Publications by authors named "Xiaoping Zhou"

112 Publications

Environmental regulation, environmental responsibility, and green technology innovation: Empirical research from China.

PLoS One 2021 22;16(9):e0257670. Epub 2021 Sep 22.

Economics and Management School, Wuhan University, Wuhan, Hubei, China.

Innovation and green are the directions to promote the circular economy and environmental sustainability at the corporate level. This paper examines the impact of environmental regulation (pollution charge) on green technology innovation and the mediating role of corporate environmental responsibility. Our results indicate that: (1) Environmental regulations stimulate manufacturing enterprises' environmental responsibility and green technology innovation. It is worth noting that corporate environmental responsibility strengthens the relationship between environmental regulation and green technology innovation. (2) Further investigation reveals that R&D expenditure and environmental investment have greatly strengthened the positive effect of environmental regulation on green technology innovation. (3) With more detailed disclosure about enterprises' environment-related information, the more outstanding stimulation effects of environmental regulation. Discussions on the features of enterprise location have revealed that, if the goal of environmental protection is set too high or if the fiscal decentralization is too strong, implementation of environmental regulation would not achieve desirable results. Accordingly, we need to optimize the collection of environmental taxes, strengthen the enterprises' environmental responsibility, and increase investment in R&D and environment protection. Meanwhile, the execution of environmental regulation should also take into account the institutional environment and governance features of the enterprise locations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257670PLOS
September 2021

Studies of Interaction Mechanism between Pyrido [3,4-] Pyrimidine Inhibitors and Mps1.

Molecules 2021 Aug 21;26(16). Epub 2021 Aug 21.

School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.

Monopolar spindle 1 (Mps1), a dual-specific kinase, is related to the proper execution of chromosome biorientation and mitotic checkpoint signaling. The overexpression of Mps1 promotes the occurrence of cancer or the survival of aneuploid cancer cells, in other words, the reduction of Mps1 will severely reduce the viability of human cancer cells. Therefore, Mps1 is a potential target for cancer treatment. Recently, a series of novel pyrido [3,4-] pyrimidine derivatives targeting Mps1 with high biological activity were synthesized. The crystal structure of Mps1 in complex with pyrido [3,4-] pyrimidine derivatives was also reported, but there were no specific mechanism studies for this series of small molecule inhibitors. In this study, complexes binding modes were probed by molecular docking and further validated by molecular dynamics simulations and the molecular mechanics/generalized Born surface area (MM/GBSA) method. The results indicated that the van der Waals interactions and the nonpolar solvation energies were responsible to the basis for favorable binding free energies, all inhibitors interacted with residues I531, V539, M602, C604, N606, I607, L654, I663, and P673 of Mps1. By analyzing the hydrogen bonds, we found the residues G605 and K529 in Mps1 formed stable hydrogen bonds with compounds, it was more conducive to activities of Mps1 inhibitors. According to the above analysis, we further designed five new compounds. We found that compounds IV and V were better potential Mps1 inhibitors through docking and ADMET prediction. The obtained new insights not only were helpful in understanding the binding mode of inhibitors in Mps1, but also provided important references for further rational design of Mps1 inhibitors.
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http://dx.doi.org/10.3390/molecules26165075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401005PMC
August 2021

Caspase-3-mediated GSDME induced Pyroptosis in breast cancer cells through the ROS/JNK signalling pathway.

J Cell Mol Med 2021 Sep 8;25(17):8159-8168. Epub 2021 Aug 8.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.

Pyroptosis is a new form of programmed cell death generated by some inflammasomes, piloting the cleavage of gasdermin (GSDM) and stimulation of dormant cytokines like IL-18 and IL-1β; these reactions are narrowly linked to certain diseases like diabetic nephropathy and atherosclerosis. Doxorubicin, a typical anthracycline, and famous anticancer drug has emerged as a prominent medication in several cancer chemotherapies, although its application is accompanied with expending of dose-dependent, increasing, irreversible and continuing cardiotoxic side effects. However, the exact path that links the induced pyroptosis to the mechanism by which Doxorubicin (DOX) acts against breast cancer cells is still puzzling. The present study seeks to elucidate the potential link between DOX-induced cell death and pyroptosis in two human breast cancer cell lines (MDA-MB-231 and T47D). We proved that treatment with DOX reduced the cell viability in a dose-dependent way and induced pyroptosis morphology in MDA-MB-231 and T47D cells. Also, protein expression analyses revealed GSDME as a key regulator in DOX-induced pyroptosis and highlighted the related role of Caspase-3 activation. Furthermore, DOX treatments induced intracellular accumulation of ROS, stimulated the phosphorylation of JNK, and Caspase-3 activation, subsequently. In conclusion, the study suggests that GSDME triggered DOX-induced pyroptosis in the caspase-3 dependent reactions through the ROS/JNK signalling pathway. Additionally, it showed that the DOX-induced cardiotoxicity and pyroptosis in breast cancer cells can be minimized by reducing the protein level of GSDME; thus, these outcomes provide a new research target and implications for the anticancer investigations and therapeutic applications.
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http://dx.doi.org/10.1111/jcmm.16574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419174PMC
September 2021

Occurrence, Distribution, and Ecological Risk Assessment of Antibiotics in Different Environmental Media in Anqing, Anhui Province, China.

Int J Environ Res Public Health 2021 07 30;18(15). Epub 2021 Jul 30.

School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.

The widespread usage of antibiotics in human and animal medication has brought global concerns over environmental contamination of antibiotic residues. In this study, 16 kinds of antibiotics in different environmental media of water, sediments, and soils in Anqing city, Anhui province were determined by ultra-performance liquid chromatography tandem mass spectrometry. A total of fourteen kinds of antibiotics were detected in surface water, with a total concentration up to 479 ng·L, while six kinds of antibiotics were detected in sediment and soil with concentrations ranging from 15.1 to 108 μg·kg. Ciprofloxacin (12.8-99.5 ng·L) and tetracycline (17.2-225 μg·kg) antibiotics exhibited the highest concentration in water and soil, respectively. In spatial distribution, the total concentration of antibiotics in surface water from the highest to the lowest followed the order of urban area, mainstream of Wan River, suburbs, tributaries of Wan River, indicating that the level of antibiotic concentration in surface water is positively associated with the frequency of human activities. In addition, the antibiotic mass fraction in agriculture land and fishpond were found higher than that in other sampling sites. Moreover, the environmental risk assessment results showed that ciprofloxacin, erythromycin, ofloxacin, enrofloxacin and tetracycline might pose medium to high risks to algae and bacteria in aquatic ecosystem.
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http://dx.doi.org/10.3390/ijerph18158112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346025PMC
July 2021

Real-time confocal microscopy imaging of corneal cytoarchitectural changes induced by different stresses.

