Publications by authors named "Min Hao"

114 Publications

Preparation of Graphene Oxide-Embedded Hydrogel as a Novel Sensor Platform for Antioxidant Activity Evaluation of .

Front Chem 2021 16;9:675346. Epub 2021 Apr 16.

Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.

Antioxidation is very important in medicine and food. The current evaluation technologies often have many shortcomings. In this work, an improved electrochemical sensing platform for the evaluation of antioxidant activity has been proposed. A hydrogel was prepared based on graphene oxide, zinc ions, and chitosan. Zinc ions play the role of crosslinking agents in hydrogels. The structure of chitosan can be destroyed by injecting hydrogen peroxide into the hydrogel, and the free zinc ions can diffuse to the surface of the electrode to participate in the electrochemical reaction. This electrochemical sensor can evaluate the antioxidant activity by comparing the current difference of zinc reduction before and after adding the antioxidant. With the help of graphene oxide, this hydrogel can greatly enhance the sensing effect. We conducted tests on 10 real samples. This proposed electrochemical platform has been successfully applied for evaluating the antioxidant activity of , and the results were compared to those obtained from the 2,2-diphenyl-1-picrylhydrazyl-based traditional analysis technique.
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http://dx.doi.org/10.3389/fchem.2021.675346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087177PMC
April 2021

Dissection of Genetic Basis Underpinning Kernel Weight-Related Traits in Common Wheat.

Plants (Basel) 2021 Apr 7;10(4). Epub 2021 Apr 7.

The Key Laboratory of Crop Genetics and Breeding of Hebei Province, Institute of Cereal and Oil Crops, Hebei Academy of Agricultural and Forestry Sciences, Shijiazhuang 050035, China.

Genetic dissection kernel weight-related traits is of great significance for improving wheat yield potential. As one of the three major yield components of wheat, thousand kernel weight (TKW) was mainly affected by grain length (GL) and grain width (GW). To uncover the key loci for these traits, we carried out a quantitative trait loci (QTL) analysis of an F recombinant inbred lines (RILs) population derived from a cross of Henong 5290 (small grain) and 06Dn23 (big grain) with a 50 K single nucleotide polymorphism (SNP) array. A total of 17 stable and big effect QTL, including 5 for TKW, 8 for GL and 4 for GW, were detected on the chromosomes 1B, 2A, 2B, 2D, 4B, 5A, 6A and 6D, respectively. Among these, there were two co-located loci for three traits that were mapped on the chromosome 4BS and 6AL. The QTL on 6AL was the most stable locus and explained 15.4-24.8%, 4.1-8.8% and 15.7-24.4% of TKW, GW and GL variance, respectively. In addition, two more major QTL of GL were located on chromosome arm 2BL and 2DL, accounting for 9.7-17.8% and 13.6-19.8% of phenotypic variance, respectively. In this study, we found one novel co-located QTL associated with GL and TKW in 2DL, /, which could explain 13.6-19.8% and 9.8-10.7% phenotypic variance, respectively. Genetic regions and linked markers of these stable QTL will help to further refine mapping of the corresponding loci and marker-assisted selection (MAS) breeding for wheat grain yield potential improvement.
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http://dx.doi.org/10.3390/plants10040713DOI Listing
April 2021

Actin-Like Protein 8 Promotes the Progression of Triple-Negative Breast Cancer via Activating PI3K/AKT/mTOR Pathway.

Onco Targets Ther 2021 12;14:2463-2473. Epub 2021 Apr 12.

Breast and Thyroid Surgery, Dongying People's Hospital, Dongying, Shandong, 257091, People's Republic of China.

Objective: The purpose of this study was to investigate the function of actin-like protein 8 (ACTL8) on triple-negative breast cancer (TNBC) and its potential mechanisms.

Methods: In our study, ACTL8 expression and the prognostic values of ACTL8 were evaluated via the dataset from the Cancer Genome Atlas (TCGA). At the same time, the expression of ACTL8 in TNBC cells was measured by Western blot and qRT-PCR. Then, the effects of ACTL8 on the growth and metastasis of TNBC were investigated by using 5-ethynyl-20-deoxyuridine (EdU), colony formation, flow cytometry, wound healing and transwell assays. Mechanistically, Western blot was performed to confirm the interaction between ACTL8 and phosphatidylinositol 3'-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in TNBC.

Results: ACTL8 expression was upregulated in TNBC and associated with the poor prognosis of TNBC. Silencing ACTL8 suppressed the proliferation, migration and invasion, also promoted the apoptosis in MDA-MB-231 and BT-549 cells. Moreover, we found that silencing ACTL8 could inhibit the activation of PI3K/AKT/mTOR signaling pathway in MDA-MB-231 and BT-549 cells. Meanwhile, the impact of silencing ACTL8 on the proliferation, apoptosis, migration and invasion was enhanced by PI3K/AKT/mTOR pathway inhibitor (Wortmannin) and reversed by PI3K/AKT/mTOR pathway activator (740Y-P).

Conclusion: Our data demonstrated that ACTL8 may facilitate the proliferation, migration and invasion, while inhibiting apoptosis through activating PI3K/Akt/mTOR signaling pathway in TNBC.
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http://dx.doi.org/10.2147/OTT.S291403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053609PMC
April 2021

Bioactive constituents and the molecular mechanism of Curcumae Rhizoma in the treatment of primary dysmenorrhea based on network pharmacology and molecular docking.

Phytomedicine 2021 Mar 27;86:153558. Epub 2021 Mar 27.

Department of Pharmacy, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, China. Electronic address:

Background: Curcumae Rhizoma (CR) has a clinical efficacy in activating blood circulation to dissipate blood stasis and has been used for the clinical treatment of qi stagnation and blood stasis (QSBS) primary dysmenorrhea for many years. However, its molecular mechanism is unknown.

Objective: The present study aimed to demonstrate the multicomponent, multitarget and multipathway regulatory molecular mechanisms of CR in the treatment of QSBS primary dysmenorrhea.

Methods: Observations of pathological changes in uterine tissues and biochemical assays were used to confirm that a rat model was successfully established and that CR was effective in the treatment of QSBS primary dysmenorrhea. The main active components of CR in rat plasma were identified and screened by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). The component-target-disease network and protein-protein interaction (PPI) network of CR were constructed by a network pharmacology approach. Then, we performed Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was adopted to verify the interactions between the core components and targets of CR to confirm the accuracy of the network pharmacology prediction results. Furthermore, we evaluated the bioactive constituents of CR and molecular mechanism of by which CR promote blood circulation and remove blood stasis via platelet tests in vivo and in vitro and Western blot analysis.

