Publications by authors named "Liang YU"

1,126 Publications

  • Page 1 of 1

COVID-19 vaccine hesitancy among Chinese residents under the free vaccination policy.

Rev Assoc Med Bras (1992) 2021 Sep;67(9):1317-1321

Wannan Medical College, School of Innovation and Entrepreneurship - Anhui, China.

Objective: This study aimed to assess the attitudes of Chinese residents toward COVID-19 vaccines and explore the potential drivers for Chinese residents' vaccine hesitancy.

Methods: A cross-sectional survey was conducted from February 16 to March 16, 2021, by administering an online questionnaire to the Chinese residents.

Results: Of 5240 residents who completed the survey, 464 (8.9%) participants reported to have had one shot, and 348 (6.6%) reported to have had 2 shots. At the time the questionnaire was administered, 2298 (43.9%) participants reported they wanted to get vaccinated, while 2255 (43.0%) declared that they still did not know, and 687 (13.1%) respondents declared vaccine refusal. Overall, 2255 (43%) participants were categorized as vaccine hesitancy. Female participants (p=0.000), <20 years old (p=0.000), have low risk of COVID-19 (p=0.000) infection and strong associations of vaccine hesitancy. eHealth literacy was a protective factor.

Conclusions: The results of this study show high rates of vaccine hesitancy in China. This could pose a serious threat to the preventive measures that aimed at controlling COVID-19 spread in the country. The government and different media platforms should encourage the dissemination of correct information about vaccines, the communities and medical staff to improve residents' knowledge about vaccines, and strive to improve residents' electronic health literacy.
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http://dx.doi.org/10.1590/1806-9282.20210633DOI Listing
September 2021

The genetic analysis of Chinese patients with clonal cytopenias using targeted next-generation sequencing.

Mol Cytogenet 2021 Nov 18;14(1):52. Epub 2021 Nov 18.

Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, 223300, Jiangsu, People's Republic of China.

Background: Clonal hematopoiesis (CH) can be found in various myeloid neoplasms (MN), such as myelodysplastic syndromes (MDS), myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), also in pre-MDS conditions.

Methods: Cytogenetics is an independent prognostic factor in MDS, and fluorescence in-situ hybridization (FISH) can be used as an adjunct to karyotype analysis. In the past 5 years, only 35 of 100 newly diagnosed MDS and MDS/MPN patients were identified abnormalities, who underwent the FISH panel. In addition, we examined a cohort of 51 cytopenic patients suspected MDS or MDS/MPN with a 20-gene next generation sequencing (NGS), including 35 newly diagnosed MN patients and 16 clonal cytopenias of undetermined significance (CCUS) patients.

Results: Compared with the CCUS group, the MN group had higher male ratio (22/13 vs 10/6), cytogenetics abnormalities rate (41.4% vs 21.4%) and frequency of a series of mutations, such as ASXL1 (28.6% vs 25%), U2AF1 (25.7% vs 25%), RUNX1 (20% vs 0.0%); also, higher adverse mutations proportion (75% vs 85.2%), and double or multiple mutations (54.3% vs 43.75%). There were 7 MN patients and 4 CCUS patients who experienced cardio-cerebrovascular embolism events demonstrated a significant difference between the two groups (25% vs 20%). Ten of the 11 patients had somatic mutations, half had DNA methylation, while the other half had RNA splicing. Additionally, six patients had disease transformation, and four patients had mutated U2AF1, including two CCUS cases and two MDS-EB cases. Following up to January 2021, there was no significant difference in over survival between the CCUS and MN groups.

Conclusion: NGS facilitates the diagnosis of unexplained cytopenias. The monitoring and management of CCUS is necessary, also cardio-cerebrovascular embolism events in patients with CH need attention in the clinical practice.
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http://dx.doi.org/10.1186/s13039-021-00572-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600778PMC
November 2021

Correction to: Rapid Acquisition of High-Quality SARS-CoV-2 Genome via Amplicon-Oxford Nanopore Sequencing.

Virol Sin 2021 Nov 17. Epub 2021 Nov 17.

CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.

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http://dx.doi.org/10.1007/s12250-021-00465-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596092PMC
November 2021

Diagnosis and treatment of acute graft-versus-host disease after liver transplantation: Report of six cases.

World J Clin Cases 2021 Oct;9(30):9255-9268

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

Background: Graft-versus-host disease (GVHD) following liver transplantation (LT) is an unpredictable complication with poor outcome. However, consensus regarding the diagnosis and therapeutic regimen for the disease is yet lacking. The present study summarized the clinical experience on the diagnosis and treatment of acute GVHD (aGVHD) following LT and reviewed the pertinent literature.

Case Summary: Between January 1, 2000 and December 31, 2020, a total of 1053 LT were performed in the First Affiliated Hospital of Xi'an Jiaotong University. Six recipients developed aGVHD with clinical symptoms of fever, rash, diarrhea, and pancytopenia. The incidence of aGVHD was 0.57%. The median time from LT to the clinical presentation of aGVHD was 22.17 d. The median time from the beginning of the clinical symptom to histopathological diagnosis was 7.5 d. All six cases underwent treatment of immunosuppressant adjustment, corticosteroids, human normal immunoglobulin, and antithymocyte globulin/IL-2 antagonists. Despite intensive treatment strategies, 4 patients were deceased due to sepsis, multiple organ failure, and cerebral hemorrhage. The remaining two cases were discharged as treatment successfully. However, one died because of tuberculosis infection on the 6th month of follow-up, the other one was alive healthy during 30 mo of follow-up.