Exp Eye Res 2021 09 26;210:108706. Epub 2021 Jul 26.

Eye Institute & Affiliated Xiamen Eye Center, School of Pharmaceutical Sciences & School of Medicine, Xiamen University, Xiamen, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China. Electronic address:

Maintenance of the corneal refractive power and tissue transparency is essential for normal vision. Real-time characterization of changes in corneal cells during suffering stresses or wound healing may provide a way to identify novel targets, whose therapeutic manipulation can improve the outcome of this response induced by injury. Here we describe a novel user friendly and effective confocal real-time confocal microscopy attachment that monitors the effects of anisoosmotic stress on cell morphology and corneal thickness in situ. Corneal epithelial nuclei gradually became highly reflective in the isotonic group and the corneal stroma was slightly thickened as compared with that seen prior to 60 min exposure to a hypotonic solution. After 30 min of exposure to hypertonic stress, the corneal stromal cells became crenate and shriveled. The hyper-reflective area of the corneal stroma in the hypo-osmotic group was significantly larger than that in the other two groups, as demonstrated by 3D reconstruction imaging. The hypotonic fresh chlorinated pool water was observed to cause atrophy of corneal epithelial nuclei, while the isosmotic bee venom solution caused high reflection of the corneal stroma layer and corneal endothelial cell damage. With the microscopic attachment, the inward movement of corneal epithelial cells toward the denuded central region was detected in the serum-treated group. The microscopy attachment is an effective system for obtaining a more detailed understanding of the time dependent losses in the corneal cell structure and tissue architecture of full thickness corneas induced by osmotic stress or cytotoxic agents.
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http://dx.doi.org/10.1016/j.exer.2021.108706DOI Listing
September 2021

Novel Cell Culture Paradigm Prolongs Mouse Corneal Epithelial Cell Proliferative Activity and .

Front Cell Dev Biol 2021 30;9:675998. Epub 2021 Jun 30.

Eye Institute & Affiliated Xiamen Eye Center, School of Pharmaceutical Sciences, School of Medicine, Xiamen University, Xiamen, China.

It has been a long-standing challenge to obtain from cell cultures adequate amounts of mouse corneal epithelial cells (mCEC) to perform transplantation surgery. This limitation is attributable to the passage dependent declines in their proliferative activity. We describe here development of a novel 6C medium that contains six different modulators of different signaling pathways, which control proliferative mCEC activity. Its usage shortens the time and effort required to obtain epithelial sheets for hastening healing of an epithelial wound in an experimental animal model. This serum-free 6C medium contains:Y27632, forskolin, SB431542, DAPT, IWP-2, LDN-193189 and also DermaLife K keratinocyte calcium. Their inclusion inhibits rises in four specific markers of epithelial mesenchymal transdifferentiation:, , β and α. This medium is applied in a feeder-free air-lifted system to obtain sufficient populations of epithelial progenitor cells whose procurement is facilitated due to suppression of progenitor epithelial cell transdifferentiation into epithelial-mesenchymal cells. Diminution of this decline in transdifferentiation was confirmed based on the invariance of , , , and gene expression levels. This cell culture technique is expected to facilitate characterization of mechanisms underlying cell fate determination. Furthermore, its implementation will improve yields of progenitor mouse corneal epithelial cells, which increases the likelihood of using these cells as a source to generate epithelial sheets for performing transplantation surgery to treat limbal stem cell deficiency in a clinical setting. In addition, the novel insight obtainable from such studies is expected to improve the outcomes of corneal regenerative medicine.
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http://dx.doi.org/10.3389/fcell.2021.675998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278007PMC
June 2021

Design, synthesis, and biological evaluation of 5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1-Indole-2-Carbohydrazide derivatives: the methuosis inducer 12A as a Novel and selective anticancer agent.

J Enzyme Inhib Med Chem 2021 Dec;36(1):1436-1453

School of Pharmaceutical Sciences and School of Public Health, Xiamen University, Xiamen 361102, China.

This study describes the synthesis and vacuole-inducing activity of 5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1-indole-2-carbohydrazide derivatives, including five potent derivatives , , , , and that exhibit excellent vacuole-inducing activity. Remarkably, effectively induces methuosis in tested cancer cells but not human normal cells. In addition, exhibits high pan-cytotoxicity against different cancer cell lines but is hardly toxic to normal cells. It is found that the -induced vacuoles are derived from macropinosomes but not autophagosomes. The -induced cytoplasmic vacuoles may originate from the endoplasmic reticulum (ER) and be accompanied by ER stress. The MAPK/JNK signalling pathway is involved in the -induced methuotic cell death. Moreover, exhibits significant inhibition of tumour growth in the MDA-MB-231 xenograft mouse model. The excellent potency and selectivity of prompt us to select it as a good lead compound for further development of methuosis inducers and investigation of the molecular and cellular mechanisms underlying methuosis.
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http://dx.doi.org/10.1080/14756366.2021.1940992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266240PMC
December 2021

Sparse Bayes Tensor and DOA Tracking Inspired Channel Estimation for V2X Millimeter Wave Massive MIMO System.

Sensors (Basel) 2021 Jun 10;21(12). Epub 2021 Jun 10.

The College of Information, Mechanical and Electrical Engineering, Shanghai Normal University, Shanghai 200234, China.

Efficient vehicle-to-everything (V2X) communications improve traffic safety, enable autonomous driving, and help to reduce environmental impacts. To achieve these objectives, accurate channel estimation in highly mobile scenarios becomes necessary. However, in the V2X millimeter-wave massive MIMO system, the high mobility of vehicles leads to the rapid time-varying of the wireless channel and results in the existing static channel estimation algorithms no longer applicable. In this paper, we propose a sparse Bayes tensor and DOA tracking inspired channel estimation for V2X millimeter wave massive MIMO system. Specifically, by exploiting the sparse scattering characteristics of the channel, we transform the channel estimation into a sparse recovery problem. In order to reduce the influence of quantization errors, both the receiving and transmitting angle grids should have super-resolution. We obtain the measurement matrix to increase the resolution of the redundant dictionary. Furthermore, we take the low-rank characteristics of the received signals into consideration rather than singly using the traditional sparse prior. Motivated by the sparse Bayes tensor, a direction of arrival (DOA) tracking method is developed to acquire the DOA at the next moment, which equals the sum of the DOA at the previous moment and the offset. The obtained DOA is expected to provide a significant angle information update for tracking fast time-varying vehicular channels. The proposed approach is evaluated over the different speeds of the vehicle scenarios and compared to the other methods. Simulation results validated the theoretical analysis and demonstrate that the proposed solution outperforms a number of state-of-the-art researches.
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http://dx.doi.org/10.3390/s21124021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230479PMC
June 2021

Outcomes of Traumatic Brain-Injured Patients With Glasgow Coma Scale < 5 and Bilateral Dilated Pupils Undergoing Decompressive Craniectomy.

