Publications by authors named "Chao Han"

491 Publications

A P3-Type KMnMgNiO Cathode Material for Potassium-Ion Batteries with High Structural Reversibility Secured by the Mg-Ni Pinning Effect.

ACS Appl Mater Interfaces 2021 Jun 9. Epub 2021 Jun 9.

Institute for Superconducting & Electronic Materials, AIIM Building, Innovation Campus, University of Wollongong, Wollongong, NSW 2522, Australia.

Mn-based layered oxides are very attractive as cathodes for potassium-ion batteries (PIBs) due to their low-cost and environmentally friendly precursors. Their transfer to practical application, however, is inhibited by some issues including consecutive phase transitions, sluggish K deintercalation/intercalation, and serious capacity loss. Herein, Mg-Ni co-substituted KMnMgNiO is designed as a promising cathode material for PIBs, with suppressed phase transitions that occurred in KMnO and improved K storage performance. Part of Mg and Ni occupies the K layer, playing the role of a "nailed pillar", which restrains metal oxide layer gliding during the K (de)intercalation. The "Mg-Ni pinning effect" not only suppresses the phase transitions but also reduces the cell volume variation, leading to the improved cycle performance. Moreover, KMnMgNiO has low activation barrier energy for K diffusion and high electron conductivity as demonstrated by first-principles calculations, resulting in better rate capability. In addition, KMnMgNiO also delivers a higher reversible capacity owing to the participation of the Ni element in electrochemical reactions and the pseudocapacitive contribution. This study provides a basic understanding of structural evolution in layered Mn-based oxides and broadens the strategic design of cathode materials for PIBs.
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http://dx.doi.org/10.1021/acsami.1c07220DOI Listing
June 2021

Proteomics, Personalized Medicine and Cancer.

Cancers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.

As of 2020 the human genome and proteome are both at >90% completion based on high stringency analyses. This has been largely achieved by major technological advances over the last 20 years and has enlarged our understanding of human health and disease, including cancer, and is supporting the current trend towards personalized/precision medicine. This is due to improved screening, novel therapeutic approaches and an increased understanding of underlying cancer biology. However, cancer is a complex, heterogeneous disease modulated by genetic, molecular, cellular, tissue, population, environmental and socioeconomic factors, which evolve with time. In spite of recent advances in treatment that have resulted in improved patient outcomes, prognosis is still poor for many patients with certain cancers (e.g., mesothelioma, pancreatic and brain cancer) with a high death rate associated with late diagnosis. In this review we overview key hallmarks of cancer (e.g., autophagy, the role of redox signaling), current unmet clinical needs, the requirement for sensitive and specific biomarkers for early detection, surveillance, prognosis and drug monitoring, the role of the microbiome and the goals of personalized/precision medicine, discussing how emerging omics technologies can further inform on these areas. Exemplars from recent onco-proteogenomic-related publications will be given. Finally, we will address future perspectives, not only from the standpoint of perceived advances in treatment, but also from the hurdles that have to be overcome.
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http://dx.doi.org/10.3390/cancers13112512DOI Listing
May 2021

Factors associated with negative pleural adenosine deaminase results in the diagnosis of childhood pleural tuberculosis.

BMC Infect Dis 2021 May 25;21(1):473. Epub 2021 May 25.

Department of Lab Medicine, Shandong Provincial Chest Hospital, Cheeloo College of Medicine, Shandong University, 46# Lishan Road, Jinan city, Shandong, 250013, P. R. China.

Background: Until now, the influential factors associated with pleural adenosine deaminase (ADA) activity among children remain unclear. This retrospective study was therefore conducted aiming to investigate the factors associated with negative pleural ADA results in the diagnosis of childhood pleural tuberculosis (TB).

Methods: Between January 2006 and December 2019, children patients with definite or possible pleural TB were recruited for potential analysis. Then, patients were stratified into two categories: negative pleural ADA results group (experimental group, ≤40 U/L) and positive pleural ADA results group (control group, > 40 U/L). Univariate and multivariate logistic regression analyses were performed to estimate risk factors for negative pleural ADA results.

Results: A total of 84 patients with pleural TB were recruited and subsequently classified as experimental (n = 17) and control groups (n = 67). Multivariate analysis (Hosmer-Lemeshow goodness-of-fit test: χ = 1.881, df = 6, P = 0.930) revealed that variables, such as chest pain (age-adjusted OR = 0.0510, 95% CI: 0.004, 0.583), pleural total protein (≤45.3 g/L, age-adjusted OR = 27.7, 95% CI: 2.5, 307.7), pleural lactate dehydrogenase (LDH, ≤505 U/L, age-adjusted OR = 59.9, 95% CI: 4.2, 857.2) and blood urea nitrogen (≤3.2 mmol/L, age-adjusted OR = 32.0, 95% CI: 2.4, 426.9), were associated with negative pleural ADA results when diagnosing childhood pleural TB.

Conclusion: Our findings demonstrated that chest pain, pleural total protein, pleural LDH, and blood urea nitrogen were associated with a negative pleural ADA result for the diagnosis of pleural TB among children. When interpreting pleural ADA levels in children with these characteristics, a careful clinical assessment is required for the pleural TB diagnosis.
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http://dx.doi.org/10.1186/s12879-021-06209-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152150PMC
May 2021

Use of the Dynamic Technique DGT to Determine the Labile Pool Size and Kinetic Resupply of Pesticides in Soils and Sediments.

Environ Sci Technol 2021 May 24. Epub 2021 May 24.

Lancaster Environment Centre, Lancaster University, Lancaster, LA1 4YQ, U.K.

The diffusive gradients in thin films (DGT) technique has been successfully and widely applied to investigate the labile fractions of inorganic contaminants in soils and sediments, but there have been almost no applications to organic contaminants. Here we developed and tested the approach for the pesticide Atrazine (ATR) in a controlled soil experiment and in situ in an intact lake sediment core. The soil study explored the relationships between soil solution, DGT measured labile ATR and solvent extractable ATR in dosed soils of different organic matter, pH status and incubation times. The results are further interpreted using the DIFS (DGT-induced fluxes in soils and sediments) model. Resupply of ATR to the soil solution was partially sustained by the solid phase in all the soils. This was due to small labile pool size and slow kinetics, with soil pH being an important controlling factor. The in situ sediment study successfully used a DGT probe to examine labile ATR distribution through the core on the subcm scale. It demonstrated-for the first time-an easy to use in situ technique to investigate the effects of redox on resupply kinetics and biogeochemical processes of trace organic contaminants in sediments.
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http://dx.doi.org/10.1021/acs.est.1c01354DOI Listing
May 2021

Synergistic Catalysis of SnO-CNTs Composite for /VO and V/V Redox Reactions.

