Publications by authors named "Ning Zhu"

332 Publications

The regulatory role of gibberellin related genes DKGA2ox1 and MIR171f_3 in persimmon dwarfism.

Plant Sci 2021 Sep 1;310:110958. Epub 2021 Jun 1.

College of Horticulture, Nanjing Agricultural University, Nanjing, 210095, PR China. Electronic address:

'Nantongxiaofangshi' (Diospyros kaki Thunb., D. kaki Thunb.) is a local cultivar of persimmon with dwarf-like traits in Jiangsu, China. Closely spaced planting afforded by dwarfism is usually one of the most important ways to promote fruit cultivation and production. However, the understanding of dwarfism in D. kaki Thunb. is very limited at the molecular level, which hinders the further increase of the fruit production. In this work, a persimmon transgenic system was successfully established, and the field experiments of grafting phenotype were carried out. The results showed that D. kaki Thunb. could be used as an interstock to induce dwarfing in grafted scions, and the dwarf character was better when interstock lengths were between 20 and 25 cm. Furthermore, the key genes related to dwarfism in D. kaki Thunb. were screened and verified, and subsequently, the regulatory role of related genes in persimmon dwarfism was figured out. It was found that the gene encoding gibberellin 2-oxidase-1 (DkGA2ox1) involved in GA biosynthesis was associated with the dwarfing in D. kaki Thunb. Overexpression of DkGA2ox1 in Diospyros lotus resulted in a typical dwarf phenotype. Meanwhile, the microRNA data showed that the miR171f_3 demonstrated the active involvement in GA pathway response in persimmon dwarfism. DkGA2ox1 and MIR171f_3, as two highly expressed genes in D. kaki Thunb. interstock, could be used as stimulus signals to affect the content of GA in scion, however, the specific transmission mechanism still needs to be further explored. Ultimately, the bioactive GA level was decreased, resulting in the scion dwarfism.
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http://dx.doi.org/10.1016/j.plantsci.2021.110958DOI Listing
September 2021

Identification and prognostic analysis of the cetuximab resistance-related gene in wild-type metastatic colorectal cancer.

Am J Cancer Res 2021 15;11(6):2769-2781. Epub 2021 Jun 15.

Department of Medical Oncology, Key Labaratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou, Zhejiang, China.

The survival of patients with wild-type metastatic colorectal cancer (mCRC) has improved markedly since the introduction of cetuximab, which is an anti-epidermal growth factor receptor monoclonal antibody. However, not all RAS wild-type patients respond to cetuximab treatment. Although some genetic alterations associated with cetuximab resistance have been identified, they cannot fully explain all cases of cetuximab resistance. Thus, in this research, we aimed to identify new genetic alterations associated with resistance to this treatment. The study retrospectively analyzed 70 patients diagnosed with RAS wild-type mCRC at our hospital between November 2009 and July 2018. First, five progression-free survival (PFS)-longest and 5 PFS-shortest tumor deoxyribonucleic acid were analyzed by whole-exome sequencing (WES) to identify differentially mutated genes. Then, PFS analysis of the 70 patients was used to verify the correlation between the candidate gene and cetuximab sensitivity. Finally, data from public databases were used to further verify the relationship between the mRNA expression level of the candidate gene and cetuximab responsiveness. The WES results indicated : c.2108G > A was a candidate gene mutation related to the effectiveness of cetuximab. Survival analysis suggested : c.2108G > A was associated with rapid disease progression (median PFS time, mutant vs. wild-type: 4.4 months vs. 8.7 months, P = 0.034). Data from the Genomics of Drug Sensitivity in Cancer and the Gene Expression Omnibus databases suggested low REV1 mRNA levels might be related to the poor response of CRC cells and reduced cetuximab efficacy among mCRC patients. In conclusion, expression levels and the : c.2108G > A mutation may be related to cetuximab resistance in wild-type mCRC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263679PMC
June 2021

A new application of terahertz time-domain absorption spectra in luminescent complexes: characterization of the C-Hπ weak interactions in Cu(I) complexes.

Dalton Trans 2021 Jul;50(29):10214-10224

Faculty of Food Science and Technology, Suzhou Polytechnical Institute of Agriculture, Suzhou 215008, P. R. China.

