Publications by authors named "Weiwei Zhao"

228 Publications

Photoluminescence enhancement at a high generation rate induced by exciton localization.

Opt Lett 2021 Jun;46(11):2774-2777

The photoluminescence (PL) efficiency of two-dimensional (2D) transition metal dichalcogenides (TMDs) is extremely low under high power excitation, limiting its potential in display and light-emission application. This arises from the much shorter lifetime of non-radiative recombination than radiative recombination, wherein photo-carriers tend to decay through non-radiative processes. Herein, a "molecular state" near the valence band is successfully introduced into the ${{\rm MoS}_2}$ monolayer to increase the density of radiative states and speed up the exciton relaxation. This reduces the recombination lifetime of excitons by two orders of magnitude and forms vigorous competition with non-radiative decays. As a consequence, dozens of times enhancement of PL in ${{\rm MoS}_2}$ monolayers under high excitation power (${\rm G}\sim{{10}^{19}}\;{{\rm cm}^{- 2}}\cdot{{\rm S}^{- 1}}$) is realized. These results provide an effective method to improve PL efficiency under high injection levels for applications of 2D materials in light-emission industry.
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http://dx.doi.org/10.1364/OL.420709DOI Listing
June 2021

In Situ Synthesized Selenium Nanoparticles-Decorated Bacterial Cellulose/Gelatin Hydrogel with Enhanced Antibacterial, Antioxidant, and Anti-Inflammatory Capabilities for Facilitating Skin Wound Healing.

Adv Healthc Mater 2021 May 29:e2100402. Epub 2021 May 29.

National Engineering Research Center for Nano-Medicine, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.

Bacterial-associated wound infection and antibiotic resistance have posed a major burden on patients and health care systems. Thus, developing a novel multifunctional antibiotic-free wound dressing that cannot only effectively prevent wound infection, but also facilitate wound healing is urgently desired. Herein, a series of multifunctional nanocomposite hydrogels with remarkable antibacterial, antioxidant, and anti-inflammatory capabilities, based on bacterial cellulose (BC), gelatin (Gel), and selenium nanoparticles (SeNPs), are constructed for wound healing application. The BC/Gel/SeNPs nanocomposite hydrogels exhibit excellent mechanical properties, good swelling ability, flexibility and biodegradability, and favorable biocompatibility, as well as slow and sustainable release profiles of SeNPs. The decoration of SeNPs endows the hydrogels with superior antioxidant and anti-inflammatory capability, and outstanding antibacterial activity against both common bacteria (E. coli and S. aureus) and their multidrug-resistant counterparts. Furthermore, the BC/Gel/SeNPs hydrogels show an excellent skin wound healing performance in a rat full-thickness defect model, as evidenced by the significantly reduced inflammation, and the notably enhanced wound closure, granulation tissue formation, collagen deposition, angiogenesis, and fibroblast activation and differentiation. This study suggests that the developed multifunctional BC/Gel/SeNPs nanocomposite hydrogel holds a great promise as a wound dressing for preventing wound infection and accelerating skin regeneration in clinic.
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http://dx.doi.org/10.1002/adhm.202100402DOI Listing
May 2021

Immunomodulatory mechanism of Bacillus subtilis R0179 in RAW 264.7 cells against Candida albicans challenge.

Microb Pathog 2021 May 24;157:104988. Epub 2021 May 24.

Department of Oral Medicine, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China; Central Laboratory, Peking University School and Hospital of Stomatology, China; National Center of Stomatology, Peking University School and Hospital of Stomatology, China. Electronic address:

This study was aimed to explore the immunomodulatory and anti-Candida mechanisms of Bacillus subtilis (B. subtilis) R0179 in macrophages. RAW 264.7 cells were first challenged with B. subtilis R0179. B. subtilis R0179 was found to down-regulate the signals of Dectin-1, Card9, P-Iκ-Bα, Iκ-Bα, and NF-κB. Meanwhile, it reduced the levels of cytokines interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor (TNF)-α, but increased the level of cytokine IL-10. Then RAW 264.7 cells were pretreated with B. subtilis R0179 before challenged with Candida albicans (C. albicans) or RAW 264.7 cells were co-treated with B. subtilis R0179 and C. albicans. In the presence of C. albicans, B. subtilis R0179 also showed the similar immunomodulatory effects on RAW 264.7 cells. Hence, this study provides the first insight into the immunomodulatory mechanisms of B. subtilis R0179 on the Dectin-1-related downstream signaling pathways in macrophages, which may prevent tissue damage caused by excessive pro-inflammatory response during the infection of C. albicans.
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http://dx.doi.org/10.1016/j.micpath.2021.104988DOI Listing
May 2021

The clinical features and prognosis of patients with mucinous breast carcinoma compared with those with infiltrating ductal carcinoma: a population-based study.

BMC Cancer 2021 May 11;21(1):536. Epub 2021 May 11.

Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No 41 Damucang Hutong, Xicheng District, Beijing, 100032, China.

Background: At present, the characteristics of mucinous breast carcinoma (MBC) and the factors affecting its prognosis are controversial. We compared the clinical features of MBC with those of infiltrating ductal carcinoma (IDC) and summarized the relevant prognostic factors.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database includes information on 10,593 patients diagnosed with MBC between 2004 and 2016. Chi-square tests and analyses were used to analyze differences in variables between the MBC and IDC groups. Univariate and multivariate Cox proportional hazards models were used to assess the relative impacts of risk factors on cancer-specific survival (CSS) in patients. Kaplan-Meier survival curves were constructed to assess cancer-specific mortality and were compared using the log-rank test.

