Publications by authors named "Yan Pan"

367 Publications

inhibitory effects of glucosamine, chondroitin and diacerein on human hepatic CYP2D6.

Drug Metab Pers Ther 2021 Apr 8. Epub 2021 Apr 8.

School of Pharmacy, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000Kuala Lumpur, Malaysia.

Objectives: Glucosamine, chondroitin and diacerein are natural compounds commonly used in treating osteoarthritis. Their concomitant intake may trigger drug-natural product interactions. Cytochrome P450 (CYP) has been implicated in such interactions. Cytochrome P450 2D6 (CYP2D6) is a major hepatic CYP involved in metabolism of 25% of the clinical drugs. This study aimed to investigate the inhibitory effect of these antiarthritic compounds on CYP2D6.

Methods: CYP2D6 was heterologously expressed in . CYP2D6-antiarthritic compound interactions were studied using enzyme kinetics assay and molecular docking.

Results: The high-performance liquid chromatography (HPLC)-based dextromethorphan -demethylase assay was established as CYP2D6 marker. All glucosamines and chondroitins weakly inhibited CYP2D6 (IC values >300 µM). Diacerein exhibited moderate inhibition with IC and values of 34.99 and 38.27 µM, respectively. Its major metabolite, rhein displayed stronger inhibition potencies (IC=26.22 μM and =32.27 μM). Both compounds exhibited mixed-mode of inhibition. molecular dockings further supported data from the study. From - extrapolation, rhein presented an area under the plasma concentration-time curve (AUC) ratio of 1.5, indicating low potential to cause inhibition.

Conclusions: Glucosamine, chondroitin and diacerein unlikely cause clinical interaction with the drug substrates of CYP2D6. Rhein, exhibits only low potential to cause inhibition.
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http://dx.doi.org/10.1515/dmdi-2020-0182DOI Listing
April 2021

The complete chloroplast genome of (Thunb.) Sweet, a traditional Chinese medicinal plant.

Mitochondrial DNA B Resour 2021 Mar 15;6(3):851-852. Epub 2021 Mar 15.

Key Laboratory of Forest Genetics & Biotechnology of Ministry of Education, Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing, China.

(Thunb.) sweet, a member of Verbenaceae, is a traditional Chinese medicinal plant mainly distributed in tropical and subtropical Asia. Herein, we reported the complete chloroplast genome sequence of . The size of the chloroplast genome is 152,171 bp in length, including a large single-copy region (LSC) of 83,415 bp, a small single-copy region (SSC) of 17,318 bp, which was separated by a pair of inverted repeated regions of 25,719 bp. The chloroplast genome encodes 133 genes, including 88 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic tree showed that is closely related to and
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http://dx.doi.org/10.1080/23802359.2021.1885316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971232PMC
March 2021

The PIN gene family in relic plant L. chinense: Genome-wide identification and gene expression profiling in different organizations and abiotic stress responses.

Plant Physiol Biochem 2021 May 19;162:634-646. Epub 2021 Mar 19.

Key Laboratory of Forest Genetics and Biotechnology of Ministry of Education, Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing, 210037, China. Electronic address:

The auxin efflux carrier PIN-FORMED (PIN) proteins are required for the polar transport of auxin between cells through their asymmetric distribution on the plasma membrane, thus mediating the differential distribution of auxin in plants, finally, affecting plant growth and developmental processes. In this study, 11 LcPIN genes were identified. The structural characteristics and evolutionary status of LcPIN genes were thoroughly investigated and interpreted combining physicochemical property analysis, evolutionary analysis, gene structure analysis, chromosomal localization, etc. Multi-species protein sequence analysis showed that angiosperm PIN genes have strong purification options and some functional sites were predicted about PIN protein polarity, trafficking and activity in L. chinense. Further qRT-PCR and transcriptome data analysis indicated that the long LcPINs have highly expressed from globular embryo to plantlet, and the LcPIN6a started upregulated in cotyledon embryo. The LcPIN3 and LcPIN6a are both highly expressed during the development of stamens and petals and the expression of LcPIN2 is related to root elongation, suggesting that they may play an important role in these processes. Experiment data indicates that LcPIN5 and LcPIN8 might play a key role in auxin transport in Liriodendron stems and leaves under abiotic stress. Analyzed the response of LcPIN genes to abiotic stress and as a basis for uncovering the biological role of LcPIN genes in development and adaption to adverse environments. This study provides a foundation for further genetic and functional analyses.
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http://dx.doi.org/10.1016/j.plaphy.2021.03.030DOI Listing
May 2021

Carbon Monoxide-Releasing Molecule-3 Regulates the Polarization of Lipopolysaccharide-Induced Macrophages.

Inflammation 2021 Mar 22. Epub 2021 Mar 22.

Department of Vip Center, School and Hospital of Stomatology & Shandong Provincial Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Cheeloo College of Medicine, Shandong University, No.44-1 Wenhua Road West, Jinan, 250012, Shandong, China.

Macrophages show two main phenotypes, the M1-type (pro-inflammatory) and the M2-type (anti-inflammatory). The purpose of this research was to investigate the regulatory effect of carbon monoxide releasing molecule-3 (CORM-3) on LPS-induced macrophage polarization. LPS-induced RAW264.7 cells were exposed to CORM-3 for 24 h. Polarization of cells was checked by flow cytometry; expression of M1 or M2 macrophage-related factors and NF-κB signaling factors was examined by RT-PCR, ELISA, and Western blot. Male C57 mice were divided into three groups: normal group; periodontitis group, where experimental periodontitis was established in mice; LPS+CORM-3 group, where mice with experimental periodontitis were treated with CORM-3. Polarization of macrophages and the expression of M1 or M2 macrophage-related factors were detected by immunofluorescence, ELISA, and RT-PCR. CORM-3 significantly reduced M1 macrophage proportion, but increased M2 proportion in LPS-stimulated cells. Accordingly, CORM-3 significantly suppressed the expression of M1 macrophage-related TNF-α, iNOS, IL-1β, and IL-6, but promoted M2-related IL-10 and Arg-1. The expression of p-p65, p-p50, and p-IκB induced with LPS was inhibited by CORM-3. In vivo experiments indicated that CORM-3 induced more M2 macrophages in periodontal tissues in mice with experimental periodontitis. The expression of M1 macrophage-related factor in periodontitis was inhibited, but the expression of M2-related factors was increased by CORM-3. CORM-3 inhibits macrophage polarization to pro-inflammatory M1-type and promotes to anti-inflammatory M2-type, which provides scientific basis for the application of CORM-3 in the treatment of periodontitis.
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http://dx.doi.org/10.1007/s10753-021-01450-xDOI Listing
March 2021

A comprehensive quality evaluation method of Corydalis yanhusuo by HPLC fingerprints, chemometrics, and correlation analysis.

