Publications by authors named "Li Han"

1,343 Publications

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Effects of biochar on NO emission in denitrification pathway from paddy soil: A drying incubation study.

Sci Total Environ 2021 May 8;787:147591. Epub 2021 May 8.

Liaoning Biochar Engineering & Technology Research Center, Shenyang Agricultural University, Shenyang 110866, China. Electronic address:

NO emission from paddy soil is a potential environmental risk, especially when the soil moisture content of paddy soil changes and excessive nitrogen retention occurs. Biochar is known to have a positive effect on reducing NO emissions. However, the influence of different types of biochar on NO emission with varying soil moisture contents is unclear. The objective of this study was to investigate the effects of biochar made from different feedstocks and at different pyrolysis temperatures on the release of NO during drying process of paddy soil. An incubation experiment with four kinds of biochar (rice straw and rice husk biochar pyrolyzed at 400 °C and 700 °C, respectively) applied at 1% (w/w) was conducted on paddy soil with the same initial moisture content (105% water-filled pore space). The emission rate of NO, concentrations of ammonium and nitrate, and the abundance of NO related microbial functional genes (narG and nosZ) were monitored throughout the incubation period. Biochar amendments reduced cumulative NO emissions by 56.8-90.1% compared to the control. Low-temperature rice straw biochar decreased nosZ gene abundance, downregulated the denitrification pathway, and reduced nitrogen loss and NO emission. The low-temperature pyrolysis rice husk biochar and the control showed similar trends in narG and nosZ gene abundance and NO emission. The high-temperature pyrolysis of rice straw and rice husk biochar showed opposite trends in narG gene abundance, but both increased nosZ gene abundance at the later incubation period. Different feedback on denitrification-derived NO emission in biochar application was revealed in this study by establishing a link between biotic and abiotic factors, showing that caution should be exercised when considering the use of biochar to mitigate NO emission under drying soil conditions.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147591DOI Listing
May 2021

Comparative analysis of the main outer membrane proteins of Brucella in the diagnosis of brucellosis.

Biochem Biophys Res Commun 2021 May 11;560:126-131. Epub 2021 May 11.

Key Lab of Environment and Health, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, China. Electronic address:

Brucellosis has placed a heavy economic burden on numerous countries and has consumed considerable medical resources worldwide. To improve the specificity and sensitivity of serological methods for diagnosing brucellosis, it is important to develop new diagnostic antigens. Brucella outer membrane proteins(omps) possess good immunogenicity, but there is a scarcity of comparative studies of these proteins in the clinical diagnosis of brucellosis. In this study, six recombinant Brucella outer membrane proteins, omp10, omp16, omp19, omp25, omp31 and BP26, were expressed in prokaryotic cells and utilized as diagnostic antigens. The clinical sera of humans, bovines and goats with brucellosis were analyzed by indirect ELISA using these proteins, lipopolysaccharide(LPS) and Rose Bengale Ag, served as positive-control antigens. In diagnosing human and goat serum, BP26 exhibited the highest diagnostic accuracy of 96.45% and 95.00%, respectively, while omp31 exhibited the strongest ability to detect Brucella in bovine serum with an accuracy of 84.03%. Cross-reaction experiments also confirmed that the diagnostic specificities of omp31 and BP26 were higher than those of the LPS and Rose Bengale Ag antigens. The results of this study indicate that omp31 and BP26 are candidate antigens with high potential application value in the clinical diagnosis of brucellosis.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.127DOI Listing
May 2021

Granulocytes Acquire Antiapoptosis Activity and Promote Tumor Growth during Tumor Progress.

Glob Med Genet 2021 Jun 16;8(2):72-77. Epub 2021 Mar 16.

Med-X Research Institute & School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai, People's Republic of China.

Granulocytes play important roles in cancer, and their apoptotic status is often changed by the influence of tumor environment. However, the changes and the function on granulocyte apoptosis in cancer are unclear. In this study, we used tumor-bearing mouse model and tumor patients to analyzed the apoptosis of granulocytes in different tissues by flow analysis and TUNEL fluorescence staining, and found that the percentage of apoptosis cells in granulocytes was significantly decreased in late-stage tumor-bearing mouse and patients. The in vitro co-culture experiment showed that these antiapoptotic granulocytes could significantly inhibit T cell proliferation, and RNA-seq proved that there was obvious difference on the transcriptome between these cells and control cells, particularly immune-related genes. What is important, adoptive transfer of these antiapoptotic granulocytes promoted tumor progress in mouse model. Conclusively, we found that granulocytes in late-stage tumor could delay the process of apoptosis, inhibit T cell proliferation, and acquire pro-tumor activity, which provides a new therapeutic target for tumor immunity.
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http://dx.doi.org/10.1055/s-0041-1726335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110362PMC
June 2021

Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma.

Med Sci Monit 2021 May 12;27:e929333. Epub 2021 May 12.

Department of Respiratory Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China (mainland).

BACKGROUND Lung adenocarcinoma (LUAD) is a type of non-small cell carcinoma. Its pathogenesis is being explored and there is no cure for the disease. MATERIAL AND METHODS The Gene Expression Omnibus (GEO) was searched to obtain data on expression of messenger RNA. GEO2R, an interactive web tool, was used to calculate the differentially expressed genes (DEGs) in LUAD. All the DEGs from different datasets were imported into VENNY 2.1 (https://bioinfogp.cnb.csic.es/tools/venny/index.html) to identify the intersection of the DEGs. An online analysis tool, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), was used to help understand the biological meaning of DEG enrichment in LUAD. Cytoscape 3.7.2 was used to perform centrality analysis and visualize hub genes and related networks. Furthermore, the prognostic value of the hub genes was evaluated with the Kaplan-Meier plotter survival analysis tool. RESULTS The GEO database was used to obtain RNA sequencing information for LUAD and normal tissue from the GSE118370, GSE136043, and GSE140797 datasets. A total of 376 DEGs were identified from GSE118370, 248 were identified from GSE136403, and 718 DEGs were identified from GSE140797. The 10 genes with the highest degrees of expression - the hub genes - were CAV1, TEK, SLIT2, RHOJ, DGSX, HLF, MEIS1, PTPRD, FOXF1, and ADRB2. In addition, Kaplan-Meier survival evaluation showed that CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1, and ADRB2 were associated with favorable outcomes for LUAD. CONCLUSIONS CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1, and ADRB2 are hub genes in the DEG interaction network for LUAD and are involved in the development of and prognosis for the disease. The mechanisms underlying these genes should be the subject of further studies.
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http://dx.doi.org/10.12659/MSM.929333DOI Listing
May 2021