Results: From 2004 to 2016, 10,593 people were diagnosed with MBC, and 402,797 were diagnosed with IDC. Patients with MBC had significantly higher 5-/10-year CSS rates (96.4%/93.4%) than those with IDC (89%/83.8%). Compared with IDC patients, MBC patients had less lymph node metastasis, an earlier stage, a higher rate of hormone receptor positivity and a lower expression rate of HER2. Univariate and multivariate analyses showed that age ≥ 60 years old (HR = 1.574, 95%CI: 1.238-2.001, P < 0.001), singled status (HR = 1.676, 95%CI: 1.330-2.112, P < 0.001) and advanced TNM/SEER stage were independent prognostic risk factors for MBC. In addition, positive estrogen receptor (HR = 0.577, 95%CI: 0.334-0.997, P = 0.049), positive progesterone receptor (HR = 0.740, 95%CI: 0.552-0.992, P = 0.044), surgical treatment (HR = 0.395, 95%CI: 0.288-0.542, P < 0.001) and radiotherapy (HR = 0.589, 95%CI: 0.459-0.756, P < 0.001) were identified as protective factors.

Conclusion: Compared with IDC, MBC has a better prognosis. For patients with MBC, we identified prognostic factors that can help clinicians better assess patient outcomes and guide individualized treatment.
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http://dx.doi.org/10.1186/s12885-021-08262-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111957PMC
May 2021

The binding behaviours between cyclopentanocucurbit[6]uril and three amino acids.

R Soc Open Sci 2021 Mar 31;8(3):202120. Epub 2021 Mar 31.

Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, People's Republic of China.

Binding behaviours between cyclopentanocucurbit[6]uril (CyPQ[6]) and three amino acids have been investigated by means of X-ray crystallography, proton nuclear magnetic resonance spectroscopy and isothermal titration calorimetry. The results showed that CyPQ[6] forms a 1 : 2 inclusion complex with glycine, but 1 : 1 complexes with both leucine and lysine. Whereas the carboxyl group of glycine can enter the interior of the cavity of CyPQ[6], only the alkyl chains of leucine and lysine can enter this cavity. Interestingly, leucine can adopt two different self-assembly modes upon its interaction with cucurbituril, depending on the external conditions, whereas glycine and lysine do not exhibit such behaviour.
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http://dx.doi.org/10.1098/rsos.202120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074881PMC
March 2021

Trimeric Cationic Surfactant Coacervation as a Versatile Approach for Removing Organic Pollutants.

Langmuir 2021 May 6;37(19):5993-6001. Epub 2021 May 6.

Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Colloid, Interface and Chemical Thermodynamics, CAS Research/Education Center for Excellence in Molecular Sciences, and Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

A versatile method to remove a broad spectrum of dye pollutants from wastewater rapidly and efficiently is highly desirable. Here, we report that the complex coacervation of cationic trimeric imine-based surfactants (TIS) with negatively charged hydrolyzed polyacrylamide (HPAM) can be used for this purpose. The coacervation occurs in a wide concentration and composition range and requires the HPAM and TIS concentrations as low as 0.1 g/L and 0.1 mM, respectively. Dye effluents treated by trimeric surfactants and HPAM complete phase separation within 30 s under turbulent conditions, which generates an exceedingly small volume fraction (0.4%) of viscoelastic coacervate and a clear supernatant with a dye removal efficiency of up to 99.9% for anionic and neutral dyes in dosages of up to 120 mg/L. Crowded molecular arrangement and thick framework in coacervate are responsible for the rapid phase separation rate and low volume fraction. The trimeric imine surfactant/polymer coacervation provides a simple, effective, and sustainable approach for the rapid removal of dyes and other organic pollutants.
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http://dx.doi.org/10.1021/acs.langmuir.1c00557DOI Listing
May 2021

Paper Information Recording and Security Protection Using Invisible Ink and Artificial Intelligence.

ACS Appl Mater Interfaces 2021 Apr 20;13(16):19443-19449. Epub 2021 Apr 20.

Key Laboratory of Micro-systems and Micro-structures Manufacturing of Ministry of Education, Institution Harbin Institute of Technology, Harbin 150001, China.

Conventional paper information protection mainly relies on stimuli-responsive functional materials that can display color or luminescence under external stimuli; however, this method is rather predictable and can be easily cracked. In this work, a paper information protection scheme combining fluorescent invisible ink and artificial intelligence was proposed. The ink was prepared by dissolving carbon nanoparticles in water, which has a high quantum yield and outstanding light stability and salt stability, thus ensuring the integrity of information in complex environments. A five-layer convolutional neural network (one of the two mainstream architectures in today's artificial intelligence fields) was specially trained based on ultraviolet light excited symbols printed by invisible ink. Using this scheme, the correct information could only be read with the specially trained neural network after ultraviolet (UV) irradiation. Without this trained neural network or UV irradiation, misleading messages will be presented. Moreover, it was possible to design unpredictable and highly complex password books to further increase information security. This smart strategy provides new opportunities for high-level paper information encryption and also proposes new ideas for the applications of carbon nanoparticles and artificial intelligence.
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http://dx.doi.org/10.1021/acsami.1c01179DOI Listing
April 2021

Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis.

Bioact Mater 2021 Oct 26;6(10):3596-3607. Epub 2021 Mar 26.

State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.

The occurrence of osteoarthritis (OA) is highly associated with the reduced lubrication property of the joint, where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the mechanism. In this study, bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel, we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment. Particularly, the lubricating microspheres ([email protected]) were fabricated by dip coating a self-adhesive polymer (DMA-MPC, synthesized by free radical copolymerization) on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres (GelMA, prepared via microfluidic technology), and encapsulated with an anti-inflammatory drug of diclofenac sodium (DS) to achieve the dual-functional performance. The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the [email protected] microspheres. In addition, the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model, and the biological tests including qRT-PCR, immunofluorescence staining assay, X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of OA. In summary, the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release, therefore representing a facile and promising technique for the treatment of OA.
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http://dx.doi.org/10.1016/j.bioactmat.2021.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022850PMC
October 2021

Development of a Ni-Doped VAl Topological Semimetal with a Significantly Enhanced HER Catalytic Performance.

