Publications by authors named "Yi-Fei Wang"

194 Publications

Topological quantum phase transitions on the breathing kagomé lattice.

J Phys Condens Matter 2021 Sep 13;33(47). Epub 2021 Sep 13.

Center for Statistical and Theoretical Condensed Matter Physics, and Department of Physics, Zhejiang Normal University, Jinhua 321004, People's Republic of China.

We explore extensively topological quantum phase transitions (TQPTs) of the breathing kagomé lattice model in the presence of staggered fluxes. We obtain rich topological phases, including the Chern insulator (CI) and the second-order topological insulator (SOTI) phases, by tuning the dimerized hopping parameter' and the staggered-flux parameter. The CI phases can be identified on the basis of the chiral edge states and the non-zero Chern numbers. However, in sharp contrast to the CI phases, the SOTI phases are characterized by the robust corner states and the quantized polarizations. In addition, we explore the TQPTs considering the next-nearest-neighbor hopping parameter. We demonstrate the existence of two-dimensional SOTIs with broken time-reversal symmetry and reveal the TQPTs between the CIs and the SOTIs.
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http://dx.doi.org/10.1088/1361-648X/ac2204DOI Listing
September 2021

Etiological and epidemiological features of acute respiratory infections in China.

Nat Commun 2021 08 18;12(1):5026. Epub 2021 Aug 18.

Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China.

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.
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http://dx.doi.org/10.1038/s41467-021-25120-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373954PMC
August 2021

Insights into the Role of the Fungal Community in Variations of the Antibiotic Resistome in the Soil Collembolan Gut Microbiome.

Environ Sci Technol 2021 Sep 10;55(17):11784-11794. Epub 2021 Aug 10.

State Key Laboratory of Urban and Regional Ecology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Fertilization is known to affect antibiotic-resistance gene (ARG) patterns in the soil, even in the gut of soil fauna. Here, we conducted a microcosm experiment to investigate differences of effects of different fertilizers on collembolan gut ARG profiles and to further explore the microecological mechanisms that cause the differences. Although fertilization increased the abundance of ARGs, compared with the conventional manure, the application of antibiotic-reduced manure and vermicompost all curbed the enrichment of ARGs in the gut of collembolans. The results of the structural equation model revealed that changes in the microbial community caused by fertilizations have an important contribution to variations in the ARGs. We further found that the fungal community, like bacterial community, is also an important driver of ARG patterns in the collembolan gut. The fungi belonging to and were significantly correlated with the ARGs in the gut of collembolans. In addition, the application of vermicompost significantly increased the abundance of agricultural beneficial microbes in the soil environment. Together, our results provide an insight into the role of the fungal community on ARG patterns in the soil collembolan gut microbiome and highlight environmental friendliness of vermicomposting.
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http://dx.doi.org/10.1021/acs.est.0c08752DOI Listing
September 2021

[Effect of transcutaneous auricular vagus nerve stimulation on the expression of TLR4、MyD88、IL-18 protein in the prefrontal cortex of depression rats].

Zhen Ci Yan Jiu 2021 Jul;46(7):580-5

Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700.

Objective: To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the depressive behavior in depression rats, so as to explore its mechanism underlying improvement of depression.

Methods: A total of 24 male Sprague Dawley rats were randomly divided into normal, depression model, taVNS, tnVNS (transcutaneous auricular none-vagus nerve stimulaton) groups (=6 in each group). The depression model was established by chronic unpredictable mild stimulation combined with solitary raising for 35 consecutive days. After 14 days modeling, transcutaneous electrostimulation (2 mA, 2 Hz/15 Hz) was applied to auricular concha or auricular margin, respectively. Each intervention was conducted for 30 minutes, once daily for 21 days. The depression-like behavior was evaluated by forced swimming immobility time and body weight. The expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and interleukin-18 (IL-18) protein in the prefrontal cortex were detected by Western blot.

Results: Following modeling, the increase amount of body weight was decreased, the forced swimming immobility time and expression TLR4, MyD88 and IL-18 protein in the prefrontal cortex were increased in the model group than those in the normal group (<0.01). Following the treatment and compared with the model group, the increase amount of body weight in the taVNS group was obviously increased (<0.05), the swimming immobility time and the expression of TLR4, MyD88, IL-18 protein in the taVNS and tnVNS groups were significantly decreased (<0.01).

Conclusion: TaVNS is able to improve depression in depression rats, which is probably related to its effect in inhibiting inflammatory response of TLR4/MyD88 signaling pathway in prefrontal cortex.
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http://dx.doi.org/10.13702/j.1000-0607.20210180DOI Listing
July 2021

Characteristics of diarrheagenic Escherichia coli among patients with acute diarrhea in China, 2009‒2018.

J Infect 2021 Aug 3. Epub 2021 Aug 3.

Chinese Centre for Disease Control and Prevention, Beijing, China.