Six Cu(i) complexes, [Cu(2,3-f)(bdppmapy)]BF4 (1), [Cu(2,3-f)(bdppmapy)]ClO4 (2), [Cu(2,3-f)(bdppmapy)]CF3SO3 (3), [Cu(imidazo[4,5-f])(bdppmapy)]BF4 (4), [Cu(imidazo[4,5-f])(bdppmapy)]ClO4 (5), and [Cu(imidazo[4,5-f])(bdppmapy)]CF3SO3·MeOH (6·MeOH) (bdppmapy = N,N-bis[(diphenylphosphino)methyl]-2-pyridinamine, 2,3-f = pyrazine[2,3-f][1,10]-phenanthroline, and imidazo[4,5-f] = 1H-imidazo[4,5-f][1,10]-phenanthroline), have been synthesized to explore the effects of counteranions on their crystal structures, photophysical properties, and terahertz (THz) spectra. Time-dependent density functional theory (TD-DFT) shows that the luminescence performance of these complexes is attributed to the metal-to-ligand charge transfer (MLCT) in combination with ligand-to-ligand charge transfer (LLCT). In complexes 1-3, the characteristic peak at 1.4 THz is mainly related to the C-Hπ interaction formed by the H atom on the 4#/5# position of 2,3-f and the benzene ring from the bdppmapy on the adjacent asymmetric unit. The common C-Hπ interaction enhances the rigidity of the structure and has non-negligible influence on the photoluminescence quantum yields (PLQYs): the stronger the C-Hπ interaction is, the higher the quantum yield (QY) is. In complexes 4-6, similar absorption peaks (1.10-1.30 THz) are mainly related to the C-Hπ interactions, and strong absorption peaks (1.50-1.90 THz) are affected by the typical hydrogen bonds N-HF/O and O-HO. These results show that some weak interactions can be characterized by THz time-domain spectroscopy (THz-TDS). So, the THz spectroscopy method would make it possible to tune some of the weak interactions in complex structures to regulate the luminescence of materials.
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http://dx.doi.org/10.1039/d1dt01023aDOI Listing
July 2021

Increased enzyme activities and fungal degraders by Gloeophyllum trabeum inoculation improve lignocellulose degradation efficiency during manure-straw composting.

Bioresour Technol 2021 Oct 19;337:125427. Epub 2021 Jun 19.

School of Environment and Safety Engineering, Jiangsu University, Zhenjiang 212013, China.

The present study investigated the effect of brown-rot fungus Gloeophyllum trabeum inoculation on lignocellulose degradation, enzyme activities and fungal community during co-composting of swine manure and wheat straw. G. trabeum inoculation shortened the maturation period of composting from 39 to 30 days. Composting piles inoculated with G. trabeum showed a higher degree of maturity as indicated by 31.6% lower C/N ratio and 29.4% higher GI. The decomposition rate of cellulose, hemicellulose and lignin was increased by 181.1%, 49.4% and 109.4%, respectively, due to higher activities of filter paper enzyme, xylanase, manganese peroxidase and laccase. Redundancy analysis showed that inoculating G. trabeum influenced the succession of fungal communities by changing the main physicochemical parameters, resulting in the increased relative abundance of Aspergillus, Mycothermus and Melanocarpus. Pearson correlation analysis indicated that more dominant fungal genera were involved in the production of lignocellulose-degrading enzymes after G. trabeum inoculation.
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http://dx.doi.org/10.1016/j.biortech.2021.125427DOI Listing
October 2021

The copper-catalyzed synthesis of dihydrooxazoles from α,β-unsaturated ketoximes and activated ketones.

Chem Commun (Camb) 2021 Jul 1;57(59):7272-7275. Epub 2021 Jul 1.

College of Biotechnology and Pharmaceutical Engineering, State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, 30 Puzhu Rd S, Nanjing, 211816, China.

The first copper-catalyzed [3+2]-type condensation reaction of α,β-unsaturated ketoximes with activated ketones has been described for the synthesis of dihydrooxazoles, especially trifluoromethyl-decorated dihydrooxazoles. Notable features of this method include its broad substrate scope, good functional group tolerance, and simple operation.
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http://dx.doi.org/10.1039/d1cc02422aDOI Listing
July 2021

MET and FASN as Prognostic Biomarkers of Triple Negative Breast Cancer: A Systematic Evidence Landscape of Clinical Study.

Front Oncol 2021 27;11:604801. Epub 2021 May 27.

Hunan University of Medicine, Huaihua, China.

Background: To know the expression of Mesenchymal-Epithelial Transition factor (MET) and Fatty Acid Synthase (FASN) in Triple Negative Breast Cancer (TNBC) patients, as well as its relationship with clinical pathological characteristic and prognosis.

Methods: we used immunohistochemistry staining to detect the expression of MET and FASN for those 218 TNBC patients, and analyze their relationship with the clinical pathological characteristic and prognosis.