J Sep Sci 2021 Mar 8. Epub 2021 Mar 8.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, P. R. China.

A novel quality evaluation method of Corydalis yanhusuo was established by researching the high-performance liquid chromatography behavior of alkaloids under different buffer solutions and exploring the correlation between alkaloids in C. yanhusuo. The retention times of tetrahydropalmatine and corydaline were significantly influenced by pH, while the peak shape was affected by buffer types and ionic strength. The resolution of compounds in fingerprint was satisfactory under acetonitrile-0.2% phosphoric acid buffer (adjusted pH to 5.0 with triethylamine). Twelve common peaks were found by comparing 20 batches of C. yanhusuo fingerprints, and three tertiary alkaloids and four quaternary alkaloids were identified. The fingerprints were analyzed by similarity analysis, hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis. All samples were divided into three groups, and the contents of dehydrocorydaline and coptisine from Zhejiang province were relatively higher than other origins. There were six components performing more contributions to the quality of C. yanhusuo. The correlations between alkaloids were conducted by Pearson correlation analysis and mathematical model analysis. The content correlation between palmatine and berberine was y = 0.28x  + 0.03x + 0.03, and the dehydrocorydaline and coptisine was y = -7.54/(1 + (x/0.14) ) + 2.61. The established mathematical model of alkaloids provided a guiding significance for the quality control of C. yanhusuo.
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http://dx.doi.org/10.1002/jssc.202001250DOI Listing
March 2021

Analysis of Differentially Expressed Genes in Endothelial Cells Following Tumor Cell Adhesion, and the Role of PRKAA2 and miR-124-3p.

Front Cell Dev Biol 2021 19;9:604038. Epub 2021 Feb 19.

Department of Pharmacology, Health Science Center, School of Basic Medical Sciences, Peking University, Beijing, China.

Tumor cell adhesion to the endothelium is one pattern of tumor-endothelium interaction and a key step during tumor metastasis. Endothelium integrity is an important barrier to prevent tumor invasion and metastasis. Changes in endothelial cells (ECs) due to tumor cell adhesion provide important signaling mechanisms for the angiogenesis and metastasis of tumor cells. However, the changes happened in endothelial cells when tumor-endothelium interactions are still unclear. In this study, we used Affymetrix Gene Chip Human Transcriptome Array 2.0. and quantitative real-time PCR (qPCR) to clarify the detailed gene alteration in endothelial cells adhered by prostate tumor cells PC-3M. A total of 504 differentially expressed mRNAs and 444 lncRNAs were obtained through chip data analysis. Gene Ontology (GO) function analysis showed that differentially expressed genes (DEGs) mainly mediated gland development and DNA replication at the biological level; at the cell component level, they were mainly involved in the mitochondrial inner membrane; and at the molecular function level, DEGs were mainly enriched in ATPase activity and catalytic activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway analysis showed that the DEGs mainly regulated pathways in cancer, cell cycle, pyrimidine metabolism, and the mTOR signaling pathway. Then, we constructed a protein-protein interaction functional network and mRNA-lncRNA interaction network using Cytoscape v3.7.2. to identify core genes, mRNAs, and lncRNAs. The miRNAs targeted by the core mRNA PRKAA2 were predicted using databases (miRDB, RNA22, and Targetscan). The qPCR results showed that miR-124-3p, the predicted target miRNA of PRKAA2, was significantly downregulated in endothelial cells adhered by PC-3M. With a dual luciferase reporter assay, the binding of miR-124-3p with PRKAA2 3'UTR was confirmed. Additionally, by using the knockdown lentiviral vectors of miR-124-3p to downregulate the miR-124-3p expression level in endothelial cells, we found that the expression level of PRKAA2 increased accordingly. Taken together, the adhesion of tumor cells had a significant effect on mRNAs and lncRNAs in the endothelial cells, in which PRKAA2 is a notable changed molecule and miR-124-3p could regulate its expression and function in endothelial cells.
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http://dx.doi.org/10.3389/fcell.2021.604038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933219PMC
February 2021

Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas.

Cancer Biol Med 2021 Feb;18(1):283-297

State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital, Air Force Medical University of PLA, Xi'an 710032, China.

Objective: The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer.

Methods: A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m.

Results: Among 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069-1.430; and HR: 1.600, 95% CI: 1.350-1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054-1.434; and HR: 1.658, 95% CI: 1.389-1.979, respectively). Patients with both NLR ≥ 3 and underweight ( neither) had much worse OS (HR: 2.445, 95% CI: 1.853-3.225) and RFS (HR: 2.405, 95% CI: 1.802-3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy.

Conclusions: Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877168PMC
February 2021

The CYP2R1 Enzyme: Structure, Function, Enzymatic Properties and Genetic Polymorphism.

J Pharm Pharm Sci 2021 ;24:94-112

Monash University Malaysia.

Since the discovery of its role in vitamin D metabolism, significant progress has been made in the understanding of gene organisation, protein structure, catalytic function, and genetic polymorphism of cytochrome P450 2R1 (CYP2R1). Located on chromosome 11p15.2, CYP2R1 possesses five exons, unlike most other CYP isoforms that carry nine exons. CYP2R1 crystal structure displays a fold pattern typical of a CYP protein, with 12 a-helices as its structural core, and b-sheets mostly arranged on one side, and the heme buried in the interior part of the protein. Overall, CYP2R1 structure adopts a closed conformation with the B' helix serving as a gate covering the substrate access channel, with the substrate vitamin D3 occupying a position with the side chain pointing toward the heme group. In liver, CYP2R1 25-hydroxylates vitamin D and serves as an important determinant of 25(OH)D level in the tissue and in circulation. While substrate profile has been well studied, inhibitor specificity for CYP2R1 requires further investigation. Both exonic and non-exonic single nucleotide polymorphisms (SNPs) have been reported in CYP2R1, including the CYP2R1*2 carrying Leu99Pro exchange, and a number of non-exonic SNPs with variable functional consequences in gene regulation. A non-exonic SNP, rs10741657, has its causal relationship with diseases established, including that of rickets, ovarian cancer, and multiple sclerosis. The role of other CYP2R1 SNPs in vitamin D deficiency and their causal link to other traits however remain uncertain currently and more studies are warranted to help identify possible physiological mechanisms underlying those complex traits.
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http://dx.doi.org/10.18433/jpps31305DOI Listing
January 2021

Cognitive status of nurses in Shanghai on pulmonary rehabilitation.