Front Neurol 2021 25;12:656369. Epub 2021 May 25.

Department of Neurosurgery, Ganzhou People's Hospital, Ganzhou, China.

Decompressive craniectomy (DC) plays an important role in the treatment of patients with severe traumatic brain injury (sTBI) with mass lesions and intractably elevated intracranial hypertension (ICP). However, whether DC should be performed in patients with bilateral dilated pupils and a low Glasgow Coma Scale (GCS) score is still controversial. This retrospective study explored the clinical outcomes and risk factors for an unfavorable prognosis in sTBI patients undergoing emergency DC with bilateral dilated pupils and a GCS score <5. The authors reviewed the data from patients who underwent emergency DC from January 2012 to March 2019 in a medical center in China. All data, such as patient demographics, radiological findings, clinical parameters, and preoperative laboratory variables, were extracted. Multivariate logistic regression analysis was performed to determine the factors associated with 30-day mortality and 6-month negative neurological outcome {defined as death or vegetative state [Glasgow Outcome Scale (GOS) score 1-2]}. A total of 94 sTBI patients with bilateral dilated pupils and a GCS score lower than five who underwent emergency DC were enrolled. In total, 74 patients (78.7%) died within 30 days, and 84 (89.4%) had a poor 6-month outcome (GOS 1-2). In multivariate analysis, advanced age (OR: 7.741, CI: 2.288-26.189), prolonged preoperative activated partial thromboplastin time (aPTT) (OR: 7.263, CI: 1.323-39.890), and low GCS (OR: 6.162, CI: 1.478-25.684) were associated with a higher risk of 30-day mortality, while advanced age (OR: 8.812, CI: 1.817-42.729) was the only independent predictor of a poor 6-month prognosis in patients undergoing DC with preoperative bilateral dilated pupils and a GCS score <5. The mortality and disability rates are extremely high in severe TBI patients undergoing emergency DC with bilateral fixed pupils and a GCS score <5. DC is more valuable for younger patients.
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http://dx.doi.org/10.3389/fneur.2021.656369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185205PMC
May 2021

Sodium/glucose cotransporter 1-dependent metabolic alterations induce tamoxifen resistance in breast cancer by promoting macrophage M2 polarization.

Cell Death Dis 2021 05 18;12(6):509. Epub 2021 May 18.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, Heilongjiang, China.

Endocrine therapy is the standard treatment for estrogen receptor (ER)-positive breast cancer, but tumors eventually develop resistance. However, endocrine therapy resistance mechanisms mediated through interactions between breast cancer cells and tumor-associated macrophages (TAMs) are still unclear. Here, we characterized sodium/glucose cotransporter 1 (SGLT1) overexpression drives the highly glycolytic phenotype of tamoxifen-resistant breast cancer cells where enhanced lactic acid secretion promotes M2-like TAM polarization via the hypoxia-inducible factor-1α/signal transducer and activator of transcription-3 pathway. In turn, M2-like TAMs activate breast cancer cells through EGFR/PI3K/Akt signaling, providing feedback to upregulate SGLT1 and promote tamoxifen resistance and accelerate tumor growth in vitro and in vivo. Higher expression of SGLT1 and CD163 TAMs was associated with endocrine-resistant ER-positive breast cancers. Our study identifies a novel vicious cycle of metabolic reprogramming, M2-like TAM polarization, and endocrine therapy resistance, which involves SGLT1, proposing SGLT1 as a therapeutic target to overcome endocrine therapy resistance in breast cancer.
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http://dx.doi.org/10.1038/s41419-021-03781-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131586PMC
May 2021

LncRNA ST7-AS1 is a Potential Novel Biomarker and Correlated With Immune Infiltrates for Breast Cancer.

Front Mol Biosci 2021 12;8:604261. Epub 2021 Apr 12.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.

Long noncoding RNA (lncRNA) ST7-AS1 can be observed in various cancers, but its role in breast cancer (BRC) remains unclear. Our aim is to, on the basis of The Cancer Genome Atlas (TCGA) database, prove the correlation between lncRNA ST7-AS1 and BRC. The lncRNA ST7-AS1 expression and its roles in the prognosis of BRC were explored using data from the TCGA database. The expression level of lncRNA ST7-AS1 in BRC samples was detected using RT-PCR. The 1-, 3-, or 5-year survival rate was predicted using a nomogram established through Cox proportional hazard regression. At last, the biological function was explored through gene ontology (GO) analysis and gene set enrichment analysis (GSEA). The hallmark pathways significantly involved in hub genes were described through functional enrichment analysis. The correlation between lncRNA ST7-AS1 expression and immune infiltration was analyzed through single-sample GSEA (ssGSEA). LncRNA ST7-AS1 expression was downregulated in BRC. Decreased lncRNA ST7-AS1 expression in BRC was correlated with advanced clinical pathologic characteristics (high grade, histological type, age, menopause status, and HER2 status), survival time, and poor prognosis. The nomogram was established for using lncRNA ST7-AS1 to predict 1-, 3-, or 5-year survival in patients with BRC. In addition, GO and pathway analyses suggested the involvement of lncRNA ST7-AS1 in cell cycle, DNA repair, and immune cell infiltration in the BRC immune microenvironment. We found the correlation of lncRNA ST7-AS1 with T helper cells and DC cells. Low expression of lncRNA ST7-AS1 indicates poor prognosis and has an impact on cell cycle, DNA repair, and proportion of infiltrating immune cells in the BRC microenvironment. Therefore, lncRNA ST7-AS1 can be used as a protective prognostic marker and a potential treatment target for BRC.
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http://dx.doi.org/10.3389/fmolb.2021.604261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075053PMC
April 2021

HMGB1 is a key factor for tamoxifen resistance and has the potential to predict the efficacy of CDK4/6 inhibitors in breast cancer.

Cancer Sci 2021 Apr 26;112(4):1603-1613. Epub 2021 Feb 26.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.