Front Chem 2021 5;9:671575. Epub 2021 May 5.

School of Chemical Engineering, North China University of Science and Technology, Tangshan, China.

In this study, a SnO-carbon nanotube (SnO-CNT) composite as a catalyst for vanadium redox flow battery (VRFB) was prepared using a sol-gel method. The effects of this composite on the electrochemical performance of /VO, and on the V/V redox reactions and VRFB performance were investigated. The SnO-CNT composite has better catalytic activity than pure SnO and CNT due to the synergistic catalysis of SnO and the CNT. SnO mainly provides the catalytic active sites and the CNTs mainly provide the three-dimensional structure and high electrical conductivity. Therefore, the SnO-CNT composite has a larger specific surface area and an excellent synergistic catalytic performance. For cell performance, it was found that the SnO-CNT cell shows a greater discharge capacity and energy efficiency. In particular, at 150 mA cm, the discharge capacity of the SnO-CNT cell is 28.6 mAh higher than that of the pristine cell. The energy efficiency of the modified cell (7%) is 7.2% higher than that of the pristine cell (62.8%). This study shows that the SnO-CNT is an efficient and promising catalyst for VRFB.
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http://dx.doi.org/10.3389/fchem.2021.671575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131550PMC
May 2021

Lactate oxidative phosphorylation by annulus fibrosus cells: evidence for lactate-dependent metabolic symbiosis in intervertebral discs.

Arthritis Res Ther 2021 May 21;23(1):145. Epub 2021 May 21.

Department of Orthopaedic Surgery, Ferguson Laboratory for Orthopedic and Spine Research, University of Pittsburgh, 200 Lothrop Street, E1644 Biomedical Science Tower, Pittsburgh, PA, 15261, USA.

Background: Intervertebral disc degeneration contributes to low back pain. The avascular intervertebral disc consists of a central hypoxic nucleus pulpous (NP) surrounded by the more oxygenated annulus fibrosus (AF). Lactic acid, an abundant end-product of NP glycolysis, has long been viewed as a harmful waste that acidifies disc tissue and decreases cell viability and function. As lactic acid is readily converted into lactate in disc tissue, the objective of this study was to determine whether lactate could be used by AF cells as a carbon source rather than being removed from disc tissue as a waste byproduct.

Methods: Import and conversion of lactate to tricarboxylic acid (TCA) cycle intermediates and amino acids in rabbit AF cells were measured by heavy-isotope (C-lactate) tracing experiments using mass spectrometry. Levels of protein expression of lactate converting enzymes, lactate importer and exporter in NP and AF tissues were quantified by Western blots. Effects of lactate on proteoglycan (S-sulfate) and collagen (H-proline) matrix protein synthesis and oxidative phosphorylation (Seahorse XFe96 Extracellular Flux Analyzer) in AF cells were assessed.

Results: Heavy-isotope tracing experiments revealed that AF cells imported and converted lactate into TCA cycle intermediates and amino acids using in vitro cell culture and in vivo models. Addition of exogenous lactate (4 mM) in culture media induced expression of the lactate importer MCT1 and increased oxygen consumption rate by 50%, mitochondrial ATP-linked respiration by 30%, and collagen synthesis by 50% in AF cell cultures grown under physiologic oxygen (2-5% O) and glucose concentration (1-5 mM). AF tissue highly expresses MCT1, LDH-H, an enzyme that preferentially converts lactate to pyruvate, and PDH, an enzyme that converts pyruvate to acetyl-coA. In contrast, NP tissue highly expresses MCT4, a lactate exporter, and LDH-M, an enzyme that preferentially converts pyruvate to lactate.

Conclusions: These findings support disc lactate-dependent metabolic symbiosis in which lactate produced by the hypoxic, glycolytic NP cells is utilized by the more oxygenated AF cells via oxidative phosphorylation for energy and matrix production, thus shifting the current research paradigm of viewing disc lactate as a waste product to considering it as an important biofuel. These scientifically impactful results suggest novel therapeutic targets in disc metabolism and degeneration.
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http://dx.doi.org/10.1186/s13075-021-02501-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139157PMC
May 2021

Intelligent phototriggered nanoparticles induce a domino effect for multimodal tumor therapy.

Theranostics 2021 19;11(13):6477-6490. Epub 2021 Apr 19.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.

: Integration of several monotherapies into a single nanosystem can produce remarkable synergistic antitumor effects compared with separate delivery of combination therapies. We developed near-infrared (NIR) light-triggered nanoparticles that induce a domino effect for multimodal tumor therapy. : The designed intelligent phototriggered nanoparticles (IPNs) were composed of a copper sulfide-loaded upconversion nanoparticle core, a thermosensitive and photosensitive enaminitrile molecule (EM) organogel shell loaded with anticancer drugs, and a cancer cell membrane coating. Irradiation with an NIR laser activated a domino effect beginning with photothermal generation by copper sulfide for photothermal therapy that also resulted in phase transformation of the EM gel to release the anticancer drug. Meanwhile, the NIR light energy was converted to ultraviolet light by the upconversion core to excite the EM, which generated reactive oxygen species for photodynamic therapy. : IPNs achieved excellent antitumor effects and with little systemic toxicity, indicating that IPNs could serve as a safe and high-performance instrument for synergetic antitumor therapy. : This intelligent drug delivery system induced a chain reaction generating multiple antitumor therapies after a single stimulus.
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http://dx.doi.org/10.7150/thno.55708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120229PMC
April 2021

Atherogenic Index of Plasma, Triglyceride-Glucose Index and Monocyte-to-Lymphocyte Ratio for Predicting Subclinical Coronary Artery Disease.

Am J Med Sci 2021 May 11. Epub 2021 May 11.

Department of Cardiology, The Affiliated Hospital of Chengde Medical University, Chengde, HeBei, China. Electronic address:

Background: The atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, and monocyte-to-lymphocyte ratio (MLR) are strongly associated with atherogenesis of the coronary artery. This study aimed to investigate the association of the AIP, TyG index, and MLR with subclinical coronary artery disease (CAD) and evaluate their ability to predict subclinical CAD.

