle are determining factors and target traits for rice (Oryza sativa L.) yield improvement. Cytokinin promotes rice lateral branching; however, the mechanism underlying the fine-tuning of cytokinin homeostasis in rice branching remains largely unknown. Here, we report the map-based cloning of RLB (RICE LATERAL BRANCH) encoding a nuclear-localized, KNOX-type homeobox protein from a rice cytokinin-deficient mutant showing more tillers, sparser panicles, defected floret morphology as well as attenuated shoot regeneration from callus. RLB directly binds to the promoter and represses the transcription of OsCKX4, a cytokinin oxidase gene with high abundance in panicle branch meristem. OsCKX4 over-expression lines phenocopied rlb which showed up-regulated OsCKX4 levels. Meanwhile, RLB physically binds to Polycomb repressive complex 2 (PRC2) component OsEMF2b and co-localized with H3K27me3, a suppressing histone modification mediated by PRC2, in the OsCKX4 promoter. We proposed that RLB recruits PRC2 to the OsCKX4 promoter to epigenetically repress its transcription, which suppresses the catabolism of cytokinin, thereby promoting rice lateral branching. Moreover, antisense inhibition of OsCKX4 under the LOG promoter successfully increased panicle size and spikelet number per plant without affecting other major agronomic traits. The current study provides insight into cytokinin homeostasis, lateral branching in plants, and also promising target genes for rice genetic improvement.
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http://dx.doi.org/10.1093/plphys/kiab494DOI Listing
November 2021

Chondroitin sulfate-mediated albumin corona nanoparticles for the treatment of breast cancer.

Asian J Pharm Sci 2021 Jul 20;16(4):508-518. Epub 2021 Apr 20.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy, Sichuan University, Chengdu, 610064, China.

Chondroitin sulfate-mediated albumin corona nanoparticles were readily prepared without any chemical reaction, and their active tumor targeting and therapeutic effects were examined. Negatively charged chondroitin sulfate (CS) and positively charged doxorubicin (DOX) self-assembled into nanoparticles (CS-DOX-NPs) via electrostatic interactions. Bovine serum albumin (BSA) was then adsorbed on the surface of CS-DOX-NPs to form albumin corona nanoparticles (BC-DOX-NPs) protected from endogenous proteins. Due to the dual effect of BSA and CS, BC-DOX-NPs interacted with the gp60, SPARC and CD44 receptors on tumor cells, facilitating their rapid and efficient transcytosis and improving their accumulation and uptake within tumor tissues. The simultaneous presence of BSA and CS also allowed BC-DOX-NPs to target CD44 efficiently, leading to greater cellular uptake and cytotoxicity against 4T1 cells than CS-DOX-NPs or free DOX. Intravenous injection of BC-DOX-NPs into orthotopic 4T1 tumor-bearing mice led to greater drug accumulation at the tumor site than with CS-DOX-NPs or free DOX, resulting in significant inhibition of tumor growth and lower exposure of major organs to the drug.
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http://dx.doi.org/10.1016/j.ajps.2021.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520051PMC
July 2021

Ultrafast Structure and Vibrational Dynamics of a Cyano-Containing Non-Fullerene Acceptor for Organic Solar Cells Revealed by Two-Dimensional Infrared Spectroscopy.

J Phys Chem B 2021 Nov 21;125(43):11987-11995. Epub 2021 Oct 21.

Beijing National Laboratory for Molecular Sciences, Chinese Academy of Sciences, Beijing 100190, P. R. China.