Results: The results of HE staining and biochemical assays of PGF2α, TXB2 and Ca showed that CR was effective in the treatment of QSBS primary dysmenorrhea. A total of 36 active components were identified in CR, and 329 common targets were obtained and used to construct the networks. Of these, 14 core components and 10 core targets of CR in the treatment of primary dysmenorrhea were identified. The GO and KEGG enrichment analyses revealed that the common targets were involved in multiple signaling pathways, including the calcium, cAMP, MAPK, and PI3K-Akt signaling pathways, as well as platelet activation, which is closely related to platelet aggregation. The molecular docking results showed that the 14 core components and 10 core targets could bind spontaneously. Two core targets (MAPK1 and CCR5) and 7 core components (Isoprocurcumenol, Curcumadione, Epiprocurcumenol, (+)-Curdione, Neocurdione, Procurcumenol, and 13-Hydroxygermacrone) were closely related to CR in the treatment of primary dysmenorrhea. Furthermore, the in vivo platelet test showed that CR clearly inhibited platelet aggregation. Five core components ((+)-Curdione, Neocurdione, Isoprocurcumenol, Curcumadione and Procurcumenol) obviously inhibited platelet aggregation in vitro. In addition, based on the relationships among the signaling pathways, we confirmed that CR can effectively inhibit the expression of MAPK and PI3K-Akt signaling pathway-related proteins and decrease the protein expression levels of ERK, JNK, MAPK, PI3K, AKT and CCR5, thereby inhibiting platelet aggregation.

Conclusion: This study demonstrated the bioactive constituents and mechanisms of CR in promoting blood circulation and removing blood stasis and its multicomponent, multitarget and multipathway treatment characteristics in primary dysmenorrhea. The results provide theoretical evidence for the development and utilization of CR.
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http://dx.doi.org/10.1016/j.phymed.2021.153558DOI Listing
March 2021

Efficient combination of Human Papillomavirus Genotyping for the triage of women with Atypical Squamous Cells of Undetermined Significance in Chinese rural population: A population-based study.

J Cancer 2021 14;12(10):2815-2824. Epub 2021 Mar 14.

Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China.

In this prospective, population-based study, we evaluated the utility of high-risk human papillomavirus (HR-HPV) genotyping for triaging women with atypical squamous cells of undetermined significance (ASC-US) in the Chinese rural area. A total of 40,000 women were recruited from rural areas of Shanxi Province, China, between June 2014 and December 2014. Women with Pap results of ASC-US underwent HPV genotyping, colposcopy and histopathological examination. For those with normal cervixes or cervical intraepithelial neoplasia (CIN) 1 on the initial evaluation, a 2-year follow-up study was performed. The reporting rate of ASC-US was 5.76% (2,304/40,000) in the study population. The detection rates of CIN 2 or above (CIN2+) and CIN 3 or above (CIN3+) in women with ASC-US were 7.28% and 1.75%, respectively. HPV 16 (39.53%), HPV 58 (17.83%), and HPV 52 (15.50%) were the three most prevalent HR-HPV genotypes among all women with ASC-US cytology. The five most common HR-HPV genotypes in CIN3+ lesions were HPV16, HPV58, HPV33, HPV31 and HPV18. Compared with the 15 HR-HPV testing, genotyping for a combination of HPV16/18/31/33/58 increased specificity significantly with virtually no loss of sensitivity for detecting CIN2+ and CIN3+ lesions, as well as significantly reduced colposcopy referral rate (23.15% vs 33.70%, p<0.01). In addition, in the 2-year follow-up period, women with infection of HPV16, 18, 31, 33 or 58 genotypes were the most likely population (92%, 23/25) to develop CIN2 lesion. Our results demonstrate that genotyping for a combination of HPV16/18/31/33/58 provides a more efficient and cost-effective model to risk-stratify women with ASC-US in the Chinese rural population.
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http://dx.doi.org/10.7150/jca.55771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040879PMC
March 2021

Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis.

Cancer Cell Int 2021 Jan 7;21(1):29. Epub 2021 Jan 7.

Department of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China.

Background: Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug, which is widely used in clinical treatment of endometrial cancer. However, the underlying regulatory mechanism of metapristone on endometrial cancer is still unclear, especially the regulatory effect on microRNAs. The aim of this study is to investigate the specific molecular mechanism of metapristone regulating microRNAs in the treatment of endometrial cancer.

Methods: RL95-2 cells and Ishikawa cells were used as the endometrial cancer models. MiR-492 or si-miR-492 was transfected into RL95-2 cells and Ishikawa cells to explore the role of miR-492 in endometrial cancer. The cell cancer model and mice cancer model were used to confirm the function and mechanism of metapristone affected on endometrial cancer in vitro and in vivo. Mechanically, cell proliferation was monitored using MTT assay, cell colony formation assay and EdU assay. Luciferase reporter assay was used to identify the downstream target gene of miR-492. The protein expression and RNA expression were respectively measured by western blot and qRT-PCR for cell signaling pathway research, subsequently, were verified in the mice tumor model via immunohistochemistry.

Results: Metapristone as a kind of hormone-related drug significantly inhibited the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Mechanically, miR-492 and its target genes Klf5 and Nrf1 were highly expressed in the endometrial cancer cell lines, which promoted cell proliferation and inhibited cell apoptosis. Metapristone decreased the expression of miR-492 and its target genes Klf5 and Nrf1, leading to endometrial cancer cell growth inhibition in vitro and in vivo.

Conclusion: Metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis-related signaling pathway and decreasing the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis in clinical treatment of endometrial cancer.
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http://dx.doi.org/10.1186/s12935-020-01682-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792070PMC
January 2021

Two immune-enhanced molecular subtypes differ in inflammation, immune checkpoints, mutations, and prognostic outcome in stage I-II colonic carcinoma.

J Biochem Mol Toxicol 2021 Apr 6;35(4):e22703. Epub 2021 Jan 6.

School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

The purpose of this paper is to investigate the immune function of the tumor microenvironment and its clinical correlation with colonic carcinoma. Immune genes were downloaded from the The Cancer Genome Atlas database. Five subtypes are obtained by cluster screening based on immune gene expression data. The C3 and C4 subtypes show stronger immune activity. In addition, the C4 subtype has the largest number of gene mutations and the worst prognosis. Most of the immune signatures are upregulated in the C4 subtype, while most of the immune infiltration-related cells are upregulated in the C3 and C4 subtypes. The different immune microenvironments between these subtypes may provide new ideas for immunotherapy strategies in colon carcinoma.
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http://dx.doi.org/10.1002/jbt.22703DOI Listing
April 2021

LINC00665 enhances tumorigenicity of endometrial carcinoma by interacting with high mobility group AT-hook 1.

Cancer Cell Int 2021 Jan 6;21(1). Epub 2021 Jan 6.

Department of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China.

Background: Endometrial carcinoma is a frequently diagnosed cancer among females. LncRNAs are reported to be associated with various cancers. Their biological roles in endometrial carcinoma progression is an emerging scientific area. LINC00665 can exert a significant role in many cancers. However, its potential function in endometrial carcinoma is still poorly known.