Methods: A total of 697 asymptomatic patients were enrolled in this study and assigned to the subclinical CAD group (n=332) and control group (n=365). The clinical data, coronary artery calcification score, and calculated AIP, TyG index, and MLR were collected by graduate students in the cardiology division. Multivariate logistic regression models were set up to assess the risk factors for subclinical CAD.

Results: The AIP, TyG index and MLR values were higher in the subclinical CAD group than in the control group (all P<0.05). In addition to the classic independent clinical risk factors, increased AIP, TyG index and MLR values were all independent risk factors for subclinical CAD (all P<0.05). The AUCs were higher after combining clinical risk factors than the AIP, TyG index, or MLR alone (all P<0.05).

Conclusions: The AIP, TyG index and MLR are independent risk factors for subclinical CAD, which can be useful for improving the diagnosis and prevention of CAD.
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http://dx.doi.org/10.1016/j.amjms.2021.05.001DOI Listing
May 2021

[Effects of calcium on the structure of intestinal microbiota in ovariectomized rats].

Wei Sheng Yan Jiu 2021 Mar;50(2):267-273

Key Laboratory of Trace Element Nutrition, National Health Commission of the People's Republic of China;National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Objective: To study the effect of calcium content on bone mineral density and intestinal microbiota in ovariectomized rats.

Methods: A total of 30 Wistar rats were randomly divided into 3 groups, namely the sham operation group, the model group and the calcium carbonate supplement group. Postmenopausal osteoporosis rats were established by ovariectomy(OVX). After the first week of modeling, each group was intragastric separately. The calcium carbonate solution was given to the calcium carbonate supplement group, and the same amount of sterile water was given to the other two groups. The animals were executed at the end of the 12 weeks. Left femur was taken and bone mineral density(BMD) was detected by dual-energy X-ray absorptiometry. The total DNA of fecal samples was aseptically extracted and the Illumina Miseq platform was to carry out high-throughput sequencing.

Results: Compared with the sham operation group, the body mass increment of rats in the model group was significantly increased, the level of BMD was significantly reduced(P<0. 05), the intestinal microbiota diversity was not significantly changed, the Firmicutes abundance was decreased, and the Bacteroidetes abundance was increased. Compared with the model group, the body mass increment of rats in the calcium carbonate supplementation group was significantly reduced and BMD was significantly increased(P<0. 05). There was no significant change in the intestinal microbiota diversity, Firmicutes were increased, and Bacteroidetes were decreased.

Conclusion: Calcium supplementation can improve bone mineral density and inhibit the increase of body mass during the experiment period, and its mechanism may be related to regulating the structure of intestinal microbiota.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2021.02.017DOI Listing
March 2021

Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2.

Cell Chem Biol 2021 Apr 27. Epub 2021 Apr 27.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China. Electronic address:

The COVID-19 pandemic has been disastrous to society and effective drugs are urgently needed. The papain-like protease domain (PLpro) of SARS-CoV-2 (SCoV2) is indispensable for viral replication and represents a putative target for pharmacological intervention. In this work, we describe the development of a potent and selective SCoV2 PLpro inhibitor, 19. The inhibitor not only effectively blocks substrate cleavage and immunosuppressive function imparted by PLpro, but also markedly mitigates SCoV2 replication in human cells, with a submicromolar IC. We further present a convenient and sensitive activity probe, 7, and complementary assays to readily evaluate SCoV2 PLpro inhibitors in vitro or in cells. In addition, we disclose the co-crystal structure of SCoV2 PLpro in complex with a prototype inhibitor, which illuminates their detailed binding mode. Overall, these findings provide promising leads and important tools for drug discovery aiming to target SCoV2 PLpro.
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http://dx.doi.org/10.1016/j.chembiol.2021.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075810PMC
April 2021

A hafnium oxide-coated dendrite-free zinc anode for rechargeable aqueous zinc-ion batteries.

J Colloid Interface Sci 2021 Oct 24;599:467-475. Epub 2021 Apr 24.

School of Chemical Engineering, North China University of Science and Technology, Tangshan 063009, PR China. Electronic address:

In aqueous zinc-ion batteries, metallic zinc is widely used as an anode because of its non-toxicity, environmental benignity, low cost, high abundance and theoretical capacity. However, growth of zinc dendrites, corrosion of zinc anode, passivation, and occurrence of side reactions during continuous charge-discharge cycling hinder development of zinc-ion batteries. In this study, a simple strategy involving application of a HfO coating was used to guide uniform deposition of Zn to suppress formation of zinc dendrites. The HfO-coated zinc anode improves electrochemical performance compared with bare Zn anode. Therefore, for zinc-zinc symmetric cells, zinc anode with HfO coating (48 mV) shows lower voltage hysteresis than that of bare Zn anode (63 mV) at a current density of 0.4 mA cm. Moreover, cell with HfO coating also shows good cycling performance in Zn-MnO full cells. At a constant current density of 1.0 A g, discharge capacity of bare Zn-MnO full cell is only 37.9 mAh g after 500 cycles, while that of [email protected] full cell is up to 78.3 mAh g. This good electrochemical performance may be the result of confinement effect and reduction of side reactions. Overall, a simple and beneficial strategy for future development of rechargeable aqueous zinc-ion batteries is provided.
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http://dx.doi.org/10.1016/j.jcis.2021.04.113DOI Listing
October 2021

The peripheral and core regions of virus-host network of COVID-19.

Brief Bioinform 2021 May 6. Epub 2021 May 6.

School of Computer Science and Technology, Xidian University, Xi'an 710071, China.

Two thousand nineteen novel coronavirus SARS-CoV-2, the pathogen of COVID-19, has caused a catastrophic pandemic, which has a profound and widespread impact on human lives and social economy globally. However, the molecular perturbations induced by the SARS-CoV-2 infection remain unknown. In this paper, from the perspective of omnigenic, we analyze the properties of the neighborhood perturbed by SARS-CoV-2 in the human interactome and disclose the peripheral and core regions of virus-host network (VHN). We find that the virus-host proteins (VHPs) form a significantly connected VHN, among which highly perturbed proteins aggregate into an observable core region. The non-core region of VHN forms a large scale but relatively low perturbed periphery. We further validate that the periphery is non-negligible and conducive to identifying comorbidities and detecting drug repurposing candidates for COVID-19. We particularly put forward a flower model for COVID-19, SARS and H1N1 based on their peripheral regions, and the flower model shows more correlations between COVID-19 and other two similar diseases in common functional pathways and candidate drugs. Overall, our periphery-core pattern can not only offer insights into interconnectivity of SARS-CoV-2 VHPs but also facilitate the research on therapeutic drugs.
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http://dx.doi.org/10.1093/bib/bbab169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136014PMC
May 2021

A systematic study of Tupaia as a model for human acute hepatitis B infection.