J Phys Chem Lett 2021 Apr 12;12(15):3740-3748. Epub 2021 Apr 12.

Sauvage Laboratory for Smart Materials, School of Materials Science and Engineering, Harbin Institute of Technology, Shenzhen 518055, People's Republic of China.

Topological materials with robust topological surface states appear to be well-suited as electrochemical catalysts. However, few studies have been published on the development of non-noble metal topological catalysts, most likely because the topological properties tend to be attributed to the and orbital electrons, while transition-metal catalysis mainly involves orbital electrons. Herein, we proposed a topological semimetallic (TSM) compound, VAl, with a surface state consisting mainly of orbital electrons, as an electrocatalyst for the hydrogen evolution reaction (HER). Density functional theory (DFT) calculations showed that the surface state electrons enhanced the adsorption of H atoms. Moreover, the transfer of surface state electrons between the surface and adsorbed H atoms was optimized through nickel doping. We experimentally prepared single-crystals VAl and VNiAl alloys. Electrochemical analysis showed that not only did VNiAl outperform VAl but also it was among the best non-noble metal topological HER electrocatalysts currently available.
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http://dx.doi.org/10.1021/acs.jpclett.1c00238DOI Listing
April 2021

Induction of macrophage pyroptosis-related factors by pathogenic E. coli high pathogenicity island (HPI) in Yunnan Saba pigs.

BMC Vet Res 2021 Mar 7;17(1):114. Epub 2021 Mar 7.

College of Veterinary Medicine, Yunnan Agricultural University, Kunming, 650201, China.

Background: Pyroptosis plays a pivotal role in the pathogenesis of many inflammatory diseases. The molecular mechanism by which pyroptosis is induced in macrophages following infection with pathogenic E. coli high pathogenicity island (HPI) will be evaluated in our study.

Results: After infection with the HPI/HPI strains and LPS, decreased macrophage cell membrane permeability and integrity were demonstrated with propidium iodide (PI) staining and the lactate dehydrogenase (LDH) assay. HPI/HPI-infection was accompanied by upregulated expression levels of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD, with significantly higher levels detected in the HPI group compared to those in the HPI group (P < 0.01 or P < 0.05). HPI strain is more pathogenic than HPI strain.

Conclusion: Our findings indicate that pathogenic E. coli HPI infection of Saba pigs causes pyroptosis of macrophages characterized by upregulated expression of pyroptosis key factors in the NLRP3/ASC/caspase-1 signaling pathway, direct cell membrane pore formation, and secretion of the inflammatory factor IL-1β and IL-18 downstream of NLRP3 and caspase-1 activation to enhance the inflammatory response.
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http://dx.doi.org/10.1186/s12917-021-02824-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938518PMC
March 2021

Alterations of housekeeping proteins in human aged and diseased hearts.

Pflugers Arch 2021 Mar 26;473(3):351-362. Epub 2021 Feb 26.

Department of Physiology and Biophysics, Rush University Medical Center, 1750 West Harrison St. 1255 Jelke South, Chicago, IL, 60612, USA.

Pathological remodeling includes alterations of ion channel function and calcium homeostasis and ultimately cardiac maladaptive function during the process of disease development. Biochemical assays are important approaches for assessing protein abundance and post-translational modification of ion channels. Several housekeeping proteins are commonly used as internal controls to minimize loading variabilities in immunoblotting protein assays. Yet, emerging evidence suggests that some housekeeping proteins may be abnormally altered under certain pathological conditions. However, alterations of housekeeping proteins in aged and diseased human hearts remain unclear. In the current study, immunoblotting was applied to measure three commonly used housekeeping proteins (β-actin, calsequestrin, and GAPDH) in well-procured human right atria (RA) and left ventricles (LV) from diabetic, heart failure, and aged human organ donors. Linear regression analysis suggested that the amounts of linearly loaded total proteins and quantified intensity of total proteins from either Ponceau S (PS) blot-stained or Coomassie Blue (CB) gel-stained images were highly correlated. Thus, all immunoblotting data were normalized with quantitative CB or PS data to calibrate potential loading variabilities. In the human heart, β-actin was reduced in diabetic RA and LV, while GAPDH was altered in aged and diabetic RA but not LV. Calsequestrin, an important Ca regulatory protein, was significantly changed in aged, diabetic, and ischemic failing hearts. Intriguingly, expression levels of all three proteins were unchanged in non-ischemic failing human LV. Overall, alterations of human housekeeping proteins are heart chamber specific and disease context dependent. The choice of immunoblotting loading controls should be carefully evaluated. Usage of CB or PS total protein analysis could be a viable alternative approach for some complicated pathological specimens.
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http://dx.doi.org/10.1007/s00424-021-02538-xDOI Listing
March 2021

Light-responsive dual-functional biodegradable mesoporous silica nanoparticles with drug delivery and lubrication enhancement for the treatment of osteoarthritis.

Nanoscale 2021 Apr 25;13(13):6394-6399. Epub 2021 Feb 25.

State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.

Visible light-responsive dual-functional biodegradable mesoporous silica nanoparticles with drug delivery and lubrication enhancement were constructed by supramolecular interaction between azobenzene-modified mesoporous silica nanoparticles (bMSNs-AZO) and β-cyclodextrin-modified poly(2-methacryloyloxyethyl phosphorylcholine) (CD-PMPC). Visible light could effectively trigger azobenzene isomerization and thus induce drug release after passing through the dermal tissue. Additionally, the hydration layer formed by CD-PMPC on the surface of the nanoparticles played an important role in lubrication enhancement, which was beneficial for the treatment of osteoarthritis.
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http://dx.doi.org/10.1039/d0nr08887kDOI Listing
April 2021

Self-adhesive lubricated coating for enhanced bacterial resistance.