Method: qRT-PCR was carried out to test expression of LINC00665 and HMGA1. Western blot analysis was carried out to detect protein expression of HMGA1. Cell proliferation was evaluated using Cell Counting Kit-8 (CCK-8) and EdU assay. Flow cytometry assay was used to determine cell apoptosis and cell cycle. Wound healing and transwell invasion assay was carried out to test cell migration and invasion. Immunohistochemical staining and HE staining were conducted to assess Ki-67 and tumor growth respectively.

Results: Expression of LINC00665 in clinical endometrial carcinoma tissues and cells was obviously up-regulated. Loss of LINC00665 could repress endometrial carcinoma cell viability, induce cell apoptosis and block cell cycle in G1 phase. KLE and HHUA cell migration and invasion ability were depressed by LINC00665 shRNA. Decrease of LINC00665 suppressed endometrial carcinoma tumorigenicity in vivo. RIP assay proved that LINC00665 directly bound with HMGA1 protein. shRNA of HMGA1 obviously restrained endometrial carcinoma cell growth and cell invasion.

Conclusions: LINC00665 might promote endometrial carcinoma progression by positively modulating HMGA1.
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http://dx.doi.org/10.1186/s12935-020-01657-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789558PMC
January 2021

Lower dietary mineral intake is significantly associated with cervical cancer risk in a population-based cross-sectional study.

J Cancer 2021 1;12(1):111-123. Epub 2021 Jan 1.

Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Population-based studies investigating the association between dietary mineral intake and risk of cervical intraepithelial neoplasia (CIN) or cervical cancer in Chinese women are few. We performed a cross-sectional analysis of screening data obtained from 2,304 women in 2014 within an ongoing cohort study comprising 40,000 women in China. Dietary intake was assessed using a semiquantitative food frequency questionnaire. Nutrition intake was calculated using a 26-item list of food sources drawn from a validated, comprehensive database. All participants were surveyed through in-person interviews, physical examinations, and laboratory tests. The Pearson chi-square test was used for categorical variables. Multivariable logistic regression models were used to evaluate the relationship between dietary mineral intake and CIN+ risk. The food frequency questionnaire exhibited acceptable reproducibility and reasonable validity in assessing nutrient intakes among these women. After adjusting for multiple potential confounders, low dietary calcium intake was associated with CIN2+ risk (first versus fourth quartile: odds ratio [OR]=1.52, 95% confidence interval [CI]: 1.01-2.32). Similar for magnesium (OR=1.80, 95% CI: 1.20-2.68), phosphorus (OR=1.69, 95% CI: 1.12-2.55), zinc (OR=1.55, 95% CI: 1.03-2.34), and potassium (OR=1.92, 95% CI: 1.28-2.88). Low dietary intakes of calcium and potassium were significantly associated with CIN1 risk. Increased CIN2+ risk correlated with rates of no oral contraceptives and lower levels of dietary Potassium. These results thus proposed that low dietary mineral intake was an independent risk factor, potential synergy may exist between low dietary mineral levels and oral contraceptives contribute to the development of higher-grade CIN and cervical cancer.
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http://dx.doi.org/10.7150/jca.39806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738836PMC
January 2021

Prevalence and Genotype Distribution of High-Risk Human Papillomavirus Infection in Women with Abnormal Cervical Cytology: A Population-Based Study in Shanxi Province, China.

Cancer Manag Res 2020 8;12:12583-12591. Epub 2020 Dec 8.

Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030000, People's Republic of China.

Purpose: High-risk human papillomavirus (HR-HPV) infection is widely known as the major cause of cervical cancer and there are notable differences in HR-HPV prevalence and genotype distribution in different populations. Women with abnormal cervical cytology are at increased risk of cervical cancer; however, the genotype distribution of HR-HPV in women with abnormal cervical cytology remains unclear.

Methods: A total of 2,300 women with abnormal cervical cytology (from 39,988 women completing a baseline survey in a cohort established during June 2014 to December 2014) were enrolled in this study. All participants gave informed consent and completed a questionnaire about characteristics related to HPV infection. HPV genotypes were identified using flow-through hybridization, and cytology was assessed by the ThinPrep cytological test. Data were analyzed using SPSS 22.0 for Windows.

Results: The overall prevalence of HR-HPV in the 2,300 women with abnormal cervical cytology was 32%, with single and multiple HR-HPV infections making up 70.2% and 29.8%, respectively. The top-five HR-HPV genotypes were HPV16 (13.5%), HPV58 (5.7%), HPV52 (4.9%), HPV53 (2.5%), and HPV51 (2.3%). The prevalence of HR-HPV in atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions or higher was 30.8%, 36.5%, and 54.9%, respectively, showing an increasing trend with severity of cervical cytology (=13.952, <0.001). The prevalence of HPV16 and HPV33 increased significantly with the degree of cytological abnormality. HR-HPV infection risk was statistically higher in women aged 35-45 years, with low education, infrequent bathing, multiple gravidity, multiple parity, history of gynecological diseases, and premenopause.

Conclusion: HR-HPV infection in women with abnormal cervical cytology was 32%, and the top-five HR-HPV genotypes were HPV16, HPV58, HPV52, HPV53, and HPV51 in Shanxi Province, China. These results shed light on demographic and behavioral characteristics related to HR-HPV infection in women with abnormal cervical cytology and provide an insight for the development of HPV vaccines.
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http://dx.doi.org/10.2147/CMAR.S269050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733379PMC
December 2020

Dietary nutrient intake related to higher grade cervical intraepithelial neoplasia risk: a Chinese population-based study.

Nutr Metab (Lond) 2020 Nov 30;17(1):100. Epub 2020 Nov 30.

Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, 382 Wuyi Rd, Taiyuan, 030001, Shanxi, China.

Background: Dietary nutrient intake plays a significant role in carcinogenesis. Few studies have investigated the association between dietary nutrient intake and cervical intraepithelial neoplasia (CIN) risk in China.

Methods: Data on 2304 women from an ongoing cohort comprising 40,000 women from China in 2014 were included. Study randomly selected 218 out of 2304 people as subjects during 2019. All participants were surveyed through in-person interviews, physical examinations, and laboratory tests. Clinical data were obtained from physical examinations and laboratory tests. Dietary intakes were assessed using a semiquantitative food frequency questionnaire. Nutrition intakes from 26 food sources were calculated using a comprehensive validated database. Descriptive statistics were used to describe the frequency and proportion, and mean and standard deviation of the demographic characteristics. Characteristics were examined for significant differences, and Pearson chi-square tests were used for categoric variables. Logistic regression was used to obtain odds ratios (ORs) and confidence intervals (CIs) for CIN risk in each nutrient intake quartile relative to that in the highest quartile.