J Vet Med Sci 2021 Apr 29. Epub 2021 Apr 29.

Institute of Immunology, Third Military Medical University.

The molecular features of hepatitis B virus (HBV) infection, eradication, and pathogenesis are poorly understood, partly due to the lack of an adequate animal model that faithfully reproduces the course of infection. Although Tupaia belangeri were previously recognized as HBV-susceptible animals, the course of infection in adult tupaias remains obscure. Herein, we performed a longitudinal study and demonstrated that adult tupaias were efficiently infected (90% infection rate) with 10 copies of the HBV genome. HBV replicated vigorously, produced high levels of covalently closed circular DNA (cccDNA) in hepatocytes, and released hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAg), and HBV DNA into the serum at day 9 post-inoculation (p.i.), which then decreased on day 15 p.i. The kinetics were consistent with the expression of liver HBsAg and HBeAg, as determined with immunohistochemistry. The viral products in serum at day 9 and 15 p.i. represented de novo synthesized viral products, as treatment with a viral entry inhibitor completely abolished these products from the serum. Viral clearance and serological conversion occurred at day 21 p.i. and were accompanied by elevated alanine transaminase (ALT) levels and liver pathology, such as inflammatory infiltration and hepatocyte ballooning degeneration. Although ALT levels eventually returned to normal levels by day 42 p.i., the liver pathology persisted until at least day 120 p.i. The HBV infection process in tupaia, therefore, exhibits features similar to that of human acute HBV infection, including viral replication, viral eradication, ALT elevation, and liver pathology. Thus, adopting the tupaia model to study host-HBV interactions presents an important advance which could facilitate further investigation and understanding of human HBV infection, especially for features like cccDNA that current small-animal models cannot effectively model.
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http://dx.doi.org/10.1292/jvms.21-0026DOI Listing
April 2021

Detection of Motor Dysfunction With Wearable Sensors in Patients With Idiopathic Rapid Eye Movement Disorder.

Front Bioeng Biotechnol 2021 15;9:627481. Epub 2021 Apr 15.

Department of Neurobiology, Neurology and Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing Institute of Geriatrics, Beijing, China.

Patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) are at high risk for conversion to synucleinopathy and Parkinson disease (PD). This can potentially be monitored by measuring gait characteristics of iRBD patients, although quantitative data are scarce and previous studies have reported inconsistent findings. This study investigated subclinical gait changes in polysomnography-proven iRBD patients compared to healthy controls (HCs) during 3 different walking conditions using wearable motor sensors in order to determine whether gait changes can be detected in iRBD patients that could reflect early symptoms of movement disorder. A total 31 iRBD patients and 20 HCs were asked to walk in a 10-m corridor at their usual pace, their fastest pace, and a normal pace while performing an arithmetic operation (dual-task condition) for 1 min each while using a wearable gait analysis system. General gait measurements including stride length, stride velocity, stride time, gait length asymmetry, and gait variability did not differ between iRBD patients and HCs; however, the patients showed decreases in range of motion ( = 0.004) and peak angular velocity of the trunk ( = 0.001) that were significant in all 3 walking conditions. iRBD patients also had a longer step time before turning compared to HCs ( = 0.035), and the difference between groups remained significant after adjusting for age, sex, and height. The decreased trunk motion while walking and increased step time before turning observed in iRBD may be early manifestations of body rigidity and freezing of gait and are possible prodromal symptoms of PD.
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http://dx.doi.org/10.3389/fbioe.2021.627481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084288PMC
April 2021

Surgical treatment of partial anomalous pulmonary venous connection misdiagnosed as atrial septal defect underwent transcatheter occlusion: A case report.

Clin Case Rep 2021 Apr 11;9(4):2345-2349. Epub 2021 Mar 11.

Department of Cardiovascular Surgery State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.

This case highlights the importance of coordinating with cardiopediatricians or congenitalists in the evaluation and treatment of ASD.
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http://dx.doi.org/10.1002/ccr3.4032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077342PMC
April 2021

Evidence for an Interaction Between and Childhood Trauma on Clinical Characters of Schizophrenia With Family History of Psychosis.

Front Psychiatry 2021 8;12:608231. Epub 2021 Apr 8.

Shandong Key Laboratory of Mental Disorders, Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Shandong University, Jinan, China.

Neural precursor cell-expressed developmentally downregulated 4 () polymorphisms and childhood trauma (CT) are associated with schizophrenia. However, whether interacts with CT on symptoms of schizophrenia remains unknown. This study aimed to investigate the gene-environment interaction effect. We recruited 289 schizophrenia patients and 487 controls and genotyped rs2303579, rs3088077, rs7162435, rs11550869, and rs62043855 in their gene. We found significant differences in the rs2303579 and rs3088077 between the two groups. Patients with the rs2303579 CC genotype had higher scores compared with other genotype ( = 0.026) in the test of positive schizophrenia syndrome scores, whereas patients with the rs3088077 TT ( = 0.037) and rs7162435 CC genotypes ( = 0.009) had higher scores compared with the other genotypes in the test of excitement factor. Patients with a family history of psychosis (FH+) reported higher negative scores ( = 0.012) than those without. Patients exposed to physical abuse (PA) reported a lower language learning and memory score ( = 0.017) and working memory score ( = 0.047) than those not. Patients exposed to sexual abuse (SA) reported a lower reasoning and problem-solving skills score ( = 0.025); those exposed to emotional neglect (EN) reported a lower social cognition score ( = 0.044); and those exposed to physical neglect reported a lower social cognition score ( = 0.036) but higher visual learning and memory score ( = 0.032). Rs3088077 could interact with EN to increase risk for schizophrenia. Optimal model rs62043855 × EA, rs3088077 × rs7162435 × rs11550869 × SA × EN and rs2303579 × rs7162435 × rs11550869 × rs62043855 × EA × PA could explain positive symptom, excitement symptom and working memory, respectively, in FH+ group. The study highlighted that the combined interaction of and CT may be associated with symptoms of schizophrenia especially for those with FH+.
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http://dx.doi.org/10.3389/fpsyt.2021.608231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060471PMC
April 2021

Increased Accumulation of α-Synuclein in Inflamed Appendices of Parkinson's Disease Patients.

