Publications by authors named "Qiao Jin"

133 Publications

Circ_ROBO2/miR-149 Axis Promotes the Proliferation and Migration of Human Aortic Smooth Muscle Cells by Activating NF-κB Signaling.

Cytogenet Genome Res 2021 Oct 14:1-11. Epub 2021 Oct 14.

Department of Cardiovascular Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China.

Atherosclerosis is the leading global cause of mortality. The occurrence of coronary artery disease (CAD) is regulated by a diversity of pathways, including circRNAs. However, the potential mechanisms of circRNAs in CAD remain unclear. Here, qRT-PCR was used to examine the expressions of miR-149 and circ_ROBO2. Their influences on cell proliferation, migration, and apoptosis were measured by CCK-8, trans-well, and flow cytometry assays, respectively. The protein levels of p-IκBα and NF-κB p65 were examined using western blot. The molecular interactions were validated using dual luciferase reporter and RNA pull-down assays. The expression patterns of circ_ROBO2 and miR-149 in CAD patients and PDGF-BB-treated human aortic smooth muscle cells (HASMCs) were upregulated and downregulated, respectively. Knockdown of circ_ROBO2 could markedly inhibit the capabilities of proliferation and migration, enhance the apoptotic rate, and suppress NF-κB signaling in PDGF-BB-treated HASMCs. Mechanistically, circ_ROBO2 acted as a sponge of miR-149 to activate TRAF6/NF-κB signaling. Rescue studies demonstrated that neither silencing miR-149 nor activation of NF-κB signaling obviously abolished the biological roles of circ_ROBO2 knockdown in PDGF-BB treated-HASMCs. This discovery elucidated a functional mechanism of circ_ROBO2 in CAD, suggesting that circRNAs serve a vital role in the progression of CAD.
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http://dx.doi.org/10.1159/000517294DOI Listing
October 2021

Iron toxicity-induced regulation of key secondary metabolic processes associated with the quality and resistance of Panax ginseng and Panax quinquefolius.

Ecotoxicol Environ Saf 2021 Aug 25;224:112648. Epub 2021 Aug 25.

Institute of Special Wild Economic Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Jilin 130112, China; College of Pharmacy and biological Engineering, Chengdu University, Chengdu 610106, China. Electronic address:

Panax ginseng and Panax quinquefolius can survive for long periods of time in iron toxicity-stressed environments, which cause rusty roots and reduced productivity. To reveal the proteomic changes in these two Panax species in response to iron toxicity stress, plants of these two species were divided into a control group and an iron toxicity-stress group. An isobaric tags for relative and absolute quantitation (iTRAQ) proteomics approach was used to explore the changes in protein accumulation and the potential mechanisms underlying the response to iron toxicity stress in the two Panax species. Proteomic analyses revealed approximately 725 differentially expressed proteins (DEPs) in the iron toxicity-stress and control groups, including 233 and 492 proteins whose expression was upregulated and downregulated, respectively. The expression of DEPs related to photosynthesis was significantly downregulated, and DEPs whose expression was significantly upregulated were associated with redox reactions. Many upregulated DEPs were also involved in pathways such as those involving phenylpropanoid, flavonoid, isoflavone and ginsenoside synthesis. The abundance of some ginsenoside monomers (Rg and Rb) also significantly increased in P. ginseng and P. quinquefolius. Moreover, P. quinquefolius contained 455 DEPs whose expression was higher than that in P. ginseng, including many proteins related to the regulation of ion homeostasis, indicating that P. quinquefolius is more resistant to iron toxicity stress than P. ginseng is.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112648DOI Listing
August 2021

Skin autofluorescence is associated with higher risk of cardiovascular events in Chinese adults with type 2 diabetes: A prospective cohort study from the Hong Kong Diabetes Biobank.

J Diabetes Complications 2021 Oct 4;35(10):108015. Epub 2021 Aug 4.

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, Chinese University of Hong Kong, Hong Kong, China. Electronic address:

Aims: To investigate association between skin autofluorescence (SAF) and cardiovascular events (CVE) and assess its predictive value in Chinese adults with type 2 diabetes (T2D).

Materials And Methods: SAF was measured non-invasively in 3806 Chinese adults with T2D between 2016 and 2019 with CVE as primary endpoint and individual components as secondary endpoints. Cox proportional hazard models were used to examine associations between SAF and endpoints with adjustment for conventional risk factors. C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were performed to evaluate SAF's predictive value.

Results: During a median 1.8 (interquartile range, 1.2-3.1) years of follow-up, 172 individuals experienced CVE. Multivariate Cox model showed that SAF was independently associated with CVE (HR 1.18 per SD, 95% CI [1.02, 1.37]), coronary heart disease (HR 1.29 per SD, 95% CI [1.02, 1.63]), and congestive heart failure (HR 1.53 per SD, 95% CI [1.14, 2.05]). SAF yielded additional value on CVE risk stratification with enhanced IDI (95% CI) (0.023 [0.001, 0.057]) and continuous NRI (0.377 [0.002, 0.558]) over traditional risk factors.

Conclusions: Higher SAF was independently associated with CVE in Chinese adults with T2D and yielded incremental predictive information for CVE. SAF has potential as a prognostic maker for CVE.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.108015DOI Listing
October 2021

Redox-Neutral Rhodium(III)-Catalyzed Chemospecific and Regiospecific [4+1] Annulation between Indoles and Alkenes for the Synthesis of Functionalized Imidazo[1,5-]indoles.

J Org Chem 2021 Aug 23;86(15):10591-10607. Epub 2021 Jul 23.

Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, P. R. China.