Results: The food frequency questionnaire exhibited acceptable reproducibility and reasonable validity in assessing nutrient intakes among these women. After adjusting for multiple confounders, several dietary nutrients showed significant associations with CIN2+ risk. Low dietary folate intake was associated with the risk of CIN2+ (first versus fourth quartile: OR = 1.55, 95% CI 1.03-2.33). Similar results were also observed for vitamin B6 (OR = 1.63, 95% CI 1.08-2.46), vitamin C (OR = 1.59, 95% CI 1.05-2.42), niacin (OR = 1.65, 95% CI 1.08-2.51), and vitamin K (second versus fourth quartile: OR = 1.60, 95% CI 1.05-2.44).

Conclusions: Low folate; vitamin B6, C, and K; and niacin intakes were associated with CIN2+ risk. Nutrients may influence the development of higher grade CIN and cervical cancer. Trial registration The study was registered in the Chinese Clinical Trial Register (ChiCTR-ROC-15006479) ( https://www.chictr.org.cn ).
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http://dx.doi.org/10.1186/s12986-020-00521-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708219PMC
November 2020

RamA upregulates multidrug resistance efflux pumps AcrAB and OqxAB in Klebsiella pneumoniae.

Int J Antimicrob Agents 2021 Feb 28;57(2):106251. Epub 2020 Nov 28.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China, and Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of PR China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

Overexpression of the acrAB genes regulated by RamA and overexpression of oqxAB regulated by RarA have been reported to mediate multidrug resistance in Gram-negative bacilli. In this study, regulation of acrAB and oqxAB simultaneously by the global regulator RamA was investigated in a multidrug-resistant Klebsiella pneumoniae clinical isolate (KP22) resistant to tigecycline and other antimicrobials. KP22 overexpressed ramA due to a ramR mutation, along with an unexpected overexpression of oqxB. Deletion of ramA led to a 16-fold decrease in the tigecycline minimum inhibitory concentration (MIC) with decreased expression of acrB (4.3-fold) and oqxB (7.1-fold) compared with KP22. Transcomplementation of KP22ΔramA with the wild-type ramA gene restored the tigecycline MIC and upregulation of the acrB (3.9-fold) and oqxB (4.0-fold) genes compared with KP22. When oqxB was knocked out, MICs of ciprofloxacin, olaquindox and nitrofurantoin were considerably decreased, while deletion of acrB led to MIC decreases for cefepime, piperacillin/tazobactam and tigecycline in addition to the above three antimicrobials. The results of electrophoretic mobility shift assay showed that RamA could bind the promoter regions of both the acrAB and oqxAB operons. This study demonstrates for the first time that RamA can directly regulate multidrug resistance efflux pumps AcrAB and OqxAB in K. pneumoniae.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.106251DOI Listing
February 2021

The Anti-colitis Effect of Polysaccharide Is Associated With the Regulation of the Composition and Metabolism of Gut Microbiota.

Front Cell Infect Microbiol 2020 21;10:519479. Epub 2020 Oct 21.

College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

The pathogenesis of inflammatory bowel disease (IBD) is linked to an intricate association of environmental, microbial, and host-related factors. Polysaccharide affects host immunity by regulating the composition and metabolism of gut microbiota is the common mechanism of disease resistance. However, the efficacy and mechanism of polysaccharide (SCP) in the treatment of inflammatory bowel disease have not been studied. To explore the effect and mechanism of SCP on dextran sodium sulfate (DSS) - induced ulcerative colitis (UC) in mice. In this study, we established a mouse model of UC, and used SCP for treatment intervention. The biochemical indexes related to inflammation were determined by ELISA kit, and the therapeutic effect of SCP on UC was clarified. Then, 16S rDNA sequencing was used to study the effect of SCP on the composition and diversity of gut microbiota. At the same time, GC-MS was used to determine the content of short chain fatty acids in intestinal contents. Finally, the relationship among gut microbiota, short chain fatty acids and inflammatory factors was analyzed, and to comprehensively explain the effect and mechanism of SCP on UC. The results showed that SCP could significantly improve the physiological state of UC mice and regulate the level of inflammatory factors to normal levels. Meanwhile, SCP could significantly regulate the imbalance of gut microbiota and increase the content of SCFAs. In addition, the results of the correlation between gut microbiota and SCFAs showed that butyric acid, isobutyric acid and valeric acid had the highest correlation with gut microbiota. In conclusion, this research showed that SCP can inhibit inflammatory bowel disease by regulating the composition and metabolism of gut microbiota, and indicating that SCP may be used as adjuvant therapy for IBD patients.
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http://dx.doi.org/10.3389/fcimb.2020.519479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609416PMC
October 2020

Development of Electrochemical Oscillation Method for Identification of , and Nuts.

Front Chem 2020 11;8:748. Epub 2020 Sep 11.

School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.

In this work, an electrochemical oscillation system has been developed using the Belousov-Zhabotinsky reaction. The effect of the combination of each reagent, reaction temperature, and stirring speed on the induction period, oscillating period, and oscillating life were optimized. The nuts of , and have been widely used for medical purposes. The proposed electrochemical oscillation system was then used for the identification of , and . Three nuts exhibited very different electrochemical oscillation profiles. The dendrogram was divided into three main principal infrageneric clades. Each cluster only contains one species, suggesting that no outlier was observed in this study. Based on the discussed results, we proposed a simple method for herbal medicine identification.
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http://dx.doi.org/10.3389/fchem.2020.00748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516034PMC
September 2020

Impact of neoadjuvant chemotherapy on the postoperative pathology of locally advanced cervical squamous cell carcinomas: 1:1 propensity score matching analysis.

Eur J Surg Oncol 2020 Sep 18. Epub 2020 Sep 18.

Department of Obstetrics and Gynecology, Nan Fang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Objective: To assess the impact of neoadjuvant chemotherapy on postoperative pathology for stage IB2 and IIA2 cervical squamous cell carcinoma.

Methods: Postoperative pathology was compared between patients who received neoadjuvant chemotherapy followed by radical hysterectomy (NACT group) and patients who received upfront radical hysterectomy (URH group). Then, patients in the NACT group were divided into a chemotherapy-sensitive group and a chemotherapy-insensitive group according to their response to chemotherapy.

Results: After 1:1 propensity score matching (PSM), the positive rates of lymphovascular space invasion (LVSI) (7.9% vs 17.7%, P = 0.001) and cervical deep stromal invasion (60.4% vs 76.2%, P < 0.001) in the NACT group were significantly lower than those in the URH group, while the positive rates of parametrial invasion, lymph node metastasis, and vaginal margin invasion were not significantly different between the two groups. The rate of positive lymph node metastasis in the chemotherapy-sensitive group was significantly lower than that in the URH group (18.1% vs 26.5%, P = 0.037).