Objectives To investigate the epidemiological features of diarrheagenic Escherichia coli (DEC) in patients with acute diarrhea in China. Methods An active sentinel surveillance was performed in all-age patients with acute diarrhea in China, 2009‒2018. DEC was isolated and identified by serological assay and PCR from stool samples. Results DEC was determined in 6.68% (6,119/91,651) of the patients, with higher positive rates among females than among males (6.97% vs. 6.46%) and among 18‒59 years patients (7.88%) than among other age groups. Five pathotypes were identified, the most prevalent was enteroaggregative E. coli (EAEC), followed by enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). Pediatric patients <5 years had higher positive rate of EAEC (2.07%), followed by EPEC (1.81%), and enterohemorrhagic E. coli (EHEC) (0.31%), while the 18‒59 years patients had higher infection of ETEC (2.36%). ETEC and EPEC were more frequently identified in urban than rural areas, with age and gender adjusted positive rate of 1.68% vs. 1.14% respectively, and 1.77% vs. 1.55%, while EIEC and EHEC were more frequently identified in rural areas. Conclusions These findings highlight the epidemiology features of DEC and underscores the need for conducting DEC surveillance.
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http://dx.doi.org/10.1016/j.jinf.2021.08.001DOI Listing
August 2021

Summarizing the Effective Herbs for the Treatment of Hypertensive Nephropathy by Complex Network and Machine Learning.

Evid Based Complement Alternat Med 2021 11;2021:5590743. Epub 2021 Jun 11.

The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China.

Hypertensive nephropathy is a common complication of hypertension. Traditional Chinese medicine has been used in the clinical treatment of hypertensive nephropathy for a long time, but the commonly used prescriptions have not been summarized, and the basic therapeutic approaches have not been discussed. Based on data from 3 years of electronic medical records of traditional Chinese medicine used at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, a complex network and machine learning algorithm was used to explore the prescribed herbs of traditional Chinese medicine in the treatment of hypertensive nephropathy (HN). In this study, complex network algorithms were used to describe traditional Chinese medicine prescriptions for HN treatment. The Apriori algorithm was used to analyze the compatibility of these treatments with modern medicine. Data on the targets and regulatory genes related to hypertensive nephropathy and the herbs that affect their expression were obtained from public databases, and then, the signaling pathways enriched with these genes were identified on the basis of their participation in biological processes. A clustering algorithm was used to analyze the therapeutic pathways at multiple levels. A total of 1499 prescriptions of traditional Chinese medicines used for the treatment of hypertensive renal damage were identified. Fourteen herbs used to treat hypertensive nephropathy act through different biological pathways: huangqi, danshen, dangshen, fuling, baizhu, danggui, chenpi, banxia, gancao, qumai, cheqianzi, ezhu, qianshi, and niuxi. We found the formulae of these herbs and observed that they could downregulate the expression of inflammatory cytokines such as TNF, IL1B, and IL6 and the NF-B and MAPK signaling pathways to reduce the renal inflammatory damage caused by excessive activation of RAAS. In addition, these herbs could facilitate the deceleration in the decline of renal function and relieve the symptoms of hypertensive nephropathy. In this study, the traditional Chinese medicine approach for treating hypertensive renal damage is summarized and effective treatment prescriptions were identified and analyzed. Data mining technology provided a feasible method for the collation and extraction of traditional Chinese medicine prescription data and provided an objective and reliable tool for use in determining the TCM treatments of hypertensive nephropathy.
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http://dx.doi.org/10.1155/2021/5590743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214481PMC
June 2021

Identification of Hypertension Subgroups through Topological Analysis of Symptom-Based Patient Similarity.

Chin J Integr Med 2021 May 31. Epub 2021 May 31.

Department of Urology, the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.

Objective: To obtain the subtypes of the clinical hypertension population based on symptoms and to explore the relationship between hypertension and comorbidities.

Methods: The data set was collected from the Chinese medicine (CM) electronic medical records of 33,458 hypertension inpatients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between July 2014 and May 2017. Then, a hypertension disease comorbidity network (HDCN) was built to investigate the complicated associations between hypertension and their comorbidities. Moreover, a hypertension patient similarity network (HPSN) was constructed with patients' shared symptoms, and 7 main hypertension patient subgroups were identified from HPSN with a community detection method to exhibit the characteristics of clinical phenotypes and molecular mechanisms. In addition, the significant symptoms, diseases, CM syndromes and pathways of each main patient subgroup were obtained by enrichment analysis.

Results: The significant symptoms and diseases of these patient subgroups were associated with different damaged target organs of hypertension. Additionally, the specific phenotypic features (symptoms, diseases, and CM syndromes) were consistent with specific molecular features (pathways) in the same patient subgroup.

Conclusion: The utility and comprehensiveness of disease classification based on community detection of patient networks using shared CM symptom phenotypes showed the importance of hypertension patient subgroups.
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http://dx.doi.org/10.1007/s11655-021-3336-3DOI Listing
May 2021

Total Flavonoids of Rhizoma Drynariae Restore the MMP/TIMP Balance in Models of Osteoarthritis by Inhibiting the Activation of the NF- and PI3K/AKT Pathways.

Evid Based Complement Alternat Med 2021 19;2021:6634837. Epub 2021 Apr 19.

Department of TCM Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China.