Conclusion: The rapid diagnosis of aGVHD is mainly based on the time from the first symptom, histopathological features, and the donor T-lymphocyte chimerism. Our cases report highlights massive corticosteroid therapy and age difference between donors and recipients could accelerate to aGVHD. Moreover, gut microbial interventions and donor-targeted serotherapy may provide novel therapeutics.
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http://dx.doi.org/10.12998/wjcc.v9.i30.9255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567504PMC
October 2021

Neuroprotective effects of long noncoding RNAs involved in ischemic postconditioning after ischemic stroke.

Neural Regen Res 2022 Jun;17(6):1299-1309

Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan Province, China.

During acute reperfusion, the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes. However, whether long noncoding RNAs are involved in neuroprotective effects following focal ischemic stroke in rats remains unclear. In this study, RNA isolation and library preparation was performed for long noncoding RNA sequencing, followed by determining the coding potential of identified long noncoding RNAs and target gene prediction. Differential expression analysis, long noncoding RNA functional enrichment analysis, and co-expression network analysis were performed comparing ischemic rats with and without ischemic postconditioning rats. Rats were subjected to ischemic postconditioning via the brief and repeated occlusion of the middle cerebral artery or femoral artery. Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of differentially expressed long noncoding RNAs after ischemic postconditioning in a rat model of ischemic stroke. The results showed that ischemic postconditioning greatly affected the expression profile of long noncoding RNAs and mRNAs in the brains of rats that underwent ischemic stroke. The predicted target genes of some of the identified long noncoding RNAs (cis targets) were related to the cellular response to ischemia and stress, cytokine signal transduction, inflammation, and apoptosis signal transduction pathways. In addition, 15 significantly differentially expressed long noncoding RNAs were identified in the brains of rats subjected to ischemic postconditioning. Nine candidate long noncoding RNAs that may be related to ischemic postconditioning were identified by a long noncoding RNA expression profile and long noncoding RNA-mRNA co-expression network analysis. Expression levels were verified by quantitative real-time reverse transcription-polymerase chain reaction. These results suggested that the identified long noncoding RNAs may be involved in the neuroprotective effects associated with ischemic postconditioning following ischemic stroke. The experimental animal procedures were approved by the Animal Experiment Ethics Committee of Kunming Medical University (approval No. KMMU2018018) in January 2018.
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http://dx.doi.org/10.4103/1673-5374.327346DOI Listing
June 2022

Pore Distortion in a Metal-Organic Framework for Regulated Separation of Propane and Propylene.

J Am Chem Soc 2021 Nov 15;143(46):19300-19305. Epub 2021 Nov 15.

Hoffmann Institute of Advanced Materials, Shenzhen Polytechnic, 7098 Liuxian Boulevard, Shenzhen, Guangdong 518055, P. R. China.

The development of porous solids for adsorptive separation of propylene and propane remains an important and challenging line of research. State-of-the-art sorbent materials often suffer from the trade-off between adsorption capacity and selectivity. Here, we report the regulated separation of propylene and propane in a metal-organic framework designed pore distortion. The distorted pore structure of HIAM-301 successfully excludes propane and thus achieved simultaneously high selectivity (>150) and large capacity (∼3.2 mmol/g) of propylene at 298 K and 1 bar. Dynamic breakthrough measurements validated the excellent separation of propane and propylene. neutron powder diffraction and inelastic neutron scattering revealed the binding domains of adsorbed propylene molecules in HIAM-301 as well as host-guest interaction dynamics. This study presents a new benchmark for the adsorptive separation of propylene and propane.
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http://dx.doi.org/10.1021/jacs.1c10423DOI Listing
November 2021

Influence of Material Parameters on the Contact Pressure Characteristics of a Multi-Disc Clutch.

Materials (Basel) 2021 Oct 25;14(21). Epub 2021 Oct 25.

School of Mechanical Engineering, Beijing Institute of Technology, Beijing 100081, China.

As an essential part of the transmission, the life of the clutch directly affects the stability of the transmission. In this paper, a finite element model and a thermodynamic numerical model of a multi-disc clutch are established to investigate the influence of material parameters on the contact pressure distribution. The pressure distribution index (PDI) is firstly proposed to evaluate the pressure difference among friction pairs. Moreover, the correctness of the numerical model is verified by the clutch static pressure experiment. The results show that increasing the elastic modulus and Poisson's ratio of the backplate can effectively improve the uniformity of the contact pressure. However, the variations in material parameters of other clutch components can not easily smooth the pressure difference. Therefore, optimized material parameters for the clutch are proposed, where the maximum pressure and temperature differences are reduced by about 27.2% and 10.3%, respectively.
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http://dx.doi.org/10.3390/ma14216391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585393PMC
October 2021

Evaluating the Efficacy of VitalStim Electrical Stimulation Combined with Swallowing Function Training for Treating Dysphagia following an Acute Stroke.