Conclusion: Among patients with stage IB2 and IIA2 cervical squamous cell carcinomas, NACT can reduce the positive rate of intermediate-risk factors, such as deep cervical stromal invasion and LVSI, but cannot reduce the positive rate of high-risk factors. For patients who are chemotherapy sensitive, NACT can reduce the positive rate of lymph node metastasis.
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http://dx.doi.org/10.1016/j.ejso.2020.09.013DOI Listing
September 2020

A Cu(II)-ATP complex efficiently catalyses enantioselective Diels-Alder reactions.

Nat Commun 2020 09 22;11(1):4792. Epub 2020 Sep 22.

Department of Chemistry and Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz, Konstanz, Germany.

Natural biomolecules have been used extensively as chiral scaffolds that bind/surround metal complexes to achieve stereoselectivity in catalytic reactions. ATP is ubiquitously found in nature as an energy-storing molecule and can complex diverse metal cations. However, in biotic reactions ATP-metal complexes are thought to function mostly as co-substrates undergoing phosphoanhydride bond cleavage reactions rather than participating in catalytic mechanisms. Here, we report that a specific Cu(II)-ATP complex (Cu·ATP) efficiently catalyses Diels-Alder reactions with high reactivity and enantioselectivity. We investigate the substrates and stereoselectivity of the reaction, characterise the catalyst by a range of physicochemical experiments and propose the reaction mechanism based on density functional theory (DFT) calculations. It is found that three key residues (N7, β-phosphate and γ-phosphate) in ATP are important for the efficient catalytic activity and stereocontrol via complexation of the Cu(II) ion. In addition to the potential technological uses, these findings could have general implications for the chemical selection of complex mixtures in prebiotic scenarios.
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http://dx.doi.org/10.1038/s41467-020-18554-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508818PMC
September 2020

Metabolomics study on the therapeutic effect of the Chinese herb pair Fructus Aurantii Immaturus and Rhizoma Atractylodis Macrocephalae in constipated rats based on UPLC-Q/TOF-MS analysis.

Ann Palliat Med 2020 Sep 21;9(5):2837-2852. Epub 2020 Aug 21.

Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.

Background: In China, Zhishi (Aurantii Fructus Immaturus) - Baizhu (Atractylodis Macrocephalae Rhizoma) is a well-known herb pair used to treat gastrointestinal motility disorders for thousands of years, and it has especially shown a definite advantage in the treatment of slow transit constipation (STC). However, the mechanism of Zhishi-Baizhu (ZSBZ) in the treatment of STC remains unclear. In this study, plasma metabolomics research combined with metabolic pathway analysis has been used to illuminate the potential mechanism of its effects against STC.

Methods: Parameters of intestinal transit ratio, plasma motilin (MTL), substance P (SP), adenosine triphosphate (ATP), histological alteration of the colon and MLCK expression in the colon were detected to evaluate the effects with respect to STC. Principal component analysis (PCA) was used to investigate the global metabolite alterations, while orthogonal partial least squares discriminant analysis (OPLS-DA) and t-test were used to filter potential metabolite markers. Moreover, metabolic pathway analysis was employed.

Results: Oral administration of ZSBZ significantly prevented the development of STC. It increased the expression of MTL and SP in serum, as well as the expression of ATP and MLCK in the colon. ZSBZ administration alleviated symptoms in loperamide-induced constipated rats, evidenced by the increase of intestinal transit ratio. Futhermore, 9 potential biomarkers of STC were screened, and the levels were all reversed to different degrees after ZSBZ administration. Metabolic pathway analysis showed that the improvement of STC by ZSBZ was mainly related to caffeine and vitamin B6 metabolism.

Conclusions: Our study identifies the metabolic networks of constipated rats and demonstrates the efficacy of this metabolomics approach to systematically study the therapeutic effects of ZSBZ on constipation.
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http://dx.doi.org/10.21037/apm-20-280DOI Listing
September 2020

Change in the active component of processed Tetradium ruticarpum extracts leads to improvement in efficacy and toxicity attenuation.

J Ethnopharmacol 2021 Jan 22;264:113292. Epub 2020 Aug 22.

School of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China. Electronic address:

Ethnopharmacological Relevance: The dried and nearly ripe fruits of Tetradium ruticarpum (A. Juss.) T.G. Hartley (TR) have long been used in treating headache and gastrointestinal disorders in oriental medicine. TR is usually processed by stir-frying with licorice extract before use. Although processing procedure is considered as the way to relieve pungent smell, reduce toxicity, and improve efficacy, its effects on TR's toxicity and efficacy and bioactive compound profiles are largely unknown.

Aim Of The Study: The purposes of the study are to evaluate the acute toxicity, efficacy and variation of toxic and effective components of TR before and after processing, and to explore the possible mechanism of how the processing procedure affect the quality of TR as a herbal medicine.

Materials And Methods: Volatile oil, aqueous extract and ethanol extract of raw and processed TR were tested for their acute toxicity, analgesic, and anti-inflammatory effects in mouse models, respectively. To identify potential toxic and effective components, the extracts were analyzed with gas chromatography-mass spectrometry and ultra-performance liquid chromatography - quadrupole time-of-flight mass spectrometry, followed by fold-change-filtering analysis.

Results: LD and LD tests indicated that although the aqueous extract has higher toxicity than volatile oil and ethanol extract, the use of TR is safe under the recommended does. The processing procedure could effectively decrease the toxicity of all three extracts with the largest decrease in volatile oil, which is likely due to the loss of volatile compounds during processing. Analgesic and anti-inflammatory studies suggested that volatile oil and ethanol extract of TR have better efficacy than the aqueous extract and the processing procedure significantly enhanced the efficacy of these two former extracts, whereas processing showed no substantially effects on the bioactivities of aqueous extract. Integrated analysis of animal trial and chromatographic analyses indicated that indole and quinolone type alkaloids, limonoids, amides and 18β-glycyrrhetinic acid were identified as the potential main contributors of TR's efficacy, whereas hydroxy or acetoxy limonoid derivates and coumarins could be the major causes of toxicity. Moreover, the reduced toxicity and improved efficacy of the processed TR are liked due to the licorice ingredients and altered alkaloids with better solubility.

Conclusions: In summary, the integrated toxicity and efficacy analyses of volatile, aqueous and ethanol extracts of TR indicated that the processing procedure could effectively reduce its acute toxicity in all three extracts and enhance its analgesic and anti-inflammatory effects in volatile and ethanol extracts. The promising candidate compounds related to the toxicity and efficacy of TR were also identified. The results could expand our understanding of the value of the standard processing procedure of TR, be valuable to the quality control of TR manufacturing and administration, as well as support clinical rational and safety applications of this medicinal plant.
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http://dx.doi.org/10.1016/j.jep.2020.113292DOI Listing
January 2021

MicroRNA-154-5p regulates the HPV16 E7-pRb pathway in Cervical Carcinogenesis by targeting CUL2.

J Cancer 2020 11;11(18):5379-5389. Epub 2020 Jul 11.

Department of Obstetrics and Gynecology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.