Total flavonoids of (TFRD) have been shown to have beneficial effects on osteoarthritis (OA) clinically, but the mechanisms have not been elucidated. In this study, we investigated the effect of TFRD on articular cartilage in an OA rat model established by the Hulth method and in SW1353 chondrocytes induced by the proinflammatory factor interleukin-1 (IL-1). The results showed that TFRD could alleviate the pathological changes in knee cartilage in OA model rats. In vivo, the qPCR analysis indicated that the mRNA levels of matrix metalloproteinases, MMP-1, MMP-3, and MMP-13, were decreased, while tissue inhibitor of matrix metalloproteinases- (TIMP-) 4 was increased in cartilage, and these changes could be partially prevented by TFRD. In vitro experiments showed that IL-1 could significantly increase the expression of MMP-1, MMP-3, and MMP-13 and decrease the expression of TIMP-4 in SW1353 cells at the mRNA and protein levels. TFRD could increase the expression of MMP-3 and MMP-13 and decrease the expression of TIMP-4. Transfection of siRNA and addition of pathway inhibitors were used to clarify that inhibition of NF- and PI3K/AKT pathway decreased MMP-1, MMP-3, and MMP-13 and increased TIMP-4 expression. We also found that in IL-1-induced SW1353 cells, TFRD pretreatment had a modest inhibitory effect on p-AKT (Ser473) and reversed the increase of nuclear factor kappa-B (NF-) p65 in nuclear fraction and the decrease of inhibitor of NF-()- in the cytosolic fraction. Further immunofluorescence confirmed that TFRD can inhibit IL-1-induced NF- p65 translocation to the nucleus to some extent. In conclusion, TFRD showed chondroprotective effects by restoring the MMP/TIMP balance in OA models by suppressing the activation of the NF- and PI3K/AKT pathways.
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http://dx.doi.org/10.1155/2021/6634837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081598PMC
April 2021

Fatty acid-binding protein 7 triggers α-synuclein oligomerization in glial cells and oligodendrocytes associated with oxidative stress.

Acta Pharmacol Sin 2021 May 2. Epub 2021 May 2.

Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.

We previously show that fatty acid-binding protein 3 (FABP3) triggers α-synuclein (Syn) accumulation and induces dopamine neuronal cell death in Parkinson disease mouse model. But the role of fatty acid-binding protein 7 (FABP7) in the brain remains unclear. In this study we investigated whether FABP7 was involved in synucleinopathies. We showed that FABP7 was co-localized and formed a complex with Syn in Syn-transfected U251 human glioblastoma cells, and treatment with arachidonic acid (100 M) significantly promoted FABP7-induced Syn aggregation, which was associated with cell death. We demonstrated that synthetic FABP7 ligand 6 displayed a high affinity against FABP7 with K value of 209 nM assessed in 8-anilinonaphthalene-1-sulfonic acid (ANS) assay; ligand 6 improved U251 cell survival via disrupting the FABP7-Syn interaction. We showed that activation of phospholipase A2 (PLA2) by psychosine (10 M) triggered oligomerization of endogenous Syn and FABP7, and induced cell death in both KG-1C human oligodendroglia cells and oligodendrocyte precursor cells (OPCs). FABP7 ligand 6 (1 M) significantly decreased Syn oligomerization and aggregation thereby prevented KG-1C and OPC cell death. This study demonstrates that FABP7 triggers α-synuclein oligomerization through oxidative stress, while FABP7 ligand 6 can inhibit FABP7-induced Syn oligomerization and aggregation, thereby rescuing glial cells and oligodendrocytes from cell death.
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http://dx.doi.org/10.1038/s41401-021-00675-8DOI Listing
May 2021

Etiological, epidemiological, and clinical features of acute diarrhea in China.

Nat Commun 2021 04 29;12(1):2464. Epub 2021 Apr 29.

The Institute for Disease Prevention and Control of PLA, Beijing, China.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.
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http://dx.doi.org/10.1038/s41467-021-22551-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085116PMC
April 2021

Corrigendum: MicroRNA-608 Promotes Apoptosis in Non-Small Cell Lung Cancer Cells Treated With Doxorubicin Through the Inhibition of TFAP4.

Front Genet 2021 30;12:649586. Epub 2021 Mar 30.

School of Basic Medical Sciences, Qingdao University, Qingdao, China.

[This corrects the article DOI: 10.3389/fgene.2019.00809.].
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http://dx.doi.org/10.3389/fgene.2021.649586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042386PMC
March 2021

Overexpression of Stat3 increases circulating cfDNA in breast cancer.

Breast Cancer Res Treat 2021 May 25;187(1):69-80. Epub 2021 Feb 25.

Laboratory of Molecular Oncology, Weifang Medical College, Weifang, 261053, Shandong, China.

Purpose: Current studies on circulating cell-free DNA (cfDNA) have been focusing on its potential as biomarkers in liquid biopsy by detecting its content or genetic and epigenetic changes for the evaluation of tumor burden and therapeutic efficacy. However, the regulatory mechanism of cfDNA release remains unclear. Stat3 has been documented as an oncogene for the development and metastasis of breast cancer cells. In this study, we investigated whether Stat3 affects the release of cfDNA into blood and its association with the number of circulating tumor cells (CTCs).

Methods: The cfDNA level in plasma of patients with breast cancer and healthy volunteers were determined by quantitative real-time PCR. Three mouse breast cancer models with different Stat3 expression were generated and used to established three breast cancer orthotopic animal models to examine the effect of Stat3 on cfDNA release in vivo. Stat3 mediated Epithelial-mesenchymal phenotype transition of CTCs was determined by immunofluorescence assay and Western blot assay.