Mov Disord 2021 Apr 20. Epub 2021 Apr 20.

Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Background: The accumulation of α-synuclein (α-Syn) aggregates that leads to the onset of Parkinson's disease (PD) has been postulated to begin in the gastrointestinal tract. The normal human appendix contains pathogenic forms of α-Syn, and appendectomy has been reported to affect the incidence of PD.

Objective: This study investigated appendix abnormality in patients with PD.

Methods: We assessed appendix morphology in 100 patients with PD and 50 control subjects by multislice spiral computed tomography. We analyzed the clinical characteristics of patients with PD with diseased appendices, which was confirmed in seven patients by histopathological analysis.

Results: Chronic appendicitis-like lesions were detected in 53% of patients with PD, but these were not associated with the duration of motor symptoms. Appendicitis-like lesions, impaired olfaction, and rapid eye movement sleep behavior disorder were risk factors for PD. The following clinical symptoms could be used to identify patients with PD with appendicitis-like lesions: first motor symptoms were bradykinesia/rigidity, onset of motor symptoms in the central axis or left limb, prodromal constipation, high ratio of Unified Parkinson's Disease Rating Scale Part III score to symptom duration, low Montreal Cognitive Assessment score, and high Epworth Sleepiness Scale score. The seven patients with PD who were diagnosed with chronic appendicitis underwent appendectomy, and histopathological analysis revealed structural changes associated with chronic appendicitis and α-Syn aggregation.

Conclusions: These results indicate an association between chronic appendicitis-like lesions and PD, and suggest that α-Syn accumulation in the diseased appendix occurs in PD. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28553DOI Listing
April 2021

TTP-mediated regulation of mRNA stability in immune cells contributes to adaptive immunity, immune tolerance and clinical applications.

RNA Biol 2021 Apr 27:1-7. Epub 2021 Apr 27.

Institute of Immunology, PLA, Third Military Medical University (Army Medical University), Chongqing, PR China.

Dendritic cells (DCs) form a sentinel network to induce protective immunity against pathogens or self-tolerance. mRNA stability is an important part of the post-transcriptional regulation (PTR) that controls the maturation and function of DCs. In this review, we summarize the effects of TTP-mediated regulation of mRNA stability in DCs, focusing on DC maturation and antigen presentation, T cell activation and differentiation, immune tolerance and inflammation. We also discuss the potential DC-based immune treatment for HIV patients through regulation of mRNA stability. This review proposes the regulation of mRNA stability as a novel immune therapy for various inflammatory diseases, such as arthritis and dermatitis.
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http://dx.doi.org/10.1080/15476286.2021.1917185DOI Listing
April 2021

Global research status of gastroenterology and hepatology: A bibliometrics study.

Medicine (Baltimore) 2021 Apr;100(15):e25291

Department of Gastroenterology, Changhai Hospital.

Background: There are no reports on global research status of gastroenterology and hepatology (GI). This study was conducted to reveal the current global research status and trends in GI.

Methods: Articles published during 2009 to 2018 in international GI journals were retrieved from the PubMed database. The top 20 countries by output were determined. The gross domestic product (GDP) of each country was also retrieved to figure out the correlation between outputs in GI and economy. The 5 highest-ranking countries were compared in the number of total articles, articles per capita, articles published in top journals, the accumulated impact factor (IF), and average IF. Total articles and articles per capita of the 5 countries were conducted time-trend analysis. The frequently-used terms in titles and abstracts of articles published in 2009 and 2018 were retrieved to conduct co-occurrence analysis to figure out the change of research highlights in GI.

Results: A total of 120,267 articles were included, of which 116,485 articles were from 20 highest-output countries. There was a positive correlation between output and GDP (r = 0.921, P < .001). The USA, Japan, China, Italy, and the UK were the 5 highest-ranking countries. The USA was the largest contributor with 26,215 articles, accounting for 17.4% of the total, but with no significant increasing trend (P = .122). Other 4 countries all showed increasing trends (all P < .001). For articles per capita, Italy ranked 1st among the 5 countries with 1591.0 articles per 10 million. The USA showed a decreasing trend (P = .026), other 4 countries all showed increasing trends (all P < .001). The UK had the highest average IF (6.685). For change of research highlights, it is more inclined to research of endoscopy, inflammatory bowel diseases, and nonalcoholic fatty liver disease.

Conclusion: It is delightful that the global research output in GI field would be continuingly increased as the major highest-output countries showed increasing trends. However, the developing countries fell behind both in quantity and quality when compared with developed countries.
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http://dx.doi.org/10.1097/MD.0000000000025291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051975PMC
April 2021

Are need for affect and cognition culture dependent? Implications for global public health campaigns: a cross-sectional study.

BMC Public Health 2021 04 9;21(1):693. Epub 2021 Apr 9.

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Cultural differences in affective and cognitive intrinsic motivation could pose challenges for global public health campaigns, which use cognitive or affective goals to evoke desired attitudes and proactive health-promoting actions. This study aimed to identify cross-cultural differences in affective and cognitive intrinsic motivation and discuss the potential value of this information for public health promotion.

Methods: A cross-sectional survey using cross-culturally validated need for affect (NFA) and need for cognition (NFC) scales was carried out among 1166 Chinese participants, and the results were compared with published data from 980 American participants. Additionally, we assessed a highly prevalent symbolic geriatric health condition, hearing loss, in 500 Chinese community-dwelling seniors. The Chinese NFA scale was developed following the translation-back translation procedure, and the psychometric evaluation was performed by applying confirmatory factor analysis (CFA), exploratory structural equation modeling (ESEM), correlation analysis and multigroup invariance test. MANOVA and Hedge's g statistic were employed to compare the NFA and NFC levels between individuals from different countries and between Chinese seniors with and without hearing loss. The relation of early hearing intervention intention to NFA and NFC was also explored in the Chinese sample.

Results: A basic two-factor model of NFA adequately fit the sample data from Chinese and American cultures. The questionnaire demonstrated reasonable invariance of the factor structure and factor loadings across the groups. Those in the primary Chinese sample had lower NFA and NFC than their American peers. This difference held in the senior sample. Moreover, Chinese seniors with hearing loss had even lower NFA and NFC than those without hearing loss. Their early hearing intervention intention was low but was associated with intrinsic motivation.