The Intestinal Microbiome Primes Host Innate Immunity against Enteric Virus Systemic Infection through Type I Interferon.

mBio 2021 May 11;12(3). Epub 2021 May 11.

Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, People's Republic of China

Intestinal microbiomes are of vital importance in antagonizing systemic viral infection. However, very little literature has shown whether commensal bacteria play a crucial role in protecting against enteric virus systemic infection from the aspect of modulating host innate immunity. In the present study, we utilized an enteric virus, encephalomyocarditis virus (EMCV), to inoculate mice treated with phosphate-buffered saline (PBS) or given an antibiotic cocktail (Abx) orally or intraperitoneally to examine the impact of microbiota depletion on virulence and viral replication Microbiota depletion exacerbated the mortality, neuropathogenesis, viremia, and viral burden in brains following EMCV infection. Furthermore, Abx-treated mice exhibited severely diminished mononuclear phagocyte activation and impaired type I interferon (IFN) production and expression of IFN-stimulated genes (ISG) in peripheral blood mononuclear cells (PBMC), spleens, and brains. With the help of fecal bacterial 16S rRNA sequencing of PBS- and Abx-treated mice, we identified a single commensal bacterium, , that can restore mononuclear phagocyte- and IFNAR (IFN-α/β receptor)-dependent type I IFN responses to restrict systemic enteric virus infection. These findings may provide insight into the development of novel therapeutics for preventing enteric virus infection or possibly alleviating clinical diseases by activating host systemic innate immune responses via respective probiotic treatment using While cumulative data indicate that indigenous commensal bacteria can facilitate enteric virus infection, little is known regarding whether intestinal microbes have a protective role in antagonizing enteric systemic infection by modulating host innate immunity. Although accumulating literature has pointed out that the microbiota has a fundamental impact on host systemic antiviral innate immune responses mediated by type I interferon (IFN), only a few specific commensal bacteria species have been revealed to be capable of regulating IFN-I and ISG expression, not to mention the underlying mechanisms. Thus, it is important to understand the cross talk between microbiota and host anti-enteric virus innate immune responses and characterize the specific bacterial species that possess protective functions. Our study demonstrates how fundamental innate immune mediators such as mononuclear phagocytes and type I IFN are regulated by commensal bacteria to antagonize enteric virus systemic infection. In particular, we have identified a novel commensal bacterium, , that can restrict enteric virus replication and neuropathogenesis by activating IFN-I and ISG responses in mononuclear phagocytes via an IFNAR- and STAT1-mediated signaling pathway.
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http://dx.doi.org/10.1128/mBio.00366-21DOI Listing
May 2021

Advances in the Application of Natural Products and the Novel Drug Delivery Systems for Psoriasis.

Front Pharmacol 2021 21;12:644952. Epub 2021 Apr 21.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Psoriasis, an incurable autoimmune skin disease, is one of the most common immune-mediated disorders. Presently, numerous clinical research studies are underway, and treatment options are available. However, these treatments focus on improving symptoms of the disease and fail to achieve a radical cure; they also have certain toxic side effects. In recent years, natural products have increasingly gained attention because of their high efficiency and low toxicity. Despite their obvious therapeutic effects, natural products' biological activity was limited by their instability, poor solubility, and low bioavailability. Novel drug delivery systems, including liposomes, lipospheres, nanostructured lipid carriers, niosomes, nanoemulsions, nanospheres, microneedles, ethosomes, nanocrystals, and foams could potentially overcome the limitations of poor water solubility and permeability in traditional drug delivery systems. Thus, to achieve a therapeutic effect, the drug can reach the epidermis and dermis in psoriatic lesions to interact with the immune cells and cytokines.
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http://dx.doi.org/10.3389/fphar.2021.644952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097153PMC
April 2021

Suppression of neuropathic pain and comorbidities by recurrent cycles of repetitive transcranial direct current motor cortex stimulation in mice.

Sci Rep 2021 May 6;11(1):9735. Epub 2021 May 6.

Institute of Pharmacology, Medical Faculty Heidelberg, Heidelberg University, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany.

Transcranial, minimally-invasive stimulation of the primary motor cortex (M1) has recently emerged to show promise in treating clinically refractory neuropathic pain. However, there is a major need for improving efficacy, reducing variability and understanding mechanisms. Rodent models hold promise in helping to overcome these obstacles. However, there still remains a major divide between clinical and preclinical studies with respect to stimulation programs, analysis of pain as a multidimensional sensory-affective-motivational state and lack of focus on chronic phases of established pain. Here, we employed direct transcranial M1 stimulation (M1 tDCS) either as a single 5-day block or recurring blocks of repetitive stimulation over early or chronic phases of peripherally-induced neuropathic pain in mice. We report that repeated blocks of stimulation reverse established neuropathic mechanical allodynia more strongly than a single 5-day regime and also suppress cold allodynia, aversive behavior and anxiety without adversely affecting motor function over a long period. Activity mapping revealed highly selective alterations in the posterior insula, periaqueductal gray subdivisions and superficial spinal laminae in reversal of mechanical allodynia. Our preclinical data reveal multimodal analgesia and improvement in quality of life by multiple blocks of M1 tDCS and uncover underlying brain networks, thus helping promote clinical translation.
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http://dx.doi.org/10.1038/s41598-021-89122-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102487PMC
May 2021

Modulation of the EMT/MET Process by E-Cadherin in Airway Epithelia Stress Injury.