Bioact Mater 2021 Aug 4;6(8):2535-2545. Epub 2021 Feb 4.

State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.

Limited surface lubrication and bacterial biofilm formation pose great challenges to biomedical implants. Although hydrophilic lubricated coatings and bacterial resistance coatings have been reported, the harsh and tedious synthesis greatly compromises their application, and more importantly, the bacterial resistance property has seldom been investigated in combination with the lubrication property. In this study, bioinspired by the performances of mussel and articular cartilage, we successfully synthesized self-adhesive lubricated coating and simultaneously achieved optimal lubrication and bacterial resistance properties. Additionally, we reported the mechanism of bacterial resistance on the nanoscale by studying the adhesion interactions between biomimetic coating and hydrophilic/hydrophobic tip or living bacteria via atomic force microscopy. In summary, the self-adhesive lubricated coating can effectively enhance lubrication and bacterial resistance performances based on hydration lubrication and hydration repulsion, and represent a universal and facial strategy for surface functionalization of biomedical implants.
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http://dx.doi.org/10.1016/j.bioactmat.2021.01.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868611PMC
August 2021

Butyrylcholinesterase nanodepots with enhanced prophylactic and therapeutic performance for acute organophosphorus poisoning management.

J Mater Chem B 2021 02;9(7):1877-1887

School of Materials Science and Engineering, Harbin Institute of Technology, Shenzhen 518055, P. R. China. and Research Centre of Printed Flexible Electronics, School of Materials Science and Engineering, Harbin Institute of Technology, Shenzhen 518055, P. R. China.

Acute organophosphorus pesticide poisoning (AOPP) is a worldwide health concern that has threatened human lives for decades, which attacks acetylcholinesterase (AChE) and causes nervous system disorders. Classical treatment options are associated with short in vivo half-life and side effects. As a potential alternative, delivery of mammalian-derived butyrylcholinesterase (BChE) offers a cost-effective way to block organophosphorus attack on acetylcholinesterase, a key enzyme in the neurotransmitter cycle. Yet the use of exotic BChE as a prophylactic or therapeutic agent is compromised by short plasma residence, immune response and unfavorable biodistribution. To overcome these obstacles, BChE nanodepots (nBChE) composed of a BChE core/polymorpholine shell structure were prepared via in situ polymerization, which showed enhanced stability, prolonged plasma circulation, attenuated antigenicity and reduced accumulation in non-targeted tissues. In vivo administration of nBChE pre- or post-organophosphorus exposure in a BALB/C mouse model resulted in potent prophylactic and therapeutic efficiency. To our knowledge, this is the first systematic delivery of non-human BChE to tackle AOPP. In addition, this work also opens up a new avenue for real applications in both research and clinical settings to cope with acute intoxication-related diseases.
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http://dx.doi.org/10.1039/d0tb02478cDOI Listing
February 2021

High pathogenicity island is associated with enhanced autophagy in pathogenic Escherichia coli HPI - infected macrophages.

Res Vet Sci 2021 Mar 5;135:113-120. Epub 2021 Jan 5.

College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China. Electronic address:

High pathogenicity island (HPI), which is widely distributed in Escherichia coli (E. coli), can enhance the pathogenicity of E. coli. Thus the HPI positive E. coli could pose a threat to human and animal health. It remains to be elucidated how HPI affects the virulence of pathogenic E. coli. Autophagy is an important mechanism to maintain cellular homeostasis and an innate immunity responses of organisms against pathogens. The interaction between pathogenic E. coli possessing HPI (E. coli HPI) and host autophagy system has not been reported. In this study, it was demonstrated that pathogenic E. coli induced autophagy in 3D4/21 macrophages and HPI was associated with enhanced autophagy through transmission electron microscopy, immunofluorescence and real-time PCR. The PI3K/Akt/mTOR pathway is an important negative regulatory pathway for autophagy. Through detecting the expression of key genes of PI3K/Akt/mTOR pathway, it was speculated that HPI enhanced the inhibition of the signaling pathway stimulated by pathogenic E. coli. Furthermore, HPI inhibited the secretion of IFN-γ, while the presence of HPI did not significantly affect the secretion of IL-1β. This work is the first attempt to explore the interplay between HPI carried by pathogenic E. coli and host cell autophagy. The findings might enable better understanding of the contribution of HPI to pathogenicity.
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http://dx.doi.org/10.1016/j.rvsc.2021.01.006DOI Listing
March 2021

Redox-Sensitive Hyaluronic Acid Polymer Prodrug Nanoparticles for Enhancing Intracellular Drug Self-Delivery and Targeted Cancer Therapy.

ACS Biomater Sci Eng 2020 07 16;6(7):4106-4115. Epub 2020 Jun 16.

State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Shenzhen 518055, China.

Currently, available nanoscale anticancer drug delivery systems have low targeting and release efficiency, limiting their therapeutic effects. Thus, tumor-targeting nanocarriers for self-assembly of amphiphilic polymer-drug conjugates are urgently needed to improve drug targeting and treatment efficacy. Here, we report the construction of a stable, reduction-sensitive prodrug conjugate based on hyaluronic acid-grafted pH-sensitive doxorubicin (DOX). The amphiphilic prodrug copolymer self-assembled into spherical nanoparticles in aqueous solution and exhibited an average diameter of 150 nm. Prodrug micelles were stable in a normal physiological environment and achieve selective and rapid release under acidic pH and/or high reduction conditions. Cell Counting Kit-8, flow cytometry, and live cell imaging assays showed that the prodrug had high targeting and antitumor activity against CD44 receptors. Moreover, pharmacokinetics and biodistribution studies showed that the prodrug had a longer circulation time in BALB/c mice and higher accumulation in 4T1 tumors. Interestingly, the prodrug could effectively treat tumors with few side effects. These results showed that the DOX prodrug micelles developed in this study may have great potential in targeted therapy.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00762DOI Listing
July 2020

Interface-induced sign reversal of the anomalous Hall effect in magnetic topological insulator heterostructures.