Cervical cancer, induced by persistent HPV infection, has a high mortality rate. The E3 ubiquitin ligase Cullin 2 (CUL2) is critical for HPV16 E7-mediated degradation of retinoblastoma protein (pRb). Dysregulation of microRNAs (miRNAs) is induced during tumorigenesis; however, the association between miRNA networks and CUL2, specific to cervical cancer, remains unknown. Herein, we determined miRNA profiles in cervical cancer tissues using an Affymetrix miRNA array. We found that miR-154-5p was downregulated during cancer progression using real-time quantitative reverse transcription PCR in 130 biopsy specimens. Bioinformatics analysis and dual-luciferase reporter assays indicated that miR-154-5p directly targets the CUL2 3'UTR. To determine the functional consequences of modulating miR-154-5p and CUL2 levels, HPV16-positive cervical cancer cell line (SiHa) was transfected with miR-154-5p mimic, miR-154-5p inhibitor, or CUL2 siRNA. The proliferation, migration, and invasion of transfected cells were evaluated using CCK8 cell counting kit, wound-healing assay, and Transwell invasion assay. Increased miR-154-5p expression promoted significantly reduced SiHa cell proliferation, migration, and invasion, whereas the miR-154-5p inhibitor had the opposite effect. CUL2 silencing had similar effects to those of the miR-154-5p mimic. Consistent with the inverse correlation between miR-154-5p and CUL2 levels, CUL2 silencing also increased pRb expression. To our knowledge, this is the first study to demonstrate that miR-154-5p regulates pRb expression by targeting CUL2 3'UTR, thereby playing a tumor-suppressive role in HPV16 E7-induced cervical carcinogenesis.
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http://dx.doi.org/10.7150/jca.45871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391205PMC
July 2020

A mixed culture of bacterial cells enables an economic DNA storage on a large scale.

Commun Biol 2020 Jul 31;3(1):416. Epub 2020 Jul 31.

School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.

DNA emerged as a novel potential material for mass data storage, offering the possibility to cheaply solve a great data storage problem. Large oligonucleotide pools demonstrated high potential of large-scale data storage in test tube, meanwhile, living cell with high fidelity in information replication. Here we show a mixed culture of bacterial cells carrying a large oligo pool that was assembled in a high-copy-number plasmid was presented as a stable material for large-scale data storage. The underlying principle was explored by deep bioinformatic analysis. Although homology assembly showed sequence context dependent bias, the large oligonucleotide pools in the mixed culture were constant over multiple successive passages. Finally, over ten thousand distinct oligos encompassing 2304 Kbps encoding 445 KB digital data, were stored in cells, the largest storage in living cells reported so far and present a previously unreported approach for bridging the gap between in vitro and in vivo systems.
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http://dx.doi.org/10.1038/s42003-020-01141-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395121PMC
July 2020

Comparison of laparoscopic and abdominal radical hysterectomy for early stage cervical cancer: oncologic outcomes based on tumor diameter.

Int J Gynecol Cancer 2020 09 22;30(9):1308-1316. Epub 2020 Jul 22.

Department of Obstetrics and Gynecology, Southern Medical University Nanfang Hospital, Guangzhou, China

Background: Early stage cervical cancer is prevalent in China and remains a major public health burden in developing countries. We aimed to determine the long term oncologic outcomes between laparoscopic and abdominal radical hysterectomy in patients with early cervical cancer.

Methods: We conducted a multicenter, retrospective, case-control study of 37 hospitals. All consecutive early stage cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA1 with lymphovascular space invasion to IB1, who underwent laparoscopic or abdominal radical hysterectomy between January 2004 and December 2016, were included. We compared the disease free survival and overall survival of the two approaches in 1:1 case-control matched settings based on prognosis related factors.

Results: We selected 8470 of 46 313 patients. After matching (n=1601/1601), we found that laparoscopic surgery was associated with significantly worse 5 year disease free survival (89.5% vs 93.1%, p=0.001; hazard ratio (HR) 1.60, p=0.001), but not 5 year overall survival (94.3% vs 96.0%, HR=1.48, p=0.058). In the subgroup analysis, in patients with a tumor diameter <2 cm (n=739/739), both 5 year disease free survival and overall survival were similar between the laparoscopic and abdominal radical hysterectomy groups. However, when tumor diameter was 2-4 cm (n=898/898), laparoscopic surgery was a poor prognosis risk factor for 5 year disease free survival (84.7% vs 90.8%, p=0.001; HR=1.81, p<0.001), but not 5 year overall survival (90.9% vs 93.8%, p=0.077; HR=1.53, p=0.059).

Conclusions: In patients with early cervical cancer, laparoscopic radical hysterectomy was associated with significantly poorer long term oncologic outcome, although in patients with tumors <2 cm, the 5 year overall survival and 5 year disease free survival were similar.
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http://dx.doi.org/10.1136/ijgc-2020-001504DOI Listing
September 2020

Mesenchymal Stem Cell in Mice Uterine and Its Therapeutic Effect on Osteoporosis.

Rejuvenation Res 2021 Apr 3;24(2):139-150. Epub 2020 Nov 3.

Department of Biochemistry and Molecular Biology, Basic Medical College of Shanxi Medical University, Taiyuan, China.

Osteoporosis is a silent disease caused by low bone mineral density and is complicated by fractures. This study was designed to examine the differentiation of uterine stem cell-derived osteoprogenitor cells (UOPCs) both and , assessing their effectiveness in treating osteoporosis. CD271/CD45 UOPCs were isolated from the endometrial tissue of inbred Balb/c mice through magnetic activated cell sorting. Stem cell differentiation assays were used for CD271/CD45 UOPCs . , the UOPCs were implanted into mouse osteoporosis models through tail-vein injection for 8 weeks. Osteogenic differentiation was examined by X-rays and computed tomography (CT) scans. Enhanced green fluorescent protein (EGFP)-labeled UOPCs, obtained from C57BL/6-Tg (ACTb-EGFP) 1Osb/J mice, were used to assess cell survival in the osteoporosis model. The levels of osteogenic markers were assessed by enzyme-linked immunosorbent assay. , UOPCs were able to form into typical spheres and various differentiations. , implantation of UOPCs into osteoporosis model significantly increased bone mineral densities and bone microstructure parameters. The levels of a biochemical marker of bone metabolism, , increased significantly. However, levels of receptor activator of nuclear factor kappa-B ligand decreased. Immunofluorescence staining of osteoporosis mice injected with green fluorescent protein+ UOPCs showed their survival for up to 7 days. In conclusion, stem cells with osteogenic differentiation potential can be isolated from uterine or endometrial tissue. These UOPCs can stably proliferate and differentiate or , which can inhibit bone resorption and osteoclast marker expression. , UOPCs significantly improved reduction in bone density caused by reduced estrogen levels. Such cell transplantation approach is potentially useful in the treatment of osteoporosis.
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http://dx.doi.org/10.1089/rej.2019.2262DOI Listing
April 2021

Construction of a system for single-stranded DNA isolation.