Clinics (Sao Paulo) 2021 8;76:e3069. Epub 2021 Nov 8.

Pediatric Area II, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, China.

Objectives: This study explored the clinical efficacy of VitalStim electrical stimulation combined with swallowing function training for patients with dysphagia following an acute stroke.

Methods: Seventy-two patients with dysphagia following an acute stroke were admitted to our hospital and were further divided into two groups using prospective research methods. There were 36 cases in each group according to the random number table method. The control group received conventional medical treatment and swallowing function training while the experimental group received conventional medical treatment and VitalStim electrical stimulation combined with swallowing function training.

Results: The overall response rate of the experimental group (94.44%) was higher than that of the control group (77.78%), and the difference was statistically significant (p<0.05). Compared with before treatment, the upward and forward movement speeds of the hyoid bone, anterior movement speed, the grading score of the Kubota drinking water test, Caiteng's grading score, serum superoxide dismutase, 5-hydroxytryptamine, and norepinephrine levels, Fugl-Meyer Assessment score, and multiple quality of life scores of the two groups showed improvement after treatment. While the standard swallowing assessment score, serum malondialdehyde level, and National Institutes of Health Stroke Scale score decreased, the aforementioned indices showed a significant improvement in the experimental group (p<0.05).

Conclusion: The results of this study indicate that VitalStim electrical stimulation combined with swallowing function is effective for treating dysphagia following an acute stroke. It can effectively improve swallowing, neurological, and limb motor functions, reduce complications, promote physical recovery, and improve overall quality of life of patients.
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http://dx.doi.org/10.6061/clinics/2021/e3069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552953PMC
November 2021

Correction to: DLX6-AS1/miR-204-5p/OCT1 positive feedback loop promotes tumor progression and epithelial-mesenchymal transition in gastric cancer.

Gastric Cancer 2021 Nov 9. Epub 2021 Nov 9.

Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, No. 4 Chongshan East Road, Shenyang, 110032, China.

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http://dx.doi.org/10.1007/s10120-021-01263-9DOI Listing
November 2021

Prognostic Significance of Circulating Lymphocyte Subsets Before Treatment in Patients with Nasopharyngeal Carcinoma.

Cancer Manag Res 2021 27;13:8109-8120. Epub 2021 Oct 27.

Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People's Republic of China.

Purpose: We set out to explore the prognostic value of circulating lymphocyte subsets in patients with nasopharyngeal carcinoma (NPC) before treatment and to investigate changes in lymphocyte subsets resulting from chemoradiotherapy.

Patients And Methods: This retrospective study included 677 patients with non-metastatic NPC. The cutoff value of lymphocyte subsets was determined by the receiver operating characteristic curve (ROC), and the prognostic significance of lymphocyte subsets was evaluated by the Log rank test and Cox proportional hazards model. The endpoints were overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). Differences in lymphocyte subsets before and after chemoradiotherapy were analyzed by Wilcoxon signed rank test.

Results: NPC patients with high levels of CD19 B cells (>9.55%) had better 5-year OS (90.4% VS 76.8%, P < 0.001), 5-year PFS (85.3% VS 71.6%, P < 0.001) and 5-year DMFS (94% VS 86.8%, P = 0.002) than patients with low levels of CD19 B cells. Patients with high levels of CD4 T cells (> 37.05%) had better 5-year PFS (83% VS 74.2%, P = 0.015) and better 5-year DMFS (95.8% VS 86.7%, P < 0.001) than those with low levels of CD4 T cells. Multivariate analyses indicated that CD19 B cell was an independent prognostic factor for OS, PFS and DMFS in NPC. And CD4 T cell was an independent prognostic factor for PFS and DMFS. Within 1 month after chemoradiotherapy, the percentages of CD4 T cells, CD19 B cells, and the CD4/CD8 ratio decreased significantly, while the percentages of CD8 T cells increased significantly.

Conclusion: NPC patients with low levels of CD19 B cells or CD4 T cells before treatment have a poor prognosis. In addition, chemoradiotherapy may reduce the body's immune function in NPC patients.
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http://dx.doi.org/10.2147/CMAR.S334094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558319PMC
October 2021

Becker muscular dystrophy: case report, review of the literature, and analysis of differentially expressed hub genes.

Neurol Sci 2021 Nov 3. Epub 2021 Nov 3.

Institute of Neural Regeneration and Repair, Department of Neurology, The First People's Hospital of Yichang, China Three Gorges University, Yichang, 443000, China.

Introduction: Becker muscular dystrophy (BMD) is a genetic and progressive neuromuscular disease caused by mutations in the dystrophin gene with no available cure. A case report and comprehensive review of BMD cases aim to provide important clues for early diagnosis and implications for clinical practice. Genes and pathways identified from microarray data of muscle samples from patients with BMD help uncover the potential mechanism and provide novel therapeutic targets for dystrophin-deficient muscular dystrophies.

Methods: We describe a BMD family with a 10-year-old boy as the proband and reviewed BMD cases from PubMed. Datasets from the Gene Expression Omnibus database were downloaded and integrated with the online software.

Results: The systematic review revealed the clinical manifestations and mutation points of the dystrophin gene. Gene ontology analysis showed that extracellular matrix organization and extracellular structure organization with enrichment of upregulated genes coexist in three datasets. We present the first report of TUBA1A involvement in the development of BMD/Duchenne muscular dystrophy (DMD).