Breast cancer is the leading cause of cancer death in women. Hormone-receptor-positive breast cancer (HR + BC) is the most common pathological type of breast cancer, of which the main treatment method is endocrine therapy. Unfortunately, primary or acquired drug resistance greatly limits its efficacy. In recent years, the newly launched CDK4/6 inhibitors could effectively reverse endocrine resistance in breast cancer. However, considering their expensive price and side effects, it is particularly important to find out effective biomarkers and screen sensitive patients. Here, we found through bioinformatics analysis that high mobility group box 1 (HMGB1) expression increased in endocrine-resistant HR + BC. In clinical specimens, the higher expression of HMGB1 was associated with shorter progression-free survival (PFS) for HR + BC patients with endocrine therapy after surgery. For endocrine-resistant breast cancer, compared with HMGB1-negative patients, HMGB1-positive patients who received CDK4/6 inhibitors treatment benefited more in PFS. Moreover, we demonstrated that HMGB1 promoted tamoxifen resistance by combining with the Toll-like receptor 4 (TLR4) and activating nuclear factor kappa B (NF-κB) pathway. CDK4/6 inhibitors could downregulate the expression of HMGB1 and suppress the TLR4-NF-κB pathway, and in turn reverse tamoxifen resistance. These results illuminated the critical role of HMGB1 in the process of tamoxifen resistance, explained the mechanism of CDK4/6 inhibitors reversing tamoxifen resistance, and suggested the feasibility of HMGB1 as a potential biomarker for screening sensitive patients receiving CDK4/6 inhibitors.
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http://dx.doi.org/10.1111/cas.14813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019207PMC
April 2021

Application of Joanna Briggs Institute physical restraint standards to critical emergency department patients following CONSORT guidelines.

Medicine (Baltimore) 2020 Dec;99(50):e23108

Department of Emergency Medicine.

To explore the effect of Joanna Briggs Institute (JBI) physical restraint standards in improving physical restraint in critical and emergency department patients.Enrolled 300 critical patients admitted in our hospital's emergency department from January to December 2019: 150 patients admitted January to June 2019 as control group and 150 patients admitted July to December 2019 as observation group. Routine restraints were applied in control group. Emergency department nurses in the observation group received thematic and practical JBI standardized training. This included pre-restraint assessment, principles of physical restraint, informed consent, using a restraint decision-making wheel, and alternatives to physical restraint. The incidence of restraint-associated adverse events (e.g., skin bruising, swelling) and restraint utilization rate were examined between 2 groups.The incidence of adverse events and the restraint utilization rate were significantly lower in the observation group (P < .05).The application of JBI physical restraint standards for emergency department patients can effectively reduce the incidence of adverse events and the restraint utilization rate.
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http://dx.doi.org/10.1097/MD.0000000000023108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738102PMC
December 2020

An assessment of chromosomal alterations detected by fluorescence in situ hybridisation in pancreatobiliary tract malignancy.

BMC Gastroenterol 2020 Nov 4;20(1):367. Epub 2020 Nov 4.

Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.

Background: Using fluorescence in situ hybridisation (FISH) to detect any gain of chromosomes 3, 7, or 17 and loss of the 9p21 locus has been proven to be sensitive in the diagnosis of pancreatobiliary tumors. However, both genetic and environmental factors contribute to the pathogenesis of pancreatobiliary tumors. Therefore, it is unknown whether this method is suitable for Chinese patients with pancreatobiliary tumors. This study aims to compare the sensitivity, specificity, predictive values and accuracy of cytology, ERCP/MRCP and FISH based on Chinese patients with pancreatobiliary tumors,and to analyze differences between brushing-based and formalin-fixed paraffin-embedded (FFPE)-based FISH.

Methods: A total of 66 brush cytology specimens obtained during ERCP were detected by FISH and cytology test respectively to compare the sensitivity, specificity, predictive values and accuracy. Besides, FFPE-based FISH was performed on 46 corresponding paraffin sections of pancreatobiliary tumors obtained by surgical resection.

Results: Our findings demonstrate that FISH greatly improves diagnostic sensitivity and negative predictive value compared to ERCP/MRCP and cytology without much reduction in specificity and positive predictive value. However, our results also indicate that FFPE-based FISH could not effectively identify the false-negative of brushing-based FISH.

Conclusions: We believe that FISH can effectively distinguish true positive and false positive results of cytological or radiological suspicions of malignancy. However, FFPE-based FISH still does not precisely recognize the false-negative of brushing-based FISH. Both cytology-based and PPFE-based FISH had limitation in some specimens.
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http://dx.doi.org/10.1186/s12876-020-01439-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641847PMC
November 2020

Selective and simultaneous sensing of ascorbic acid, dopamine and uric acid based on nitrogen-doped mesoporous carbon.

Anal Methods 2020 11 26;12(44):5344-5352. Epub 2020 Oct 26.

Department of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.

Development of novel sensing nanostructures for facile, economical and fast applications has attracted more and more interest. Herein, a nitrogen-doped mesoporous carbon (NMC) was synthesized by pyrolyzing a mixture of melamine and carbon black at a low-temperature (600 °C) and exploited for the simultaneous sensing of ascorbic acid (AA), dopamine (DA) and uric acid (UA). The as-made NMC exhibits a rougher surface and smaller size than carbon black. Such a one-pot method is very versatile, quick and inexpensive, easy to handle (solvent-, catalyst-, and template-free) and scalable. The oxidation potentials of the NMC/GCE negatively shift and the current responses are enhanced greatly towards the oxidation of AA, DA and UA thanks to the large surface area, mesoporous structure and N-doped active sites. The peak to peak potential separations are 258 and 410 mV for AA-DA and AA-UA. The linear ranges of AA, DA and UA are 5-4500 μM, 0.005-35 μM and 0.5-3500 μM, respectively, and their detection limits are 0.15 μM (AA), 1.6 nM (DA) and 0.15 μM (UA). Meanwhile, the NMC/GCE exhibits satisfactory stability and anti-interference ability. These results show that NMC could be a promising candidate material for electrochemical sensor construction.
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http://dx.doi.org/10.1039/d0ay01486aDOI Listing
November 2020

Research progress of mTOR inhibitors.

Eur J Med Chem 2020 Dec 13;208:112820. Epub 2020 Sep 13.