Results: The data showed that Stat3 increased circulating cfDNA, which is correlated with the increased volume of primary tumors and number of CTCs, accompanied with the dynamic EMT changes regulated by Snail induction. Furthermore, the high level of total circulating cfDNA and Stat3-cfDNA in patients with breast cancer were detected by quantitative real-time PCR using GAPDH and Stat3 primers.

Conclusion: Our results suggested that Stat3 increases the circulating cfDNA and CTCs in breast cancer.
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http://dx.doi.org/10.1007/s10549-021-06142-6DOI Listing
May 2021

SARS-CoV-2 M inhibitors with antiviral activity in a transgenic mouse model.

Science 2021 03 18;371(6536):1374-1378. Epub 2021 Feb 18.

State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (M) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing M inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 M activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of M in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.
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http://dx.doi.org/10.1126/science.abf1611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099175PMC
March 2021

Suppression of Esophageal Cancer Stem-like Cells by SNX-2112 Is Enhanced by STAT3 Silencing.

Front Pharmacol 2020 16;11:532395. Epub 2020 Dec 16.

State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, SunYat-Sen University Cancer Center, Guangzhou, China.

Many studies have demonstrated that cancer stem cells (CSCs) or tumor-initiating cells (TICs) are responsible for tumor cell proliferation, chemotherapy resistance, metastasis, and relapse in various cancers. We, and others, have previously shown that the signal transducer and activator of transcription 3 (STAT3) signaling pathway is responsible for CSCs and TICs growth. Recent reports have indicated that the heat shock protein 90 (Hsp90) is also essential for the survival of CSCs and TICs. SNX-2112 is an Hsp90 inhibitor. However, it remains unclear whether proliferation of esophageal cancer stem-like cells (ECSLCs) is suppressed by SNX-2112 with knockdown of STAT3 (shSTAT3). Here, we explored the association between SNX-2112 with shSTAT3 and the suppression of ECSLCs growth. We found that the expression level of both STAT3 and p-STAT3 was higher in clinical esophageal cancer tissue than in the adjacent normal tissue, using western blot and qPCR analysis. Furthermore, differential expression analysis demonstrated that STAT3 was overexpressed in clinical specimens. We demonstrated that SNX-2112 inhibited cancer cell proliferation, decreased and gene expression levels and reduced the colony formation capacity of ECSLCs, which was enhanced by STAT3 silencing. Flow cytometry analysis revealed that the combination of SNX-2112 and shSTAT3 significantly induced apoptosis and cell cycle arrest at G2/M phase in ECSLCs. Levels of proliferation pathway proteins, including p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) which were also client proteins of Hsp90, were also reduced. In addition, SNX-2112 with shSTAT3 inhibited the proliferation of ECSLCs . Finally, STAT3 overexpression eliminated the apoptotic and antiproliferative effects of SNX-2112 on ECSLCs. Hence, these results provide a rationale for the therapeutic potential of the combination of SNX-2112 with shSTAT3 in esophageal cancer, and may indicate new targets for clinical intervention in human cancer.
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http://dx.doi.org/10.3389/fphar.2020.532395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772942PMC
December 2020

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application.

Neurosci Bull 2021 Jun 23;37(6):853-862. Epub 2020 Dec 23.

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China.

Whether in the West or the East, the connection between the ear and the rest of the body has been explored for a long time. Especially in the past century or more, the relevant theoretical and applied research on the ear has greatly promoted the development of ear therapy, and finally the concept of transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed. The purpose of taVNS is to treat a disease non-invasively by applying electrical current to the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear. In the past two decades, taVNS has been a topic of basic, clinical, and transformation research. It has been applied as an alternative to drug treatment for a variety of diseases. Based on the rapid understanding of the application of taVNS to human health and disease, some limitations in the development of this field have also been gradually exposed. Here, we comprehensively review the origin and research status of the field.
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http://dx.doi.org/10.1007/s12264-020-00619-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192665PMC
June 2021

Differential responses of bone to angiotensin II and angiotensin(1-7): beneficial effects of ANG(1-7) on bone with exposure to high glucose.

Am J Physiol Endocrinol Metab 2021 01 26;320(1):E55-E70. Epub 2020 Oct 26.