Conclusions: The Need for Affect (NFA) construct may be generalized beyond its Western origins. There was a general lack of affective and cognitive intrinsic motivation in Chinese individuals, particularly in seniors with hearing loss, compared with their American peers. These differences point to a potential challenge in framing effective messages for some cultures in the geriatric public health domain. Ideally, recognizing and understanding this challenge will inspire the consideration of novel persuasive strategies for these audiences.
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http://dx.doi.org/10.1186/s12889-021-10689-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034077PMC
April 2021

Reactive microglia enhance the transmission of exosomal alpha-synuclein via toll-like receptor 2.

Brain 2021 Apr 1. Epub 2021 Apr 1.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Increasing evidence suggests that microglial activation is strongly linked to the initiation and progression of Parkinson's disease (PD). Cell-to-cell propagation of α-synuclein (α-syn) pathology is a highlighted feature of PD, and the focus of such research has been primarily on neurons. However, recent studies as well as the data contained herein suggest that microglia, the primary phagocytes in the brain, play a direct role in the spread of α-syn pathology. Recent data revealed that plasma exosomes derived from PD patients (PD-EXO) carry pathological α-syn and target microglia preferentially. Hence, PD-EXO is likely a key tool for investigating the role of microglia in α-syn transmission. We showed that intrastriatal injection of PD-EXO resulted in the propagation of exosomal α-syn from microglia to neurons following microglia activation. Toll-like receptor 2 (TLR2) in microglia was activated by exosomal α-syn and acted as a crucial mediator of PD-EXO-induced microglial activation. Additionally, partial microglia depletion resulted in a significant decrease of exogenous α-syn in the substantia nigra (SN). Furthermore, exosomal α-syn internalization was initiated by binding to TLR2 of microglia. Excessive α-syn phagocytosis may induce the inflammatory responses of microglia and provide the seed for microglia-to-neuron transmission. Consistently, TLR2 silencing in microglia mitigated α-syn pathology in vivo. Overall, the present data support the idea that the interaction of exosomal α-syn and microglial TLR2 contribute to excessive α-syn phagocytosis and microglial activation, which lead to the further propagation and spread of α-syn pathology, thereby highlighting the pivotal roles of reactive microglia in α-syn transmission.
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http://dx.doi.org/10.1093/brain/awab122DOI Listing
April 2021

[Distribution of Nitrogen and Phosphorus in Lake Chaohu Sediments and Pollution Evaluation].

Huan Jing Ke Xue 2021 Feb;42(2):699-711

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography & Limnology, Chinese Academy of Sciences, Nanjing 210008, China.

We investigated the spatial distribution and storage of nitrogen and phosphorus in Lake Chaohu sediments and evaluated the sediment nitrogen and phosphorus pollution index. Results show that the average total nitrogen (TN) and total phosphorus (TP) content in the surface-layer sediments of Lake Chaohu were 1088 mg·kg and 585 mg·kg, respectively, and 666 mg·kg and 509 mg·kg in the bottom-layer sediments, respectively. TN content in the surface layer was significantly higher than in the bottom layer (<0.01). Spatially, TN, TP, and sediment thickness were ranked in the order western lake area > eastern lake area > middle lake area, and the TN and TP contents were significantly different in the surface sediments from the middle and eastern areas of the lake (<0.05, <0.01). TN and TP storage in the lake sediments was 1.58×10 t and 0.98×10 t, respectively. TN and TP were significantly correlated in both the western and middle parts of the lake (<0.01). In addition, TN was significantly correlated with sediment thickness in middle area of the lake, which indicated that TN may have the same pollution sources as TP and both were affected by sediment thickness. TN pollution index (), TP pollution index (), and comprehensive pollution index (FF) values were 1.09, 1.39, and 1.32, respectively, indicating light-to-moderate levels of pollution. Specifically, the western lake surface sediments were heavily polluted with respect to TP, the eastern lake surface sediments were moderately polluted, and the middle lake surface sediments were slightly polluted. Nutrient pollution varied widely between different areas of the lake, with sediments in the western part of the lake presenting a higher safety risk. Overall, these observations indicate that Lake Chaohu is threatened by internal nutrient loading.
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http://dx.doi.org/10.13227/j.hjkx.202006216DOI Listing
February 2021

Targeted Regulation of Blood-Brain Barrier for Enhanced Therapeutic Efficiency of Hypoxia-Modifier Nanoparticles and Immune Checkpoint Blockade Antibodies for Glioblastoma.

ACS Appl Mater Interfaces 2021 Mar 8;13(10):11657-11671. Epub 2021 Mar 8.

Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

Glioblastoma is the most destructive type of brain cancer. The blood-brain barrier (BBB) is a tremendous obstacle that hinders therapeutic agents, such as chemical drugs and antibodies, from reaching glioblastoma tissues. Meanwhile, the abnormal microenvironment of glioblastoma extremely restricts the expected therapeutic effects of accumulated drugs. Therefore, in the present study, BBB-regulating nanovesicles (BRN) are developed to achieve targeted and controlled BBB regulation, carrying adenosine 2A receptor (AR) agonists and perfluorocarbon (PF). The red-blood-cell membrane (RBCM) is included on the outside to avoid the premature release of therapeutic agents. In the presence of ultrasonication (US), AR agonists are released and induce effects on both F-actin and tight junctions of endothelial cells. Subsequently, BBB permeability is temporarily increased and enables small molecules and nanoparticles to enter brain parenchymal tissues. The high affinity between manganese dioxide and temozolomide (TMZ) is utilized to form multifunctional nanoparticles to ameliorate the hypoxic microenvironment, which yields improved glioblastoma inhibition combined with radiotherapy. Moreover, with the aid of targeted BBB regulation, programmed death ligand-1 (PD-L1) antibody induces a tumor-specific immune response. Taken together, the findings suggest that synergistic combination may have the potential in amplifying the therapeutic efficacies of clinical drugs and immune checkpoint blockade antibodies to overcome the therapeutic resistance of glioblastoma.
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http://dx.doi.org/10.1021/acsami.1c00347DOI Listing
March 2021

Radiomics Models Based on Apparent Diffusion Coefficient Maps for the Prediction of High-Grade Prostate Cancer at Radical Prostatectomy: Comparison With Preoperative Biopsy.