School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, China. Electronic address:

Mammalian target of rapamycin (mTOR) is a highly conserved Serine/Threonine (Ser/Thr) protein kinase, which belongs to phosphatidylinositol-3-kinase-related kinase (PIKK) protein family. mTOR exists as two types of protein complex: mTORC1 and mTORC2, which act as central controller regulating processes of cell metabolism, growth, proliferation, survival and autophagy. The mTOR inhibitors block mTOR signaling pathway, producing anti-inflammatory, anti-proliferative, autophagy and apoptosis induction effects, thus mTOR inhibitors are mainly used in cancer therapy. At present, mTOR inhibitors are divided into four categories: Antibiotic allosteric mTOR inhibitors (first generation), ATP-competitive mTOR inhibitors (second generation), mTOR/PI3K dual inhibitors (second generation) and other new mTOR inhibitors (third generation). In this article, these four categories of mTOR inhibitors and their structures, properties and some clinical researches will be introduced. Among them, we focus on the structure of mTOR inhibitors and try to analyze the structure-activity relationship. mTOR inhibitors are classified according to their chemical structure and their contents are introduced systematically. Moreover, some natural products that have direct or indirect mTOR inhibitory activities are introduced together. In this article, we analyzed the target, binding mode and structure-activity relationship of each generation of mTOR inhibitors and proposed two hypothetic scaffolds (the inverted-Y-shape scaffold and the C-shape scaffold) for the second generation of mTOR inhibitors. These findings may provide some help or reference for drug designing, drug modification or the future development of mTOR inhibitor.
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http://dx.doi.org/10.1016/j.ejmech.2020.112820DOI Listing
December 2020

LncRNA Linc-PINT inhibits miR-523-3p to hamper retinoblastoma progression by upregulating Dickkopf-1 (DKK1).

Biochem Biophys Res Commun 2020 09 29;530(1):47-53. Epub 2020 Jul 29.

Department of Ophthalmology, Shenzhen Eye Hospital, Shenzhen Eye Institute, School of Optometry, Shenzhen University Department of Ophthalmology, Zetian Road No. 18, Shenzhen, 518040, Guangdong, China. Electronic address:

Emerging evidences indicated that long non-coding RNAs (LncRNAs) regulated the pathogenesis of retinoblastoma (RB). However, up until now, the role of LncRNA Linc-PINT in the regulation of RB progression is still largely unknown. The present study identified LncRNA Linc-PINT as a tumor suppressor to hinder RB development by regulating miR-523-3p/Dickkopf-1 (DKK1) axis. Mechanistically, Linc-PINT was low-expressed, while miR-523-3p was high-expressed in RB cells, compared to the normal retinal epithelial cells (ARPE-19). Further gain- and loss-function experiments verified that both upregulation of Linc-PINT and miR-523-3p downregulation slowed down cell growth, invasion and migration, and promoted cell apoptosis in RB cells, but Linc-PINT ablation and miR-523-3p overexpression promoted malignant phenotypes in RB cells. In addition, the dual-luciferase reporter gene system and RNA pull-down assay validated that Linc-PINT positively regulated DKK1 expressions by sponging miR-523-3p, and Linc-PINT inhibited RB progression by regulating miR-523-3p/DKK1 axis. Functionally, we found that both miR-523-3p overexpression and DKK1 silence abrogated the anti-cancer effects of overexpressed Linc-PINT on RB cells. Finally, Linc-PINT inhibited tumorigenicity of RB cells in xenograft mice models. In general, analysis of the data suggested that Linc-PINT inhibited miR-523-3p to upregulate DKK1, resulting in the inhibition of RB, and we demonstrated that Linc-PINT and miR-523-3p could be utilized as potential diagnostic and therapeutic biomarkers for RB in clinic.
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http://dx.doi.org/10.1016/j.bbrc.2020.06.120DOI Listing
September 2020

Design, synthesis and biological evaluation of methylenehydrazine-1-carboxamide derivatives with (5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole scaffold: Novel potential CDK9 inhibitors.

Bioorg Chem 2020 09 30;102:104064. Epub 2020 Jun 30.

School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, South Xiang-An Road, Xiamen 361102, China. Electronic address:

In continuation of our previous work on the investigation of CDK9 inhibitors bearing indole moiety for the discovery of novel anticancer agents, novel methylenehydrazine-1-carboxamide derivatives with (5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole scaffold were designed, synthesized, and evaluated for the CDK9 inhibitory activity and anticancer activity. Biological activity results demonstrated that most of these derivatives possessed good inhibitory on the kinase activity of CDK9 such as blocking its phosphorylation function and inhibiting HIV-1 transcription. Compound 12i was found to be the most potent CDK9 inhibitor and exhibited excellent anticancer activity against HepG2, A375, MCF-7, and A549, but low toxic on normal cells including HaCaT and MCF-10A. Further studies revealed that as a result of CDK9 inhibition and subsequent inhibition of phosphorylation at Serine 2 of the RNAPII CTD, the representative compound 12i dose-dependently increased cleaved PARP level, exerting its antiproliferative effect through induction of apoptosis in cancer cells. Finally, the molecular docking analysis implied that 12i had a good binding affinity with CDK9. In summary, 12i is a potent CDK9 inhibitor and can be considered as a good lead-candidate for developing potential anticancer drugs.
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http://dx.doi.org/10.1016/j.bioorg.2020.104064DOI Listing
September 2020

Genetic diversity of toll-like receptor genes in the vulnerable Chinese egret (Egretta eulophotes).

PLoS One 2020 29;15(5):e0233714. Epub 2020 May 29.

Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, College of the Environment and Ecology, Xiamen University, Xiamen, Fujian, People's Republic of China.

Toll-like receptor (TLR) genes have recently been employed to assess genetic diversity, as they can be used to infer both demographic history and adaptation to environments with different pathogen pressure. Here, we sampled 120 individuals of the Chinese egret (Egretta eulophotes), a globally vulnerable species, from four breeding populations across China. We assessed the levels of genetic diversity, selection pressure, and population differentiation at seven TLR loci (TLR1LB, TLR2A, TLR3, TLR4, TLR5, TLR7, and TLR15). Using a variety of metrics (SNPs, heterozygosity, nucleotides, haplotypes), our analyses showed that genetic diversity was lower at 4 of the 7 TLR loci in the vulnerable Chinese egret compared to the more common little egret (Egretta garzetta). The selection test indicated TLRs, except for TLR5, were under purifying selection in TLR evolution, suggesting that low TLR genetic diversity in the Chinese egret may be caused by purifying selection. Moreover, analysis of molecular variance indicated low but significant population differentiation among four populations at all of the TLR loci in this egret. However, some comparisons based on fixation index analyses did not show significant population differentiation, and Bayesian clustering showed admixture. Our finding suggested that these four populations of the Chinese egret in China may be considered a single unit for conservation planning. These results, the new report of TLR genetic diversity in a long-distance migratory vulnerable Ardeid species, will provide fundamental TLR information for further studies on the conservation genetics of the Chinese egret and other Ardeids.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233714PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259618PMC
August 2020

Cyberphysical Human Sexual Behavior Acquisition System (SeBA): Development and Implementation Study in China.