Nat Commun 2021 Jan 4;12(1):79. Epub 2021 Jan 4.

Department of Physics, The Pennsylvania State University, University Park, PA, 16802, USA.

The Berry phase picture provides important insights into the electronic properties of condensed matter systems. The intrinsic anomalous Hall (AH) effect can be understood as the consequence of non-zero Berry curvature in momentum space. Here, we fabricate TI/magnetic TI heterostructures and find that the sign of the AH effect in the magnetic TI layer can be changed from being positive to negative with increasing the thickness of the top TI layer. Our first-principles calculations show that the built-in electric fields at the TI/magnetic TI interface influence the band structure of the magnetic TI layer, and thus lead to a reconstruction of the Berry curvature in the heterostructure samples. Based on the interface-induced AH effect with a negative sign in TI/V-doped TI bilayer structures, we create an artificial "topological Hall effect"-like feature in the Hall trace of the V-doped TI/TI/Cr-doped TI sandwich heterostructures. Our study provides a new route to create the Berry curvature change in magnetic topological materials that may lead to potential technological applications.
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http://dx.doi.org/10.1038/s41467-020-20349-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782489PMC
January 2021

Transient Receptor Potential Melastatin 8 (TRPM8) Channel Regulates Proliferation and Migration of Breast Cancer Cells by Activating the AMPK-ULK1 Pathway to Enhance Basal Autophagy.

Front Oncol 2020 4;10:573127. Epub 2020 Dec 4.

National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan, China.

The calcium-permeable cation channel TRPM8 (transient receptor potential melastatin 8) is a member of the TRP superfamily of cation channels that is upregulated in various types of cancer with high levels of autophagy, including prostate, pancreatic, breast, lung, and colon cancers. Autophagy is closely regulated by AMP-activated protein kinase (AMPK) and plays an important role in tumor growth by generating nutrients through degradation of intracellular structures. Additionally, AMPK activity is regulated by intracellular Ca concentration. Considering that TRPM8 is a non-selective Ca-permeable cation channel and plays a key role in calcium homoeostasis, we hypothesized that TRPM8 may control AMPK activity thus modulating cellular autophagy to regulate the proliferation and migration of breast cancer cells. In this study, overexpression of TRPM8 enhanced the level of basal autophagy, whereas TRPM8 knockdown reduced the level of basal autophagy in several types of mammalian cancer cells. Moreover, the activity of the TRPM8 channel modulated the level of basal autophagy. The mechanism of regulation of autophagy by TRPM8 involves autophagy-associated signaling pathways for activation of AMPK and ULK1 and phagophore formation. Impaired AMPK abolished TRPM8-dependent regulation of autophagy. TRPM8 interacts with AMPK in a protein complex, and cytoplasmic C-terminus of TRPM8 mediates the TRPM8-AMPK interaction. Finally, basal autophagy mediates the regulatory effects of TRPM8 on the proliferation and migration of breast cancer cells. Thus, this study identifies TRPM8 as a novel regulator of basal autophagy in cancer cells acting by interacting with AMPK, which in turn activates AMPK to activate ULK1 in a coordinated cascade of TRPM8-mediated breast cancer progression.
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http://dx.doi.org/10.3389/fonc.2020.573127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746826PMC
December 2020

JNK2, a Newly-Identified SERCA2 Enhancer, Augments an Arrhythmic [Ca] Leak-Load Relationship.

Circ Res 2021 Feb 18;128(4):455-470. Epub 2020 Dec 18.

Physiology and Biophysics, Rush University Medical Center, Chicago, IL (J.Y., D.J.B., J.D., W.Z., Y.M., X.A.).

Rationale: We recently discovered pivotal contributions of stress kinase JNK2 (c-Jun N-terminal kinase isoform 2) in increased risk of atrial fibrillation through enhanced diastolic sarcoplasmic reticulum (SR) calcium (Ca) leak via RyR2 (ryanodine receptor isoform 2). However, the role of JNK2 in the function of the SERCA2 (SR Ca-ATPase), essential in maintaining SR Ca content cycling during each heartbeat, is completely unknown.

Objective: To test the hypothesis that JNK2 increases SERCA2 activity SR Ca content and exacerbates an arrhythmic SR Ca content leak-load relationship.

Methods And Results: We used confocal Ca imaging in myocytes and HEK-RyR2 (ryanodine receptor isoform 2-expressing human embryonic kidney 293 cells) cells, biochemistry, dual Ca/voltage optical mapping in intact hearts from alcohol-exposed or aged mice (where JNK2 is activated). We found that JNK2, but not JNK1 (c-Jun N-terminal kinase isoform 1), increased SERCA2 uptake and consequently elevated SR Ca content load. JNK2 also associates with and phosphorylates SERCA2 proteins. JNK2 causally enhances SERCA2-ATPase activity via increased maximal rate, without altering Ca affinity. Unlike the CaMKII (Ca/calmodulin-dependent kinase II)-dependent JNK2 action in SR Ca leak, JNK2-driven SERCA2 function was CaMKII independent (not prevented by CaMKII inhibition). With CaMKII blocked, the JNK2-driven SR Ca loading alone did not significantly raise leak. However, with JNK2-CaMKII-driven SR Ca leak present, the JNK2-enhanced SR Ca uptake limited leak-induced reduction in SR Ca, normalizing Ca transient amplitude, but at a higher arrhythmogenic SR Ca leak. JNK2-specific inhibition completely normalized SR Ca handling, attenuated arrhythmic Ca activities, and alleviated atrial fibrillation susceptibility in aged and alcohol-exposed myocytes and intact hearts.