Exploiting internal alkenes embedded with an oxidizing function/leaving group as a rare and unconventional one-carbon unit, a redox-neutral rhodium(III)-catalyzed chemo- and regiospecific [4+1] annulation between indoles and alkenes for the synthesis of functionalized imidazo[1,5-]indoles has been achieved. Internal alkenes employed here can fulfill an unusual [4+1] annulation rather than normal [4+2] annulation/C-H alkenylation. This method is characterized by excellent chemo- and regioselectivity, broad substrate scope, good functional group tolerance, good to high yields, and redox-neutral conditions.
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http://dx.doi.org/10.1021/acs.joc.1c01256DOI Listing
August 2021

Rh(III)-Catalyzed Divergent Synthesis of Alkynylated Imidazo[1,5-]indoles and α,α-Difluoromethylene Tetrasubstituted Alkenes.

Org Lett 2021 08 19;23(15):5766-5771. Epub 2021 Jul 19.

Jinhua Branch, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Jinhua 321007, China.

Herein, we report the divergent synthesis of alkynylated imidazo[1,5-]indoles and α,α-difluoromethylene tetrasubstituted alkenes through Rh(III)-catalyzed [4 + 1] annulation/alkyne moiety migration and C-H alkenylation/DG migration, respectively. This protocol features tunable product selectivity, excellent chemo-, regio-, and stereoselectivity, broad substrate scope, moderate to high yields, good tolerance of functional groups, and mild redox-neutral conditions.
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http://dx.doi.org/10.1021/acs.orglett.1c01929DOI Listing
August 2021

LncRNA-TCONS_00034812 is upregulated in atherosclerosis and upregulates miR-21 through methylation in vascular smooth muscle cells.

Ann Transl Med 2021 Jun;9(12):1005

Department of Cardiovascular Medicine, University of South China Affiliated Changsha Central Hospital, Changsha, China.

Background: LncRNA-TCONS_00034812 is a critical player in the proliferation of aortic smooth muscle cells. It is known that artery injury plays an important role in atherosclerosis. However, the potential implication of LncRNA-TCONS_00034812 in atherosclerosis remains unclear. In this study, we collected artery specimens from patients with atherosclerosis and healthy controls to investigate the involvement of LncRNA-TCONS_00034812 in atherosclerosis.

Methods: Sixty patients with atherosclerosis and 60 controls, admitted at The First Hospital of Changsha (Changsha, China), between March 2017 and March 2019, were included. An artery biopsy was performed on all participants to obtain the artery specimens. Real-time quantitative PCR were performed to quantify the relative expression level of LncRNA-TCONS_00034812. Its role in atherosclerotic lesion was evaluated in (high fat diet) HFD-induced ApoE mice. Moreover, human aortic smooth muscle cells (HAOSMCs) was employed to study functional role of LncRNA-TCONS_00034812 overexpression and knockdown by methylation-specific PCR and cell proliferation assay.

Results: Overexpression of TCONS_00034812 resulted in miR-21 upregulation and a decrease of miR-21 gene methylation. In contrast, silencing of TCONS_00034812 caused miR-21 downregulation and an increase of miR-21 gene methylation. Cell proliferation analysis indicated that the overexpression of TCONS_00034812 and miR-21 promoted cell proliferation, while silencing of TCONS_00034812 played an opposite role. Moreover, miR-21 overexpression weakened the effects of silencing TCONS_00034812 on cell proliferation.

Conclusions: In summary, LncRNA-TCONS_00034812 is upregulated in atherosclerotic samples, and its overexpression upregulates miR-21 through methylation in human aortic smooth muscle cells (HAOSMCs). Our study indicates that LncRNA-TCONS_00034812 could serve as a potential biomarker for diagnosis of atherosclerosis.
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http://dx.doi.org/10.21037/atm-21-2632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267259PMC
June 2021

LC-MS-based lipidomic analysis in distinguishing patients with nonalcoholic steatohepatitis from nonalcoholic fatty liver.

Hepatobiliary Pancreat Dis Int 2021 Oct 25;20(5):452-459. Epub 2021 Jun 25.

Department of Medical Microbiology and Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China; Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China; Laboratory of Fatty Liver and Metabolic Diseases, Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China. Electronic address:

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the main liver diseases, and its pathologic profile includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). However, there is no reliable non-invasive parameter in distinguishing NASH from NAFL in clinical practice. The present study was to find a non-invasive way to differentiate these two categories of NAFLD via lipidomic analysis.

Methods: Lipidomic analysis was used to determine the changes of lipid moieties in blood from 20 NAFL and 10 NASH patients with liver biopsy. Liver histology was evaluated after hematoxylin and eosin staining and Masson's trichrome staining. The profile of lipid metabolites in correlation with steatosis, inflammation, hepatocellular necroptosis, fibrosis, and NAFLD activity score (NAS) was analyzed.

Results: Compared with NAFL patients, NASH patients had higher degree of steatosis, ballooning degeneration, lobular inflammation. A total of 434 different lipid molecules were identified, which were mainly composed of various phospholipids and triacylglycerols. Many lipids, such as phosphatidylcholine (PC) (P-22:0/18:1), sphingomyelin (SM) (d14:0/18:0), SM (d14:0/24:0), SM (d14:0/22:0), phosphatidylethanolamine (PE) (18:0/22:5), PC (O-22:2/12:0), and PC (26:1/11:0) were elevated in the NASH group compared to those in the NAFL group. Specific analysis revealed an overall lipidomic profile shift from NAFL to NASH, and identified valuable lipid moieties, such as PCs [PC (14:0/18:2), PE (18:0/22:5) and PC (26:1/11:0)] or plasmalogens [PC (O-22:0/0:0), PC (O-18:0/0:0), PC (O-16:0/0:0)], which were significantly altered in NASH patients. In addition, PC (14:0/18:2), phosphatidic acid (18:2/24:4) were positively correlated with NAS; whereas PC (18:0/0:0) was correlated positively with fibrosis score.