Results: 130 and 65 out of 218 TNBC patients were positive for MET in the cancer and adjacent tissues respectively. 142 and 30 out of 218 TNBC patients were positive for FASN in the cancer and adjacent tissues respectively. Positive expression of MET and FASN were significantly correlated with lymph node metastasis, pathological TNM, and pathological Stage. In addition, the positive expression of MET and FASN were correlated with recurrence and metastasis. The combined use of MET and FASN can better predict the survival condition.

Conclusions: Our results indicated that MET and FASN showed good predictive ability for TNBC. Combined use of MET and FASN were recommended in order to make a more accurate prognosis for TNBC.
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http://dx.doi.org/10.3389/fonc.2021.604801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190390PMC
May 2021

CO2 Improved Synthesis of Benzimidazole with the Catalysis of a New Calcium 4-Amino-3-hydroxybenzoate.

Acta Chim Slov 2021 Mar;68(1):205-211

In this paper, we explored the synthesis of benzimidazole by the reaction of DMF and o-phenylenediamine. In the process of catalyst screening, we found that 4-amino-3-hydroxybenzoic acid, benzoic acid, and benzene-1,3,5-tricarboxylic acid could catalyze the reaction. Moreover, the calcium 4-amino-3-hydroxybenzoate and CO2 could more effectively catalyze the reaction, the synergistic effect of CO2 and 4-amino-3-hydroxybenzoic acid calcium salt can increase the yield of benzimidazole from 28% to 94%.
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March 2021

Noninvasive Three-Dimensional and Characterization of Bioprinted Hydrogel Scaffolds Using the X-ray Propagation-Based Imaging Technique.

ACS Appl Mater Interfaces 2021 Jun 26;13(22):25611-25623. Epub 2021 May 26.

Department of Mechanical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, SK S7N 5A9, Canada.

Hydrogel-based three-dimensional (3D) bioprinting has been illustrated as promising to fabricate tissue scaffolds for regenerative medicine. Notably, bioprinting of hydrated and soft 3D hydrogel scaffolds with desired structural properties has not been fully achieved so far. Moreover, due to the limitations of current imaging techniques, assessment of bioprinted hydrogel scaffolds is still challenging, yet still essential for scaffold design, fabrication, and longitudinal studies. This paper presents our study on the bioprinting of hydrogel scaffolds and on the development of a novel noninvasive imaging method, based on synchrotron propagation-based imaging with computed tomography (SR-PBI-CT), to study the structural properties of hydrogel scaffolds and their responses to environmental stimuli both and . Hydrogel scaffolds designed with varying structural patterns were successfully bioprinted through rigorous printing process regulations and then imaged by SR-PBI-CT within physiological environments. Subjective to controllable compressive loadings, the structural responses of scaffolds were visualized and characterized in terms of the structural deformation caused by the compressive loadings. Hydrogel scaffolds were later implanted in rats as nerve conduits for SR-PBI-CT imaging, and the obtained images illustrated their high phase contrast and were further processed for the 3D structure reconstruction and quantitative characterization. Our results show that the scaffold design and printing conditions play important roles in the printed scaffold structure and mechanical properties. More importantly, our obtained images from SR-PBI-CT allow us to visualize the details of hydrogel 3D structures with high imaging resolution. It demonstrates unique capability of this imaging technique for noninvasive, characterization of 3D hydrogel structures pre- and post-implantation in diverse physiological milieus. The established imaging platform can therefore be utilized as a robust, high-precision tool for the design and longitudinal studies of hydrogel scaffold in tissue engineering.
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http://dx.doi.org/10.1021/acsami.1c02297DOI Listing
June 2021

Peroxisome proliferator-activated receptor γ improves pemetrexed therapeutic efficacy in non-squamous non-small cell lung cancer.

Am J Transl Res 2021 15;13(4):2296-2307. Epub 2021 Apr 15.

Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University Shanghai, China.

Objective: The folic acid analog pemetrexed (PMX) is recommended for the first-line chemotherapy for advanced non-squamous non-small cell lung cancer (NSCLC). However, the mechanisms underlying PMX cytotoxicity in NSCLC remain to be fully explored.

Methods: PMX effect was evaluated in a urethane-induced lung adenocarcinoma mouse model. The interaction between PMX and intracellular proteins, particularly peroxisome proliferator-activated receptor γ (PPARγ), was investigated. The role of PPARγ in mediating pemetrexed cytotoxicity was investigated using NSCLC cell lines, mouse models and clinical specimens.

Results: This study found that PPARγ expression was correlated with prolonged progression-free survival in NSCLC patients. PPARγ downregulated hypoxanthine-guanine phosphoribosyl transferase (HGPRT), a key enzyme for nucleotide salvage synthesis, thereby sensitizing cells to PMX inhibition on nucleotide de novo synthesis. PMX was also a candidate partial agonist of PPARγ, and PMX-activated PPARγ bound to NF-κB and transcriptionally suppressed the NF-κB target gene, . PMX inhibited tumor growth by activating PPARγ in a urethane-induced lung cancer model characterized by elevated NF-κB activity.