Ann Palliat Med 2021 Feb 19;10(2):2184-2194. Epub 2021 Feb 19.

Department of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: The nurse's specific understanding of pulmonary rehabilitation is not clear. The aim of the present study was to analyze the cognitive status of Shanghai nurses on pulmonary rehabilitation, and to provide a basis for the development of pulmonary rehabilitation work.

Methods: The cognitive status of pulmonary rehabilitation of nursing staff in Shanghai was investigated in the form of a questionnaire. The questionnaire included three main aspects of the function, content and indication of pulmonary rehabilitation, with 10 options for each aspect. The total score was 30 points, with 0-17 points indicating a low score and 18-30 points indicating a high score.

Results: A total of 960 valid questionnaires were collected. The average score of pulmonary rehabilitation knowledge was 18.48 points, with a median of 19 [14-23] points. There were statistically significant differences in the total scores of pulmonary rehabilitation knowledge among nurses of different ages, types of hospitals, levels of hospitals, education levels, professional titles, positions, departments, and theoretical knowledge of pulmonary rehabilitation (P<0.05). There were no statistically significant differences in the scores among nurses of different sexes (P>0.05). The high-score group included age ≥40 years (79.5%), respiratory hospital (71.7%), tertiary hospital (65.5%), bachelor degree or above (66.5%), nurse-in-charge or above (77.9%), managerial position (72.7%), pulmonary rehabilitation-related departments (71.9%), and theoretical knowledge of lung rehabilitation (79.5%). Logistic regression analysis showed that age, education level, professional title, discipline, and theoretical knowledge of lung rehabilitation were the main factors influencing the score of pulmonary rehabilitation knowledge of nursing staff in Shanghai (P<0.05).

Conclusions: More than half of the nurses surveyed in Shanghai scored high on the cognition of lung rehabilitation knowledge, but there were still many nurses who had poor theoretical knowledge of lung rehabilitation and had an insufficient understanding of the specific content of lung rehabilitation; therefore, there is room for improvement. More opportunities to develop understanding of pulmonary rehabilitation theory should be provided.
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http://dx.doi.org/10.21037/apm-21-190DOI Listing
February 2021

Naringin as a plant-derived bitter tastant promotes proliferation of cultured human airway epithelial cells via activation of TAS2R signaling.

Phytomedicine 2021 Apr 5;84:153491. Epub 2021 Feb 5.

Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, China. Electronic address:

Background: Bitter tastants can activate bitter taste receptors (TAS2Rs) and thus initiate relaxation of airway smooth muscle cells (ASMCs), which have great potential in the development of novel bronchodilator drugs for asthma therapy. However, the canonical bitter substance, denatonium is known to induce apoptosis of airway epithelial cells (AECs), indicating that other bitter tastants may also impair the epithelial integrity to prevent hazardous particulate matters such as coronaviruses. Therefore, any bitter tastants intended for treating airway disease should be carefully evaluated for potential toxicity to AECs.

Hypothesis/purpose: Considering the vast diversity of bitter tastants in nature and different types of TAS2Rs expressed in airway cells, we hypothesized that there must be some natural bitter tastants to be not only potent in inducing relaxation of ASMCs but also unharmful to AECs.

Study Design And Methods: Here we evaluated a group of bitter flavonoids that are derived from fruits and commonly used in traditional herbal medicine, including apigenin, hesperetin, kaempferol, naringenin, quercetin, and naringin, for their effects on the proliferation of human airway epithelial-like (16HBE14o-, BEAS-2B, and A549) cells cultured in vitro. Cell proliferation and associated signaling pathways were assessed by cell counting, ATP assay, cell cycling assay, quantitative RT-PCR, Fluo-4 labeling, and fluorescence resonance energy transfer, respectively.

Results: The results show that five of the six tested bitter tastants inhibited, but only naringin promoted the proliferation of the 16HBE14o-, BEAS-2B, and A549 cells at the dose of a few hundred micromoles. Furthermore, the naringin-promoted proliferation of the 16HBE14o- cells was associated with enhanced cell cycle progression, mRNA expression of cyclin E, and evoked calcium signaling/ERK signaling, which were all attenuated by inhibition of the TAS2R signaling pathways with specific blockers.

Conclusion: These findings indicate that although the majority of the bitter flavonoids may inhibit the proliferation of AECs, naringin emerged as one to promote the proliferation of AECs via cell cycle progression and TAS2R-activated intracellular signaling. It suggests that naringin and not a few other bitter tastants can be proven with nontoxicity to the airway epithelial structure and function, which provides further confidence in the development of safe and effective TAS2R-based bronchodilators for asthma therapy.
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http://dx.doi.org/10.1016/j.phymed.2021.153491DOI Listing
April 2021

lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway.

Int J Mol Sci 2021 Jan 30;22(3). Epub 2021 Jan 30.

Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.
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http://dx.doi.org/10.3390/ijms22031407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866785PMC
January 2021

Radiation engenders converse migration and invasion in colorectal cancer cells through opposite modulation of ANXA2/AKT/GSK3β pathway.

Am J Cancer Res 2021 1;11(1):61-78. Epub 2021 Jan 1.

Institute of Radiation Medicine, Shanghai Medical College, Fudan University No. 2094 Xie-Tu Road, Shanghai 200032, China.