Non-fullerene molecules, such as ITIC (3,9-bis(2-methylene-(3-(1,1-dicyanomethylene) indanone)-5,5,11,11-tetrakis(4-hexylphenyl)dithieno[2,3-:2',3'-']--indaceno[1,2-:5,6-']-dithiophene), are among the most promising non-fullerene acceptors for organic solar cells (OSCs). In this work, using the cyano stretching mode as a vibrational marker, the structural and vibrational energy dynamics of ITIC were examined on an ultrafast time scale with two-dimensional infrared spectroscopy. Two IR-active modes studied here mainly correspond to two anti-symmetric combinations of symmetric and asymmetric stretching vibrations of two C≡N modes originating from two -C(CN) chromophores that are located across the ITIC system, which were found to have significantly larger off-diagonal anharmonicity than their corresponding diagonal anharmonicities. This indicates strong anharmonic vibrational coupling between the two modes, which is supported by ab initio anharmonic frequency computations. Transient IR results indicate picosecond intramolecular vibrational energy transfer between the two C≡N modes upon excitation. The structural basis for these vibrational and energetic features is the conjugating molecular frame that is composed of a network of single/double bonds connecting the two -C(CN) chromophores and may enable efficient vibration delocalization, in addition to its well-known electron delocalization capability. The importance of the results for the OSC applications is discussed.
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http://dx.doi.org/10.1021/acs.jpcb.1c04758DOI Listing
November 2021

Biocontrol Potential of Trichoderma afroharzianum TM24 Against Grey Mould on Tomato Plants.

Curr Microbiol 2021 Dec 20;78(12):4115-4126. Epub 2021 Oct 20.

Institute of Plant and Environment Protection, Beijing Academy of Agriculture and Forestry Sciences, Beijing, 100097, People's Republic of China.

Grey mould caused by Botrytis cinerea leads to severe economic loss on commercial tomato production. Application of beneficial microorganism offers an eco-friendly alternative for mitigation of tomato fungal disease damage, considering negative influences of fungicides. In the present study, an antagonistic Trichoderma afroharzianum isolate TM24 was evaluated for its biocontrol potential on tomato grey mould. The isolate TM24 showed obviously antagonistic effect on B. cinerea mycelium growth and production of glucanase and chitinase. Leaf spraying with spore suspension of isolate TM24 showed a biocontrol efficiency of over 54% against tomato grey mould in greenhouse pot experiment. The activities of plant defense-related enzymes including polyphenol oxidase, phenylalanine ammonialyase, superoxide dismutase, and peroxidase were all increased to varying degrees in tomato leaves after isolate TM24 treatment. Transcriptome analysis showed that, a total of 1941, 1753 and 38 differentially expressed genes (DEGs) were obtained at 24, 48 and 72 hpi, respectively, in tomato leaves pretreated with T. afroharzianum TM24, and then challenged with B. cinerea inoculation. The DEGs were mainly enriched in MAPK signaling pathway and plant hormones signal transduction pathway. Multiple genes that regulated crucial nodes of defense-related pathways, like flavonoid, phenylpropanoid, jasmonic acid and ethylene metabolisms were also identified, which may have positive correlations with the biocontrol potential of isolate TM24 in tomato plants. These promising results provided valuable information on using T. afroharzianum TM24 as a beneficial biocontrol agent in tomato grey mould management.
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http://dx.doi.org/10.1007/s00284-021-02671-xDOI Listing
December 2021

Optimization of Machine Online Translation System Based on Deep Convolution Neural Network Algorithm.

Authors:
Juan Zhao

Comput Intell Neurosci 2021 29;2021:7388825. Epub 2021 Sep 29.

School of Foreign Studies, North China University of Water Resources and Electric Power, Zhengzhou, Henan 450046, China.

In order to effectively optimize the machine online translation system and improve its translation efficiency and translation quality, this study uses the deep separable convolution neural network algorithm to construct a machine online translation model and evaluates the quality on the basis of pseudo data learning. In order to verify the performance of the model, the regression performance experiment of the model, the method performance experiment of generating pseudo data for specific tasks, the sorting task performance experiment of the model, and the machine translation quality comparison experiment are designed. RMSE and MAE were used to evaluate the regression task performance of the model. Spearman rank correlation coefficient and delta AVG value were used to evaluate the sorting task performance of the model. The experimental results show that the MAE and RMSE values of the model are decreased by 2.28% and 1.39%, respectively, compared with the baseline system under the same experimental conditions, and the Spearman and delta AVG values are increased by 132% and 100.7%, respectively, compared with the baseline system. The method of generating pseudo data for specific tasks needs less data and can make the translation system reach a better level faster. When the number of instances is more than 10, the quality score of the model output is higher than that of Google translation whose similarity is more than 0.8.
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http://dx.doi.org/10.1155/2021/7388825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494562PMC
October 2021

Identifying Potential Therapeutic Applications and Diagnostic Harms of Increased Bilirubin Concentrations: A Clinical and Genetic Approach.