Biotechnol Lett 2020 Sep 5;42(9):1663-1671. Epub 2020 May 5.

School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.

Objective: The system of Strep-Tactin and StrepII tag-SSB proteins binding (ST-SSB) was established to isolate the purified single-stranded DNA in a single step with low cost and high efficiency.

Results: We demonstrate that in the presence of large amounts of dsDNA, the ssDNA binding specificity of Escherichia coli (E. coli) single stranded DNA binding (EcSSB) protein was stronger than gene-5-protein (g5p). ST-SSB system relies on the affinity between Strep-Tactin, StrepII tag-SSB protein and ssDNA in binding buffer. Here, we successfully isolated the purified ssDNA from mixed DNA (ds- and ss-DNA form) samples and asymmetric polymerase chain reaction (aPCR) products. This system can purify ssDNA in a single tube within 1 h, and the recovery efficiency of purified ssDNA was around 60%.

Conclusions: The ST-SSB system has obvious advantages of high efficiency and one-step purification to recycle any ssDNA.
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http://dx.doi.org/10.1007/s10529-020-02905-1DOI Listing
September 2020

miR-183-5p suppressed the invasion and migration of HTR-8/SVneo trophoblast cells partly via targeting MMP-9 in preeclampsia.

Biosci Rep 2020 06;40(6)

Department of Obstetrics and Gynecology, The First Hospital of Shanxi Medical University, Taiyuan 030001, China.

Preeclampsia (PE), a common obstetrical disorder, is characterized by impaired migration and invasion abilities of trophoblastic cells. MicroRNA-183-5p (miR-183) was reported to regulate cell migration and invasion in various types of human cancers; however, its role in the pathogenesis of PE remains elusive. Herein, we investigated the role of miR-183 in HTR-8/SVneo trophoblast cells invasion and migration and explored the underlying mechanism. Our results showed that miR-183 was significantly up-regulated in placental tissues from pregnant women compared with that in normal pregnant women. Overexpression of miR-183 inhibited proliferation, migration and invasion, as well as induced apoptosis in HTR-8/SVneo cells. Otherwise, down-regulation of miR-183 achieved the opposite effects. Bioinformatics prediction and luciferase reporter assay confirmed that matrix metalloproteinase-9 (MMP-9) is a target of miR-183. In addition, MMP-9 expression was significantly down-regulated, and inversely correlated with the miR-183 level in placental tissues from pregnant women with severe PE. Down-regulation of MMP-9 suppressed the trophoblast cell invasion and migration, whereas overexpression of MMP-9 promoted cell invasion and migration in HTR-8/SVneo cells. More importantly, up-regulation of MMP-9 reversed the inhibitory effects of miR-183 on cell invasion and migration in trophoblast cells. Collectively, our findings suggested that miR-183 may play critical roles in the pathogenesis of PE and serve as a potential biomarker for severe PE.
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http://dx.doi.org/10.1042/BSR20192575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273907PMC
June 2020

Neuron-like cell differentiation of hADSCs promoted by a copper sulfide nanostructure mediated plasmonic effect driven by near-infrared light.

Nanoscale 2020 May;12(17):9833-9841

State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100, China. and Institute for Advanced Interdisciplinary Research, Jinan University, 250022, China.

Nerve tissues are one of the most difficult tissues to repair due to the limited source of neural stem cells and the difficulty in promoting the neural differentiation of mesenchymal stem cells by growth factors. Electromagnetic field has been proved to have the ability to regulate stem cell differentiation. Although some research studies promoted the neural differentiation of stem cells using an external power source, it is still a big challenge to realize nerve repair in bodies because of the unwieldiness and complexity of the power supply equipment. Surface plasmons (SP) are electromagnetic oscillations caused by the interaction of free electrons and photons on a metal surface, and almost no one has used these localized electromagnetic oscillations to regulate stem cell differentiation. In this study, based on the concept proposed by our group that "the stem cell fate can be regulated by nanostructure mediated physical signals", the localized electromagnetic oscillation generated by the localized surface plasmon resonance (LSPR) of copper sulfide (CuS) nanostructures irradiated with near-infrared light has been proved to have positive regulation on stem cell maturation and neuron-like cell differentiation of human adipose-derived stem cells (hADSCs). This regulation method avoids the use of wire connection of an external power source, which realizes the stem cell fate regulation by an external field. In addition, this work demonstrated that it is promising to realize the light promoted nerve repair in bodies by using an implantable plasmonic nanomaterial with absorption in the near-infrared region within a human "optical window", which has important academic value and application prospect. As we know, this is the first time to use semiconductor nanostructures as a medium to regulate stem cell neuron-like cell differentiation by near-infrared light and the LSPR of a plasmonic nanomaterial, which will have great influence on biomedical engineering and attract broad attention from nanomaterials scientists, neurobiologists, and neurosurgeons.
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http://dx.doi.org/10.1039/d0nr02319aDOI Listing
May 2020

Diagnostic Yield and Performance of a Large Population-Based Cervical Cancer Screening Program in High-Risk Rural China.

J Cancer 2020 6;11(13):4000-4006. Epub 2020 Apr 6.

Department of Obstetrics and Gynecology, the Second Hospital of Shanxi Medical University, Taiyuan, China.

Primary cervical cancer screening by liquid-based cytology alone or with adjunctive HPV testing are available worldwide. However, little if any information is available about cervical cancer diagnostic yield of population-based cervical cancer screening in China. In response to it, we conducted a large prospective study on 40,000 women cervical cancer screening within six-month period in rural Shanxi Province, where has been reported as the highest cervical cancer rates in China. A standard cross-sectional survey by self-completed questionnaire was collected and followed by the liquid-based cytology screening. Follow-up biopsy with the diagnosis of cervical intraepithelial neoplasia 2 or higher lesion (CIN2+) were analyzed. Of initial 40,000 women participating in this study, 6.76% (2702/40,000) women had ASC-US or higher cytology screening results with ASC/SIL ratio at 6.14 (2381:388). Among them, 1.96% (782/40,000) women were found CIN lesions (95% CI, 1.68-2.23%) on confirmatory biopsies, including 0.55% (218/40,000) CIN2+ and 19 SCCa (47.5/100,000, 95% CI, 29-74/100,000). Women in Yangqu County had lower ASC/SIL ratio, but higher CIN2+ detection rate in comparison with that of Jiexiu County (6.69 vs. 8.84 and 56.7% vs. 43.9%), which reflects the cervical cancer distribution in different populations and regions. Analysis in age-stratified cytology results indicated women aged 60-65 years had the highest incidence of cytologic abnormality among all the age group; likewise, women aged >50 years were at higher risk in developing cervical high grade dysplasia or cancer than women aged <50 years (0.82% vs. 0.49%). This large-scale cervical cancer screening study provided important references as the instructive for establishing the nation-wide cervical cancer screening strategy.
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http://dx.doi.org/10.7150/jca.41472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171492PMC
April 2020

Piezoelectric nylon-11 nanoparticles with ultrasound assistance for high-efficiency promotion of stem cell osteogenic differentiation.