Radiation therapy is an effective non-surgical means to achieve local control for various solid tumors including colorectal cancer (CRC), but metastasis and recurrences after conventional radiotherapy remains a major obstacle in clinical practice, and the knowledge concerning the changes of metastatic potential after heavy ion radiation is still limited. This study investigated how radiation, including γ- and carbon ion radiation, would change the metastatic capacity of two CRC cell lines, HCT116 and DLD-1, and examined the underlying molecular mechanisms. We found that the migration and invasion was enhanced in DLD-1 cells but impaired in HCT116 cells in vitro and in vivo after radiation of γ-rays or carbons, and radiation induced epithelial mesenchymal transition (EMT) in DLD-1 cells but mesenchymal epithelial transition (MET) in HCT116 cells. The expression of snail, a key inducer of EMT, was significantly enhanced by inhibition of glycogen synthase kinase-3β (GSK3β) in both cell lines, suggesting the modulation of snail was alike in the two CRC cell lines. However, radiation inactivated GSK3β through stimulating the phosphorylation of AKT and GSK3β at Ser473 and Ser9 in DLD-1 cells respectively, but activated GSK3β by decreasing the expression of pAKT and pGSK3β or increasing the phosphorylation of GSK3β at Tyr216 in HCT116 cells. Therefore, the above inverted motility changes was due to the opposite modulation of AKT/GSK3β signaling pathway by radiation, which was further verified in other type of cancer cell lines including MCF-7, U251 and A549 cells. Moreover, it was found that annexin A2 (ANAX2) directly bound with GSK3β and acted as a negative regulator of GSK3β upon radiation. Knocking-down gene reversed the enhanced migration of the irradiated DLD-1 cells and strengthened radiation-impaired migration of HCT116 cells. Collectively, this study reveals that the change of cellular motility after radiation is independent of radiation type but is correlated with the inherent of cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840724PMC
January 2021

Study of vibrational resonance in nonlinear signal processing.

Philos Trans A Math Phys Eng Sci 2021 Mar 18;379(2192):20200235. Epub 2021 Jan 18.

Centre for Biomedical Engineering and School of Electrical and Electronic Engineering, The University of Adelaide, Adelaide, Southern Australia 5005, Australia.

Vibrational resonance (VR) intentionally applies high-frequency periodic vibrations to a nonlinear system, in order to obtain enhanced efficiency for a number of information processing tasks. Note that VR is analogous to stochastic resonance where enhanced processing is sought via purposeful addition of a random noise instead of deterministic high-frequency vibrations. Comparatively, due to its ease of implementation, VR provides a valuable approach for nonlinear signal processing, through detailed modalities that are still under investigation. In this paper, VR is investigated in arrays of nonlinear processing devices, where a range of high-frequency sinusoidal vibrations of the same amplitude at different frequencies are injected and shown capable of enhancing the efficiency for estimating unknown signal parameters or for detecting weak signals in noise. In addition, it is observed that high-frequency vibrations with differing frequencies can be considered, at the sampling times, as independent random variables. This property allows us here to develop a probabilistic analysis-much like in stochastic resonance-and to obtain a theoretical basis for the VR effect and its optimization for signal processing. These results provide additional insight for controlling the capabilities of VR for nonlinear signal processing. This article is part of the theme issue 'Vibrational and stochastic resonance in driven nonlinear systems (part 1)'.
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http://dx.doi.org/10.1098/rsta.2020.0235DOI Listing
March 2021

Inputs from paraventricular nucleus of thalamus and locus coeruleus contribute to the activation of central nucleus of amygdala during context-induced retrieval of morphine withdrawal memory.

Exp Neurol 2021 Apr 13;338:113600. Epub 2021 Jan 13.

State Key Laboratory of Medical Neurobiology, Department of Neurology of Zhongshan Hospital, MOE Frontier Center for Brain Science, School of Basic Medical Sciences, Institutes of Brain Science, Fudan University, Shanghai, China; Shanghai Blue Cross Brain Hospital, Shanghai, China. Electronic address:

Drug relapse can be mainly ascribed to the retrieval of drug withdrawal memory induced by conditioned context. Previous studies have shown that the central nucleus of the amygdala lateral division (CeL) could be activated by conditioned context. However, what source of input that activates the CeL during conditioned context-induced retrieval of morphine-withdrawal memory remains unknown. In this study, using retrograde labeling, immunohistochemistry, local microinjection and chemogenetic technologies, we found that (1) Conditioned context induced an activation of the CeL and the inhibition of the CeL inhibited the context-induced retrieval of morphine-withdrawal memory; (2) the inhibition of the paraventricular nucleus of thalamus (PVT) or PVT-CeL projection neurons caused an attenuation of the activation of the CeL by conditioned context and conditioned place aversion (CPA); (3) the inhibition of the locus coeruleus (LC) or LC-CeL projection neurons decreased the activation of the CeL by conditioned context and CPA. These results suggest that the CeL is necessary for conditioned context-induced retrieval of morphine-withdrawal memory and inputs from PVT and LC contribute to the activation of the CeL during context-induced retrieval of morphine withdrawal memory.
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http://dx.doi.org/10.1016/j.expneurol.2021.113600DOI Listing
April 2021

Novel copolymers drive differentiation of human adipose derived stem cells towards chondrocytes and osteoblasts identified by high-throughput approach.

Biomed Phys Eng Express 2020 02 17;6(2):025005. Epub 2020 Feb 17.

Jiangsu Key Laboratory of Environmentally Friendly Polymeric Materials, School of Materials Science and Engineering, Changzhou University, Changzhou 213164, People's Republic of China.

Human adipose derived stem cells (hASCs) were seeded onto polymer microarrays that had been fabricated using a variety of acrylate monomers to discover novel substrates that induced differentiation towards chondrocytes and osteoblasts. Flow cytometric analysis showed that both CD105 and CD49d positive hASCs increased rapidly with passage number on the lead polymers, while quantitative PCR analysis showed that the substrate synthesized from methacryloxyethyltrimethyl ammonium chloride, N,N-diethylaminoethyl methacrylate and cyclohexyl methacrylate enhanced chondrogenesis and osteogenensis some 4 and 25 times respectively in terms of the expression of SOX9 and ALP in differentiated stem cells. These copolymers substrates thus have great potential for application in the purification, generation and expansion of defined hASC's and the controlled differentiation of of cells for possible clinical application.
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http://dx.doi.org/10.1088/2057-1976/ab7155DOI Listing
February 2020

Research Progress on Pulmonary Arterial Hypertension and the Role of the Angiotensin Converting Enzyme 2-Angiotensin-(1-7)-Mas Axis in Pulmonary Arterial Hypertension.

Cardiovasc Drugs Ther 2021 Jan 4. Epub 2021 Jan 4.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.