Biomolecules 2021 Apr 30;11(5). Epub 2021 Apr 30.

Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410007, China.

Persistent injury and the following improper repair in bronchial epithelial cells are involved in the pathogenesis of airway inflammation and airway remodeling of asthma. E-cadherin (ECAD) has been shown to be involved in airway epithelium injury repair, but its underlying mechanisms to this process is poorly understood. Here, we describe a previously undetected function of ECAD in regulating the balance of EMT and MET during injury repair. Injury in mice and human bronchial epithelial cells (HBECs) was induced by successive ozone stress for 4 days at 30 min per day. ECAD overexpression in HBECs was induced by stable transfection. EMT features, transforming growth factor beta1 (TGF-β1) secretion, transcriptional repressor Snail expression, and β-catenin expression were assayed. Ozone exposure and then removal successfully induced airway epithelium injury repair during which EMT and MET occurred. The levels of TGF-β1 secretion and Snail expression increased in EMT process and decreased in MET process. While ECAD overexpression repressed EMT features; enhanced MET features; and decreased TGF-β1 secretion, Snail mRNA level, and β-catenin protein expression. Moreover, activating β-catenin blocked the effects of ECAD on EMT, MET and TGF-β1 signaling. Our results demonstrate that ECAD regulates the balance between EMT and MET, by preventing β-catenin to inhibit TGFβ1 and its target genes, and finally facilitates airway epithelia repair.
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http://dx.doi.org/10.3390/biom11050669DOI Listing
April 2021

Correlations of social isolation and anxiety and depression symptoms among patients with breast cancer of Heilongjiang province in China: The mediating role of social support.

Nurs Open 2021 May 3. Epub 2021 May 3.

Department of Neurosurgery, the Tumor Hospital Affiliated of Harbin Medical University, Harbin, China.

Objectives: To explore the correlations among social isolation and symptoms of anxiety and depression among patients with breast cancer in China and to further verify the mediating role of social support in social isolation and symptoms of depression or anxiety.

Design: A cross-sectional survey.

Settings: The cluster sampling method was conducted for 456 female inpatients diagnosed with breast cancer at the Tumor Hospital Affiliated of Harbin Medical University from April 2019-September 2019.

Methods: Pearson correlation analysis was used for identifying correlations among all the variables. Mediation effect analysis was used to examine the role of social support in social isolation and symptoms of depression or anxiety.

Results: The results showed a prevalence of 73.26% and 70.44% for anxiety and depression symptoms in patients with breast cancer, respectively. Anxiety was significantly negatively correlated with social support (r = -.334, p < .01) and significantly positively correlated with social isolation (r = .369, p < .01). Similarly, depression was significantly negatively correlated with social support (r = -.289, p < .01) and significantly positively correlated with social isolation (r = .466, p < .01). Social support played a mediating role in social isolation and f symptoms of anxiety or depression among these patients.

Conclusions: Social isolation was positively correlated with symptoms of anxiety and depression in patients with breast cancer, respectively. Social support for patients with breast cancer has a mediating effect on the patients' social isolation and symptoms of anxiety and depression. Therefore, the support of family, friends, hospitals, and organizations plays a positive role in reducing social isolation as well as symptoms of depression and anxiety in these patients.
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http://dx.doi.org/10.1002/nop2.876DOI Listing
May 2021

ALG3 contributes to stemness and radioresistance through regulating glycosylation of TGF-β receptor II in breast cancer.

J Exp Clin Cancer Res 2021 Apr 30;40(1):149. Epub 2021 Apr 30.

Department of Radiotherapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.

Background: Radiotherapy is a conventional and effective local treatment for breast cancer. However, residual or recurrent tumors appears frequently because of radioresistance. Novel predictive marker and the potential therapeutic targets of breast cancer radioresistance needs to be investigated.

Methods: In this study, we screened all 10 asparagine-linked glycosylation (ALG) members in breast cancer patients' samples by RT-PCR. Cell viability after irradiation (IR) was determined by CCK-8 assay and flow cytometry. The radiosensitivity of cell lines with different ALG3 expression was determined with the colony formation assay by fitting the multi-target single hit model to the surviving fractions. Cancer stem-like traits were assessed by RT-PCR, Western blot, and flow cytometry. The mechanisms of ALG3 influencing radiosensitivity was detected by Western blot and immunoprecipitation. And the effect of ALG3 on tumor growth after IR was verified in an orthotopic xenograft tumor models. The association of ALG3 with prognosis of breast cancer patients was confirmed by immunohistochemistry.

Results: ALG3 was the most significantly overexpressing gene among ALG family in radioresistant breast cancer tissue. Overexpression of ALG3 predicted poor clinicopathological characteristics and overall survival (OS), and early local recurrence-free survival (LRFS) in breast cancer patients. Upregulating ALG3 enhanced radioresistance and cancer stemness in vitro and in vivo. Conversely, silencing ALG3 increased the radiosensitivity and repressed cancer stemness in vitro, and more importantly inhibition of ALG3 effectively increased the radiosensitivity of breast cancer cells in vivo. Mechanistically, our results further revealed ALG3 promoted radioresistance and cancer stemness by inducing glycosylation of TGF-β receptor II (TGFBR2). Importantly, both attenuation of glycosylation using tunicamycin and inhibition of TGFBR2 using LY2109761 differentially abrogated the stimulatory effect of ALG3 overexpression on cancer stemness and radioresistance. Finally, our findings showed that radiation played an important role in preventing early recurrence in breast cancer patients with low ALG3 levels, but it had limited efficacy in ALG3-overexpressing breast cancer patients.