Discussion: This study provides important implications for clinical practice, uncovering the potential mechanism of the progress of BMD/DMD, and provided new therapeutic targets.
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http://dx.doi.org/10.1007/s10072-021-05499-2DOI Listing
November 2021

Tumor microenvironments self-activated nanoscale metal-organic frameworks for ferroptosis based cancer chemodynamic/photothermal/chemo therapy.

Acta Pharm Sin B 2021 Oct 23;11(10):3231-3243. Epub 2021 Jan 23.

Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.

Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS Fenton reaction, therefore causing ferroptosis. More ROS could be generated by the acceleration of Fenton reaction due to the released Cu ions and the intrinsic photothermal capability of FCSP MOFs. The overexpressed GSH and HO in TME could ensure the specific TME self-activated therapy. Better tumor therapeutic efficiency could be achieved by doxorubicin (DOX) loading since it can not only cause apoptosis, but also indirectly produce HO to amplify Fenton reaction. Remarkable anti-tumor effect of obtained [email protected] MOFs was verified both and assays.
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http://dx.doi.org/10.1016/j.apsb.2021.01.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546666PMC
October 2021

Micro telecom computing architecture.4-based beam position monitor electronics design for storage ring of Hefei advanced light facility.

Rev Sci Instrum 2021 Oct;92(10):104711

National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, Anhui 230026, China.

The Hefei Advanced Light Facility (HALF) is a fourth-generation vacuum ultraviolet and x-ray diffraction limit synchrotron radiation (DLSR) light source now under preliminary research. To achieve ultralow beam emittance and small beam size, the orbit of the beam in the DLSR storage ring should meet the stability requirement at submicrometer scale. The beam position monitor (BPM) electronics measures the orbit and is hence an essential part of the beam orbit control system. In this article, we design a BPM electronics based on the MicroTCA.4 (Micro Telecom Computing Architecture) standards platform, which consists of a MicroTCA.4 module (including a chassis, a power supply, and a digital board), a customized RF front end module, and a frequency synthesizer. In-phase and quadrature sampling and digital signal processing algorithms are implemented to obtain turn-by-turn data, fast acquisition data at a 10 kHz rate, and slow acquisition data at a 10 Hz rate. To evaluate the performance and function of BPM electronics, we conducted offline tests in the laboratory and beam tests based on the storage ring of Hefei Light Source II (HLS II), a light source similar to the HALF as an alternative. Test results indicate that the performance of MicroTCA.4-based BPM electronics can meet the requirements of the HALF storage ring.
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http://dx.doi.org/10.1063/5.0061502DOI Listing
October 2021

Thirteen cyathane diterpenoids with acetylcholinesterase inhibitory effects from the fungus Cyathus africanus.

Phytochemistry 2021 Oct 23;193:112982. Epub 2021 Oct 23.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People's Republic of China. Electronic address:

Eight undescribed cyathane diterpenoids, representative specialised metabolites of the genus Cyathus, named cyathins Q-X, along with five known congeners, were isolated from the liquid fermentation of Cyathus africanus. Their structures and absolute configurations were elucidated by integrating NMR spectroscopic analyses, electronic circular dichroism (ECD) calculations, and X-ray diffraction. Reasonable correction to the C-12 configuration of cyathin I was corroborated by the crystal data. The structural identification in this research expanded the number of candidates to allow for more bioactivity-screening options. Among them, (12S)-11α,14α-epoxy-13α,14β,15-trihydroxycyath-3-ene displayed significant acetylcholinesterase (AChE) inhibitory effect with an IC value of 4.60 ± 0.85 μM. Molecular docking studies were also performed to unravel the underlying modes of interactions with the active sites of AChE for active compounds.
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http://dx.doi.org/10.1016/j.phytochem.2021.112982DOI Listing
October 2021

Dead-end hybridization in walnut trees revealed by large-scale genomic sequence data.

Mol Biol Evol 2021 Oct 23. Epub 2021 Oct 23.

State Key Laboratory of Earth Surface Processes and Resource Ecology and Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.

While hybridization plays a large role in speciation, some unknown fraction of hybrid individuals never reproduces, instead remaining as genetic dead-ends. We investigated a morphologically distinct and culturally important Chinese walnut, Juglans hopeiensis, suspected to have arisen from hybridization of Persian walnut (J. regia) with Asian butternuts (J. cathayensis, J. mandshurica and hybrids between J. cathayensis and J. mandshurica). Based on 151 whole-genome sequences of the relevant taxa, we discovered that all J. hopeiensis individuals are first-generation hybrids, with the time for the onset of gene flow estimated as 370,000 years, implying both strong postzygotic barriers and the presence of J. regia in China by that time. Six inversion regions enriched for genes associated with pollen germination and pollen tube growth may be involved in the postzygotic barriers that prevent sexual reproduction in the hybrids. Despite its long-recurrent origination and distinct traits, J. hopeiensis does not appear on the way to speciation.
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http://dx.doi.org/10.1093/molbev/msab308DOI Listing
October 2021

Preparation of TiO/Black Talc Composite Photocatalyst and the Research on Its Adsorption-Degradation Coupling Effects.