Pulmonary arterial hypertension (PAH) is a progressive disease with a complex aetiology and high mortality. Functional and structural changes in the small pulmonary arteries lead to elevated pulmonary arterial pressure, resulting in right heart failure. The pathobiology of PAH is not fully understood, and novel treatment targets in PAH are desperately needed. The renin-angiotensin system is critical for maintaining homeostasis of the cardiovascular system. The system consists of the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-angiotensin type 1 receptor (ATR) axis and the ACE2-Ang-(1-7)-Mas receptor axis. The former, the ACE-Ang II-ATR axis, is involved in vasoconstrictive and hypertensive actions along with cardiac and vascular remodelling. The latter, the ACE2-Ang-(1-7)-Mas axis, generally mediates counterbalancing effects against those mediated by the ACE-Ang II-ATR axis. Based on established functions, the ACE2-Ang-(1-7)-Mas axis may represent a novel target for the treatment of PAH. This review focuses on recent advances in pulmonary circulation science and the role of the ACE2-Ang-(1-7)-Mas axis in PAH.
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http://dx.doi.org/10.1007/s10557-020-07114-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779643PMC
January 2021

A polymorphism in the 3'-untranslated region of the matrix metallopeptidase 9 gene is associated with susceptibility to idiopathic calcium nephrolithiasis in the Chinese population.

J Int Med Res 2020 Dec;48(12):300060520980211

Department of Clinical Laboratory, Lianshui County People's Hospital, Lianshui, Jiangsu, P.R. China.

Objective: To investigate whether single nucleotide polymorphisms (SNPs) in the 3' untranslated region (UTR) of the matrix metallopeptidase 9 gene () are associated with susceptibility to calcium oxalate stones.

Methods: A total of 428 patients with kidney stone disease (KSD) and 450 control individuals were enrolled. Three SNPs (rs20544, rs9509, and rs1056628) were genotyped, and mRNA and protein expression was determined in patients and controls. The dual luciferase reporter gene assay was conducted by transfecting HEK293 cells with miR-491-5p mimics and plasmids containing with rs1056628 AA/CC genotypes.

Results: The rs1056628 CC genotype was significantly increased in KSD patients compared with controls (CC vs AA: odds ratio [OR] = 2.279, 95% confidence interval [CI] = 1.048-4.956). The rs1056628 C allele frequency was higher in KSD patients than controls. The increased KSD risks associated with rs1056628 were more evident in individuals aged <30 years (OR = 3.504, 95% CI = 1.102-11.139) and men (OR = 2.522, 95% CI = 1.004-6.334). mRNA and protein levels of were significantly higher in KSD patients with the CC genotype than in those with the AA genotype.

Conclusion: This study demonstrates that SNP rs1056628 is associated with a significant KSD risk in Chinese Han individuals.
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http://dx.doi.org/10.1177/0300060520980211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756046PMC
December 2020

Sensing Traction Force on the Matrix Induces Cell-Cell Distant Mechanical Communications for Self-Assembly.

ACS Biomater Sci Eng 2020 10 19;6(10):5833-5848. Epub 2020 Sep 19.

Institute of Biomedical Engineering and Health Sciences, School of Medicine, Changzhou University, 1 Gehu Road, Wujin District, Changzhou City, Jiangsu Province 213164, China.

The long-range biomechanical force propagating across a large scale may reserve the capability to trigger coordinative responses within cell population such as during angiogenesis, epithelial tubulogenesis, and cancer metastasis. How cells communicate in a distant manner within the group for self-assembly remains largely unknown. Here, we found that airway smooth muscle cells (ASMCs) rapidly self-assembled into a well-constructed network on 3D Matrigel containing type I collagen (COL), which relied on long-range biomechanical force across the matrix to direct cell-cell distant interactions. Similar results happened by HUVEC cells to mimic angiogenesis. Interestingly, single ASMCs initiated multiple extended protrusions precisely pointing to neighboring cells in distance (100-300 μm away or 5-10 folds of the diameter of a round single cell), depending on traction force sensing. Individual ASMCs mechanosensed each other to move directionally on both nonfibrous Matrigel only and Matrigel containing fibrous COL but lost mutual sensing on the cross-linked gel or coated glass due to no long-range force transmission. The bead tracking assay demonstrated distant transmission of traction force (up to 400 μm) during the matrix deformation, and finite element method modeling confirmed the consistency between maximum strain distribution on the matrix and cell directional movements in experiments. Furthermore, ASMCs recruited COL from the hydrogel to build a fibrous network to mechanically stabilize the cell network. Our results revealed principally that cells can sense traction force transmitted through the matrix to initiate cell-cell distant mechanical communications, resulting in cell directional migration and coordinated cell and COL self-assembly with active matrix remodeling. As an interesting phenomenon, cells seem to be able to "make a phone call" via long-range biomechanics, which implicates physiological importance such as for tissue pattern formation.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01035DOI Listing
October 2020

Overexpression of microRNA-221 promotes the differentiation of stem cells from human exfoliated deciduous teeth to neurons through activation of Wnt/β-catenin pathway via inhibition of CHD8.

Cell Cycle 2020 Dec 17;19(23):3231-3248. Epub 2020 Nov 17.

Department of Stomatology, The First Affiliated Hospital of Nanchang University , Nanchang, P.R. China.

microRNAs have been proved to function in some processes of differentiation and the effect is favorable. At present, the differentiation of stem cells is not so ideal because of the high expenses and inaccessibility. Therefore, we explored the possibility that microRNA-221 (miR-221) affects differentiation from stem cells from human deciduous tooth (SHEDs) to neurons through Wnt/β-catenin pathway via binding to CHD8. After collection of SHEDs, differentiation from SHEDs to neurons was conducted by neurotrophic factor induction method in vitro, followed by gain- and loss-of-function experiments. Expression of neuron-related genes in SHEDs was examined by immunohistochemistry. The relationship between CHD8 and miR-221 was detected by dual luciferase reporter gene assay. RT-qPCR and Western blot analysis were used to determine miR-221 expression, and the mRNA and protein expression of CHD8, Wnt/β-catenin pathway- and neuron-related genes. Cell viability, and cell cycle and apoptosis were investigated by MTT assay and flow cytometry respectively. Dual luciferase reporter assay displayed that miR-221 targeted CHD8 and then affected the differentiation progression. Results of RT-qPCR and Western blot analysis showed that expression of Wnt/β-catenin pathway-related genes increased significantly, CHD8 expression decreased in neuron-induced SHEDs after miR-221 overexpression or CHD8 silencing. In response to miR-221 overexpression and CHD8 silencing, cell viability and cell cycle entry were increased, and apoptosis was reduced. Moreover, overexpression of miR-221 or silencing of CHD8 elevated the expression of neuron-related genes in neuron-induced SHEDs. Taken together, upregulation of miR-221 promotes differentiation from SHEDs to neuron cells through activation of Wnt/β-catenin pathway by binding to CHD8.
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http://dx.doi.org/10.1080/15384101.2020.1816308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751633PMC
December 2020

Melatonin ameliorated CUMS-induced depression-like behavior via restoring endoplasmic reticulum stress in rat hippocampus.