JMIR Mhealth Uhealth 2020 04 3;8(4):e12677. Epub 2020 Apr 3.

School of Information Science, Qufu Normal University, Qufu, China.

Background: Sexual health is one of the principal components of human well-being. Traditional methods for observing human sexual behavior typically adopt manual intervention approaches (eg, interviews). However, the data obtained by such traditional approaches suffer from intrinsic bias and limited sample sizes. Sexual behavioral data that are more reflective of the actual situation can be collected by equipping sex toys with sensors.

Objective: To address the limitations of traditional human sexual behavior data observation methods, a novel cyberphysical system is proposed to capture natural human sexual behavior data in China at the nationwide level.

Methods: A cyberphysical human sexual behavior acquisition system (SeBA) was designed and implemented. SeBA jointly utilizes state of the art information and communication technologies such as smart sex toys, smartphones, and mobile social networks. Smart sex toys enable objective collection of data on human sexual behavior, while the mobile social network provides the possibility of partnered sex in a cyberphysical manner. The objectives and function settings are discussed, and the overall framework of the system architecture is presented.

Results: Operation and privacy policies are proposed and the technical solution of SeBA is described. The effectiveness of SeBA was verified based on analysis of users' human sexual behavior data collected from January 2016 to June 2017. A total of 103,424 solo sexual behaviors were recorded involving 13,047 users, and 61,007 partnered sexual behaviors from 7,140 users were observed. The proportions of males and females in the solo and partnered sex groups were fairly consistent with recent statistics on unmarried individuals in China. We also found that only a small portion of individuals provided information on at least one other attribute besides the required input of gender, such as age, height, location, job, sex preferences, purposes, and interests.

Conclusions: To the best of our knowledge, this is the first study to analyze objective human sexual behavior data at the nationwide level. Although the data are restricted to China, this study can provide insight for further research on human sexual behavior based on the huge amount of data available from wireless smart sex toys worldwide. It is anticipated that findings from such objective big data analyses can help deepen our understanding of sexual behavior, as well as improve sexual health and sexual wellness.
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http://dx.doi.org/10.2196/12677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180515PMC
April 2020

Design, synthesis, and biological evaluation of 3-amino-2-oxazolidinone derivatives as potent quorum-sensing inhibitors of Pseudomonas aeruginosa PAO1.

Eur J Med Chem 2020 May 20;194:112252. Epub 2020 Mar 20.

School of Life Sciences, Jilin University, Changchun, 130012, China. Electronic address:

Due to the increasing resistance of Pseudomonas aeruginosa to most clinically relevant antimicrobials, it is challenging to treat bacterial infection with traditional antibiotics. Quorum sensing can regulate the production of biofilms and virulence factors which are closely related to bacterial resistance. Previously we synthesized a series of oxazolidinone compounds targeting the quorum-sensing transcriptional regulatory protein CviR and ZS-12 showed good activity against Chromobacterium violaceum CV026 quorum-sensing. In this study, eighteen 3-amino-2-oxazolidinone compounds were designed and synthesized using ZS-12 as the lead compound. We initially evaluated the inhibitory activities of novel oxazolidinone compounds against QS using C. violaceum CV026 as a reporter strain. Thirteen compounds showed good activities (IC range 3.69-63.58 μM) and YXL-13 inhibition was the most significant (IC = 3.686 ± 0.5790 μM) against biofilm formation and virulence factors determination of P. aeruginosa PAO1. In vitro, YXL-13 significantly inhibited the formation of PAO1 biofilm (range 42.98%-17.67%), the production of virulence factors (pyocyanin, elastase, rhamnolipid, and protease), and bacterial motility. Moreover, the combination of YXL-13 with an antibiotic (meropenem trihydrate) could significantly improve the antibiotic susceptibility of biofilm P. aeruginosa PAO1 cells. In vivo, YXL-13 significantly prolonged the lifespan of wildtype Caenorhabditis elegans N2 infected by P. aeruginosa PAO1. In conclusion, YXL-13 is a candidate agent for antibiotic-resistant P. aeruginosa PAO1and provides a method for finding new antibacterial drugs.
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http://dx.doi.org/10.1016/j.ejmech.2020.112252DOI Listing
May 2020

A novel classification based on B-cell receptor signal gene expression correlates with prognosis in primary breast diffuse large B-cell lymphoma.

J Cancer 2020 10;11(9):2431-2441. Epub 2020 Feb 10.

Department of Hematology, First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin 150081, Heilongjiang, China.

Primary breast diffuse large B-cell lymphoma (PB-DLBCL), the most common histologic subtype of lymphoid malignancy in the breast, is a clinically and genetically heterogeneous disease that has insufficient systematic studies on the pathological and molecular features, optimal treatment scheme, as well as the prognostic factors. The aim of our study was to identify biomarkers and distinct subtypes of PB-DLBCLs and then evaluate the prognosis of this rare malignant lymphoma. We carried out hierarchical clustering analysis to evaluate protein expressions of potential biomarkers detected by immunohistochemistry staining of samples from 68 PB-DLBCL patients. The gene expression data from TCGA database was obtained to validate the identified clusters. We identified three robust clusters based on the B-cell receptor (BCR) signaling pathway, including two recognized NF-κB-dependent and PI3K-dependent clusters, and a distinct subset of PB-DLBCL with NF-κB-independent anti-apoptotic overexpression plus PI3K signaling, which exhibited an evolving definition and distinctive characters of a cluster group. Furthermore, survival analysis results showed an inferior outcome in NF-κB-dependent cluster patients and favorable survival in the PI3K-dependent cluster patients, suggesting an important predictive value of the three clusters. Our study provided a new perspective for understanding clinical complexity of PB-DLBCLs, and gave evidence for finding targeted biomarkers and strategies.
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http://dx.doi.org/10.7150/jca.39083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066002PMC
February 2020

Pharmacological Characterization of the Novel and Selective 7 Nicotinic Acetylcholine Receptor-Positive Allosteric Modulator BNC375.

J Pharmacol Exp Ther 2020 05 24;373(2):311-324. Epub 2020 Feb 24.

Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey (X.W., C.D., V.G., H.S.L., J.D.V., M.P., X.Z., L.W., C.O.M., M.B., F.T., J.L.D., I.M.B., J.M.U.) and Bionomics Limited, Thebarton, Australia (A.J.H., A.A.G., C.J.C., S.M.O.).