J Magn Reson Imaging 2021 Mar 8. Epub 2021 Mar 8.

Department of Radiology, Peking University First Hospital, Beijing, China.

Background: It is feasible to use magnetic resonance (MR)-based radiomics to distinguish high-grade from low-grade prostate cancer (PCa), but radiomics model performance based on fully automated segmentation remains unknown.

Purpose: To develop and test radiomics models based on manually or automatically gained masks on apparent diffusion coefficient (ADC) maps to predict high-grade (Gleason score ≥ 4 + 3) PCa at radical prostatectomy (RP).

Study Type: Retrospective.

Population: A total of 176 patients (94 high-grade PCa and 82 low-grade PCa) with complete RP, preoperative biopsy, and multiparametric magnetic resonance imaging (mpMRI) were retrospectively recruited and randomly divided into training (N = 123) and test (N = 53) cohorts.

Field Strength/sequence: Using a 3.0-T MR scanner, ADC maps were calculated from diffusion-weighted imaging (b values = 0, 1400 s/mm , echo planar imaging).

Assessment: Two radiologists segmented the whole prostate gland and the most index prostate lesion. Automatic segmentation of the prostate and the lesion were performed. Four radiomics models were constructed using four masks (manual/automatic prostate gland/PCa lesion segmentation). According to the standard reference of the RP histopathologic assessment, the performance of each radiomics models was compared with that of biopsy and Prostate Imaging Reporting and Data System version 2.1 (PI-RADS) assessment.

Statistical Tests: A receiver operating characteristic curve analysis was employed to estimate the area under the curve (AUC) values of the models. The AUCs of the four models, biopsy, and PI-RADS assessment were compared using the DeLong test.

Results: The four radiomics models yielded AUCs of 0.710, 0.731, 0.726, and 0.709 in the test cohort, respectively; biopsy and PI-RADS assessment yielded AUCs of 0.793 and 0.680, respectively. No significant differences were found among model, biopsy, and PI-RADS assessment comparisons (P = 0.132-0.988).

Data Conclusion: To distinguish high-grade from low-grade PCa, radiomics models based on automatic segmentation on ADC maps exhibit approximately the same diagnostic efficacy as manual segmentation and biopsy, highlighting the possibility of a fully automatic workflow combining automated segmentation with radiomics analysis.

Evidence Level: 4 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27565DOI Listing
March 2021

Isorhamnetin Inhibits Human Gallbladder Cancer Cell Proliferation and Metastasis via PI3K/AKT Signaling Pathway Inactivation.

Front Pharmacol 2021 17;12:628621. Epub 2021 Feb 17.

Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, China.

Gallbladder cancer (GBC) is the most common biliary tract tumor with a poor prognosis. Isorhamnetin is a flavonoid compound extracted from and has several pharmacological effects including anti-inflammatory and anti-cancer properties. We treated GBC-SD and NOZ of GBC cell lines with different isorhamnetin concentrations . A cell counting kit-8 (CCK-8) assay, transwell assay, Hoechst 33342 stain assay, flow cytometric analysis, and a colony-forming assay were performed to investigate the effect of isorhamnetin on the proliferation, apoptosis, metastasis, and cycle arrest of GBC cells. A western blotting assay was conducted to explore the related protein expression level of GBC cells. A mice xenograft model and immunohistochemistry staining were employed to assess the effect of isorhamnetin . Isorhamnetin was found to suppress cell proliferation and metastasis, and trigger apoptosis and arrest the G2/M phase in GBC cells via the inactivation of the PI3K/AKT signaling cascade. Our findings are of clinical significance in providing a novel treatment approach for GBC.
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http://dx.doi.org/10.3389/fphar.2021.628621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927673PMC
February 2021

Multiscale architectures boosting thermoelectric performance of copper sulfide compound.

Rare Metals 2021 Feb 28:1-9. Epub 2021 Feb 28.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620 China.

Owing to their high performance and earth abundance, copper sulfides (Cu S) have attracted wide attention as a promising medium-temperature thermoelectric material. Nanostructure and grain-boundary engineering are explored to tune the electrical transport and phonon scattering of Cu S based on the liquid-like copper ion. Here multiscale architecture-engineered Cu S are fabricated by a room-temperature wet chemical synthesis combining mechanical mixing and spark plasma sintering. The observed electrical conductivity in the multiscale architecture-engineered Cu S is four times as much as that of the Cu S sample at 800 K, which is attributed to the potential energy filtering effect at the new grain boundaries. Moreover, the multiscale architecture in the sintered Cu S increases phonon scattering and results in a reduced lattice thermal conductivity of 0.2 W·m·K and figure of merit () of 1.0 at 800 K. Such a value is one of the record values in copper sulfide produced by chemical synthesis. These results suggest that the introduction of nanostructure and formation of new interface are effective strategies for the enhancement of thermoelectric material properties.

Supplementary Information: The online version of this article (10.1007/s12598-020-01698-6) contains supplementary material, which is available to authorized users.
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http://dx.doi.org/10.1007/s12598-020-01698-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917539PMC
February 2021

Heterogeneous Influence of Frailty Phenotypes in Age-Related Hearing Loss and Tinnitus in Chinese Older Adults: An Explorative Study.

Front Psychol 2020 16;11:617610. Epub 2021 Feb 16.

Shanghai Institute of Geriatrics and Gerontology, Shanghai Key Laboratory of Clinical Geriatrics, Huadong Hospital, Research Center of Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai, China.

Background: Fried physical frailty, with mobility frailty and non-motor frailty phenotypes, is a heterogeneous syndrome. The coexistence of the two phenotypes and cognitive impairment is referred to as cognitive frailty (CF). It remains unknown whether frailty phenotype has a different association with hearing loss (HL) and tinnitus.

Methods: Of the 5,328 community-dwelling older adults, 429 participants aged ≥58 years were enrolled in the study. The participants were divided into robust, mobility, and non-mobility frailty, mobility and non-mobility CF (subdivided into reversible and potentially reversible CF, RCF, and PRCF), and cognitive decline [subdivided into mild cognitive impairment (MCI) and pre-MCI] groups. The severity and presentations of HL and/or tinnitus were used as dependent variables in the multivariate logistic or nominal regression analyses with forward elimination adjusted for frailty phenotype stratifications and other covariates.