Conclusions: The present study revealed overall lipidomic profile shift from NAFL to NASH, identified valuable lipid moieties which may be non-invasive biomarkers in the categorization of NAFLD. The correlations between lipid moieties and NAS and fibrosis scores indicate that these lipid biomarkers may be used to predict the severity of the disease.
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http://dx.doi.org/10.1016/j.hbpd.2021.05.008DOI Listing
October 2021

Aggregation-Induced Emission-Based Platforms for the Treatment of Bacteria, Fungi, and Viruses.

Adv Healthc Mater 2021 Jun 30:e2100736. Epub 2021 Jun 30.

MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang Province, 310027, P. R. China.

The prevention and control of pathogenic bacteria, fungi, and viruses is a herculean task for all the countries since they greatly threaten global public health. Rapid detection and effective elimination of these pathogens is crucial for the treatment of related diseases. It is urgently demanded to develop new diagnostic and therapeutic strategies to combat bacteria, fungi, and viruses-induced infections. The emergence of aggregation-induced emission (AIE) luminogens (AIEgens) is a revolutionary breakthrough for the treatment of many diseases, including pathogenic infections. In this review, the main focus is on the applications of AIEgens for theranostic treatment of pathogenic bacteria, fungi, and viruses. Due to the AIE characteristic, AIEgens are promising fluorescent probes for the detection of bacteria, fungi, and viruses with excellent sensitivity and photostability. Moreover, AIEgen-based theranostic platforms can be fabricated by introducing bactericidal moieties or designing AIE photosensitizers and AIE photothermal agents. The current strategies and ongoing developments of AIEgens for the treatment of pathogenic bacteria, fungi, and viruses will be discussed in detail.
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http://dx.doi.org/10.1002/adhm.202100736DOI Listing
June 2021

Factors Associated With Individual Emergency Preparedness Behaviors: A Cross-Sectional Survey Among the Public in Three Chinese Provinces.

Front Public Health 2021 21;9:644421. Epub 2021 May 21.

School of Health Management, Harbin Medical University, Harbin, China.

This study aimed to identify factors associated with individual emergency preparedness behaviors which play an important role in effective emergency response. Data were drawn from a cross-sectional survey conducted in China's Heilongjiang, Guangdong and Sichuan provinces in 2017. Questionnaires were administered through face-to-face interviews, and 2,506 were valid for data analyses. A structural equation model was established to test the direct and indirect effects of the relevant factors on individual emergency preparedness behaviors. Low levels of emergency preparedness were found: 28% of respondents reported being fully/partly prepared. The attitudes of the respondents toward emergency preparedness had the strongest association with emergency preparedness behaviors, with a total effect of 0.483. This was followed by self-efficacy (0.305) and training/exercise (0.295). Risk perception had the weakest effect (0.045) on emergency preparedness behaviors. Improving attitudes of the public as well as their ability to prepare for emergency events is important for effective emergency management.
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http://dx.doi.org/10.3389/fpubh.2021.644421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175617PMC
June 2021

Gradient Porous Structure Templated by Breath Figure Method.

Langmuir 2021 May 5;37(19):6016-6021. Epub 2021 May 5.

MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, P. R. China.

Surfaces with gradient topography are important in various fields but are difficult to fabricate. Herein, we report a facile and robust way to fabricate a surface with gradient topography of porous structure, in one direction, based on the breath figure (BF) method for the first time. The influencing factors including relative humidity (RH), sample immersion time, and solvent composition, affecting the speed, time, and model of the droplet growth, respectively, were investigated to control gradient BF pores with different ranges of pore sizes. Applying appropriate parameters, gradient BF pores with a diameter difference over 400% were prepared on one sample. The mechanism of gradient duration of solvent evaporation at different regions of a sample for fabricating gradient pores was proposed and experimentally verified with recording optical and thermographic changes of the sample in the BF procedure. This new method provides a novel site for gradient topography fabrication.
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http://dx.doi.org/10.1021/acs.langmuir.1c00636DOI Listing
May 2021

Tailoring Supramolecular Prodrug Nanoassemblies for Reactive Nitrogen Species-Potentiated Chemotherapy of Liver Cancer.

ACS Nano 2021 05 30;15(5):8663-8675. Epub 2021 Apr 30.

MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.

The development of a controllable reactive nitrogen species (RNS) generation system for cancer treatment has remained elusive. Herein, a supramolecular prodrug nanoassemblies (SPNA) strategy that co-delivers a nitric oxide (NO) donor and a superoxide anion (O) inducing chemotherapeutic agent was reported for RNS-potentiated chemotherapy. The mole ratio of platinum(IV) prodrug and NO donor could be precisely tailored in SPNA. Platinum(II) and NO would be released intracellularly to produce a highly toxic RNS, peroxynitrite anion (ONOO). The levels of glutathione reductase (GR) and xeroderma pigmentosum group A (XPA) were down-regulated by ONOO, thus synergistically decreasing detoxification and blocking DNA damage repair of Pt-based chemotherapy. The RNS-potentiated efficacy of SPNA was validated on subcutaneous hepatoma xenograft models and an orthotopic cisplatin-resistant hepatoma model. This co-delivery strategy of NO donor and O inducing chemotherapeutic agents for RNS-mediated therapy provides an insightful direction for cancer treatment.
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http://dx.doi.org/10.1021/acsnano.1c00698DOI Listing
May 2021

A Synthetic Biodegradable Polymer Membrane for Guided Bone Regeneration in Bone Defect.