Conclusion: Our results suggest that ALG3 may serve as a potential radiosensitive marker, and an effective target to decrease radioresistance by regulating glycosylation of TGFBR2 in breast cancer. For patients with low ALG3 levels, radiation remains an effective mainstay therapy to prevent early recurrence in breast cancer.
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http://dx.doi.org/10.1186/s13046-021-01932-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086123PMC
April 2021

A Novel Blind Signal Detector Based on the Entropy of the Power Spectrum Subband Energy Ratio.

Entropy (Basel) 2021 Apr 11;23(4). Epub 2021 Apr 11.

School of Modern Post, Beijing University of Posts and Telecommunications, Beijing 100876, China.

In this paper, we present a novel blind signal detector based on the entropy of the power spectrum subband energy ratio (PSER), the detection performance of which is significantly better than that of the classical energy detector. This detector is a full power spectrum detection method, and does not require the noise variance or prior information about the signal to be detected. According to the analysis of the statistical characteristics of the power spectrum subband energy ratio, this paper proposes concepts such as interval probability, interval entropy, sample entropy, joint interval entropy, PSER entropy, and sample entropy variance. Based on the multinomial distribution, in this paper the formulas for calculating the PSER entropy and the variance of sample entropy in the case of pure noise are derived. Based on the mixture multinomial distribution, the formulas for calculating the PSER entropy and the variance of sample entropy in the case of the signals mixed with noise are also derived. Under the constant false alarm strategy, the detector based on the entropy of the power spectrum subband energy ratio is derived. The experimental results for the primary signal detection are consistent with the theoretical calculation results, which proves that the detection method is correct.
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http://dx.doi.org/10.3390/e23040448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070492PMC
April 2021

Effect of urban underlying surface on PM2.5 vertical distribution based on UAV in Xi'an, China.

Environ Monit Assess 2021 Apr 29;193(5):312. Epub 2021 Apr 29.

School of Architecture, Chang'an University, Xi'an, China.

Fine particulate matter (PM) has become a significant issue of ecological environment. However, few studies have explored the vertical distribution of PM in cities. The objectives of this paper are to reveal the vertical distribution regular pattern of PM over urban underlying surfaces near the ground with a hexacopter-type unmanned aerial vehicle (UAV) in winter. Results showed that the maximum vertical gradient of PM near the ground was typically the greatest in the morning as the stable atmospheric conditions. Moreover, regression model illustrated that relative humidity had the greatest impact on the vertical profile of PM compared to air temperature and altitude as hygroscopic of PM aerosols. Curve model shown that vertical profile of PM over the surfaces of water and green space first increased slowly and then declined, besides, the highest concentration inflection of PM above the water body (23.7 m) is higher than the green space (14.3 m). Thus, suggesting residents living vertical of 10-30 m from the ground around large water bodies and green spaces should not open windows for ventilation in the morning. Therefore, this study provides insights into the vertical distributions of PM over different underlying surfaces and should be of reference value to urban planners for designing urban spaces to optimize atmosphere environment to provide a healthy living environment.
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http://dx.doi.org/10.1007/s10661-021-09044-8DOI Listing
April 2021

Risk factors for mortality in patients undergoing peritoneal dialysis: a systematic review and meta-analysis.

Ren Fail 2021 Dec;43(1):743-753

Department of Blood Purification, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Aim: Inconsistent investigations of the risk factors for all-cause mortality in patients undergoing peritoneal dialysis (PD) were reported. The present meta-analysis aimed to assess the impact of some clinical characteristics on the risk of mortality in PD patients. PubMed and Embase were systematically searched for studies evaluating the risk factors for all-cause mortality in PD patients. Hazard ratio (HR) and 95% confidence interval (CI) were derived using a random-effect or fixed-effect model considering the heterogeneity across studies. A total of 26 studies were included in this meta-analysis in accordance with the inclusion and exclusion criteria. Age, primary cardiovascular diseases, diabetes mellitus, and high level of alkaline phosphatase showed significant positive associations with elevated risk of all-cause and cardiovascular mortality in PD patients, while hemoglobin acted as a benefit factor. Furthermore, early onset of peritonitis, high peritoneal transport status, elevated body mass index and high-sensitivity C-reactive protein could also considerably increase the risk of all-cause mortality. The absolute serum level of magnesium, potassium, and uric acid required to improve survival in PD patients should be verified further. Multiple factors could affect the risk of mortality in PD patients.
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http://dx.doi.org/10.1080/0886022X.2021.1918558DOI Listing
December 2021

New phenolic glycosides from Bunge and their antioxidant activity.

Nat Prod Res 2021 Apr 28:1-7. Epub 2021 Apr 28.

Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang, People's Republic of China.

ABATRACTNine compounds, five phenolic glycosides (, , ), three phenylpropanoids (), and a furanone glycoside (), were isolated from aqueous soluble extract of the dried roots of Bunge. The structures of new compounds () were elucidated by comprehensive spectroscopic data analysis as well as chemical evidence. Pulsatillanin A () demonstrated significant antioxidant effects through scavenging free radical in DPPH assay, and relieved the oxidative stress in LPS-induced RAW 264.7 cells by reducing ROS production, enhancing antioxidant enzyme SOD activity, replenishing depleted GSH in a dose-dependent manner. Western blot analysis revealed that showed antioxidant activity via activating Nrf2 signaling pathway.
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http://dx.doi.org/10.1080/14786419.2021.1917569DOI Listing
April 2021

A cohort study of dysmenorrhea and risk of low birth weight.

J Matern Fetal Neonatal Med 2021 Apr 25:1-7. Epub 2021 Apr 25.

Department of Sanitary Chemistry, School of Public Health, Guangxi Medical University, Nanning, China.