Treatments for cognitive deficits associated with central nervous system (CNS) disorders such as Alzheimer disease and schizophrenia remain significant unmet medical needs that incur substantial pressure on the health care system. The 7 nicotinic acetylcholine receptor (nAChR) has garnered substantial attention as a target for cognitive deficits based on receptor localization, robust preclinical effects, genetics implicating its involvement in cognitive disorders, and encouraging, albeit mixed, clinical data with 7 nAChR orthosteric agonists. Importantly, previous orthosteric agonists at this receptor suffered from off-target activity, receptor desensitization, and an inverted U-shaped dose-effect curve in preclinical assays that limit their clinical utility. To overcome the challenges with orthosteric agonists, we have identified a novel selective 7 positive allosteric modulator (PAM), BNC375. This compound is selective over related receptors and potentiates acetylcholine-evoked 7 currents with only marginal effect on the receptor desensitization kinetics. In addition, BNC375 enhances long-term potentiation of electrically evoked synaptic responses in rat hippocampal slices and in vivo. Systemic administration of BNC375 reverses scopolamine-induced cognitive deficits in rat novel object recognition and rhesus monkey object retrieval detour (ORD) task over a wide range of exposures, showing no evidence of an inverted U-shaped dose-effect curve. The compound also improves performance in the ORD task in aged African green monkeys. Moreover, ex vivo C-NMR analysis indicates that BNC375 treatment can enhance neurotransmitter release in rat medial prefrontal cortex. These findings suggest that 7 nAChR PAMs have multiple advantages over orthosteric 7 nAChR agonists for the treatment of cognitive dysfunction associated with CNS diseases. SIGNIFICANCE STATEMENT: BNC375 is a novel and selective α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator (PAM) that potentiates acetylcholine-evoked α7 currents in in vitro assays with little to no effect on the desensitization kinetics. In vivo, BNC375 demonstrated robust procognitive effects in multiple preclinical models across a wide exposure range. These results suggest that α7 nAChR PAMs have therapeutic potential in central nervous system diseases with cognitive impairments.
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http://dx.doi.org/10.1124/jpet.119.263483DOI Listing
May 2020

Influence of season and social context on male giant panda (Ailuropoda melanoleuca) vocal behaviour.

PLoS One 2019 26;14(11):e0225772. Epub 2019 Nov 26.

Institute for Conservation Research, San Diego Zoo Global, San Diego, California, United States of America.

Documenting the different social and behavioural contexts that vocalisations are produced in remains an important step towards understanding the functional relevance of specific call types in a given species' vocal repertoire. In this study we investigated whether seasonal differences and the presence or absence of male and female conspecifics influence the production of male giant panda vocal signals. To this end, captive male giant pandas were observed during and outside of the breeding season in three social contexts: only male conspecific neighbours, only female conspecific neighbours, and a context with no neighbours. We found that males were more likely to bleat, chirp, honk and moan during the breeding season, and showed a tendency to growl more outside of the reproductive period. The contextual analysis revealed that bleats were more likely to be produced by males when opposite-sexed conspecifics are in close attendance during the breeding season. Conversely, males were more likely to chirp when neighboured by males than females or no neighbours. In addition, males were more likely to honk in the absence of neighbouring conspecifics during the breeding season, raising the possibility that these calls function to signal location and gain the attention of potential mates. Moans were produced more often when male giant pandas had male than female neighbours during the breeding season, which may reflect mild aggression towards these same-sexed rivals, whereas the production of barks and growls did not vary according to season or the sex of conspecific neighbours. Our findings underscore the importance of male giant panda bleats for coordinating reproduction and promoting contact with potential mating partners in this non-gregarious species, and yield fresh insights into the function of male honks that warrant further investigation. They also provide a basis for comparison with free-ranging giant panda vocal behaviour that could potentially inform conservation efforts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225772PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879133PMC
March 2020

Tumor-associated macrophages secrete CC-chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer.

Cancer Sci 2020 Jan 19;111(1):47-58. Epub 2019 Dec 19.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.

Breast cancer is the most prevalent malignancy among women. Although endocrine therapy is effective, the development of endocrine resistance is a major clinical challenge. The tumor microenvironment (TME) promotes tumor malignancy, and tumor-associated macrophages (TAM) within the TME play a crucial role in endocrine resistance. Herein, we aimed to elucidate the relationship between TAM and the endocrine-resistant phenotype of breast cancer. Macrophages were cultured with conditioned medium (CM) from tamoxifen-sensitive (MCF7-S) or -resistant (MCF7-R) MCF7 breast cancer cells. M2 polarization was detected by CD163 immunofluorescence. To determine the effect on endocrine resistance, MCF7 cells were cultured in the supernatant of different TAM, and then treated with tamoxifen. CC-chemokine ligand 2 (CCL2) immunohistochemistry was carried out on pathological sections from 100 patients with invasive estrogen receptor-positive breast cancer. We found that macrophages cultured in the CM of MCF7-S and MCF7-R cells were induced into TAM, with a more obvious M2 polarization in the latter. Tamoxifen resistance was increased by culture in TAM medium. TAM secreted CCL2, which increased endocrine resistance in breast cancer cells through activation of the PI3K/Akt/mTOR signaling pathway. High expression of CCL2 was correlated with infiltration of CD163+macrophages (r = 0.548, P < .001), and patients with high CCL2 expression presented shorter progression-free survival than those with low CCL2 expression (P < .05). We conclude that CCL2 secreted by TAM activates PI3K/Akt/mTOR signaling and promotes an endocrine resistance feedback loop in the TME, suggesting that CCL2 and TAM may be novel therapeutic targets for patients with endocrine-resistant breast cancer.
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http://dx.doi.org/10.1111/cas.14230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942430PMC
January 2020

Plant cell-surface GIPC sphingolipids sense salt to trigger Ca influx.

Nature 2019 08 31;572(7769):341-346. Epub 2019 Jul 31.

Department of Biology, Duke University, Durham, NC, USA.

Salinity is detrimental to plant growth, crop production and food security worldwide. Excess salt triggers increases in cytosolic Ca concentration, which activate Ca-binding proteins and upregulate the Na/H antiporter in order to remove Na. Salt-induced increases in Ca have long been thought to be involved in the detection of salt stress, but the molecular components of the sensing machinery remain unknown. Here, using Ca-imaging-based forward genetic screens, we isolated the Arabidopsis thaliana mutant monocation-induced [Ca increases 1 (moca1), and identified MOCA1 as a glucuronosyltransferase for glycosyl inositol phosphorylceramide (GIPC) sphingolipids in the plasma membrane. MOCA1 is required for salt-induced depolarization of the cell-surface potential, Ca spikes and waves, Na/H antiporter activation, and regulation of growth. Na binds to GIPCs to gate Ca influx channels. This salt-sensing mechanism might imply that plasma-membrane lipids are involved in adaption to various environmental salt levels, and could be used to improve salt resistance in crops.
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http://dx.doi.org/10.1038/s41586-019-1449-zDOI Listing
August 2019

High Expression of Plakoglobin Promotes Metastasis in Invasive Micropapillary Carcinoma of the Breast via Tumor Cluster Formation.