Clin Pharmacol Ther 2021 Oct 8. Epub 2021 Oct 8.

Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Bilirubin has antioxidant and anti-inflammatory properties in vitro and in animal studies and protects against inflammatory, cardiovascular, and other diseases in observational studies; therefore, bilirubin has potential as a therapeutic agent. However, observational studies could be confounded by many factors. We used a genetic (n = 61,281) and clinical (n = 234,670) approach to define the association between bilirubin and 19 conditions with a putative protective signal in observational studies. We also tested if individuals with genetically higher bilirubin levels underwent more diagnostic tests. We used a common variant in UGT1A1 (rs6742078) associated with an 26% increase in bilirubin levels in the genetic studies. Carriers of the variant had higher bilirubin levels (P = 2.2 × 10 ) but there was no significant association with any of the 19 conditions. In a phenome-wide association study (pheWAS) to seek undiscovered genetic associations, the only significant finding was increased risk of "jaundice-not of newborn." Carriers of the variant allele were more likely to undergo an abdominal ultrasound (odds ratio = 1.04, [1.00-1.08], P = 0.03). In contrast, clinically measured bilirubin levels were significantly associated with 15 of the 19 conditions (P < 0.003) and with 431 clinical diagnoses in the pheWAS (P < 1 × 10 adjusted for sex, age, and follow-up). With additional adjustment for smoking and body mass index, 7 of 19 conditions and 260 pheWAS diagnoses remained significantly associated with bilirubin levels. In conclusion, bilirubin does not protect against inflammatory or other diseases using a genetic approach; the many putative beneficial associations reported clinically are likely due to confounding.
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http://dx.doi.org/10.1002/cpt.2441DOI Listing
October 2021

Melatonin enhances drought stress tolerance in maize through coordinated regulation of carbon and nitrogen assimilation.

Plant Physiol Biochem 2021 Oct 8;167:958-969. Epub 2021 Sep 8.

College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, 030800, China. Electronic address:

Melatonin is a pleiotropic regulatory molecule in plants and is involved in regulating plant tolerance to drought stress. Here, we conducted transcriptomic and physiological analyses to identify metabolic processes associated with the enhanced tolerance of the melatonin-treated maize (Zea mays L.) seedlings to water deficit. Maize seedlings were foliar sprayed with either 50 μM melatonin or water and exposed to drought stress for 12 d in growth chambers. Drought stress significantly suppressed seedling growth, and melatonin application partially alleviated this growth inhibition. RNA-Seq analysis revealed that genes whose expression was significantly altered by melatonin were mainly related to carbon (C) and nitrogen (N) metabolism. Analysis of transcriptomics, enzyme activity, and metabolite content data, melatonin-treated plants exhibited a higher level of relatively stable C and N metabolism than untreated plants; this phenotype of melatonin-treated plants was associated with their higher photosynthesis, sucrose biosynthesis, N assimilation, and protein biosynthesis capacities under drought stress. Overall, our results suggest that melatonin enhances drought stress tolerance in maize through coordinated regulation of C and N metabolism.
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http://dx.doi.org/10.1016/j.plaphy.2021.09.007DOI Listing
October 2021

Melatonin alleviates aluminum-induced growth inhibition by modulating carbon and nitrogen metabolism, and reestablishing redox homeostasis in Zea mays L.

J Hazard Mater 2022 Feb 12;423(Pt B):127159. Epub 2021 Sep 12.