Spine Disease Research Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Osteoporosis, diabetes, and hypertension are common concurrent chronic disorders. This study aimed to explore the respective effects of angiotensin II (ANG II) and angiotensin(1-7) [ANG(1-7)], active peptides in the renin-angiotensin system, on osteoblasts and osteoclasts under high-glucose level, as well as to investigate the osteo-preservative effects of ANG II type 1 receptor (AT1R) blocker and ANG(1-7) in diabetic spontaneously hypertensive rats (SHR). ANG II and ANG(1-7), respectively, decreased and increased the formation of calcified nodules and alkaline phosphatase activity in MC3T3-E1 cells under high-glucose level, and respectively stimulated and inhibited the number of matured osteoclasts and pit resorptive area in RANKL-induced bone marrow macrophages. Olmesartan and Mas receptor antagonist A779 could abolish those effects. ANG II and ANG(1-7), respectively, downregulated and upregulated the expressions of osteogenesis factors in MC3T3-E1 cells. ANG II promoted the expressions of cathepsin K and MMP9 in RAW 264.7 cells, whereas ANG(1-7) repressed these osteoclastogenesis factors. ANG II rapidly increased the phosphorylation of Akt and p38 in RAW 264.7 cells, whereas ANG(1-7) markedly reduced the phosphorylation of p38 and ERK under high-glucose condition. After treatments of diabetic SHR with valsartan and ANG(1-7), a significant increase in trabecular bone area, bone mineral density, and mechanical strength was only found in the ANG(1-7)-treated group. Treatment with ANG(1-7) significantly suppressed the increase in renin expression and ANG II content in the bone of SHR. Taken together, ANG II/AT1R and ANG(1-7)/Mas distinctly regulated the differentiation and functions of osteoblasts and osteoclasts upon exposure to high-glucose condition. ANG(1-7) could protect SHR from diabetes-induced osteoporosis.
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http://dx.doi.org/10.1152/ajpendo.00158.2020DOI Listing
January 2021

Printed Soft Sensor with Passivation Layers for the Detection of Object Slippage by a Robotic Gripper.

Micromachines (Basel) 2020 Oct 8;11(10). Epub 2020 Oct 8.

Research Center for Organic Electronics (ROEL), Graduate School of Science and Engineering, Yamagata University, 3-4-16, Jonan, Yonezawa, Yamagata 992-8510, Japan.

Tactile sensing, particularly the detection of object slippage, is required for skillful object handling by robotic grippers. The real-time measurement and identification of the dynamic shear forces that result from slippage events are crucial for slip detection and effective object interaction. In this study, a ferroelectric polymer-based printed soft sensor for object slippage detection was developed and fabricated by screen printing. The proposed sensor demonstrated a sensitivity of 8.2 μC·cm and was responsive to shear forces applied in both the parallel and perpendicular directions. An amplifier circuit, based on a printed organic thin-film transistor, was applied and achieved a high sensitivity of 0.1 cm/V·s. Therefore, this study experimentally demonstrates the effectiveness of the proposed printable high-sensitivity tactile sensor, which could serve as part of a wearable robotic e-skin. The sensor could facilitate the production of a system to detect and prevent the slippage of objects from robotic grippers.
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http://dx.doi.org/10.3390/mi11100927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599578PMC
October 2020

Antibiotic Resistance in the Collembolan Gut Microbiome Accelerated by the Nonantibiotic Drug Carbamazepine.

Environ Sci Technol 2020 09 20;54(17):10754-10762. Epub 2020 Aug 20.

State Key Laboratory of Urban and Regional Ecology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P. R. China.

The effects of pharmaceuticals as emerging contaminants in soil on the gut microbiome and antibiotic resistome in nontarget soil fauna are largely elusive. In this study, we explored the composition of the bacterial community and the presence of antibiotic resistance genes (ARGs) in the gut of the model soil collembolan () upon antiepileptic drug carbamazepine (CBZ) and antibiotic tetracycline (TC) exposure. Results showed that, individually or in combination, exposure to TC or CBZ significantly altered the gut community structure of , causing some enrichment of the bacteria associated with xenobiotic metabolism, such as , , , and . More importantly, oral exposure to the nonantibiotic drug CBZ enhanced the abundance and diversity of ARGs in the gut of , especially for the beta-lactams and multidrug resistance genes. Our results revealed that the most likely hosts of ARGs in the gut of were Proteobacteria and Actinobacteria. The significant positive correlation between mobile genetic elements (MGEs) and ARGs indicated the potential risk of ARGs transmission in the gut of . Overall, the nonantibiotic CBZ is likely to disturb the gut microbiota of nontarget soil fauna such as collembolans, thereby enhancing the dissemination of ARGs.
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http://dx.doi.org/10.1021/acs.est.0c03075DOI Listing
September 2020

Quantum transport in Chern insulators on Möbius strips.

J Phys Condens Matter 2020 Jul 29. Epub 2020 Jul 29.

Center for Statistical and Theoretical Condensed Matter Physics Department of Physics, Zhejiang Normal University, Jinhua 321004, Jinhua, CHINA.

Chern insulators (CIs) or quantum anomalous Hall (QAH) states have drawn more attention, with emergence of quantized Hall conductance but in absence of Landau levels. Here, we study the Haldane-type CI/QAH states on Möbius strips and focus on the quantum transport properties. The Möbius strips can be constructed from the twisted honeycomb-lattice strips with domain walls. Topological properties of the Möbius CI/QAH states can be identified by the local density of states, the real-space Chern numbers and the transport properties. Nearly perfect quantized conductance plateaus are observed in the numerical quantum-transport simulations. In addition, we found that adding magnetic flux in domain walls can induce alternating edge states. At last, we discussed in details the different lead connection schemes, and found that we can use multiple domain walls to obtain various higher quantized conductance plateaus.
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http://dx.doi.org/10.1088/1361-648X/abaa83DOI Listing
July 2020

[Bioinformatics analysis of safflower WD40 transcription factor family genes].

Zhongguo Zhong Yao Za Zhi 2020 Jul;45(14):3432-3440

College of Life Science, Jilin Agricultural University Changchun 130118, China Bioreactor and Drug Development, Ministry of Education, Jilin Agricultural University Changchun 130118, China.