Objective: Little is known about the association between maternal history of dysmenorrhea and perinatal outcomes. The aim of this study was to investigate the association between maternal history of dysmenorrhea and low birth weight (LBW).

Methods: A total of 6754 pregnant women were recruited from the ongoing prospective cohort study in Guangxi, China, in 2015-2018. Information on the maternal history of dysmenorrhea was obtained by questionnaires including visual analog scale (VAS) questions during the first antenatal care visit. The association of maternal history of dysmenorrhea and LBW was evaluated using logistic regression analyses adjusted for confounding factors (infant sex, maternal age, parity, pre-pregnancy body mass index (BMI) (kg/m), gestational age, alcohol use during pregnancy, passive smoking, and occupational status).

Results: Mothers with a history of dysmenorrhea were more likely to give birth to LBW infants (adjusted odds ratio (OR)=1.44; 95% confidence interval (CI): 1.12, 1.83). Among women with a history of dysmenorrhea, women ≥29 years old (adjusted OR 1.46; 95% CI 1.02, 2.10), multiparous (adjusted OR 1.59, 95% CI 1.12, 2.25), and women gave birth to female infant (adjusted OR = 1.53, 95% CI = 1.11, 2.11) had a higher risk of LBW.

Conclusions: As the first cohort study to investigate the association between maternal history of dysmenorrhea and LBW, our study shows that dysmenorrhea may increase the risk of LBW.
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http://dx.doi.org/10.1080/14767058.2021.1914581DOI Listing
April 2021

A high-throughput cell-based gaussia luciferase reporter assay for measurement of CYP1A1, CYP2B6, and CYP3A4 induction.

Xenobiotica 2021 May 3:1-12. Epub 2021 May 3.

Institute of Radiation Medicine Academy of Military Medical Sciences, Beijing, China.

The induction of cytochrome P450s can result in reduced drug efficacy and lead to potential drug-drug interactions. The xenoreceptors-aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR)-play key roles in CYP induction by xenobiotics. In order to be able to rapidly screen for the induction of three enzymes (CYP1A1, CYP2B6, and CYP3A4), we generated a stable AhR-responsive HepG2 cell line, a stable CAR-responsive HepG2 cell line, and a stable PXR-responsive HepG2 cell line.To validate these stable xenoreceptor-responsive HepG2 cell lines, we evaluated the induction of the different Gaussia reporter activities, as well as the mRNA and protein expression levels of endogenous CYPs in response to different inducers.The induction of luciferase activity in the stable xenoreceptor-responsive HepG2 cell lines by specific inducers occurred in a concentration dependent manner. There was a positive correlation between the induction of luciferase activities and the induction endogenous CYP mRNA expression levels. These xenoreceptor-responsive HepG2 cell lines were further validated with known CYP1A1, CYP2B6, and CYP3A4 inducers.These stable xenoreceptor-responsive HepG2 cell lines may be used in preclinical research for the rapid and sensitive detection of AhR, CAR, and PXR ligands that induce CYP450 isoforms.
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http://dx.doi.org/10.1080/00498254.2021.1918800DOI Listing
May 2021

Overview of all-trans-retinoic acid (ATRA) and its analogues: Structures, activities, and mechanisms in acute promyelocytic leukaemia.

Eur J Med Chem 2021 Apr 15;220:113451. Epub 2021 Apr 15.

Medical College, Guizhou University, Guiyang, 550025, PR China. Electronic address:

All-trans-retinoic acid (ATRA) is effective for preventing cancer and treating skin diseases and acute promyelocytic leukaemia (APL). These pharmacological effects of ATRA are mainly mediated by retinoid X receptors (RXRs) and retinoic acid receptors (RARs). This article provides a comprehensive overview of the clinical progress on and the molecular mechanisms of ATRA in the treatment of APL. ATRA can promote the transcriptional activation of differentiation-related genes and regulate autophagy by inhibiting mTOR, which results in anti-APL effects. In detail, the structures, pharmacological effects, and clinical studies of 68 types of ATRA analogues are described. These compounds have excellent antitumour therapeutic potential and could be used as lead compounds for further development and research.
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http://dx.doi.org/10.1016/j.ejmech.2021.113451DOI Listing
April 2021

The effect of prohibiting outside food during COVID-19 pandemic on the body weight of schizophrenic patients taking olanzapine or clozapine: a retrospective self-controlled study.

Ann Palliat Med 2021 Apr 19. Epub 2021 Apr 19.

Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, China.

Background: Olanzapine and clozapine are atypical antipsychotics (AAPs) with the greatest risk of weight gain, and changes in feeding behavior are among the most important underlying mechanisms. However, few studies have investigated the role of diet-alone interventions in improving individuals' weight gain by taking AAPs. In closed management mental hospitals of China, family members are allowed to bring food to patients regularly, causing patients to have caloric intake added to their 3 daily meals. However, during the global pandemic of coronavirus disease 2019 (COVID-19), bringing food to the hospital was temporarily prohibited in mental health institutions in China to prevent the spread of the virus. This study sought to compare the body weight and body mass index (BMI) changes of patients taking olanzapine or clozapine undergoing diet-alone interventions caused by this prohibition.

Methods: A retrospective self-controlled study was conducted on 90 patients with schizophrenia from a single-center treated with olanzapine or clozapine monotherapy, or combined with aripiprazole or ziprasidone which has a small metabolic impact. A paired-samples t-test was used to compare the changes in body weight and BMI before and after the 3-month prohibition, and general linear regression was used to analyze the effects of gender, age, disease course, duration of drug exposure, and equivalent dose on the BMI improvement. Also, the percentage of people who lost weight and that of individuals who lost 5% of their pre-prohibition body weight were calculated.