Conclusions: We have identified a novel JNK2-induced activation of SERCA2. The dual action of JNK2 in CaMKII-dependent arrhythmic SR Ca leak and a CaMKII-independent uptake exacerbates atrial arrhythmogenicity, while helping to maintain normal levels of Ca transients and heart function. JNK2 modulation may be a novel therapeutic target for atrial fibrillation prevention and treatment.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.318409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897290PMC
February 2021

Causal roles of stress kinase JNK2 in DNA methylation and binge alcohol withdrawal-evoked behavioral deficits.

Pharmacol Res 2021 Feb 11;164:105375. Epub 2020 Dec 11.

Department of Physiology & Biophysics, Rush University Medical Center, Chicago, IL, 60607, USA. Electronic address:

Excessive binge alcohol intake is a common drinking pattern in humans, especially during holidays. Cessation of the binge drinking often leads to aberrant withdrawal behaviors, as well as serious heart rhythm abnormalities (clinically diagnosed as Holiday Heart Syndrome (HHS)). In our HHS mouse model with well-characterized binge alcohol withdrawal (BAW)-induced heart phenotypes, BAW leads to anxiety-like behaviors and cognitive impairment. We have previously reported that stress-activated c-Jun NH(2)-terminal kinase (JNK) plays a causal role in BAW-induced heart phenotypes. In the HHS brain, we found that activation of JNK2 (but not JNK1 and JNK3) in the prefrontal cortex (PFC), but not hippocampus and amygdala, led to anxiety-like behaviors and impaired cognition. DNA methylation mediated by a crucial DNA methylation enzyme, DNA methyltransferase1 (DNMT1), is known to be critical in alcohol-associated behavioral deficits. In HHS mice, JNK2 in the PFC (but not hippocampus and amygdala) causally enhanced total genomic DNA methylation via increased DNMT1 expression, which was regulated by enhanced binding of JNK downstream transcriptional factor c-JUN to the DNMT1 promoter. JNK2-specific inhibition either by an inhibitor JNK2I or JNK2 knockout completely offset c-JUN-regulated DNMT1 upregulation and restored the level of DNA methylation in HHS PFC to the baseline levels seen in sham controls. Strikingly, either JNK2-specific inhibition or genetic JNK2 depletion or DNMT1 inhibition (by an inhibitor 5-Azacytidine) completely abolished BAW-evoked behavioral deficits. In conclusion, our studies revealed a novel mechanism by which JNK2 drives BAW-evoked behavioral deficits through a DNMT1-regulated DNA hypermethylation. JNK2 could be a novel therapeutic target for alcohol withdrawal treatment and/or prevention.
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http://dx.doi.org/10.1016/j.phrs.2020.105375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867628PMC
February 2021

Characterization and Optimization of Elastomeric Electrodes for Dielectric Elastomer Artificial Muscles.

Materials (Basel) 2020 Dec 4;13(23). Epub 2020 Dec 4.

School of Mechanical and Electronic Engineering, Wuhan University of Technology, Wuhan 430070, China.

Dielectric elastomer actuators (DEAs) are an emerging type of soft actuation technology. As a fundamental unit of a DEA, the characteristics of compliant electrodes play a crucial role in the actuation performances of DEAs. Generally, the compliant electrodes can be categorized into uncured and cured types, of which the cured one commonly involves mixing conductive particles into an elastomeric matrix before curing, thus demonstrating a better long-term performance. Along with the increasing proportion of conductive particles, the electrical conductivity increases at the cost of a stiffer electrode and lower elongation at break ratio. For different DEA applications, it can be more desirable to minimize the electrode stiffness or to maximize its conductivity. In examination of the papers published in recent years, few works have characterized the effects of elastomeric electrodes on the outputs of DEAs, or of their optimizations under different application scenarios. In this work, we propose an experimental framework to characterize the performances of elastomeric electrodes with different formulas based on the two key parameters of stiffness and conductivity. An optimizing method is developed and verified by two different application cases (e.g., quasi-static and dynamic). The findings and the methods developed in this work can offer potential approaches for developing high-performance DEAs.
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http://dx.doi.org/10.3390/ma13235542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729933PMC
December 2020

Methylation biomarkers with discriminating ability are potential therapeutic targets in lung adenocarcinoma.

Epigenomics 2020 Dec 8. Epub 2020 Dec 8.

Department of Epidemiology & Biostatistics, School of Public Health, Harbin Medical University, Harbin 150086, PR China.

Given the reversibility of methylation, biomarkers with discriminating ability are of great interest for targeted therapeutic sites. Methylation array data of 461 lung adenocarcinoma (LUAD) patients comprising of 458 tumor and 32 LUAD paracancerous samples were compared using partial least squares discrimination analysis and receiver operating characteristics analysis. A six-DNA methylation signature (corresponding to five genes) was found to significantly discriminate normal and LUAD samples. Kyoto Encyclopedia of Genes and Genomes analysis indicated enrichment of methylation sites in the Wnt pathway in LUAD compared with controls. This six-DNA methylation signature demonstrated potential as a novel biomarker for diagnosis and therapeutic targets. Further, inhibition of Wnt signaling pathway may be an important step in LUAD progression.
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http://dx.doi.org/10.2217/epi-2019-0142DOI Listing
December 2020

Management strategy of Type A Aortic Dissection in a developing center from China: 16 years experiences.

J Thorac Dis 2020 Nov;12(11):6780-6788

Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Background: Type A Aortic Dissection (TAAD) remains a lethal disease of increasing incidence. However the incidence, standardized treatment and survival rates of TAAD is still a lack in China. This study aims to share the management strategy of TAAD from a developing center of this country.