J Biomed Nanotechnol 2021 Mar;17(3):456-465

Guided bone regeneration (GBR) technique is most commonly used to treat alveolar bone defect. Polylactic acid (PLA) attracts much attention to utilize as a GBR membrane because it has relatively high mechanical strength and biodegradability. However, randomized controlled trials of PLA as a GBR membrane in animals were rare. The aim of this work is to observe the efficacy of polylactic acid membrane in guiding bone regeneration in Beagle canine alveolar bone defect restoration and to compare efficacy with the collagen membrane, providing an experimental basis for further clinical use of the polylactic acid membrane. The tests of physical and chemical properties showed that the PLA membrane has well mechanical strength to maintenance the space for the new bone, and has proper aperture for the attachment of osteoblasts. Through X-ray and histopathological examination of the different time points, the bone grafting material covered with PLA membrane can form similar mature bone compared to collagen membrane ones. Meanwhile, biodegradable speed of the PLA membrane was slower. Thus, this study showed that polylactic acid membrane as synthetic biodegradable polymer was reliably effective in guiding bone regeneration of alveolar bone defects, showed the favorable osteogenic capability and forecasts well applications in bone augmentation.
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http://dx.doi.org/10.1166/jbn.2021.3044DOI Listing
March 2021

Antimicrobial nanomedicine for ocular bacterial and fungal infection.

Drug Deliv Transl Res 2021 Aug 11;11(4):1352-1375. Epub 2021 Apr 11.

Eye Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, People's Republic of China.

Ocular infection induced by bacteria and fungi is a major cause of visual impairment and blindness. Topical administration of antibiotics remains the first-line treatment, as effective eradication of pathogens is the core of the anti-infection strategy. Whereas, eye drops lack efficiency and have relatively low bioavailability. Intraocular injection may cause concurrent ocular damage and secondary infection. In addition, antibiotic-based management can be limited by the low sensitivity to multidrug-resistant bacteria. Nanomedicine is proposed as a prospective, effective, and noninvasive platform to mediate ocular delivery and combat pathogen or even resistant strains. Nanomedicine can not only carry antimicrobial agents to fight against pathogens but also directly active microbicidal capability, killing pathogens. More importantly, by modification, nanomedicine can achieve enhanced residence time and release time on the cornea, and easy penetration through corneal tissues into anterior and posterior segments of the eye, thus improving the therapeutic effect for ocular infection. In this review, several categories of antimicrobial nanomedicine are systematically discussed, where the efficiency and possibility of further embellishment and improvement to adapt to clinical use are also investigated. All in all, novel antimicrobial nanomedicine provides potent and prospective ways to manage severe and refractory ocular infections.
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http://dx.doi.org/10.1007/s13346-021-00966-xDOI Listing
August 2021

Near-room temperature ferromagnetic insulating state in highly distorted LaCoO with CoO square pyramids.

Nat Commun 2021 Mar 25;12(1):1853. Epub 2021 Mar 25.

Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.

Dedicated control of oxygen vacancies is an important route to functionalizing complex oxide films. It is well-known that tensile strain significantly lowers the oxygen vacancy formation energy, whereas compressive strain plays a minor role. Thus, atomic reconstruction by extracting oxygen from a compressive-strained film is challenging. Here we report an unexpected LaCoO phase with a zigzag-like oxygen vacancy ordering through annealing a compressive-strained LaCoO in vacuum. The synergetic tilt and distortion of CoO square pyramids with large La and Co shifts are quantified using scanning transmission electron microscopy. The large in-plane expansion of CoO square pyramids weaken the crystal field splitting and facilitated the ordered high-spin state of Co, which produces an insulating ferromagnetic state with a Curie temperature of ~284 K and a saturation magnetization of ~0.25 μ/Co. These results demonstrate that extracting targeted oxygen from a compressive-strained oxide provides an opportunity for creating unexpected crystal structures and novel functionalities.
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http://dx.doi.org/10.1038/s41467-021-22099-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994406PMC
March 2021

Dimensional Control of Octahedral Tilt in SrRuO via Infinite-Layered Oxides.

Nano Lett 2021 Apr 22;21(7):3146-3154. Epub 2021 Mar 22.

Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

Manipulation of octahedral distortion at atomic scale is an effective means to tune the ground states of functional oxides. Previous work demonstrates that strain and film thickness are variable parameters to modify the octahedral parameters. However, selective control of bonding geometry by structural propagation from adjacent layers is rarely studied. Here we propose a new route to tune the ferromagnetism in SrRuO (SRO) ultrathin layers by oxygen coordination of adjacent SrCuO (SCO) layers. The infinite-layered CuO exhibits a structural transformation from "planar-type" to "chain-type" with reduced film thickness. Two orientations dramatically modify the polyhedral connectivity at the interface, thus altering the octahedral distortion of SRO. The local structural variation changes the spin state of Ru and orbital hybridization strength, leading to a significant change in the magnetoresistance and anomalous Hall resistivity. These findings could launch investigations into adaptive control of functionalities in quantum oxide heterostructures using oxygen coordination.
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http://dx.doi.org/10.1021/acs.nanolett.1c00352DOI Listing
April 2021

lncRNA MIR22HG-Derived miR-22-5p Enhances the Radiosensitivity of Hepatocellular Carcinoma by Increasing Histone Acetylation Through the Inhibition of HDAC2 Activity.

Front Oncol 2021 24;11:572585. Epub 2021 Feb 24.

Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, China.

Background: With the development of radiotherapy technology, radiotherapy has been increasingly used to treat primary hepatocellular carcinoma (HCC). However, due to radioresistance and the intolerance of the adjacent organs to radiation, the effects of radiotherapy are often unsatisfactory. Therefore, it is necessary to study radiosensitization in HCC.