Materials (Basel) 2021 Oct 13;14(20). Epub 2021 Oct 13.

School of Materials Science and Technology, Shenyang University of Chemical Technology, Shenyang 110142, China.

In this paper, a TiO/black talc composite photocatalyst was prepared by the sol-gel method using TBOT as titanium source and black talc as carrier. Rhodamine B was used as the targeted pollutant to study the adsorption role of carbon in black talc. The results showed that with the adsorption-degradation cycles, the illumination time can be reduced by 40%. The adsorption rate and degradation rate of the composite photocatalyst was also increased. The degradation rate of Rhodamine B reached more than 95%, which fully shows the synergistic effect between TiO nanoparticles and black talc. In this way, the adsorption-degradation coupling of the photocatalyst could be realized.
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http://dx.doi.org/10.3390/ma14206038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540955PMC
October 2021

Complete loss of miR-200 family induces EMT associated cellular senescence in gastric cancer.

Oncogene 2021 Oct 19. Epub 2021 Oct 19.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.

The EMT (epithelial-to-mesenchymal-transition) subtype of gastric cancer (GC) is associated with poor treatment responses and unfavorable clinical outcomes. Despite the broad physiological roles of the micro-RNA (miR)-200 family, they largely serve to maintain the overall epithelial phenotype. However, during late-stage gastric tumorigenesis, members of the miR-200 family are markedly suppressed, resulting in the transition to the mesenchymal state and the acquisition of invasive properties. As such, the miR-200 family represents a robust molecular marker of EMT, and subsequently, disease severity and prognosis. Most reports have studied the effect of single miR-200 family member knockdown. Here, we employ a multiplex CRISPR/Cas9 system to generate a complete miR-200 family knockout (FKO) to investigate their collective and summative role in regulating key cellular processes during GC pathogenesis. Genetic deletion of all miR-200s in the human GC cell lines induced potent morphological alterations, G1/S cell cycle arrest, increased senescence-associated β-galactosidase (SA-β-Gal) activity, and aberrant metabolism, collectively resembling the senescent phenotype. Coupling RNA-seq data with publicly available datasets, we revealed a clear separation of senescent and non-senescent states amongst FKO cells and control cells, respectively. Further analysis identified key senescence-associated secretory phenotype (SASP) components in FKO cells and a positive feedback loop for maintenance of the senescent state controlled by activation of TGF-β and TNF-α pathways. Finally, we showed that miR-200 FKO associated senescence in cancer epithelial cells significantly recruited stromal cells in the tumor microenvironment. Our work has identified a new role of miR-200 family members which function as an integrated unit serving to link senescence with EMT, two major conserved biological processes.
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http://dx.doi.org/10.1038/s41388-021-02067-yDOI Listing
October 2021

ANKRD36 Is Involved in Hypertension by Altering Expression of ENaC Genes.

Circ Res 2021 Nov 7;129(11):1067-1081. Epub 2021 Oct 7.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (Y.Y., Jin'e Wang, L.Y., B.C., H.W., X.X., Y.Z., R.H., Y.W.).

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCRESAHA.121.319883DOI Listing
November 2021

Electron penetration triggering interface activity of Pt-graphene for CO oxidation at room temperature.

Nat Commun 2021 Oct 4;12(1):5814. Epub 2021 Oct 4.

State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), College of Chemistry and Chemical Engineering, Xiamen University, 361005, Xiamen, China.

Achieving CO oxidation at room temperature is significant for gas purification but still challenging nowadays. Pt promoted by 3d transition metals (TMs) is a promising candidate for this reaction, but TMs are prone to be deeply oxidized in an oxygen-rich atmosphere, leading to low activity. Herein we report a unique structure design of graphene-isolated Pt from CoNi nanoparticles (PtǀCoNi) for efficiently catalytic CO oxidation in an oxygen-rich atmosphere. CoNi alloy is protected by ultrathin graphene shell from oxidation and therefore modulates the electronic property of Pt-graphene interface via electron penetration effect. This catalyst can achieve near 100% CO conversion at room temperature, while there are limited conversions over Pt/C and Pt/CoNiO catalysts. Experiments and theoretical calculations indicate that CO will saturate Pt sites, but O can adsorb at the Pt-graphene interface without competing with CO, which facilitate the O activation and the subsequent surface reaction. This graphene-isolated system is distinct from the classical metal-metal oxide interface for catalysis, and it provides a new thought for the design of heterogeneous catalysts.
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http://dx.doi.org/10.1038/s41467-021-26089-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490350PMC
October 2021

Interactome Analysis of the Nucleocapsid Protein of SARS-CoV-2 Virus.