Neuroreport 2021 01;32(1):8-15

The Molecular Biology Laboratory.

Melatonin is a hormone synthesized and secreted by the pineal gland with the effect of regulating sleep rhythm. Circadian and sleep disturbances may be central for understanding the pathophysiology and treatment of depression. Recently, the melatonergic system has been implicated in the pathophysiology and treatment of depression. In this study, we observed the effects of melatonin on depression-like behavior induced by chronic unpredictable mild stress (CUMS) in rats, and its molecular mechanism was explored. Adult male Sprague-Dawley rats were exposed to CUMS for 4 weeks. Melatonin or saline was injected intraperitoneally. Behavioral changes of Sprague-Dawley rats were detected by the open field test, sugar preference test, elevated O maze test and forced swimming test. In addition, the plasma corticosterone level and the expression of endoplasmic reticulum stress-related protein in the hippocampus of rats were measured. Compared with the control group, the CUMS-exposed Sprague-Dawley rats showed depression-like behavior, which was significantly improved by melatonin treatment. Moreover, CUMS induced endoplasmic reticulum stress and JNK phosphorylation in the hippocampus. Melatonin treatment could significantly reverse the endoplasmic reticulum stress and JNK phosphorylation induced by CUMS. These results suggest that melatonin improves depression-like behavior by inhibiting endoplasmic reticulum stress induced by CUMS. This study demonstrates that melatonin can improve depression-like behavior induced by CUMS, which may be related to the inhibition of endoplasmic reticulum stress and JNK phosphorylation in rat hippocampus.
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http://dx.doi.org/10.1097/WNR.0000000000001554DOI Listing
January 2021

[Expression Levels of miRNA132 in Depression Patients and Chronic Unpredictable Mild Stress Rats].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2020 Oct;42(5):573-577

Molecular Biology Laboratory.

Objective To investigate the expression levels of miRNA132 in patients with the first-episode major depressive disorder(MDD) and in chronic unpredictable mild stress(CUMS)rats.Methods Forty-one first-episode MDD patients(MDD group)were recruited from the outpatient departments of Hangzhou Seventh People's Hospital between March 2017 and May 2018,and 31 healthy volunteers(control group)were recruited.The patients' severity of symptoms was assessed with HAMD17.In addition,24 male SD rats were equally assigned into control group and CUMS group.The depression-like behaviors of rats was detected by sucrose preference test and forced swimming test.Plasma corticosterone levels of rats were assayed by ELISA.The expression levels of miRNA132 in the blood or prefrontal cortex were detected by quantitative real-time PCR.Results The expression level of miRNA132 in peripheral blood was significantly higher in MDD group(2.37±0.36)than in control group(1.34±0.16)(=2.355,=0.0213),and there was a positive correlation between miRNA132 levels and the HAMD17 score in MDD group(=0.0004,=0.5303,=41).The immobility time of CUMS group [(72.67±2.95)s] was significantly longer than that of control group [(40.00±5.49)s] in forced swim test(=2.366,=0.0395).The sucrose intake of CUMS group [(55.67±6.42)%] was significantly lower than that of control group [(98.21±1.28)%] in sucrose preference test(=6.502,<0.0001).The plasma corticosterone level in CUMS group [(1396.0±254.9)nmol/L] was significantly higher than that of control group [(557.3±158.4)nmol/L](=2.795,=0.0190).The miRNA132 levels in blood(2.32±0.88)and prefrontal cortex(2.80±0.76)of CUMS rats were significantly higher than those [1.18±0.36(=2.273,=0.0463)and 0.99±0.23(=2.553,=0.0287),respectively] of control group.Conclusions The expression trend of miRNA132 in peripheral blood is consistent between MDD patients and CUMS rats.In CUMS rats,the expression of miRNA132 in blood is also consistent with that in prefrontal cortex.The expression of miRNA132 in blood may reflect the change trend of miRNA132 expression in prefrontal cortex.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12958DOI Listing
October 2020

Effectiveness and safety of high dose clopidogrel plus aspirin in ischemic stroke patients with the single CYP2C19 loss-of-function allele: a randomized trial.

BMC Neurol 2020 Oct 29;20(1):395. Epub 2020 Oct 29.

Department of Neurology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, P.R. China.

Background: Dual antiplatelet aggregation therapy leads to better outcomes in patients with carotid artery stenosis, intracranial artery stenosis, minor strokes, or transient ischaemic attacks. However, carriers of the CYP2C19 loss-of-function allele may not experience the desired effects. We attempted to increase the clopidogrel dose to determine whether it would improve the outcomes of stroke patients who carry a single loss-of-function allele.

Methods: We recruited 131 patients with minor ischaemic stroke, within less than 7 days of stroke onset and a CYP2C19 loss-of-function allele, who had moderate-to-severe cerebral artery stenosis. Patients were divided into the high dose group (clopidogrel 150 mg per day + aspirin 100 mg per day over 21 days.) and a normal dose group (clopidogrel 75 mg per day + aspirin 100 mg per day over 21 days). The reported outcomes included any vascular or major bleeding events as the primary and safety endpoints, respectively.

Results: One and six vascular events occurred in the high dose and normal dose groups during the 3-months follow-up period, respectively. However, no significant difference was found between the two groups when adjusted for history of diabetes (hazard ratio, 5482; 95% confidence interval, 0.660 to 45.543; P = 0.115). No major bleeding events occurred.

Conclusions: In patients with ischaemic stroke who had a single CYP2C19 loss-of-function allele and moderate to severe cerebral stenosis, fewer vascular events occurred within 3 months with high dose of clopidogrel and aspirin than with normal dose of clopidogrel and aspirin. However, the difference between the two groups was not significant.

Trial Registration: Clinical study of clopidogrel in the treatment of patients with symptomatic moderate to severe cerebral artery stenosis with intermediate metabolites of CYP2C19, URL: http://www.chictr.org.cn/ . Unique identifier: ChiCTR1800017411 , 07/28/2018.
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http://dx.doi.org/10.1186/s12883-020-01974-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596994PMC
October 2020

Discovery and Evaluation of Pyrazolo[3,4-]pyridazinone as a Potent and Orally Active Irreversible BTK Inhibitor.