College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi 030800, China. Electronic address:

Melatonin, a regulatory molecule, performs pleiotropic functions in plants, including aluminum (Al) stress mitigation. Here, we conducted transcriptomic and physiological analyses to identify metabolic processes associated with the alleviated Al-induced growth inhibition of the melatonin-treated (MT) maize (Zea mays L.) seedlings. Melatonin decreased Al concentration in maize roots and leaves under Al stress. Al stress reduced the total dry weight (DW) by 41.2% after 7 days of treatment. By contrast, the total DW was decreased by only 19.4% in MT plants. According to RNA-Seq, enzyme activity, and metabolite content data, MT plants exhibited a higher level of relatively stable carbon and nitrogen metabolism than non-treated (NT) plants. Under Al stress, MT plants showed higher photosynthetic rate and sucrose content by 29.9% and 20.5% than NT plants, respectively. Similarly, the nitrate reductase activity and protein content of MT plants were 34.0% and 15.0% higher than those of NT plants, respectively. Furthermore, exogenous supply of melatonin mitigated Al-induced oxidative stress. Overall, our results suggest that melatonin alleviates aluminum-induced growth inhibition through modulating carbon and nitrogen metabolism, and reestablishing redox homeostasis in maize. Graphical Abstarct.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127159DOI Listing
February 2022

A systematic review and meta-analysis of radical cystectomy in the treatment of muscular invasive bladder cancer (MIBC).

Transl Androl Urol 2021 Aug;10(8):3476-3485

Urology Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Background: A meta-analysis was conducted to evaluate the curative effect of radical cystectomy in the treatment of muscular invasive bladder cancer (MIBC).

Methods: Chinese and English databases were searched using free combinations of the terms "bladder cancer," "radical cystectomy," "muscle invasive bladder cancer," and "bladder preservation." Review Manager 5.3 software was used for the meta-analysis.

Results: A total of 12 articles were included in the meta-analysis, most of which had low-bias risk and were of medium and high quality. A funnel chart showed that the circles of some studies were basically symmetrical with the midline, suggesting that the research accuracy was high, the publications were not biased, and the final conclusions were credible. Twelve articles analyzed patients' 5-year survival rate in randomized controlled trials (RCTs). In these RCTs, the experimental group (expt group) comprised 775 cases and the control group (ctrl group) comprised 766 cases. A heterogeneity test using the fixed-effects model (FEM) showed Chi =2.19, df =11, I=0%, P=1.00>0.1, Z =2.57, odds ratio (OR) =1.30, 95% confidence interval (CI): 1.06-1.59, and P=0.01<0.05. 3 articles analyzed patients' 10-year survival rates in RCTs. These trials comprised a total of 417 patients (209 in the expt group and 208 in the ctrl group). The overall heterogeneity test showed Chi =0.40, df =2, I=0%, P=0.82>0.1, Z =1.42, OR =1.32, 95% CI: 0.90-1.94, and P=0.16>0.05. 6 articles analyzed 5-year distant metastasis rates (DMRs) in RCTs. The overall heterogeneity test showed Chi =1.68, df =5, I=0%, P=0.89>0.1, Z =1.70, OR =1.28, 95% CI: 0.96-1.71, and P=0.09>0.05).

Discussion: Our meta-analysis confirmed that radical cystectomy is effective in the treatment of MIBC and is worthy of clinical promotion.
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http://dx.doi.org/10.21037/tau-21-564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421829PMC
August 2021

The effect of the and mutations on the survival of hepatocellular carcinoma patients with different racial backgrounds.

J Gastrointest Oncol 2021 Aug;12(4):1786-1796

Department of Hepatobiliary Surgery/Research Laboratory of Hepatobiliary Tumor, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.

Background: Racial disparities in the survival of patients with hepatocellular carcinoma (HCC) exist. Gene mutations have a profound effect on carcinogenesis, are easily affected by environment and etiology factors, and may result in survival divergences among patients with different racial backgrounds. This report explores the effects of gene mutations on the survival of American Caucasians and Asian patients.

Methods: The sequencing and clinical data of 336 HCC patients were obtained from The Cancer Genome Atlas (TCGA) database. The sequencing data was subject to gene mutation profiling, and an analysis of immune cell infiltration was conducted. A multivariate analysis was performed to assess the independent effects of gene mutations on patients' overall survival (OS) and disease-free survival (DFS).