Pathogens 2021 Sep 8;10(9). Epub 2021 Sep 8.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

SARS-CoV-2 infection has caused a global pandemic that has severely damaged both public health and the economy. The nucleocapsid protein of SARS-CoV-2 is multifunctional and plays an important role in ribonucleocapsid formation and viral genome replication. In order to elucidate its functions, interaction partners of the SARS-CoV-2 N protein in human cells were identified via affinity purification and mass spectrometry. We identified 160 cellular proteins as interaction partners of the SARS-CoV-2 N protein in HEK293T and/or Calu-3 cells. Functional analysis revealed strong enrichment for ribosome biogenesis and RNA-associated processes, including ribonucleoprotein complex biogenesis, ribosomal large and small subunits biogenesis, RNA binding, catalysis, translation and transcription. Proteins related to virus defence responses, including MOV10, EIF2AK2, TRIM25, G3BP1, ZC3HAV1 and ZCCHC3 were also identified in the N protein interactome. This study comprehensively profiled the viral-host interactome of the SARS-CoV-2 N protein in human cells, and the findings provide the basis for further studies on the pathogenesis and antiviral strategies for this emerging infection.
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http://dx.doi.org/10.3390/pathogens10091155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465953PMC
September 2021

Chiral Fluorescent Metal-Organic Framework with a Pentanuclear Copper Cluster as an Efficient Luminescent Probe for Dy Ion and Cyano Compounds.

Inorg Chem 2021 Oct 27;60(20):15085-15090. Epub 2021 Sep 27.

College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, Hunan China.

Luminescent probes have been used for the detection of various heavy metals and toxic compounds. A novel sensor with excellent sensitivity and selectivity is in high demand. Herein, we designed and synthesized a three-dimensional copper-organic framework of "pcu" α-Po primitive cubic topology with a Schläfli symbol of {4.4.4.4.4.4.4.4.4.4.4.4.*.*.*}. By taking advantage of metal clusters and a triazole ligand as the metal-organic framework (MOF) components, the newly obtained MOF is stable in various environments and can be potentially used as the sensor. Remarkably, this MOF-based sensor shows high sensitivity and selectivity toward a dysprosium ion (Dy) in a multiple-lanthanide mixed solution. Besides, it exhibits luminescent quenching toward various cyano compounds. This chiral cluster-based network provides a potential luminescent probe for various inorganic and organic compounds with high sensitivity and selectivity.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01349DOI Listing
October 2021

Adipose/Connective Tissue From Thyroid-Associated Ophthalmopathy Uncovers Interdependence Between Methylation and Disease Pathogenesis: A Genome-Wide Methylation Analysis.

Front Cell Dev Biol 2021 8;9:716871. Epub 2021 Sep 8.

Eye Institute and Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China.

In response to pathological stimulation, methylation status conversion of the genome drives changes of cell feature and is able to promote disease development. Yet the role of methylation in the development of thyroid-associated ophthalmopathy (TAO) remains to be evaluated. Overexpansion of orbital tissue is the key feature of TAO. In this study, the methylation profile of orbital adipose/connective tissue from TAO patients and normal individuals were compared. After screening 3,739 differentially methylated probes, the distribution and properties of these probes were analyzed. Furthermore, enriched biological functions of these genes associated with differential methylation and the relationship between their methylation status and expression profile were also identified, including PTPRU and VCAM-1. According to our results, methylation was involved in disregulated immune response and inflammation in TAO and might contribute to activation of fibroblast and adipogenesis, leading to the expansion of orbital tissue. Neuropathy and neurobehavioral symptoms were also potentially associated with methylation. These results may help to extend the understanding of methylation in TAO and provide more insights into diagnosis and treatment of patients.
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http://dx.doi.org/10.3389/fcell.2021.716871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457400PMC
September 2021

Comparative study between two bleeding grading systems of immune thrombocytopenia purpura.

Hematology 2021 Dec;26(1):769-774

Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China.

Objective: To explore the relationship between platelet count and bleeding score in immune thrombocytopenia purpura (ITP) and compare the clinical practicability of two bleeding grading systems with adult patients with ITP.

Methods: A total of 204 patients were retrospectively analyzed with the ITP bleeding scale (IBLS) and the ITP bleeding assessment tool (version 2016) (ITP-2016). The correlation between the two bleeding score systems and the relations among the platelet counts were respectively analyzed.

Results: (1) There is a linear relationship between platelet count and bleeding score, no matter which scoring system it is based on (rs = -0.429,  < 0.001; rs = -0.331,  < 0.001, the analysis of the number of sites of Grade 1/2 bleeding were done; and rs = -0.466,  < 0.05, the analysis between platelet count and bleeding score by ITP-2016 respectively). (2) Platelet count and bleeding scores are negatively correlated in those with extremely low platelet counts ( < 10*10/L). The number of sites of Grade 2 bleeding and the ITP-2016 scores are negatively correlated with platelet counts (rs = -0.15 and rs = -0.244,  < 0.05, respectively). Significantly, there is no correlation between the platelet count and bleeding scores when the platelet count is more than 10*10/L. (3) It takes less time to score with ITP-2016 than IBLS ( = -3.825,  < 0.001).

Conclusions: There is good responsiveness, strong assessment consistency, close correlation between ITP-2016 and IBLS. ITP-2016 takes less time-consuming in clinical application. It can be used as an effective tool of condition judgement, risk assessment and efficacy evaluation of patients with ITP.
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http://dx.doi.org/10.1080/16078454.2021.1978753DOI Listing
December 2021

E484K mutation in SARS-CoV-2 RBD enhances binding affinity with hACE2 but reduces interactions with neutralizing antibodies and nanobodies: Binding free energy calculation studies.

J Mol Graph Model 2021 12 17;109:108035. Epub 2021 Sep 17.