Method: A microarray was used to analyze the genes that were significantly associated with radiosensitivity. HCC cells, HepG2 and MHCC97H, were subjected to radiation . Real-time PCR was performed to determine MIR22HG (microRNA22 host gene) and miR-22-5p expression levels. Western blotting was performed to determine histone expression levels. A histone deacetylase (HDAC) whole cell assay was used to determine the activity of HDAC2. MTT, colony formation, 5-ethynyl-2'-deoxyuridine, and wound healing assays were performed to examine the function of MIR22HG and miR-22-5p in cellular radiosensitivity. Chromatin immunoprecipitation-PCR was used to confirm that HDAC2 affects the acetylation level of the MIR22HG promoter region. Finally, animal experiments were performed to demonstrate the effect of MIR22HG on the radiosensitivity of hepatoma.

Results: Irradiation can up-regulate MIR22HG expression and down-regulate HDAC2 expression. Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region and up-regulates MIR22HG expression. MIR22HG can increase radiosensitivity miR-22-5p in HCC.

Conclusion: Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region, thereby up-regulating the expression of MIR22HG and promoting the production of miR-22-5p, and ultimately increasing the sensitivity of liver cancer radiotherapy.
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http://dx.doi.org/10.3389/fonc.2021.572585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943860PMC
February 2021

Rapid build-up of high-throughput screening microarrays with biochemistry gradients via light-induced thiol-ene "click" chemistry.

J Mater Chem B 2021 04 11;9(13):3032-3037. Epub 2021 Mar 11.

MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.

Microarrays have become extremely powerful experimental tools for high-throughput screening of cell behaviors in multivariate microenvironments. Herein, a microarray-based high-throughput platform with biochemistry gradients was developed using poly(limonene carbonate) (PLimC) as a substrate through thiol-ene click chemistry. ATR-IR, XPS, Raman spectrum, and water contact angle results demonstrated that the sulfhydryl molecules, including PEG (polyethylene glycol) and RGD (arginine-glycine-aspartic acid) peptide, could be grafted onto PLimC substrates, while the grafting density could be well controlled by regulating the intensity of UV irradiation. Then, microarrays with a gradient of RGD grafting density were fabricated by using UV irradiation patterned by a photomask and a gradient light filter. Adhesion experiments of smooth muscle cells and 3T3-L1 mouse embryonic fibroblast cells proved that the cell behaviors were highly determined by the RGD density. This platform puts forward a facile, high-throughput method to study the effect of biochemical signal density on cell behaviors.
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http://dx.doi.org/10.1039/d1tb00167aDOI Listing
April 2021

Clinical features and relative factors of constipation in a cohort of Chinese patients with Parkinson's disease.

World J Gastrointest Pharmacol Ther 2021 Jan;12(1):21-31

Department of Rehabilitation Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.

Background: Constipation as a most common non-motor symptom of Parkinson's disease (PD), has a higher prevalence compared to the general population. The etiologies of constipation in PD are diverse. In addition to physical weakness and other factors of disease, the lifestyles and eating habits are also important factors. Therefore, the prevalence and influencing factors of constipation may vary among different populations.

Aim: To determine the prevalence of constipation and analyze relative factors in a cohort of Chinese patients with PD.

Methods: All the patients diagnosed with PD according to the movement disorders society criteria were consecutively collected by a self-developed questionnaire. Rome III diagnostic criteria were used to assess functional constipation and Wexner score was used to estimate the severity of constipation. Non-motor symptoms (NMS) were assessed with the non-motor symptoms assessment scale (NMSS). Unified Parkinson's disease Rating Scale III (UPDRS III) was used to evaluate the severity of motor symptoms. The modified Hoehn-Yahr stage was used to evaluate the severity of PD. Cognitive function was assessed using Montreal cognitive assessment (MoCA). Depression and anxiety were rated with the Hamilton depression scale (HAMD) and the Hamilton anxiety scale (HAMA). Quality of life was assessed using the Parkinson's disease Questionnaire-39 items (PDQ-39).

Results: Of 166 patients enrolled, 87 (52.41%) were accompanied with constipation, and 30 (34.48%) experienced constipation for 6.30 ± 5.06 years before motor symptoms occurred. Age, Hoehn-Yahr stage, disease duration, levodopa medication times, incidence of motor complications, the scores of UPDRS total, UPDRS III, NMSS, HAMD, HAMA, and PDQ-39 in the constipation group were higher than those in the non-constipation group ( < 0.05), but there was no difference in the scores of MoCA, clinical types, or medications between the two groups ( > 0.05). There was a higher incidence of depression in patients with constipation ( < 0.05), but there were no difference in the incidence of anxiety and cognitive impairment between the two groups ( > 0.05). As Hoehn-Yahr stages increased, the severity of constipation increased ( < 0.05), but not the incidence of constipation ( > 0.05). Pearson correlation analysis showed that constipation was moderately positively correlated with age, Hoehn-Yahr stage, and scores of NMSS, UPDRS III, UPDRS total, PDQ-39, HAMD, and HAMA ( = 0.255, 0.172, 0.361, 0.194, 0.221, 0.237, 0.238, and 0.207, < 0.05). Logistic regression analysis showed that only NMSS score was an independent risk factor for constipation ( < 0.001).

Conclusion: Our findings confirm that constipation has a relatively high frequency in patients with PD. PD patients with constipation have a higher incidence of depression, which leads to worse quality of life.
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http://dx.doi.org/10.4292/wjgpt.v12.i1.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844575PMC
January 2021

Additive-Controlled Divergent Synthesis of Tetrasubstituted 1,3-Enynes and Alkynylated 3-Pyrrolo[1,2-]indol-3-ones via Rhodium Catalysis.