The WD40 transcription factor family is a gene superfamily widely found in eukaryotes, which is closely related to plant growth and development regulation. It has been reported that the WD40 transcription factor was involved in the synthesis of anthocyanins, which is one of the vital components of safflower flavonoid compounds. In this study, 40 CtWD40 members in the safflower genome were identified though bioinformatics tools and gene expression analysis methods. According to the WD40 protein sequence and phylogenetic characteristics of Arabidopsis and other plants, the safflower CtWD40 family was classified into 7 subfamilies. Conservative motif analysis was used to reveal the specific conserved motifs and gene structures of each subfamily member, and there exist a certain degree of similarities in the conserved motifs and gene structure between the closely related family members. Subsequently, the search for cis-acting elements of gene promoters found CtWD40-specific promoter elements, revealing the metabolic pathways which may involve. Next, enrichment of function analysis was employed to analyze the functional categories and cellular localization of the CtWD40 protein. Furthermore, the interactions between CtWD40 proteins predicted its potential regulatory function. Finally, 19 members of the safflower CtWD40 subfamily were analyzed by qRT-PCR, the result showed the expression patterns of these members were different in diverse tissue and flowering period. This study provides a basis for the functional and expression research of the CtWD40 genes.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200506.107DOI Listing
July 2020

Printed Strain Sensor with High Sensitivity and Wide Working Range Using a Novel Brittle-Stretchable Conductive Network.

ACS Appl Mater Interfaces 2020 Aug 22;12(31):35282-35290. Epub 2020 Jul 22.

Research Center for Organic Electronics (ROEL), Yamagata University, 4-3-16, Jonan, Yonezawa, Yamagata 992-8510, Japan.

There are few reports on resistive strain sensors that exhibit both high sensitivity and a wide working range under stretching. We have newly developed a high-performance strain sensor based on a brittle-stretchable conductive network that consists of both brittle and stretchable conductive layers and is fabricated on a stretchable substrate using the screen-printing method. Adding strain usually generates structural cracks in brittle conductive layers leading to a significant increase in resistance, while a stretchable conductive layer bridges these cracks to maintain the conductive pathways under high-strain conditions. This novel conductive network endows superior electrical-mechanical performance to the strain sensors, which possess high sensitivity (gauge factor > 870) over the entire working range (∼100%). Additionally, the developed sensors showed unique anisotropic bend-sensing characteristics, which could be used to detect the bending directions. This high degree of comprehensive performance results in a strain sensor with the capability for full-range human motion detection and robotic motion sensing.
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http://dx.doi.org/10.1021/acsami.0c09590DOI Listing
August 2020

[Bibliometric analysis on clinical trials of auricular acupuncture treatment of obesity].

Zhen Ci Yan Jiu 2020 Apr;45(4):334-8

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700.

Objective: To review the current situation of researches on auricular acupuncture treatment for obesity by using bibliometric analysis, so as to provide a reference for clinical application and experimental research in the future.

Methods: Articles written in both Chinese and English and published from the time of establishment of the following databases were collected from databases of CNKI, Wanfang, PubMed and Web of Science by using key words of "otopoint sticking" "otopoint seed-pres-sing" "auriculotherapy" "ear/auricular acupuncture" "auricular pressure" "auricular-plaster therapy" "acupuncture and auricular pressure" "auriculopressure" "transcutaneous vagus nerve stimulation (taVNS)" "obesity" "adiposity" "adiposis" and "fatty". The articles met our inclusive criteria were analyzed for summarizing their publication years, involved journals, research organizations and selected acupoints.

Results: A total of 61 qualified Chinese and 44 English articles were retrieved and published in 45 and 25 journals, respectively. The commonly-used acupoints are "Endocrine" "Stomach" "Spleen" "Shenmen" "Hunger point" "Sanjiao" "Lung" and "Subcortex". The employed auricular acupoint therapy mainly includes auricular acupressure, ear acupuncture, auricular vagus nerve stimulation, and auricular laser radiation.

Conclusion: Current clinical literature on auricular acupuncture treatment of obesity is relatively lower in quality. Thus, strict research protocols and randomized controlled clinical trials with multiple centers and larger samples are definitely necessary for providing reliable evidence for clinical treatment of obesity by using auricular acupuncture therapy.
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http://dx.doi.org/10.13702/j.1000-0607.200088DOI Listing
April 2020

Cepharanthine hydrochloride induces mitophagy targeting GPR30 in hepatocellular carcinoma (HCC).

Expert Opin Ther Targets 2020 04 14;24(4):389-402. Epub 2020 Mar 14.

Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, P. R. China.