The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, 101111, China. Electronic address:

The pandemic of the COVID-19 disease caused by SARS-CoV-2 has led to more than 200 million infections and over 4 million deaths worldwide. The progress in the developments of effective vaccines and neutralizing antibody therapeutics brings hopes to eliminate the threat of COVID-19. However, SARS-CoV-2 continues to mutate, and several new variants have been emerged. Among the various naturally-occurring mutations, the E484K mutation shared by many variants attracted serious concerns, which may potentially enhance the receptor binding affinity and reduce the immune response. In the present study, the molecular mechanism behind the impacts of E484K mutation on the binding affinity of the receptor-binding domain (RBD) with the receptor human angiotensin-converting enzyme 2 (hACE2) was investigated by using the molecular dynamics (MD) simulations combined with the molecular mechanics-generalized Born surface area (MMGBSA) method. Our results indicate that the E484K mutation results in more favorable electrostatic interactions compensating the burial of the charged and polar groups upon the binding of RBD with hACE2, which significantly improves the RBD-hACE2 binding affinity. Besides that, the E484K mutation also causes the conformational rearrangements of the loop region containing the mutant residue, which leads to tighter binding interface of RBD with hACE2 and formation of some new hydrogen bonds. The tighter binding interface and the new hydrogen bonds formation also contribute to the improved binding affinity of RBD to the receptor hACE2. In addition, six neutralizing antibodies and nanobodies complexed with RBD were selected to explore the effects of E484K mutation on the recognition of these antibodies to RBD. The simulation results show that the E484K mutation significantly reduces the binding affinities to RBD for most of the studied neutralizing antibodies/nanobodies, and the decrease in the binding affinities is mainly owing to the unfavorable electrostatic interactions caused by the mutation. Our studies revealed that the E484K mutation may improve the binding affinity between RBD and the receptor hACE2, implying more transmissibility of the E484K-containing variants, and weaken the binding affinities between RBD and the studied neutralizing antibodies/nanobodies, indicating reduced effectiveness of these antibodies/nanobodies. Our results provide valuable information for the effective vaccine development and antibody/nanobody drug design.
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http://dx.doi.org/10.1016/j.jmgm.2021.108035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447841PMC
December 2021

Progesterone-induced blocking factor-mediated Th1/Th2 balance correlates with fetal arrest in women who underwent in vitro fertilization and embryo transfer.

Clin Immunol 2021 11 21;232:108858. Epub 2021 Sep 21.

Department of Human Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, China. Electronic address:

The role of progesterone-induced blocking factor (PIBF)-mediated Th1/Th2 balance in delivery outcomes of in vitro fertilization and embryo transfer (IVF-ET) has not been fully elucidated. In this study, 73 infertile women with successful IVF-ET were enrolled (16 fetal arrests and 57 live births). PIBF and IL-4 levels were significantly lower in the fetal arrest group than in the live birth group (p < 0.05). TNF-α level and Th1/Th2 ratios were significantly higher in the fetal arrest group than in the live birth group (p < 0.05). High TNF-α level and Th1/Th2 ratios were risk factors for fetal arrest, whereas increased PIBF and IL-4 levels were protective factors (P < 0.05). Increased TNF-α/IL-4 exhibited relatively strong predictive value for fetal arrest (AUC, 0.855; sensitivity, 93.8%; specificity, 71.9%). In summary, the PIBF-mediated Th1/Th2 balance is closely correlated with delivery outcomes of IVF-ET. TNF-α/IL-4 may be a predictive marker of fetal arrest.
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http://dx.doi.org/10.1016/j.clim.2021.108858DOI Listing
November 2021

Impact of neoadjuvant chemoradiotherapy on the local recurrence and distant metastasis pattern of locally advanced rectal cancer: a propensity score-matched analysis.

Chin Med J (Engl) 2021 Sep 15;134(18):2196-2204. Epub 2021 Sep 15.

Department of Colorectal Surgery, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Background: Previous studies have demonstrated different predominant sites of distant metastasis between patients with and without neoadjuvant chemoradiotherapy (NCRT). This study aimed to explore whether NCRT could influence the metastasis pattern of rectal cancer through a propensity score-matched analysis.

Methods: In total, 1296 patients with NCRT or post-operative chemoradiotherapy (PCRT) were enrolled in this study between January 2008 and December 2015. Propensity score matching was used to correct for differences in baseline characteristics between the two groups. After propensity score matching, the metastasis pattern, including metastasis sites and timing, was compared and analyzed.

Results: After propensity score matching, there were 408 patients in the PCRT group and 245 patients in the NCRT group. NCRT significantly reduced local recurrence (4.1% vs. 10.3%, P = 0.004), but not distant metastases (28.2% vs. 27.9%, P = 0.924) compared with PCRT. In both the NCRT and PCRT groups, the most common metastasis site was the lung, followed by the liver. The NCRT group developed local recurrence and distant metastases later than the PCRT group (median time: 29.2 [18.8, 52.0] months vs. 18.7 [13.3, 30.0] months, Z = -2.342, P = 0.019; and 21.2 [12.2, 33.8] vs. 16.4 [9.3, 27.9] months, Z = -1.765, P = 0.035, respectively). The distant metastases occurred mainly in the 2nd year after surgery in both the PCRT group (39/114, 34.2%) and NCRT group (21/69, 30.4%). However, 20.3% (14/69) of the distant metastases appeared in the 3rd year in the NCRT group, while this number was only 13.2% (15/114) in the PCRT group.