Methods: All subjects identified with TAAD in Nanjing Drum Tower Hospital, China, from Jan. 2002 to Dec. 2018 were included in this study. Of 1,037 individuals, 932 (89.9%) were underwent surgery. Based on annual case volume patients underwent surgery were stratified into three operative stages: Early, Middle and Current stage, and patient characteristics, operative trends and outcomes across the operative stages were assessed.

Results: The annual admissions of patients increased from approximately 20 during 2002-2013 (early era), 100 during 2014-2016 (middle era) to 200 during 2017-2018 (current era). The median age of patients increased from 49.0 to 53.0 among different eras (P<0.001). The overall in-hospital mortality was 16.5%, which significantly decreased from 21.3% to 13.1% with eras (P=0.023). The median time from admission to surgery was remarkedly shorted from 30.4 h during the early era to 14.0 h during the current era. Compared with in the early era, the percentages of aortic arch repair were increased in middle or current eras, while total arch replacement decreased.

Conclusions: During the last 16 years, the prevalence of TAAD was increasing, and the annual number of operations increased substantially in China. Hospital survival improved over time was challenging prompt management and suitable operations.
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http://dx.doi.org/10.21037/jtd-20-1866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711430PMC
November 2020

Boosting the Efficiency of NiO-Based Perovskite Light-Emitting Diodes by Interface Engineering.

ACS Appl Mater Interfaces 2020 Nov 12;12(47):53528-53536. Epub 2020 Nov 12.

Flexible Printed Electronics Technology Center, Harbin Institute of Technology, Shenzhen 518055, China.

Nickel oxide (NiO) is a promising hole-transporting material for perovskite light-emitting diodes (PeLEDs) because of its low cost, excellent stability, and simple fabrication process. However, the electroluminescence efficiencies of NiO-based PeLEDs are greatly limited by inefficient hole injection and exciton quenching at the NiO-perovskite interfaces. Here, a novel interfacial engineering method with sodium dodecyl sulfate-oxygen plasma (SDS-OP) is demonstrated to simultaneously overcome the aforementioned issues. Experimental results reveal that a short OP treatment on the top of the SDS-coated NiO significantly deepens the NiO work function (from 4.23 to 4.85 eV) because of the formation of a large surface dipole, allowing for efficient hole injection. Moreover, the SDS-OP layer passivates the electronic surface trap states of perovskite films and suppresses the exciton quenching by NiO. These improvements inhibit the nonradiative decays at the NiO-perovskite interface. As a result, the external quantum efficiency of CsPbBr LEDs is increased from 0.052 to 2.5%; that of FAPbBr nanocrystals LEDs is increased from 5.6 to 7.6%.
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http://dx.doi.org/10.1021/acsami.0c16139DOI Listing
November 2020

Dopamine/Phosphorylcholine Copolymer as an Efficient Joint Lubricant and ROS Scavenger for the Treatment of Osteoarthritis.

ACS Appl Mater Interfaces 2020 Nov 9;12(46):51236-51248. Epub 2020 Nov 9.

State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.

Osteoarthritis (OA) is a chronic joint disease and its progression and pathogenesis are highly associated with the significant increase of joint friction and overproduction of reactive oxygen species (ROS) in inflammation. Combination of ROS elimination and lubrication enhancement may provide a novel strategy for the treatment of OA. In the present study, a pure biomaterial and nondrug system P(DMA--MPC), synthesized via free radical copolymerization, was designed and developed for the first time using 2-methacryloxyethyl phosphorylcholine (MPC) as a bioinspired lubricant and -(3,4-dihydroxyphenethyl)methacrylamide (DMA) as an ROS scavenger. Our results showed that the P(DMA--MPC) aggregates could efficiently eliminate the ROS radicals and provide good lubrication property by adjusting the molar ratio of DMA and MPC in the copolymer. It is attributed to the antioxidant function of the hydroquinone moiety in DMA and the hydration lubrication effect of the zwitterionic phosphocholine group in MPC. Furthermore, the in vitro experiments demonstrated that the P(DMA--MPC) showed good biocompatibility with MC3T3-E1 cells and intracellular anti-inflammatory property by inhibiting the production of ROS and regulating the expression levels of pro-inflammatory cytokines, pain-related gene, anabolic genes, and catabolic genes. In conclusion, the drug-free P(DMA--MPC) aggregates developed herein can achieve dual functions of lubrication enhancement and anti-inflammatory effect and thus they may be representative as promising candidates for the treatment of OA.
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http://dx.doi.org/10.1021/acsami.0c14805DOI Listing
November 2020

Amino acid recognition by a fluorescent chemosensor based on cucurbit[8]uril and acridine hydrochloride.

Anal Chim Acta 2020 Oct 25;1135:142-149. Epub 2020 Sep 25.

Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang, 550025, China. Electronic address:

A new fluorescent chemosensor comprised of cucurbit[8]uril (Q[8]) and acridine hydrochloride (AC) has been designed and utilized for the recognition of amino acids. The AC was encapsulated by the Q[8] cavity and formed a 1:2 host-guest inclusion complex both in solution (aqueous) and in the solid-state. Whilst free AC is known to be strongly fluorescent, this strong fluorescence was quenched in the inclusion complex Q [8]-AC. This non-fluorescent complex Q[8]-AC was capable of serving as a fluorescence "off-on" probe, and was able to recognize either L-Phe or L-Trp via the competitive interaction between L-Phe or L-Trp. Moreover, the pH responsive nature of the probe allowed for the detection of basic amino acids, namely L-Arg, L-His, or L-Lys). As a result, a fluorescence method for the detection of five amino acids using a single system has been developed.
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http://dx.doi.org/10.1016/j.aca.2020.09.028DOI Listing
October 2020

Edible Plant Oil: Global Status, Health Issues, and Perspectives.