: Cepharanthine exhibits a wide range of therapeutic effects against numerous cancers by virtue of its pleiotropic mechanisms. However, cepharanthine monotherapy has insufficient drug efficacy for cancers in animal models and clinical trials. The mechanism of its limited efficacy is unknown.: We investigated the possible mechanism for the limited drug efficacy of cepharanthine in cancer therapy using both hepatocellular carcinoma (HCC) primary cells and cell lines, and in mouse xenograft models.: We found that cepharanthine hydrochloride (CH), a semi-synthetic derivative of cepharanthine, induced mitophagy independent of mTOR signaling, and played an AMPK-dependent protective role in the cell fate of HCC and . Mechanistically, we demonstrated that CH may bind to GPR30 receptor to activate the subsequent signal cascade involving mitochondrial fission, thus facilitating mitophagy. Therefore, we proposed a new therapeutic regimen for HCC involving CH combined with an autophagy inhibitor. This regimen exhibited remarkable anti-cancer effects in HCC xenograft mouse model.: These results identify CH as a new mitophagy inducer targeting GPR30 receptor. The combination therapy of CH and an autophagy inhibitor may become a novel strategy for enhancing the anti-tumor potential of cepharanthine in HCC.
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http://dx.doi.org/10.1080/14728222.2020.1737013DOI Listing
April 2020

Sanhuang Shu'ai decoction alleviates DSS-induced ulcerative colitis via regulation of gut microbiota, inflammatory mediators and cytokines.

Biomed Pharmacother 2020 May 12;125:109934. Epub 2020 Feb 12.

Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Department of Pharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, The People's Republic of China. Electronic address:

Background: Sanhuangshu'ai decoction (SH), a traditional Chinese medicine (TCM) prescription, has been safely used to treat diarrhea, dysentery and other inflammatory diseases with little side effect and low cost for thousands of years. However, its mechanism remains elusive. This study was designed to investigate the anti-ulcerative colitis (UC) activity of SH and mechanism by detecting its anti-inflammatory, anti-oxidative, and intervention effects of intestinal flora with the dextran sodium sulfate (DSS)-induced colitis mice.

Methods: The DSS-induced colitis mice was orally administered SH for 1 week with 0.8 or 1.6 g kg d dosage. A clinical disease activity score was evaluated daily. The colonic tissues of the mice were collected and prepared to detect its anti-inflammatory, anti-oxidative, intervention effects of intestinal flora and hydrogen peroxide(HO) in vivo, cytotoxicity and ROS influencing effects in vitro. Histological colitis severity and expression of cytokines were also determined.

Results: Oral administration of SH significantly prevented the development of colitis. It reduced the expression of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α in the colon. Moreover, SH administration alleviated the oxidative stress in the colon of DSS-induced colitis mice, evidenced by the decrease of myeloperoxidase (MPO) activity and malondialdehyde (MDA) level, and increase of ROS level. Furthermore, SH can prevent the decrease ofLactobacillus sp. and population abundance of intestinal flora caused by DSS.

Conclusion: SH significantly ameliorates the symptoms of DSS-induced colitis mice and the potential mechanism of SH may involve in multiple kinds of metabolic pathway including the regulation of gut microbiota, inflammatory mediators and cytokines.
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http://dx.doi.org/10.1016/j.biopha.2020.109934DOI Listing
May 2020

Fully Printed PEDOT:PSS-based Temperature Sensor with High Humidity Stability for Wireless Healthcare Monitoring.

Sci Rep 2020 02 12;10(1):2467. Epub 2020 Feb 12.

Research Center for Organic Electronics, Yamagata University, 4-3-16, Jonan, Yonezawa, Yamagata, 992-8510, Japan.

Facile fabrication and high ambient stability are strongly desired for the practical application of temperautre sensor in real-time wearable healthcare. Herein, a fully printed flexible temperature sensor based on cross-linked poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) was developed. By introducing the crosslinker of (3-glycidyloxypropyl)trimethoxysilane (GOPS) and the fluorinated polymer passivation (CYTOP), significant enhancements in humidity stability and temperature sensitivity of PEDOT:PSS based film were achieved. The prepared sensor exhibited excellent stability in environmental humidity ranged from 30% RH to 80% RH, and high sensitivity of -0.77% °C for temperature sensing between 25 °C and 50 °C. Moreover, a wireless temperature sensing platform was obtained by integrating the printed sensor to a printed flexible hybrid circuit, which performed a stable real-time healthcare monitoring.
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http://dx.doi.org/10.1038/s41598-020-59432-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016104PMC
February 2020

Discovery of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors.

Bioorg Med Chem Lett 2020 03 15;30(6):126966. Epub 2020 Jan 15.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address:

Herein, we report the discovery of a series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship studies of these compounds led to the identification of the most potent compound, 3-(3-methoxybenzyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (8k), which showed IC values of 0.004 μM and 0.001 μM against ROCK Ⅰ and ROCK Ⅱ, respectively. In vitro, 8k significantly reduced the phosphorylation level of ROCK downstream signaling protein and induce changes in cell morphology and migration. Overall, this study provides a promising lead compound for drug discovery targeting ROCKs.
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http://dx.doi.org/10.1016/j.bmcl.2020.126966DOI Listing
March 2020

Predominant Mycotoxins, Pathogenesis, Control Measures, and Detection Methods in Fermented Pastes.

Toxins (Basel) 2020 01 23;12(2). Epub 2020 Jan 23.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China.