Conclusions: The predominant site of distant metastases was the lung, followed by the liver, for both the NCRT group and PCRT group. NCRT did not influence the predominant site of distant metastases, but the NCRT group developed local recurrence and distant metastases later than the PCRT group. The follow-up strategy for patients with NCRT should be adjusted and a longer intensive follow-up is needed.
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http://dx.doi.org/10.1097/CM9.0000000000001641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478402PMC
September 2021

Genomic impact of stress-induced transposable element mobility in Arabidopsis.

Nucleic Acids Res 2021 Oct;49(18):10431-10447

Plant Breeding and Genetic Resources, Agroscope, 1260 Nyon, Switzerland.

Transposable elements (TEs) have long been known to be major contributors to plant evolution, adaptation and crop domestication. Stress-induced TE mobilization is of particular interest because it may result in novel gene regulatory pathways responding to stresses and thereby contribute to stress adaptation. Here, we investigated the genomic impacts of stress induced TE mobilization in wild type Arabidopsis plants. We find that the heat-stress responsive ONSEN TE displays an insertion site preference that is associated with specific chromatin states, especially those rich in H2A.Z histone variant and H3K27me3 histone mark. In order to better understand how novel ONSEN insertions affect the plant's response to heat stress, we carried out an in-depth transcriptomic analysis. We find that in addition to simple gene knockouts, ONSEN can produce a plethora of gene expression changes such as: constitutive activation of gene expression, alternative splicing, acquisition of heat-responsiveness, exonisation and genesis of novel non-coding and antisense RNAs. This report shows how the mobilization of a single TE-family can lead to a rapid rise of its copy number increasing the host's genome size and contribute to a broad range of transcriptomic novelty on which natural selection can then act.
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http://dx.doi.org/10.1093/nar/gkab828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501995PMC
October 2021

Flexible sigmoidoscopy may be sufficient for initial evaluation of suspected immunotherapy-mediated colitis: A cross-sectional study.

J Gastroenterol Hepatol 2021 Sep 21. Epub 2021 Sep 21.

Division of Gastroenterology, Department of Medicine, City of Hope Medical Center, Duarte, California, USA.

Background And Aim: Immune checkpoint inhibitors (ICIs) have shown promise in treating a variety of cancers. Their increased use coincides with increased incidence of immunotherapy-mediated colitis (IMC), a common adverse effect. Optimal strategy for endoscopic evaluation of IMC (full colonoscopy or flexible sigmoidoscopy) is not well-defined.

Methods: Retrospective review of all patients at City of Hope referred to gastroenterology for evaluation of IMC due to gastrointestinal symptoms was performed. Patients with an existing histologic diagnosis of IMC established at an outside hospital or a diagnosis of infectious or chronic colitis were excluded.

Results: We identified 51 symptomatic patients on ICIs prompting evaluation for IMC with colonoscopy (47/51) or flexible sigmoidoscopy (4/51). All distal rectosigmoid biopsies during flexible sigmoidoscopy demonstrated histologic evidence of IMC. In full colonoscopy, IMC was either present in all segments of colon simultaneously (35/47) or absent from all segments (12/47). No isolated proximal colonic biopsies demonstrated IMC. Endoscopically normal mucosa demonstrated histologic evidence of IMC up to 68.6% of the time. Endoscopically abnormal right, transverse, and left colon had low sensitivity (35.3%, 34.3%, and 41.7%, respectively) and high specificity (100.0%, 100.0%, and 91.7%, respectively) for histological presence of IMC.

Conclusions: Distal colon biopsies in patients on ICI therapy with diarrhea and suspected IMC were sufficient for diagnosing IMC in our cohort. Further, we found histologic evidence of IMC in biopsies taken from normal-appearing mucosa in a number of patients, suggesting that a normal endoscopic appearance does not preclude the presence of IMC and biopsies should be taken from both normal and abnormal-appearing mucosa.
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http://dx.doi.org/10.1111/jgh.15691DOI Listing
September 2021

Research progress in predicting DNA methylation modifications and the relation with human diseases.

Curr Med Chem 2021 Sep 16. Epub 2021 Sep 16.

School of Computer Science and Technology, Xidian University, Xi'an, China.

DNA methylation is an important mode of regulation in epigenetic mechanisms, and it is one of the research foci in the field of epigenetics. DNA methylation modification affects a series of biological processes, such as eukaryotic cell growth, differentiation and transformation mechanisms, by regulating gene expression. In this review, we systematically summarized the DNA methylation databases, prediction tools for DNA methylation modification, machine learning algorithms for predicting DNA methylation modification, and the relationship between DNA methylation modification and diseases such as hypertension, Alzheimer's disease, diabetic nephropathy, and cancer. An in-depth understanding of DNA methylation mechanisms can promote accurate prediction of DNA methylation modifications and the treatment and diagnosis of related diseases.
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http://dx.doi.org/10.2174/0929867328666210917115733DOI Listing
September 2021
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