Org Lett 2021 02 8;23(3):727-733. Epub 2021 Jan 8.

Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, P. R. China.

Herein, we report the additive-controlled divergent synthesis of tetrasubstituted 1,3-enynes and alkynylated 3-pyrrolo[1,2-]indol-3-ones through rhodium-catalyzed C-H alkenylation/DG migration and [3+2] annulation, respectively. This protocol features rare directing group migration in 1,3-diyne-involved C-H activation, excellent regio- and stereoselectivity, excellent monofunctionalization over difunctionalization, broad substrate scope, moderate to high yields, good functional group compatibility, and mild redox-neutral conditions.
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http://dx.doi.org/10.1021/acs.orglett.0c03950DOI Listing
February 2021

Multi-Locus Phylogeny and Taxonomy of the Fungal Complex Associated With Rusty Root Rot of in China.

Front Microbiol 2020 16;11:618942. Epub 2020 Dec 16.

Engineering Research Center, Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, China.

Panax rusty root rot caused by the species complex is a devastating disease, and it is one of the main factors contributing to the difficulty in continual cropping. Rusty root rot occurs in all ginseng fields, but little is known about the taxonomy of the fungal pathogen complex, especially and -like species. Rusty root rot samples were collected from commercial ginseng cultivation areas of China, and the pathogens were isolated and purified as single spores. Based on the combination analysis of multiple loci (rDNA-ITS, , , , , LSU, , , and SSU) and morphological characteristics, the pathogens causing ginseng rusty root rot were determined. Fungal isolates were obtained from infected roots in 56 locations within main cultivation areas in China. A total of 766 strains were identified as , -like and species, including (55.0%), (21.7%), (10.9%), (2.0%), (1.3%), (1.3%), (2.0%), (0.5%), sp. (0.5%), and (1.5%), and four novel species, (1.0%), (1.0%), (0.8%) and (0.5%), with a total of 14 species. As the pathogen present in the highest proportion, was the most prevalent and damaging species, unlike the pathogens reported previously. All of the examined strains were proven to cause ginseng rusty root rot. Our results indicate that the taxonomy of the fungal complex associated with ginseng rusty root rot includes , -like genera (, , and ) and .
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http://dx.doi.org/10.3389/fmicb.2020.618942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772391PMC
December 2020

Strong Ferromagnetism Achieved via Breathing Lattices in Atomically Thin Cobaltites.

Adv Mater 2021 Jan 13;33(4):e2001324. Epub 2020 Dec 13.

Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.

Low-dimensional quantum materials that remain strongly ferromagnetic down to monolayer thickness are highly desired for spintronic applications. Although oxide materials are important candidates for the next generation of spintronics, ferromagnetism decays severely when the thickness is scaled to the nanometer regime, leading to deterioration of device performance. Here, a methodology is reported for maintaining strong ferromagnetism in insulating LaCoO (LCO) layers down to the thickness of a single unit cell. It is found that the magnetic and electronic states of LCO are linked intimately to the structural parameters of adjacent "breathing lattice" SrCuO (SCO). As the dimensionality of SCO is reduced, the lattice constant elongates over 10% along the growth direction, leading to a significant distortion of the CoO octahedra, and promoting a higher spin state and long-range spin ordering. For atomically thin LCO layers, surprisingly large magnetic moment (0.5 μ /Co) and Curie temperature (75 K), values larger than previously reported for any monolayer oxides are observed. The results demonstrate a strategy for creating ultrathin ferromagnetic oxides by exploiting atomic heterointerface engineering, confinement-driven structural transformation, and spin-lattice entanglement in strongly correlated materials.
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http://dx.doi.org/10.1002/adma.202001324DOI Listing
January 2021

Macromolecular Platform with Super-Cation Enhanced Trans-Cornea Infiltration for Noninvasive Nitric Oxide Delivery in Ocular Therapy.

ACS Nano 2020 Dec 8. Epub 2020 Dec 8.

MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, Zhejiang Province, P.R. China.

The cornea provides important protection for human eyes from invasion of alien substances. However, its blockage on the infiltration of molecules also constitutes a great challenge for noninvasive trans-cornea delivery of drugs. Here we report polyamino acid-based -nitrosothiols with high cationic charge density as a NO carrier to overcome cornea associated blockage in ophthalmological therapy. Our results demonstrate that the cationic nature of the polymer promoted transcytosis, which greatly enhances the trans-cornea delivery of the NO donor and bypasses cornea barriers on passive drug diffusion. The combination of super cation and glutathione responsiveness synergistically enhanced intraocular delivery of topically administered poly(2-acetamido--triethylenetetramine-3-nitrosothiol-3-methylbutanamide)aspartamide, effectively alleviating high intraocular pressure in mice with glaucoma. Such a noninvasive "barrier hopping" approach not only serves as an inspiration in improving the efficiency of trans-cornea drug delivery but also has great potential in overcoming drug transporting barriers in other biomedical applications.
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http://dx.doi.org/10.1021/acsnano.0c05977DOI Listing
December 2020

Strain-Mediated High Conductivity in Ultrathin Antiferromagnetic Metallic Nitrides.

Adv Mater 2021 Jan 2;33(2):e2005920. Epub 2020 Dec 2.

Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.