ACS Med Chem Lett 2020 Oct 11;11(10):1863-1868. Epub 2019 Dec 11.

Domestic Discovery Service Unit, WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.

The identification and lead optimization of a series of pyrazolo[3,4-]pyridazinone derivatives are described as a novel class of potent irreversible BTK inhibitors, resulting in the discovery of compound . Compound exhibited high potency against BTK kinase and acceptable PK profile. Furthermore, compound demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model.
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http://dx.doi.org/10.1021/acsmedchemlett.9b00395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549109PMC
October 2020

Association of the genetic polymorphisms of metabolizing enzymes, transporters, target receptors and their interactions with treatment response to olanzapine in chinese han schizophrenia patients.

Psychiatry Res 2020 11 20;293:113470. Epub 2020 Sep 20.

Mental Health Center, Zhejiang University School of Medicine, Hangzhou 310013, China; Department of Psychiatry, Hangzhou Seventh People's Hospital, Hangzhou 310013, China. Electronic address:

Olanzapine is an atypical antipsychotic drug that has been increasingly used for treatment in schizophrenia. It has been observed that olanzapine responses in schizophrenia patients vary individually, but the reason has not been elucidated. In the study, we aimed to comprehensively explore the relationships between olanzapine responses and genetic polymorphisms of drug metabolizing enzymes, transporters and target receptors, and so as to interpret the reason of good and poor responses of olanzapine. A total of 241 Chinese Han paranoid schizophrenia who treated with olanzapine alone for 4 weeks were recruited. The positive and negative symptom scale (PANSS) was used to evaluate the efficacy of olanzapine. The genetic polymorphisms were detected by improved multiple ligase detection reaction (iMLDR). Multivariate logistic regression analysis suggested that the genetic polymorphisms of CYP1A2 rs762551, UGT1A4 rs2011425, ABCB1 rs1045642, DRD2 rs1799732 and rs1799978, 5-HTR2A rs6311 were significantly associated with olanzapine response. Multifactor dimensionality reduction (MDR) analysis showed that there was a negative interaction between CYP1A2 rs762551, ABCB1 rs1045642, DRD2 rs1799978, 5-HTR2A rs6311 and the interaction model was the optimal model. Our findings could partially explain the different olanzapine outcome and provided evidence for clarifying the predictive indicators of olanzapine response in further.
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http://dx.doi.org/10.1016/j.psychres.2020.113470DOI Listing
November 2020

Can Population Pharmacokinetics of Antibiotics be Extrapolated? Implications of External Evaluations.

Clin Pharmacokinet 2021 Jan;60(1):53-68

Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai, 200040, China.

Background And Objective: External evaluation is an important issue in the population pharmacokinetic analysis of antibiotics. The purpose of this review was to summarize the current approaches and status of external evaluations and discuss the implications of external evaluation results for the future individualization of dosing regimens.

Methods: We systematically searched the PubMed and EMBASE databases for external evaluation studies of population analysis and extracted the relevant information from these articles. A total of 32 studies were included in this review.

Results: Vancomycin was investigated in 17 (53.1%) articles and was the most studied drug. Other studied drugs included gentamicin, tobramycin, amikacin, amoxicillin, ceftaroline, meropenem, fluconazole, voriconazole, and rifampicin. Nine (28.1%) studies were prospective, and the sample size varied widely between studies. Thirteen (40.6%) studies evaluated the population pharmacokinetic models by systematically searching for previous studies. Seven (21.9%) studies were multicenter studies, and 27 (84.4%) adopted the sparse sampling strategy. Almost all external evaluation studies of antibiotics (93.8%) used metrics for prediction-based diagnostics, while relatively fewer studies were based on simulations (46.9%) and Bayesian forecasting (25.0%).

Conclusion: The results of external evaluations in previous studies revealed the poor extrapolation performance of existing models of prediction- and simulation-based diagnostics, whereas the posterior Bayesian method could improve predictive performance. There is an urgent need for the development of standards and guidelines for external evaluation studies.
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http://dx.doi.org/10.1007/s40262-020-00937-4DOI Listing
January 2021

Spatial and seasonal variation of water parameters, sediment properties, and submerged macrophytes after ecological restoration in a long-term (6 year) study in Hangzhou west lake in China: Submerged macrophyte distribution influenced by environmental variables.

Water Res 2020 Nov 2;186:116379. Epub 2020 Sep 2.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; School of Environmental Studies, China University of Geosciences, Wuhan 430074, China. Electronic address:

Submerged macrophyte restoration is the key stage in the reestablishment of an aquatic ecosystem. Previous studies have paid considerable attention to the effect of multiple environmental factors on submerged macrophytes. Meanwhile, few studies have been conducted regarding the spatial and seasonal characteristics of water and sediment properties and their long-term relationship with submerged macrophytes after the implementation of the submerged macrophytes restoration project. On a monthly basis, we monitored the spatial and seasonal variation in water parameters, sediment properties, and the submerged macrophyte characteristics of West Lake in Hangzhou from August 2013 to July 2019. From these measurements, we characterized the relationship between environmental factors and submerged macrophytes. Water nutrient concentrations continuously decreased with time, and the accumulation of sediment nutrients was accelerated as the submerged macrophyte communities developed on a long-term scale. The results indicated that the difference in water parameters was due to seasonal changes and land-use types in the watershed. The differences in the sediment properties were mainly attributed to seasonal changes and changes in the flow field. Redundancy analysis showed that the influence of water nutrients on the submerged macrophyte distribution was greater than that of sediment nutrients. The result also suggested that the developed root system, high stoichiometric homeostasis coefficients of P, and compensation ability of substantial leaf tissue may lead to a large distribution of Vallisneria natans in West Lake in Hangzhou. The correlation of water parameters and sediment properties with submerged macrophytes for a long time was very important as the restoration was achieved. To ensure the stability of the aquatic ecosystem after performing the submerged macrophyte restoration, a greater emphasis must be placed on reestablishing the entire ecosystem, including the restoration of aquatic animals and fish stocks. We expect these findings to serve as a reference for researchers and government agencies in the field of aquatic ecosystem restoration.
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http://dx.doi.org/10.1016/j.watres.2020.116379DOI Listing
November 2020

Ineffective communication equals no communication: a case report of splenic hyperfunction combined with pseudothrombocytopenia.