Results: Paired-samples t-test showed that after 3-month prohibition, the patients' body weight (71.68±6.83 vs. 66.91±7.03, P<0.001) and BMI (26.43±2.11 vs. 24.63±1.81, P<0.001) decreased significantly. Weight loss rate accounted for 99.1%, and weight loss of 5% from the pre-prohibition body weight accounted for 71.8%. General linear regression showed that the duration of drug exposure (β =-0.678, P<0.001) was significantly and negatively correlated with the BMI changes. No significant correlation of gender, age, disease course, or equivalent dose with BMI changes was found.

Conclusions: Diet-alone interventions facilitate weight loss in chronically hospitalized schizophrenia patients taking AAPs. Conduction of dietary intervention in the early stages of medication may yield greater benefits.
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http://dx.doi.org/10.21037/apm-20-2513DOI Listing
April 2021

Biomimetic synthesis and anti-inflammatory evaluation of violacin A analogues.

Bioorg Chem 2021 Apr 8;111:104898. Epub 2021 Apr 8.

Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. Electronic address:

Violacin A, a chromanone derivative, isolated from a fermentation broth of Streptomyces violaceoruber, has excellent anti-inflammatory potential. Herein, a biogenetically modeled approach to synthesize violacin A and twenty-five analogues was described, which involved the preparation of aromatic polyketide precursor through Claisen condensation and its spontaneous cyclization. The inhibitory effect on nitric oxide (NO) production of all synthetic molecules was evaluated by lipopolysaccharide (LPS)-induced Raw264.7 cells. The results revealed that introduction of aliphatic amine moieties on C-7 obviously improved the anti-inflammation effect of violacin A, and also the aromatic ether instead of ketone group at side chain was favorable to increase the activity. Among them, analogue 7a and 16d were screened as the most effective anti-inflammatory candidates. Molecular mechanism research revealed that 7a and 16d acquired anti-inflammatory ability due to the inhibition of NF-κB signaling pathway.
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http://dx.doi.org/10.1016/j.bioorg.2021.104898DOI Listing
April 2021

Thermal Conductivity Enhancement in Ion-Irradiated Hydrogenated Amorphous Carbon Films.

Nano Lett 2021 May 22;21(9):3935-3940. Epub 2021 Apr 22.

Department of Mechanical and Aerospace Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.

Amorphous solids are traditionally assumed to set the lower bound to the vibrational thermal conductivity of a material due to the high degree of structural disorder. Here, were demonstrate the ability to increase the thermal conductivity of amorphous solids through ion irradiation, in turn, altering the bonding network configuration. We report on the thermal conductivity of hydrogenated amorphous carbon implanted with C ions spanning fluences of 3 × 10-8.6 × 10 cm and energies of 10-20 keV. Time-domain thermoreflectance measurements of the films' thermal conductivities reveal significant enhancement, up to a factor of 3, depending upon the preirradiation composition. Films with higher initial hydrogen content provide the greatest increase, which is complemented by an increased stiffening and densification from the irradiation process. This enhancement in vibrational transport is unique when contrasted to crystalline materials, for which ion implantation is known to produce structural degradation and significantly reduced thermal conductivities.
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http://dx.doi.org/10.1021/acs.nanolett.1c00616DOI Listing
May 2021

Risk Factors for Adverse Pregnancy Outcomes among Zhuang Ethnic Pregnant Women: A Cohort Study in Guangxi, China.

Curr Med Sci 2021 Apr 20;41(2):219-227. Epub 2021 Apr 20.

Department of Sanitary Chemistry, School of Public Health, Guangxi Medical University, Nanning, 530021, China.

Risk factors for adverse pregnancy outcomes among Zhuang ethnic pregnant women are unclear. This study analyzed the incidence and risk factors related to preterm birth (PB), low birth weight (LBW) and macrosomia in Zhuang population. We conducted a prospective cohort study of 9965 Zhuang pregnancy women in Guangxi, China. Information on mothers and newborns was obtained by using questionnaires and referring to medical records. Multivariate logistic regression analyses were used to evaluate the association between related factors and adverse pregnancy outcomes. Our results showed that the incidence of PB, LBW and macrosomia in Zhuang people was 5.55%, 5.64% and 2.19%, respectively. Maternal age ≥36 years (OR=2.22, 95% CI: 1.51-3.27) was related to a higher incidence of PB. Those with pre-pregnancy body mass index (BMI) <18.5 kg/m (OR=1.91, 95% CI: 1.45-2.51), and had a female fetus (OR=1.74, 95% CI: 1.36-2.23) were more likely to have LBW infants. Maternal age between 31 and 35 years (OR=1.76, 95% CI: 1.03-2.99) and pre-pregnancy overweight or obesity (OR=1.79, 95% CI: 1.15-2.80) were associated with a higher risk of macrosomia. The protective factors of macrosomia were maternal pre-pregnancy BMI <18.5 kg/m (OR=0.30, 95% CI: 0.15-0.60) and female fetus (OR=0.41, 95% CI: 0.28-0.59). Our study provided a reference for maternal and childcare administration among Zhuang population.
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http://dx.doi.org/10.1007/s11596-021-2339-9DOI Listing
April 2021

The role of PTPN22 in the pathogenesis of autoimmune diseases: A comprehensive review.

Semin Arthritis Rheum 2021 Mar 4;51(3):513-522. Epub 2021 Mar 4.

Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria.