Strain engineering provides the ability to control the ground states and associated phase transition in epitaxial films. However, the systematic study of the intrinsic character and strain dependency in transition-metal nitrides remains challenging due to the difficulty in fabricating stoichiometric and high-quality films. Here the observation of an electronic state transition in highly crystalline antiferromagnetic CrN films with strain and reduced dimensionality is reported. By shrinking the film thickness to a critical value of ≈30 unit cells, a profound conductivity reduction accompanied by unexpected volume expansion is observed in CrN films. The electrical conductivity is observed surprisingly when the CrN layer is as thin as a single unit cell thick, which is far below the critical thickness of most metallic films. It is found that the metallicity of an ultrathin CrN film recovers from insulating behavior upon the removal of the as-grown strain by the fabrication of freestanding nitride films. Both first-principles calculations and linear dichroism measurements reveal that the strain-mediated orbital splitting effectively customizes the relatively small bandgap at the Fermi level, leading to an exotic phase transition in CrN. The ability to achieve highly conductive nitride ultrathin films by harnessing strain-control over competing phases can be used for utilizing their exceptional characteristics.
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http://dx.doi.org/10.1002/adma.202005920DOI Listing
January 2021

Chronic Kidney Diseases and Acute Kidney Injury in Patients With COVID-19: Evidence From a Meta-Analysis.

Front Med (Lausanne) 2020 3;7:588301. Epub 2020 Nov 3.

Department of Nephrology, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Renal involvement has been implicated in coronavirus disease 2019 (COVID-19), but the related prevalence and prognosis were largely unknown. In this meta-analysis, we searched the literature from PubMed, Embase, through bioRxiv, and medRxiv until April 26, 2020. Studies reporting chronic kidney diseases (CKDs) and/or acute kidney injury (AKI) were included. Demographics, relevant data of disease severity, and patient's prognosis were extracted and aggregated. Twenty-one thousand one hundred sixty-four patients from 52 peer-reviewed studies were included. Thirty-seven studies ( = 16,922) reported CKD in COVID-19 patients at diagnosis, and the pooled prevalence was 3.52% (95% CI, 1.98-5.48%; = 93%). Subgroup analysis showed that CKD prevalence was higher in severe cases [odds ratio (OR), 3.42; 95% CI 2.05-5.61; = 0%] compared to those with non-severe disease and deceased cases (6.46, 3.40-12.29; = 1%) compared with survivors. Pooled prevalence of CKD was lower in Chinese patients (2.56%; 95% CI, 1.79-3.47%; = 80%) compared to those outside of China (6.32%; 95% CI, 0.9-16.12%; = 93%) ( = 0.08). The summary estimates for AKI prevalence was 11.46% (95% CI, 6.93-16.94%). Patients with AKI had a higher prevalence of developing into severe cases (OR, 6.97; 95% CI, 3.53-13.75; = 0%) and mortality risk (45.79, 36.88-56.85; = 17%). The prevalence estimates of CKD or AKI were not significantly different from preprint publications ( > 0.05). Our study indicates that renal condition, either in CKD or AKI, is associated with COVID-19 prognosis, and taking care of such patients needs further awareness and investigations.
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http://dx.doi.org/10.3389/fmed.2020.588301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670057PMC
November 2020

Rhodium(III)-Catalyzed C-H Alkenylation/Directing Group Migration for the Regio- and Stereoselective Synthesis of Tetrasubstituted Alkenes.

Org Lett 2020 12 16;22(23):9163-9168. Epub 2020 Nov 16.

Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University , Chengdu 610052, China.

An efficient Rh(III)-catalyzed C-H alkenylation/directing group migration cascade between indoles and alkynes for the assembly of tetrasubstituted alkenes is reported. The carbamoyl directing group migrates to the carbon of the alkene moiety of the products through rare Rh-catalyzed C-N bond cleavage after the C-H alkenylation step and thus acts as an internal amidation reagent. This protocol shows broad substrate scope, excellent regio/stereoselectivity, and good to excellent yields.
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http://dx.doi.org/10.1021/acs.orglett.0c03077DOI Listing
December 2020

Emerging antibacterial nanomedicine for enhanced antibiotic therapy.

Biomater Sci 2020 Dec;8(24):6825-6839

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.

Antibiotic therapy is the most powerful strategy for treating bacterial infections in clinic. However, antibiotic resistance has become one of the biggest threats to public health worldwide due to the misuse and abuse of antibiotics. What is worse, the speed of the discovery of new antibiotics is largely hysteretic compared to the growth of antibiotic resistance. The world is on the threshold of the "post-antibiotic era". Nanomaterials have shown great potential in restoring the antibacterial activity of conventional antibiotics by different mechanisms, including optimizing pharmacokinetics, improving antibiotic internalization, interfering with bacterial metabolism, enhancing biofilm penetration, changing biofilm microenvironments, and so on. The combination of nanotechnology and antibiotics would be the most promising strategy to cope with antibiotic-resistant bacteria. In this review, the mechanisms of antibiotic resistance are introduced and the recent strategies for improving the therapeutic efficacy of antibiotics to combat drug resistance using nanomaterials are summarized. The advantages and mechanisms of nanoparticle-based antibiotics are overviewed as well. Moreover, the challenges of nano-antibiotics in clinical applications have also been discussed.
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http://dx.doi.org/10.1039/d0bm00974aDOI Listing
December 2020

Surging publications on the COVID-19 pandemic.

Clin Microbiol Infect 2021 Mar 22;27(3):484-486. Epub 2020 Sep 22.

School of Medicine and Vanke School of Public Health, Tsinghua University, Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.cmi.2020.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506363PMC
March 2021

Biofilm microenvironment activated supramolecular nanoparticles for enhanced photodynamic therapy of bacterial keratitis.

J Control Release 2020 11 11;327:676-687. Epub 2020 Sep 11.