Results: Patients with physical frailty (mobility frailty) or who are robust were found to have lower probability of developing severe HL and tinnitus, and presented HL and/or tinnitus than those with only cognitive decline, or CF. Patients with RCF and non-mobility RCF had higher probability with less HL and tinnitus, and the presentation of HL and/or tinnitus than those with PRCF and mobility RCF. Other confounders, age, cognitive and social function, cardiovascular disease, depression, and body mass index, independently mediated the severity of HL and tinnitus, and presented HL and/or tinnitus.

Conclusion: Frailty phenotypes have divergent association with HL and tinnitus. Further research is required to understand the differential mechanisms and the personalized intervention of HL and tinnitus.

Clinical Trial Registration: ClinicalTrials.gov identifier, NCT2017K020.
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http://dx.doi.org/10.3389/fpsyg.2020.617610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921692PMC
February 2021

Association between triglyceride glucose index and coronary artery disease with type 2 diabetes mellitus in middle-aged and elderly people.

Medicine (Baltimore) 2021 Mar;100(9):e25025

Department of Cardiology, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China.

Abstract: This study aimed to investigate the correlation between triglyceride glucose (TyG) index and coronary artery disease (CAD) with type 2 diabetes mellitus (T2DM) and identify the risk associated TyG index in different subgroups.A total of 1665 eligible inpatients (CAD with T2DM group [n = 680], non-coronary artery disease without T2DM [n = 985]) were consecutively enrolled in this study. They were assigned into 4 subgroups: middle-aged, elderly, male, and female subgroups. Receiver operating characteristic curve diagnostic test and a logistic regression model was established to analyze the risk factors for CAD with T2DM.TyG index is an independent risk factor for patients with CAD with T2DM. The risk of increased TyG index is greater in the middle-aged and male subgroups than in the elderly and female subgroups, respectively (all P < .05). The specificity and the positive predictive value of the TyG index is greater than the sensitivity and the negative predictive value, respectively (all P < .05).Increased TyG index is a new independent risk factor for CAD with T2DM, and its risk is higher in the middle-aged and male subgroups than in the elderly and female subgroups, respectively. TyG index may be used as a clinical predictor of CAD with T2DM.
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http://dx.doi.org/10.1097/MD.0000000000025025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939227PMC
March 2021

DT-diaphorase triggered theranostic nanoparticles induce the self-burst of reactive oxygen species for tumor diagnosis and treatment.

Acta Biomater 2021 04 27;125:267-279. Epub 2021 Feb 27.

State Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China. Electronic address:

On-demand therapy following effective tumor detection would considerably reduce the side effects of traditional chemotherapy. DT-diaphorase (DTD), whose level is strongly elevated in various tumors, is a cytosolic flavoenzyme that promotes intracellular reactive oxygen species (ROS) generation via the redox cycling of hydroquinones. Incorporation of the DTD-responsive substrate to the structures of the probe and prodrug may facilitate the tumor detection and therapy. Herein, we established an multifunctional drug delivery nanosystem (HTLAC) that rapidly responds to the DTD enzyme, leads to the early-stage precise detection and termination of tumors. Firstly, the synthesis of DTD-responsive withaferin A (DT-WA) and indocyanine green (DT-Cy5) was performed. In the presence of DTD, WA, which produces ROS in cells, was released from DT-WA, and the red fluorescence of DT-Cy5 was detected for tumor imaging. Additionally, these DTD enzyme reaction processes of DT-WA and DT-Cy5 induced ROS. The self-burst of ROS generation by the two enzyme reaction processes as well as the released WA then led to the apoptosis of tumor cells. To increase the bioavailability and tumor targeting of drugs, cell-penetrating peptide and hyaluronic acid functionalized liposomes were used to encapsulate the drugs. The detailed in vitro and in vivo assays showed that HTLAC achieved enhanced tumor detection and superior antitumor efficiency. According to above outcomes, results showed that HTLAC might provide an efficacious approach for the fabrication of enzyme-triggering nanosystems to detect tumor and induce the self-burst of ROS for an efficient tumor treatment. STATEMENT OF SIGNIFICANCE: We have fabricated a HTLAC nanosystem to address the need of bursting reactive oxygen species (ROS) generation within tumor site. Our goal uniquely aims at not only augmentation of ROS-inducing anticancer efficacy, but also to meet the challenges of tumor dynamic detection in the clinical practices. In this work, the DT-diaphorase responsive withaferin A (DT-WA) and indocyanine green (DT-Cy5) are synthesized, and observed more specifically toward DTD under physiological conditions. As the cell-penetrating peptide and hyaluronic acid functionalized liposome, the HTLAC not only induces antiproliferative activity by generating self-burst of ROS, but also effectively accumulate and restore its fluorescence at the tumor site because of the HA actively targeting tumor along with the prolonged presence in blood circulation. Besides, this enzyme-triggering nanosystem exhibited an effective tumor inhibition with a low systemic toxicity.
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http://dx.doi.org/10.1016/j.actbio.2021.02.033DOI Listing
April 2021

Research on micro-leverage in monolithic quartz resonant accelerometer.

Rev Sci Instrum 2021 Feb;92(2):025005

State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

In this study, the application of micro-leverage in the monolithically all-quartz resonant accelerometer is proposed. The magnification of the micro-leverage structure used for a large size double-ended tuning fork (DETF) was analyzed. The effect of DETF's dimension both on its own force-frequency sensitivity and micro-leverage's magnification was investigated. Through the study of the relationship between DETF's force-frequency sensitivity and micro-leverage's magnification, the effect of micro-leverage and the DETF system on the sensitivity of the accelerometer was obtained. The problem of big error in theoretical calculation of micro-leverage magnification was solved because the structural arrangement of the output beam was ignored in the derivation process. The correctness of the analysis was verified by theoretical calculation, simulation, and the experiment. The equivalent structures of tension (compression) stiffness and flexural stiffness of the micro-leverage output beam were obtained by analyzing and simplifying the composite structure of the link beam and DETF. By simplifying the mechanical model of micro-leverage, the amplification factor K of micro-leverage is deduced to be 23. Therefore, the theoretical sensitivity of the sensor is 15.6 Hz/g. The experimental results show that the sensitivity of the accelerometer with the micro-leverage is 16.1 Hz/g, which is close to the theoretical analysis results.
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http://dx.doi.org/10.1063/5.0028633DOI Listing
February 2021