The incidence of autoimmune diseases is increasing worldwide, thus stimulating studies on their etiopathogenesis, derived from a complex interaction between genetic and environmental factors. Genetic association studies have shown the PTPN22 gene as a shared genetic risk factor with implications in multiple autoimmune disorders. By encoding a protein tyrosine phosphatase expressed by the majority of cells belonging to the innate and adaptive immune systems, the PTPN22 gene may have a fundamental role in the development of immune dysfunction. PTPN22 polymorphisms are associated with rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, and many other autoimmune conditions. In this review, we discuss the progress in our understanding of how PTPN22 impacts autoimmunity in both humans and animal models. In addition, we highlight the pathogenic significance of the PTPN22 gene, with particular emphasis on its role in T and B cells, and its function in innate immune cells, such as monocytes, dendritic and natural killer cells. We focus particularly on the complexity of PTPN22 interplay with biological processes of the immune system. Findings highlight the importance of studying the function of disease-associated PTPN22 variants in different cell types and open new avenues of investigation with the potential to drive further insights into mechanisms of PTPN22. These new insights will reveal important clues to the molecular mechanisms of prevalent autoimmune diseases and propose new potential therapeutic targets.
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http://dx.doi.org/10.1016/j.semarthrit.2021.03.004DOI Listing
March 2021

Mechanisms exploration of Xiaojin Pills on lung cancer based on metabolomics and network pharmacology.

J Pharm Pharmacol 2021 Apr 17. Epub 2021 Apr 17.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Objectives: This study was designed to evaluate the pharmacological activity and therapeutic mechanism of Xiaojin Pills (XJW) on lung cancer.

Methods: Mice were orally administered with Xiaojin Pills for 21 days. Tumour samples were collected to evaluate the antilung cancer effect, and blood samples were collected to identify differential metabolites with metabolomics. Through the analysis of network pharmacology, the active ingredients and targets related to XJW therapy for lung cancer were filtered.

Key Findings: Different expression of seven metabolites related to seven pathways, including Arachidonic acid metabolism, Citrate cycle, tryptophan metabolism, glyoxylate and dicarboxylate metabolism, arginine and proline metabolism, primary bile acid biosynthesis and nicotinate and nicotinamide metabolism, were demonstrated to explain the efficacy of XJW in the treatment of lung cancer. Furthermore, a total of 19 active ingredients (ursolic acid, α-thujone, pelargonidin, succinic acid, boswellic acid, muscone, daidzein, xanthorrhizol, isoeugenol, oleic acid, β-caryophyllene, vanillin, β-sitosterol, lupeol, palmitic acid, eugenol, methylbutenol, β-elemene and quercetin) acted directly on 9 targets (CAT, PTGS2, PTGS1, CTH, ABTA, ALT1, ME2, AGXT and AGXT 2) and regulated 3 out of 7 metabolites (3-Hydroxyanthranilic acid, Pyruvate and Prostaglandin G2).

Conclusions: Through metabolomics and network pharmacology analyses, this study demonstrated that the major metabolites of XJW in treating lung cancer were regulated by multitarget and multicomponent interaction network.
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http://dx.doi.org/10.1093/jpp/rgab050DOI Listing
April 2021

Advancements of nature nanocage protein: preparation, identification and multiple applications of ferritins.

Crit Rev Food Sci Nutr 2021 Apr 16:1-12. Epub 2021 Apr 16.

School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, China.

Ferritin is an important iron storage protein, which is widely existed in all forms of life. Ferritin can regulate iron homeostasis when iron ions are lacking or enriched in the body, so as to avoid iron deficiency diseases and iron poisoning. Ferritin presents a hollow nanocage, which can store ions or other small molecular substances in the cavity. Therefore, ferritin shows its potential as a functional nanomaterial that can deliver nutrients or drugs in a targeted manner to improve bioavailability. Due to the special structure, the research on ferritin has attracted more and more attention in recent years. In this paper, the structural characteristics of ferritin were introduced, and the natural purification and prokaryotic expression methods of ferritin from different sources were described. At the same time, ferritin can bind to small molecules, so that it has the activity of small molecules, to construct a new type of ferritin. As a result, ferritin plays an important role as a nutrient substance, in targeted transport, and disease monitoring, etc. In conclusion, the yield of ferritin can be improved by means of molecular biology. Meanwhile, molecular modification can be used to make ferritin have unique activity and function, which lays a foundation for subsequent research. HighlightsThe molecular and structural properties of ferritins were clearly described.Isolation and purification technologies of ferritin were compared.Characterization, functions and molecular modifications mechanism of ferritin were reviewed.The applications of ferritin in pharmaceutical and food industry were prospected.
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http://dx.doi.org/10.1080/10408398.2021.1911925DOI Listing
April 2021

Discovery of Anti-TNBC Agents Targeting PTP1B: Total Synthesis, Structure-Activity Relationship, and Investigations of Jamunones.

J Med Chem 2021 May 16;64(9):6008-6020. Epub 2021 Apr 16.

Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.

Twenty-three natural jamunone analogues along with a series of jamunone-based derivatives were synthesized and evaluated for their inhibitory effects against breast cancer (BC) MDA-MB-231 and MCF-7 cells. The preliminary structure-activity relationship revealed that the length of aliphatic side chain and free phenolic hydroxyl group at the scaffold played a vital role in anti-BC activities and the methyl group on chromanone affected the selectivity of molecules against MDA-MB-231 and MCF-7 cells. Among them, jamunone M (JM) was screened as the most effective anti-triple-negative breast cancer (anti-TNBC) candidate with a high selectivity against BC cells over normal human cells. Mechanistic investigations indicated that JM could induce mitochondria-mediated apoptosis and cause G0/G1 phase arrest in BC cells. Furthermore, JM significantly restrained tumor growth in MDA-MB-231 xenograft mice without apparent toxicity. Interestingly, JM could downregulate phosphatidylinositide 3-kinase (PI3K)/Akt pathway by suppressing protein-tyrosine phosphatase 1B (PTP1B) expression. These findings revealed the potential of JM as an appealing therapeutic drug candidate for TNBC.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00085DOI Listing
May 2021

Ganoderic acid A exerted antidepressant-like action through FXR modulated NLRP3 inflammasome and synaptic activity.

Biochem Pharmacol 2021 Apr 20;188:114561. Epub 2021 Apr 20.