Front Plant Sci 2020 28;11:1315. Epub 2020 Aug 28.

Henan Province Engineering Research Center for Forest Biomass Value-added Products, College of Forestry, Henan Agricultural University, Zhengzhou, China.

Edible plant oil (EPO) is an indispensable nutritional resource for human health. Various cultivars of oil-bearing plants are grown worldwide, and the chemical compositions of different plant oils are diverse. The extremely complex components in oils lead to diverse standards for evaluating the quality and safety of different EPOs. The environment poses great challenges to the EPO safety and quality during the entire industrial chain, including plant cultivation, harvesting, oil processing, and storage. Environmental risk factors include heavy metal or pesticide residue pollution, insect or harmful microbial infestation, and rancidity. Here, the diverse components in oil and various oil-producing processes are discussed, including plant species, oil yield, and composition complexity, environmental factors that degrade oil quality. Additionally, we propose a whole-industrial-chain monitoring system instead of current single-link-monitoring approach by monitoring and tracking the quality and safety of EPOs during the entire process of plant cultivation, raw materials harvest, oil process, and EPOs storage. This will provide guidance for monitoring the quality and safety of EPOs, which were challenged by the deteriorating environment.
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http://dx.doi.org/10.3389/fpls.2020.01315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485320PMC
August 2020

Case Report: Identification of a Novel Variant (m.8909T>C) of Human Mitochondrial Gene and Its Functional Consequences on Yeast ATP Synthase.

Life (Basel) 2020 Sep 22;10(9). Epub 2020 Sep 22.

National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing 211166, China.

With the advent of next generation sequencing, the list of mitochondrial DNA (mtDNA) mutations identified in patients rapidly and continuously expands. They are frequently found in a limited number of cases, sometimes a single individual (as with the case herein reported) and in heterogeneous genetic backgrounds (heteroplasmy), which makes it difficult to conclude about their pathogenicity and functional consequences. As an organism amenable to mitochondrial DNA manipulation, able to survive by fermentation to loss-of-function mtDNA mutations, and where heteroplasmy is unstable, is an excellent model for investigating novel human mtDNA variants, in isolation and in a controlled genetic context. We herein report the identification of a novel variant in mitochondrial gene, m.8909T>C. It was found in combination with the well-known pathogenic m.3243A>G mutation in mt-tRNA. We show that an equivalent of the m.8909T>C mutation compromises yeast adenosine tri-phosphate (ATP) synthase assembly/stability and reduces the rate of mitochondrial ATP synthesis by 20-30% compared to wild type yeast. Other previously reported mutations with a well-established pathogenicity (like m.8993T>C and m.9176T>C) were shown to have similar effects on yeast ATP synthase. It can be inferred that alone the m.8909T>C variant has the potential to compromise human health.
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http://dx.doi.org/10.3390/life10090215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555451PMC
September 2020

Competition between Oxygen Curing and Ion Migration in MAPbI Induced by Irradiation Exposure.

J Phys Chem Lett 2020 Oct 23;11(20):8477-8482. Epub 2020 Sep 23.

School of Physics and Key Laboratory of MEMS of the Ministry of Education, Southeast University, Nanjing 211189, China.

Organometal halide perovskites (OHPs) have been considered as promising materials for light-emission devices. However, the factors influencing the luminescent property of OHPs are intricate. It is not only affected by the intrinsic crystalline quality but also depends on the surrounding environment. Here we demonstrate that the luminescence of CHNHPbI (MAPbI) is governed by light-irradiation-induced oxygen curing and vacancy-mediated ion migration. The luminescence increases under continuous irradiation because of the curing of iodine vacancies (V) by oxygen. While, it decreases with enhanced ion migration, which would induce excess trap states. The existence of V is proved by low-temperature photoluminescence (PL) spectra, the hysteresis effect in - curves, and the excitation density dependence of the PL lifetime. Different oxygen environments and applied biases are employed to control the degree of oxygen curving and ion migration. These results provide a perception of the correlation of the complicated influencing factors affecting the luminescence of OHPs.
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http://dx.doi.org/10.1021/acs.jpclett.0c02649DOI Listing
October 2020

Mutation landscape of TSC1/TSC2 in Chinese patients with tuberous sclerosis complex.

J Hum Genet 2021 Mar 11;66(3):227-236. Epub 2020 Sep 11.

Guangzhou KingMed Transformative Medicine Institute Co. Ltd., Guangzhou, China.

Genetic testing of TSC1 and TSC2 is important for the diagnosis of tuberous sclerosis complex (TSC), an autosomal dominant neurocutaneous disease. This study retrospectively reviewed 347 samples from patients with clinically suspected TSC being tested for mutations in TSC1 and TSC2 genes using next-generation sequencing and multiplex ligation-dependent probe amplification. Two hundred eighty-one patients (80.98%) were classified as definite/possible/uncertain diagnosis of TSC and the mutational spectrum of TSC1/TSC2 was described. Two hundred eighteen unique nonsynonymous SNVs/Indels (64 in TSC1, 154 in TSC2) and 13 copy number variants (CNVs) were identified in 241 samples (85.77%), including 82 novel variants. CNVs involving 12 large deletions and one duplication were detected exclusively in TSC2. Both TSC1 and TSC2 mutations were nearly uniformly distributed in their protein-coding regions. Furthermore, a string of non-TSC1/TSC2 deleterious variants in 12 genes was identified in the patients, especially overwhelmingly present in the patients with no mutation identified (NMI) in TSC1/TSC2. Our study provides a comprehensive TSC1/TSC2 mutation landscape and reveal some potential risk non-TSCs variants present in patients with NMI.
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http://dx.doi.org/10.1038/s10038-020-00839-0DOI Listing
March 2021