Eye Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, PR China; Zhejiang Provincial Key Lab of Ophthalmology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, PR China. Electronic address:

Infectious keratitis caused by bacterial biofilms is one of the main causes of corneal blindness, presenting a serious threat to public health. In this study, matrix metalloproteinase (MMP)-sensitive supramolecular nanoparticles (denoted as MMP-S NPs) were constructed for enhancing photodynamic antibacterial effect against biofilm-associated bacterial keratitis. MMP-S NPs were prepared by host-guest self-assembly of chlorin e6 (Ce6) conjugated β-cyclodextrin (β-CD) prodrug (β-CD-Ce6) and MMP-9-sensitive peptides (YGRKKKRRQRRR-GPLGVRG-EEEEEE) terminated with adamantane (Ad) (Ad-MMP-S PEPs). MMP-S NPs with EEEEEE peptide shell had a negatively charged surface, preventing adhesion to the normal ocular surface or healthy corneal cells, thus enhancing tear retention time. After arriving at the infected lesions, the protective EEEEEE peptide shell of MMP-S NPs was removed, triggered by overexpressed MMP-9 in the keratitis microenvironment. The subsequently exposed cationic peptides helped the nanoparticles penetrate and accumulate in biofilms as well as bind to Gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa), which eventually improved the photodynamic antibacterial effect. Furthermore, the P. aeruginosa keratitis model verified the high effectiveness of a topical eye drop formulation of MMP-S NPs in killing bacteria by destroying the bacterial membrane as a result of in situ photodynamic activation of reactive oxygen species (ROS) formation under light irradiation. Moreover, the inflammatory response in the cornea was inhibited to a great extent. As a result, further damage to the corneal tissue was completely suppressed. This research provides a viable antibacterial alternative to fight against bacterial keratitis through effective elimination of infectious bacteria and eradication of bacterial biofilms in the cornea.
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http://dx.doi.org/10.1016/j.jconrel.2020.09.014DOI Listing
November 2020

3-Bromopyruvate-Conjugated Nanoplatform-Induced Pro-Death Autophagy for Enhanced Photodynamic Therapy against Hypoxic Tumor.

ACS Nano 2020 08 31;14(8):9711-9727. Epub 2020 Jul 31.

MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, People's Republic of China.

Autophagy triggered by reactive oxygen species (ROS) in photodynamic therapy (PDT) generally exhibits an anti-apoptotic effect to promote cell survival. Herein, an innovative supramolecular nanoplatform was fabricated for enhanced PDT by converting the role of autophagy from pro-survival to pro-death. The respiration inhibitor 3-bromopyruvate (3BP), which can act as an autophagy promoter and hypoxia ameliorator, was integrated into photosensitizer chlorin e6 (Ce6)-encapsulated nanoparticles to combat hypoxic tumor. 3BP could inhibit respiration by down-regulating HK-II and GAPDH expression to significantly reduce intracellular oxygen consumption rate, which could relieve tumor hypoxia for enhanced photodynamic cancer therapy. More importantly, the autophagy level was significantly elevated by the combination of 3BP and PDT determined by Western blot, immunofluorescent imaging, and transmission electron microscopy. It was very surprising that excessively activated autophagy promoted cell apoptosis, leading to the changeover of autophagy from pro-survival to pro-death. Therefore, PDT combined with 3BP could achieve efficient cell proliferation inhibition and tumor regression. Furthermore, hypoxia-inducible factor-1α (HIF-1α) could be down-regulated after tumor hypoxia was relieved by 3BP. Tumor metastasis could then be effectively inhibited by eliminating primary tumors and down-regulating HIF-1α expression. These results provide an inspiration for future innovative approaches of cancer therapy by triggering pro-death autophagy.
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http://dx.doi.org/10.1021/acsnano.0c01350DOI Listing
August 2020

Analysis of Motor Complication and Relative Factors in a Cohort of Chinese Patients with Parkinson's Disease.

Parkinsons Dis 2020 29;2020:8692509. Epub 2020 Jul 29.

Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

Objective: Motor complications are common in Parkinson's disease (PD). The reported occurrence of motor complications varies across regions and races. The aim of our study was to describe the development of dyskinesias and motor fluctuations among Chinese PD patients and the relative risk factors.

Methods: In the current cross-sectional survey study, PD patients with motor fluctuations and dyskinesia were enrolled from March to November 2018 in Shaanxi province, a northwest area of China. Data were collected by the movement disorder specialists. A self-designed questionnaire was utilized during face-to-face interviews. In addition, the relevant factors of motor complications were analyzed by univariable and multivariable analyses.

Results: Of the166 PD patients recruited, 52 (31.33%) and 25 (15.06%) patients had motor fluctuations and dyskinesia, respectively, which occurred in 6.76 ± 3.77 and 8.61 ± 4.46 years after the onset of motor symptoms and 5.37 ± 3.33 and 6.80 ± 3.43 years after the treatment of levodopa therapy, respectively. Patients with motor fluctuations and dyskinesias had longer disease duration, younger onset age, higher Hoehn-Yahr stages and UPDRS III scores, higher daily levodopa dosage and levodopa equivalent daily dose (LEDD), and longer duration of levodopa treatment ( < 0.05). Bradykinesia-rigidity dominant patients had higher incidences of motor fluctuations (61.54% vs 38.46%) and dyskinesias (68.00% vs 32.00%) than tremor-dominant patients ( < 0.05). Results of the multivariate logistic regression analyses showed that the duration of levodopa therapy, age of the onset, and bradykinesia-rigidity dominant type were independent risk factors of motor fluctuations ( < 0.05). In addition, duration of disease and bradykinesia-rigidity dominant type were independent risk factors of dyskinesia ( < 0.05).

Conclusions: The rate of motor fluctuations was higher than dyskinesias in Chinese patients with Parkinson's disease. Patients with younger age onset, bradykinesia-rigidity dominant type, longer disease duration, and longer duration of levodopa therapy are more likely to develop motor complications.
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http://dx.doi.org/10.1155/2020/8692509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411499PMC
July 2020
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