Ann Palliat Med 2020 Sep 17;9(5):3597-3601. Epub 2020 Aug 17.

Department of Clinical Laboratory, Lianshui People's Hospital Affiliated to kangda college of Nanjing Medical University, Lianshui, China.

Thrombocytopenia may be caused by diseases of various organ systems, especially the blood system. Certain drugs may also cause thrombocytopenia. In addition, it can result from various causes of pseudo-reduction. Therefore, a correct understanding of the causes of thrombocytopenia and their underlying mechanisms has important significance for clinical diagnosis and treatment. This study aimed to report a case of a 68-year-old woman with left upper abdominal mass and loss of appetite. The auxiliary examination showed splenomegaly and thrombocytopenia. The clinician planned to perform splenectomy. However, the laboratory physician considered that thrombocytopenia might be ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP). After effective communication between laboratory physicians and clinicians, the patient was diagnosed with splenic hyperfunction and pseudothrombocytopenia, and finally saved from undergoing splenectomy. The patient has a good prognosis after oral medication. Thrombocytopenia in this patient is caused by both hypersplenism and EDTA antagonism which is different from a single factor in other reports. The diagnosis of hematological abnormality may be challenging for physicians, especially thrombocytopenia. Therefore, medical staff should possess a rigorous working style and a high sense of responsibility besides maintaining high professional quality. Further, they should actively, timely, and effectively communicate with auxiliary departments to avoid misdiagnosis and missed diagnosis.
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http://dx.doi.org/10.21037/apm-19-295DOI Listing
September 2020

Enhanced Average Thermoelectric Figure of Merit of p-Type Zintl Phase MgZnSb via Zn Vacancy Tuning and Hole Doping.

ACS Appl Mater Interfaces 2020 Aug 10;12(33):37330-37337. Epub 2020 Aug 10.

Clean Energy Materials and Engineering Center, State Key Laboratory of Electronic Thin Film and Integrated Device, School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu 611731, China.

Isoelectronic Zn substitution at the Mg site has been proved to be effective in regulating the carrier concentration of p-type MgSb Zintl phase. However, the reported thermoelectric performance is still unsatisfactory compared with that of n-type MgSb due to the poor electrical transport properties. Here, we report an enhanced average ZT through improving low-temperature ZTs by introducing Zn vacancy followed suppressing the bipolar effect by doping. First, the Zn vacancy simultaneously increases the power factor and decreases the thermal conductivity, leading to a peak ZT value of ∼0.52 at 773 K in MgZnSb. Additionally, doping Li or Ag at the Mg site is identified as a high-efficiency strategy for further increasing the carrier concentration and hence suppressing the bipolar effect. Finally, a peak ZT of ∼0.73 at 773 K and an average ZT of ∼0.46 between 300 and 773 K were obtained in MgLiZnSb.
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http://dx.doi.org/10.1021/acsami.0c09391DOI Listing
August 2020

CDK6 inhibition targeted by miR-378a-3p protects against intestinal injury induced by ionizing radiation.

Biochem Biophys Res Commun 2020 10 13;531(3):328-334. Epub 2020 Aug 13.

Institute of Radiation Medicine, Shanghai Medical College, Fudan University, No. 2094 Xie-Tu Road, Shanghai, China. Electronic address:

Radiotherapy combined with chemotherapy is a common modality in abdominal cancer treatment. However, intestinal syndrome induced by radiation is a main factor leading to the poor prognosis of radiotherapy. In this work, we found that miR-378a-3p was markedly up-regulated in the small intestines of mice after total abdominal irradiation. Knocking-down (or overexpression) of miR-378a-3p increased (or decreased) the radiosensitivity of the small intestine cells HIEC and FHs-74-Int. Comet assay and γ-H2AX staining demonstrated that miR-378a-3p exerted its radioprotective function by reducing the accumulation of DNA damage in the cells and tissues of the small intestines. Mechanistically, miR-378a-3p could interact with the 3' UTR of CDK6 through complementary sequences and thus inhibited CDK6 expression in the small intestine cells. Rescue experiments suggested that the repression of miR-378a-3p overexpression on cell radiosensitivity and DNA damage accumulation was abrogated by the forced expression of CDK6. In summary, our results revealed for the first time that miR-378a-3p regulated the radiosensitivity and DNA damage response of small intestines by targeting CDK6. MiR-378a-3p may serve as a promising biomarker and radioprotective target in abdominal cancer.
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http://dx.doi.org/10.1016/j.bbrc.2020.07.093DOI Listing
October 2020

Increased intracellular Cl concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway.

Theranostics 2020 9;10(19):8528-8540. Epub 2020 Jul 9.

School of Basic Medicine, Central South University, Changsha, Hunan 410078, China.

In the airway, Cl is the most abundant anion and is critically involved in transepithelial transport. The correlation of the abnormal expression and activation of chloride channels (CLCs), such as cystic fibrosis transmembrane conductance regulators (CFTRs), anoctamin-1, and CLC-2, with cell migration capability suggests a relationship between defective Cl transport and epithelial wound repair. However, whether a correlation exists between intracellular Cl and airway wound repair capability has not been explored thus far, and the underlying mechanisms involved in this relationship are not fully defined. In this work, the alteration of intracellular chloride concentration ([Cl]) was measured by using a chloride-sensitive fluorescent probe (N-[ethoxycarbonylmethyl]-6-methoxyquinolium bromide). We found that clamping with high [Cl] and 1 h of treatment with the CLC inhibitor CFTR blocker CFTR-172 and chloride intracellular channel inhibitor IAA94 increased intracellular Cl concentration ([Cl]) in airway epithelial cells. This effect improved epithelial cell migration. In addition, increased [Cl] in cells promoted F-actin reorganization, decreased cell stiffness, and improved RhoA activation and LIMK1/2 phosphorylation. Treatment with the ROCK inhibitor of Y-27632 and ROCK1 siRNA significantly attenuated the effects of increased [Cl] on LIMK1/2 activation and cell migration. In addition, intracellular Ca concentration was unaffected by [Cl] clamping buffers and CFTR-172 and IAA94. Taken together, these results suggested that Cl accumulation in airway epithelial cells could activate the RhoA/ROCK/LIMK cascade to induce F-actin reorganization, down-regulate cell stiffness, and improve epithelial migration.
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http://dx.doi.org/10.7150/thno.46002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392015PMC
July 2020