J Cancer 2019 2;10(12):2800-2810. Epub 2019 Jun 2.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, Heilongjiang, China.

Invasive micropapillary carcinoma of the breast (IMPC) is a rare subtype of breast cancer that has a high frequency of lymph node (LN) involvement and metastasis to distant organs. IMPC is characterized by distinct histomorphology and unfavorable prognosis when compared with invasive ductal carcinoma no special type (IDC-NST). However, the underlying molecular mechanisms remain unclear. We reported here that plakoglobin, as a key component in cell adhesion, can promote collective metastasis through facilitating IMPC clusters formation. In comparing the clinicopathological features of 451 IMPC patients and 282 IDC-NST patients, our results showed that tumor emboli were significantly higher in IMPC patients and were associated with a high frequency of metastasis. Both and data showed overexpression of plakoglobin in both the cell membrane and the cytoplasm of IMPC clusters. When plakoglobin was knocked down in IMPC cell models, the tumor cell clusters were depolymerized. Using mouse models, we validated the metastatic potential of tumor clusters was higher than single cells . Further analysis showed that higher expression of plakoglobin was able to promote activation of the PI3K/Akt/Bcl-2 pathway, which might protect the clusters from anoikis. Our data indicate that plakoglobin promotes tumor cluster formation in IMPC and downregulates apoptosis in the cell clusters through activation of PI3K/Akt/Bcl-2 signaling. These results provide a convincing rationale for the high metastatic propensity seen in IMPC.
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http://dx.doi.org/10.7150/jca.31411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584935PMC
June 2019

Molecular design and anticancer activities of small-molecule monopolar spindle 1 inhibitors: A Medicinal chemistry perspective.

Eur J Med Chem 2019 Aug 20;175:247-268. Epub 2019 Apr 20.

School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, China. Electronic address:

As a dual-specificity protein kinase, monopolar spindle 1 (Mps1) is one of the main kinases involved in kinetochore localization and the spindle assembly checkpoint (SAC). Cancer cells often display chromosomal instability, which is a consequence of disfunction of cell cycle checkpoints partially. Mps1 is overexpressed in multiple cancer types to face the pressure from aberrant chromosomes and centrosomes. Therefore, Mps1 is a potential targeting approach to cancer treatment. Several compounds targeting Mps1 have been developed and approved to begin clinical trials for advanced nonhaematologic malignancies treatments, including but not limited to triple negative breast cancer (TNBC) treatment. In this review, we will highlight typical Mps1 inhibitors developed during the last decade and provide a reference for more potential Mps1 inhibitors exploration in the future.
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http://dx.doi.org/10.1016/j.ejmech.2019.04.047DOI Listing
August 2019

Effect of Gua Sha therapy on patients with diabetic peripheral neuropathy: A randomized controlled trial.

Complement Ther Clin Pract 2019 May 25;35:348-352. Epub 2019 Mar 25.

Research Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address:

Objective: To examine the effect of Gua Sha therapy in the treatment of diabetic peripheral neuropathy (DNP).

Design: An open-label randomized controlled study was conducted with usual care as the control (60 subjects in Gua Sha group and 59 subjects in usual care group). Outcome measures included Toronto Clinical Scoring System (TCSS), Vibration Perception Threshold (VPT), Ankle Brachial Index (ABI), and fasting plasma glucose (FPG). There were 12 consecutive sessions of Gua Sha, one session per week.

Results: After the first cycle of Gua Sha intervention, only performance of sensory function measured by the VPT, and peripheral artery disease symptoms by the ABI were statistically significant differences between the two groups (both P values < 0.01), and the total TCSS score and the FPG level were no group differences (P = 0.14, and 0.25, respectively). At the eight-week and 12-week post intervention assessment, Gua Sha therapy significantly reduced severity of neuropathy symptoms, improved performance of sensory function, reduced peripheral artery disease, and better controlled plasma glucose by comparing with the control group (all P values < 0.01). The changes of mean scores of TCSS, VPT, ABI and the plasma glucose levels in the Gua Sha group showed a significant change from baseline to week 12, indicating that Gua Sha therapy induced progressive improvement in the management of DPN symptoms, sensory function, peripheral artery disease and glucose levels. No serious adverse events were reported in either arm. Gua Sha therapy in this study was effective, safe and well tolerated by patients.

Conclusion: Gua Sha therapy appears to be effective at reducing the severity of DPN in a clinically relevant dimension, and at improving other health outcomes in patients with DPN. While this study found that Gua Sha therapy is a promising treatment in reducing the symptoms of patients with DPN, further, larger sample studies are required to confirm the effects of Gua Sha therapy in patients with DPN.
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http://dx.doi.org/10.1016/j.ctcp.2019.03.018DOI Listing
May 2019

Simultaneous Quantitation of Five Bioactive Ingredients in Raw and Processed Fallopia multiflora by Employing UHPLC-Q-TOF-MS.

J Chromatogr Sci 2019 Aug;57(7):618-624

Department of Chinese Medicine Processing, Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, PR China.

Fallopia multiflora is used for treatment of premature graying hair and blood deficiency. In this study, a quantitative method was developed for determination of five bioactive components (emodin, 2,3,5,4'-tetrahydroxy-stilbene- 2-Ο-β-d-glucoside, emodin-8-O-β-d-glucopyranoside, ω-hydroxyemodin and kaempferol) in raw and processed F. multiflora by using ultra-high performance liquid chromatography (UHPLC)-quadrupole time-of-flight mass spectrometry-based method. The sample handling procedure was optimized. Chromatographic separation was carried out on a Thermo Syncronis AQ-C18 UHPLC column with mobile phase consisting of 0.01% aqueous formic acid and acetonitrile. The method was interrogated in terms of linearity, precision, stability and recovery tests. All calibration curves displayed good linearity (R2 > 0.9992). The limit of detection and limit of quantification of these components ranged from 0.01 to 0.03 μg/mL and from 0.03 to 0.07 μg/mL, respectively. The average recoveries of these components were from 98.2 to 102.9% with relative standard deviation values from 0.8 to 2.9% for F. multiflora. The developed method can be applied to quality control of raw and processed F. multiflora.
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http://dx.doi.org/10.1093/chromsci/bmz035DOI Listing
August 2019
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