School of Medicine, Yunnan University, Kunming 650091, China; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100088, China. Electronic address:

Major depressive disorder (MDD) is a common, chronic, recurrent disease. The existing drugs are ineffective for approximately half of patients, so the development of antidepressant drugs with novel mechanisms is urgent. Cumulative evidence has shown neuro-inflammation plays a key role in the etiology of major depressive disorder. Clinical studies implicated that bile acids, an important component of gut-brain axis, inhibit neuro-inflammation and mediate the pathophysiology of the MDD. Here, we found that ganoderic acid A (GAA) modulated bile acid receptor FXR (farnesoid X receptor), inhibited brain inflammatory activity, and showed antidepressant effects in the chronic social defeat stress depression model, tail suspension, forced swimming, and sucrose preference tests. GAA directly inhibited the activity of the NLRP3 inflammasome, and activated the phosphorylation and expression of the AMPA receptor by modulating FXR in the prefrontal cortex of mice. If we knocked out FXR or injected the FXR-specific inhibitor z-gugglesterone (GS), the antidepressant effects induced by GAA were completely abolished. These results suggest that GAA modulates the bile acid receptor FXR and subsequently regulates neuroimmune and antidepressant behaviors. GAA and its receptor FXR have potential as targets for the treatment of MDD.
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http://dx.doi.org/10.1016/j.bcp.2021.114561DOI Listing
April 2021

Pharmacological and clinical application of heparin progress: An essential drug for modern medicine.

Biomed Pharmacother 2021 Apr 10;139:111561. Epub 2021 Apr 10.

TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, PR China. Electronic address:

Heparin is the earliest and most widely used anticoagulant and antithrombotic drug that is still used in a variety of clinical indications. Since it was discovered in 1916, after more than a century of repeated exploration, heparin has not been replaced by other drugs, but a great progress has been made in its basic research and clinical application. Besides anticoagulant and antithrombotic effects, heparin also has antitumor, anti-inflammatory, antiviral, and other pharmacological activities. It is widely used clinically in cardiovascular and cerebrovascular diseases, lung diseases, kidney diseases, cancer, etc., as the first anticoagulant medicine in COVID-19 exerts anticoagulant, anti-inflammatory and antiviral effects. At the same time, however, it also leads to a lot of adverse reactions, such as bleeding, thrombocytopenia, elevated transaminase, allergic reactions, and others. This article comprehensively reviews the modern research progress of heparin compounds; discusses the structure, preparation, and adverse reactions of heparin; emphasizes the pharmacological activity and clinical application of heparin; reveals the possible mechanism of the therapeutic effect of heparin in related clinical applications; provides evidence support for the clinical application of heparin; and hints on the significance of exploring the wider application fields of heparin.
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http://dx.doi.org/10.1016/j.biopha.2021.111561DOI Listing
April 2021

Overexpression of fibrinogen-like protein 2 alleviates acute rejection in rat models of liver transplantation.

Ann Transl Med 2021 Mar;9(5):408

Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Background: The role of cluster of differentiation (CD)8+ regulatory T cells (Tregs) has previously been elucidated in tolerance models. Fibrinogen-like protein 2 (FGL2), that is secreted by Treg cells, which exhibited immunosuppressive functions, may alleviate acute rejection (AR). However, the precise role of CD8+ Tregs and FGL2 in the AR of rat liver transplantation remains unknown. Our previous study found that CD8+CD45RClow Tregs played crucial roles in maintaining immune tolerance. Here, we elucidated the role of CD8+ CD45RClowTreg and FGL2 in AR of rat liver transplantation.

Methods: A rat non-materialized AR of liver transplantation model was established using donors infected with no- adeno- virus and adeno-associated virus expressing .

Results: There was an accumulation of tolerogenic CD8+CD45RClow in allografts compared with blank groups. Moreover, the proportion of CD8+CD45RClow Tregs was increased with longer survival time. Furthermore, we detected higher levels of FGL2 in the allografts infected with AAV-FGL2 in rats with AR of liver transplantation. We found that FGL2 could alleviate AR, and the survival time was prolonged in the recipients of donors infected with AAV-FGL2.

Conclusions: Our data suggest that CD8+CD45RClow Tregs was accumulated in allografts. The presence of FGL2 alleviated AR and prolonged survival time in the AR of liver transplantation rat model, suggesting that FGL2 and CD8+CD45RClow Tregs may serves as novel therapeutic targets for AR in liver transplantation.
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http://dx.doi.org/10.21037/atm-20-7881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033335PMC
March 2021

Core-shell coaxially structured NiCoS@TiOnanorod arrays as advanced electrode for solid-state asymmetric supercapacitors.

Nanotechnology 2021 Apr 30;32(29). Epub 2021 Apr 30.

Materials and Energy School, Guangdong University of Technology, No. 100 Waihuan Xi Road, Guangzhou Higher Education Mega Center, Panyu District, Guangzhou 510006, People's Republic of China.

An integrated electrode of core-shell coaxially structured NiCoS@TiOnanorod arrays/carbon cloth (NiCoS@TiO@CC) have been fabricated, via a two-step hydrothermal method. Comprehensive structural and compositional analyzes are performed to understand the effects of the NiCoSshell on the TiOcore. Such core-shell arrays structure can significantly provide abundant electroactive sites for redox reactions, convenient ion transport paths, and favorable structure stability. The NiCoS@TiO@CC electrode represents a splendid specific capacitance (650 F gat 1 A g) and enhanced cycling stability (capacitance retention of 97% over 10 000 cycles at 5 A g). Additionally, the assembled NiCoS@TiO@CC//CNT@CC solid-state asymmetric supercapacitors exhibit a maximal energy density of 0.6 mWh cmat 32.4 W cm, and topping cycling stability (85% capacitance retention after 5000 cycles at 5 mA cm). The results demonstrate that the well-designed NiCoS@TiO@CC presented in this work are applicable for the development of electrode materials in energy storage devices.
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http://dx.doi.org/10.1088/1361-6528/abf693DOI Listing
April 2021