Results: Asian HCC patients had a significantly higher level of mutation frequency than Caucasian HCC patients (Asian Caucasian, 39% 23%; P=0.003). The mutation was associated with shorter OS [hazard ratio (HR), 2.33; 95% confidence interval (CI), 1.36-3.97; P=0.002] and DFS (HR, 2.2; 95% CI, 1.38-3.51; P<0.001) in Caucasian HCC patients, but had no effect on Asian HCC patients' survival. Compared to Asian HCC patients, Caucasian HCC patients with the mutation had a decreased proportion of infiltrating M2 macrophages and activating natural killer (NK) cells, and an increased proportion of follicular helper T cells. The mutation was associated with shorter OS (HR, 3.37; 95% CI, 1.73-6.57; P<0.001) in Asian HCC patients, and shorter DFS (HR, 2.11; 95% CI, 1.15-3.88; P=0.017) in Caucasian HCC patients. Asian HCC patients with the mutation had a decreased proportion of infiltrating CD8 T cells.

Conclusions: The effects of the and mutations on survival differ among Asian and Caucasian HCC patients.
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http://dx.doi.org/10.21037/jgo-21-312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421922PMC
August 2021

Prophylactic administration of recombinant human thrombopoietin attenuates XELOX or SOX regimen-induced thrombocytopaenia.

Arch Med Sci 2021 9;17(5):1440-1446. Epub 2021 Aug 9.

School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China.

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http://dx.doi.org/10.5114/aoms/141134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425230PMC
August 2021

American Heart Association Precision Medicine Platform Addresses Challenges in Data Sharing.

Circ Cardiovasc Qual Outcomes 2021 09 14;14(9):e007949. Epub 2021 Sep 14.

Quality, Outcomes Research and Analytics, American Heart Association, Dallas, TX (L.M.S., C.R., H.A., J.L.H.).

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http://dx.doi.org/10.1161/CIRCOUTCOMES.121.007949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452247PMC
September 2021

Emerging roles of kisspeptin/galanin in age-related metabolic disease.

Mech Ageing Dev 2021 10 10;199:111571. Epub 2021 Sep 10.

Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address:

Age is a major risk factor for developing metabolic diseases such as obesity and diabetes. There is an unprecedented rise in obesity and type 2 diabetes in recent decades. A convincing majority of brain-gut peptides are associated with a higher risk to develop metabolic disorders, and may contribute to the pathophysiology of age-related metabolic diseases. Accumulating basic studies revealed an intriguing role of kisspeptin and galanin involved in the amelioration of insulin resistance in different ways. In patients suffered from obesity and diabetes a significant, sex-related changes in the plasma kisspeptin and galanin levels occurred. Kisspeptin is anorexigenic to prevent obesity, its level is negatively correlative with obesity and insulin resistance. While galanin is appetitive to stimulate food intake and body weight, its level is positively correlative with obesity, HOMA-IR and glucose/triglyceride concentration. In turn, kisspeptin and galanin also distinctly increase glucose uptake and utilization as well as energy expenditure. This article reviews recent evidence dealing with the role of kisspeptin and galanin in the pathophysiology of age-related metabolic diseases. It should be therefore taken into account that the targeted modulation of those peptidergic signaling may be potentially helpful in the future treatment of age-related metabolic diseases.
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http://dx.doi.org/10.1016/j.mad.2021.111571DOI Listing
October 2021

Case Report: Complete Response of Primary Massive Hepatocellular Carcinoma to Anti-Programmed Death Ligand-1 Antibody Following Progression on Anti-Programmed Death-1 Antibody.

Front Immunol 2021 24;12:712351. Epub 2021 Aug 24.

Department of Biliary Surgery, Xiangya Hospital, Central South University, Changsha, China.

Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs due to chronic liver disease, and it has a high mortality rate and limited treatment options. Immune checkpoint inhibitors have been successfully introduced and used in cancer therapy, among which inhibitors of programmed death ligand-1 (PD-L1) and its receptor programmed death-1 (PD-1) are commonly administered for HCC as combination therapy, including combined anti-angiogenic and immunotherapy combination therapy. We report a case of a primary massive HCC patient with portal hepatic vein tumor thrombus who had a good response to atezolizumab in combination with bevacizumab, following progression of disease on combined immunotherapy with pembrolizumab and lenvatinib. This case demonstrates for the first time that an HCC patient who is resistant to anti-PD-1 antibody immunotherapy can benefit from anti-PD-L1 antibody immunotherapy, providing a potentially promising strategy for the treatment of HCC.
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http://dx.doi.org/10.3389/fimmu.2021.712351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422947PMC
August 2021

The Ubiquitin Sensor and Adaptor Protein p62 Mediates Signal Transduction of a Viral Oncogenic Pathway.

mBio 2021 Oct 7;12(5):e0109721. Epub 2021 Sep 7.

Department of Internal Medicine, Quillen College of Medicine, East Tennessee State Universitygrid.255381.8, Johnson City, Tennessee, USA.

The Epstein-Barr virus (EBV) protein LMP1 serves as a paradigm that engages complicated ubiquitination-mediated mechanisms to activate multiple transcription factors. p62 is a ubiquitin sensor and a signal-transducing adaptor that has multiple functions in diverse contexts. However, the interaction between p62 and oncogenic viruses is poorly understood. We recently reported a crucial role for p62 in oncovirus-mediated oxidative stress by acting as a selective autophagy receptor. In this following pursuit, we further discovered that p62 is upregulated in EBV type 3 compared to type 1 latency, with a significant contribution from NF-κB and AP1 activities downstream of LMP1 signaling. In turn, p62 participates in LMP1 signal transduction through its interaction with TRAF6, promoting TRAF6 ubiquitination and activation. As expected, short hairpin RNA (shRNA)-mediated knockdown (KD) of p62 transcripts reduces LMP1-TRAF6 interaction and TRAF6 ubiquitination, as well as p65 nuclear translocation, which was assessed by Amnis imaging flow cytometry. Strikingly, LMP1-stimulated NF-κB, AP1, and Akt activities are all markedly reduced in p62 mouse embryo fibroblasts (MEFs) and in EBV-negative Burkitt's lymphoma (BL) cell lines with CRISPR-mediated knockout (KO) of the p62-encoding gene. However, EBV-positive BL cell lines (type 3 latency) with CRISPR-mediated KO of the p62-encoding gene failed to survive. In consequence, shRNA-mediated p62 KD impairs the ability of LMP1 to regulate its target gene expression, promotes etoposide-induced apoptosis, and reduces the proliferation of lymphoblastic cell lines (LCLs). These important findings have revealed a previously unrecognized novel role for p62 in EBV latency and oncogenesis, which advances our understanding of the mechanism underlying virus-mediated oncogenesis. As a ubiquitin sensor and a signal-transducing adaptor, p62 is crucial for NF-κB activation, which involves the ubiquitin machinery, in diverse contexts. However, whether p62 is required for EBV LMP1 activation of NF-κB is an open question. In this study, we provide evidence that p62 is upregulated in EBV type 3 latency and, in turn, p62 mediates LMP1 signal transduction to NF-κB, AP1, and Akt by promoting TRAF6 ubiquitination and activation. In consequence, p62 deficiency negatively regulates LMP1-mediated gene expression, promotes etoposide-induced apoptosis, and reduces the proliferation of LCLs. These important findings identified p62 as a novel signaling component of the key viral oncogenic signaling pathway.
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http://dx.doi.org/10.1128/mBio.01097-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546576PMC
October 2021

Percutaneous Intracoronary Delivery of Plasma Extracellular Vesicles Protects the Myocardium Against Ischemia-Reperfusion Injury in Canis.

Hypertension 2021 Nov 7;78(5):1541-1554. Epub 2021 Sep 7.

Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University, The Sixth People's Hospital of Nantong (H.W., Y.X., C.S., M.W., J.Z., J.X., J.X.), Shanghai University, China.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17574DOI Listing
November 2021
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