Fermented pastes are some of the most popular traditional products in China. Many studies reported a strong possibility that fermented pastes promote exposure to mycotoxins, including aflatoxins, ochratoxins, and cereulide, which were proven to be carcinogenic and neurotoxic to humans. The primary mechanism of pathogenicity is by inhibiting protein synthesis and inducing oxidative stress using cytochrome P450 (CYP) enzymes. The level of mycotoxin production is dependent on the pre-harvest or post-harvest stage. It is possible to implement methods to control mycotoxins by using appropriate antagonistic microorganisms, such as , and isolated from ordinary foods. Also, drying products as soon as possible to avoid condensation or moisture absorption in order to reduce the water activity to lower than 0.82 during storage is also effective. Furthermore, organic acid treatment during the soaking process reduces toxins by more than 90%. Some novel detection technologies based on magnetic adsorption, aptamer probes, and molecular-based methods were applied to rapidly and accurately detect mycotoxins in fermented pastes.
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http://dx.doi.org/10.3390/toxins12020078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076863PMC
January 2020

MR imaging as a precise technique to evaluate skull-base tumor volume: Comparison of CT, MR imaging and FDG PET from murine and clinical data.

J Craniomaxillofac Surg 2020 Jan 13;48(1):105-110. Epub 2019 Dec 13.

Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China; National Clinical Research Center for Oral Diseases, Beijing, 100081, PR China; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, 100081, PR China; Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China. Electronic address:

In spite of the many imaging modalities used in clinics, the one that best reflects the true delineation of skull-base (infratemporal fossa, ITF) malignancies is still unknown. In order to compare the tumor recognition capabilities of different imaging modalities, established murine models and patients with skull-base tumors were evaluated by computer tomography (CT), magnetic resonance (MR) imaging, and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for delineation of gross tumor volume (GTV). PET, MR imaging, and CT enhanced by iodine staining were all sensitive to, and able to recognize, the skull-base tumor in the murine model. No significant difference (p > 0.9999) was observed between average GTV according to MR imaging (176.67 ± 19.6 mm) and the histological measurement result (170.23 ± 22.24 mm) for the murine model. In contrast, the GTVs according to CT (88.77 ± 13.03 mm, p < 0.0001) and FDG PET (35.67 ± 6.56 mm, p < 0.0001) were much smaller. In nine patients for whom the three modalities were available, tumor volume comparisons tended to be consistent with the murine model data. According to both the established murine model and clinical patient data, MR imaging possessed the optimal ability to recognize tumor contours.
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http://dx.doi.org/10.1016/j.jcms.2019.12.007DOI Listing
January 2020

[Research of hospital preparations based on QbD concept: whole process optimization strategy of gynecological antipruritic lotion].

Zhongguo Zhong Yao Za Zhi 2019 Oct;44(20):4342-4349

Fangshan Hospital,Beijing University of Chinese Medicine Beijing 102400,China.

The stable quality of hospital preparations is the basis for their clinical efficacy. Gynecological antipruritic prescription is widely used in gynecology clinics of Chinese medicine hospitals. Therefore,in this study,the production process of gynecological antipruritic lotion was optimized based on the concept of quality by design( QbD). The production process of the gynecological antipruritic lotion was developed to ensure its process stability and reliable quality,and enhance its clinical applicability. With total amount of matrine and oxymatrine used as the critical quality attribute( CQA) of the production process,parameter levels were designed based on production practice of hospital preparations,and Plackett-Burman and Box-Behnken experiments were used to optimize the water extraction and alcohol precipitation process of antipruritic lotion based on CQA of intermediates and final product. The soaking time,the first extraction time,and the second extraction time were determined as the critical process parameters( CPPs) of the production process. The optimal preparation process was as follows: water volume of 8 times,soaking for 0. 5 h,extraction for 2 times,the first extraction for 30 min,the second extraction for 56 min,alcohol concentration of 50%,and alcohol precipitation for 3 h. Furthermore,the design space was established based on the binomial regress model between CPPs and CQA,so as to set the optimization target and risk range; and the control space was displayed by overlay plot. The results of three repeated experiments in the control space showed that the relative standard deviation( RSD) of CQA was 4. 70%,and the similarity of chromatogram for gynecological antipruritic lotion was 0. 978,0. 974,and 0. 998,respectively. The above results indicated that the operation in the control space can guarantee the quality and stability of gynecological antipruritic lotion,suitable for practical application.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20190629.304DOI Listing
October 2019

[Design and development of sustained and controlled release preparations in traditional Chinese medicine based on quality by design( QbD)].

Zhongguo Zhong Yao Za Zhi 2019 Oct;44(20):4317-4321

Fangshan Hospital,Beijing University of Chinese Medicine Beijing 102400,China.

In this paper,the design and development of sustained and controlled release preparations in traditional Chinese medicine( TCM) based on quality by design( QbD) was put forward,aiming at the current situation that the final product quality is affected by multiple factors during the development of sustained and controlled release preparations in TCM. The important development of sustained and controlled release preparations in western medicine in recent years was summarized. According to the complex process of TCM,the concept of QbD was proposed to design and develop sustained and controlled release preparations in TCM. QbD concept was used to analyze the complex factors affecting sustained and controlled release preparations in TCM,and determine the high risk factors affecting the quality of the final product. The high risk factors were controlled from the process to achieve the goal of quality control.This article could provide research ideas for the sustained and controlled release preparations with complex components in TCM,so as to promote the research and development of sustained and controlled release preparations in TCM.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20190410.311DOI Listing
October 2019
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