J Mater Chem B 2019 03 22;7(11):1847-1854. Epub 2019 Feb 22.

State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong 250100, China.

Stem cell differentiation plays a significant role in tissue repair and regeneration. The interaction between stem cells and physical signals mediated by materials has significant influence on the fate of stem cells. The utilization of the stimulation originating from material physical properties to promote stem cell differentiation is being developed and has attracted much attention. However, it is difficult to induce electric signals into tissues noninvasively. In this study, piezoelectric nylon-11 nanoparticles (nylon-11 NPs) with uniform morphology were synthesized in mass production by a simple anti-solvent method. The prepared nylon-11 NPs possessed efficient piezoelectricity and high cytocompatibility. Fluorescent OPDA-coated nylon-11 NPs could image dental pulp stem cells (DPSCs) well, which demonstrated that nylon-11 NPs can be endocytosed easily by DPSCs. With the assistance of ultrasound, nylon-11 NPs could promote the osteogenic differentiation of DPSCs efficiently in a noninvasive way. Meanwhile, nylon-11 NPs could also promote the osteogenic differentiation of DPSCs to a certain extent. Therefore, piezoelectric nylon-11 NPs with the assistance of ultrasound will have enormous potential in tissue engineering, especially in stem cell fate regulation by noninvasive stimulation. This indicates that nanomaterial-mediated physical signals can regulate stem cell differentiation efficiently.
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http://dx.doi.org/10.1039/c8tb03321hDOI Listing
March 2019

Processing and Polyherbal Formulation of (A. Juss.) Hartley: Phytochemistry, Pharmacokinetics, and Toxicity.

Front Pharmacol 2020 6;11:133. Epub 2020 Mar 6.

College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China.

Herbal medicine is a major part of traditional Chinese medicine (TCM), which is evolved as a system of medical practice from ancient China. The use of herbal medicine is mainly based on practice and theories and concepts rooted in ancient philosophy. In the era of evidence-based medicine, it is essential to accurately evaluate herbal remedy with standard/modern medical practice approaches. (A. Juss.) Hartley (TR), a medicinal plant with diversify bioactive components, has been broadly used to treat pain and gastrointestinal disorders in TCM. However, TR has also been reported to have potential toxicity by long-term use or excessive doses, though the associated compounds are yet to be identified. TR is usually processed, and/or combined with other herbs in TCM formulas in order to achieve a synergistic effect or reduce its toxicity. Since processing or polyherbal formulation of TR may lead to changes in its chemical composition and contents, quality, efficacy and toxicity, comparison of TR samples before and after processing, as well as its combination with other medicines, would provide useful knowledge of bioactive compounds, efficacy and toxicity of this valuable medicinal plant. Here we reviewed the recent studies about the phytochemistry, pharmacokinetic behaviors and toxicity of TR under various processing or polyherbal formulation conditions, which would expand our understanding of mechanisms of TR's efficacy and toxicity and be valuable for quality control in industrial manufacturing, future medicinal research, and safety and rational use of TR in TCM.
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http://dx.doi.org/10.3389/fphar.2020.00133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067890PMC
March 2020

The Colonization of Carbapenem-Resistant Klebsiella pneumoniae: Epidemiology, Resistance Mechanisms, and Risk Factors in Patients Admitted to Intensive Care Units in China.

J Infect Dis 2020 03;221(Suppl 2):S206-S214

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a threat to public health, most notably as a superbug causing nosocomial infections. Patients in the intensive care unit (ICU) are at increased risk of hospital-acquired K pneumoniae infection, especially CRKP. This study was conducted to investigate the frequency of gastrointestinal and nasopharyngeal K pneumoniae colonization and its contribution to infections in ICU patients.

Methods: A 3-month prospective cohort study was performed in which 243 ICU patients were screened for intestinal and nasopharyngeal carriage of K pneumoniae at admission and once per week thereafter. The colonization and clinical infection isolates were analyzed by antimicrobial susceptibility testing to identify CRKP and were characterized by multilocus sequence typing (MLST) and whole-genome sequencing combined with epidemiological data to investigate the resistance mechanisms and assess the possible transmitted infection.

Results: Twenty-eight percent (68 of 243) of patients tested positive for carriage of K pneumoniae immediately upon admission to ICU, 54% (37 of 68) of which were nonduplicate CRKP isolates. Patients with carbapenem-susceptible K pneumoniae (CSKP) colonization at admission were more likely to acquire CRKP colonization during the ICU stay compared with patients without K pneumoniae colonization at admission. The incidence of subsequent CRKP infection in the baseline CSKP (32.3%, 10 of 31) and CRKP (45.9%, 17 of 37) carrier group was significantly higher than that of the baseline non-KP carrier group (8.6%, 15 of 175). The risk factors associated with acquired CRKP colonization during the ICU stay among negative CRKP colonization at admission included previous exposure to carbapenem, tigecycline or β-lactam/β-lactamases inhibitor, and invasive processes or surgical operations. Sixty-four percent (27 of 42) of patients with K pneumoniae infection were colonized by clonally related K pneumoniae strains according to enterobacterial repetitive intergenic consensus sequence-polymerase chain reaction analysis. ST11 (72%, 53 of 74) was the most predominant MLST type of clonally related CRKP isolate colonizing these patients, followed by ST15 (26%, 19 of 74).

Conclusions: The colonization of K pneumoniae may increase the incidence of corresponding K pneumoniae infection in critically ill patients in the ICU. High prevalence of ST11 CRKP (due to blaKPC-2) carriage and infection in ICU was observed.
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http://dx.doi.org/10.1093/infdis/jiz622DOI Listing
March 2020

A 5 GHz and 7.5 V multi-amplitude modulator driving circuit for practical high-speed quantum key distribution.

Rev Sci Instrum 2020 Feb;91(2):024705

CAS Center for Excellence and Synergetic Innovation Center in Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.

Quantum key distribution (QKD) offers the ability of information theoretic security key exchange. The secure key rate is an important indicator for the practical QKD systems, which determines what kinds of applications can be supported. One most effective way to enhance the secure key rate is to increase the system repetition frequency. Here, we report an implementation of a high-speed DC-coupled modulator driving circuit with a repetition rate of up to 5 GHz. The circuit outputs a multi-amplitude return-to-zero pattern pulse with a maximum amplitude of 7.5 V. The design adapts to the various electro-optic modulators widely employed in QKD systems. The minimum pulse width is measured as 75 ps, with the relative noise level less than 1.5% for all the output amplitudes under random modulation.
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http://dx.doi.org/10.1063/1.5140695DOI Listing
February 2020