Conclusion: PPARγ improves pemetrexed therapeutic efficacy in non-squamous NSCLC. The cytotoxicity effect of PMX can be synergized by activating PPARγ and thereby inhibiting NF-κB pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129360PMC
April 2021

An Approach for Individualized Cochlear Frequency Mapping Determined from 3D Synchrotron Radiation Phase-Contrast Imaging.

IEEE Trans Biomed Eng 2021 May 13;PP. Epub 2021 May 13.

Objective: Cochlear implants are traditionally programmed to stimulate according to a generalized frequency map, where individual anatomic variability is not considered when selecting the centre frequency of stimulation of each implant electrode. However, high variability in cochlear size and spatial frequency distributions exist among individuals. Generalized cochlear implant frequency maps can result in large pitch perception errors and reduced hearing outcomes for cochlear implant recipients. The objective of this work was to develop an individualized frequency mapping technique for the human cochlea to allow for patient-specific cochlear implant stimulation.

Methods: Ten cadaveric human cochleae were scanned using synchrotron radiation phase-contrast imaging (SR-PCI) combined with computed tomography (CT). For each cochlea, ground truth angle-frequency measurements were obtained in three-dimensions using the SR-PCI CT data. Using an approach designed to minimize perceptual error in frequency estimation, an individualized frequency function was determined to relate angular depth to frequency within the cochlea.

Results: The individualized frequency mapping function significantly reduced pitch errors in comparison to the current gold standard generalized approach.

Conclusion And Significance: This paper presents for the first time a cochlear frequency map which can be individualized using only the angular length of cochleae. This approach can be applied in the clinical setting and has the potential to revolutionize cochlear implant programming for patients worldwide.
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http://dx.doi.org/10.1109/TBME.2021.3080116DOI Listing
May 2021

Guard cell redox proteomics reveals a role of lipid transfer protein in plant defense.

J Proteomics 2021 06 30;242:104247. Epub 2021 Apr 30.

Department of Biology, University of Florida Genetics Institute, Gainesville, FL 32610, USA; Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL 32610, USA; Proteomics and Mass Spectrometry, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL 32610, USA. Electronic address:

Redox-based post-translational modifications (PTMs) involving protein cysteine residues as redox sensors are important to various physiological processes. However, little is known about redox-sensitive proteins in guard cells and their functions in stomatal immunity. In this study, we applied an integrative protein labeling method cysTMTRAQ, and identified guard cell proteins that were altered by thiol redox PTMs in response to a bacterial flagellin peptide flg22. In total, eight, seven and 20 potential redox-responsive proteins were identified in guard cells treated with flg22 for 15, 30 and 60 min, respectively. The proteins fall into several functional groups including photosynthesis, lipid binding, oxidation-reduction, and defense. Among the proteins, a lipid transfer protein (LTP)-II was confirmed to be redox-responsive and involved in plant resistance to Pseudomonas syringe pv. tomato DC3000. This study not only creates an inventory of potential redox-sensitive proteins in flg22 signal transduction in guard cells, but also highlights the biological relevance of the lipid transfer protein in plant defense against bacterial pathogens. SIGNIFICANCE: Protein redox modifications play important roles in many physiological processes. However, redox proteomics has rarely been studied in plant single cell-types. In this study, isobaric tandem mass tag-based redox proteomics technology was applied to discover redox-sensitive proteins and corresponding cysteine residues in guard cell response to a bacterial flagellin peptide flg22. Many redox-responsive proteins related to photosynthesis, lipid binding, oxidation-reduction, and defense were identified. Using reverse genetics and biochemical analyses, a lipid transfer protein was functionally characterized to be involved in plant defense against pathogens. The study highlights the utility of redox proteomics in discovering new proteins and redox modifications in important stomatal guard cell functions. Furthermore, detailed functional characterization demonstrates the biological relevance of the redox-responsive lipid transfer protein in plant pathogen defense.
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http://dx.doi.org/10.1016/j.jprot.2021.104247DOI Listing
June 2021

Emergence of additional drug resistance during treatment of multidrug-resistant tuberculosis in China: a prospective cohort study.

Clin Microbiol Infect 2021 Apr 23. Epub 2021 Apr 23.

Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, China. Electronic address:

Objectives: Little is known about how additional second-line drug resistance emerges during multidrug-resistant tuberculosis (MDR-TB) treatment. The present study aimed to investigate the influence of microevolution, exogenous reinfection and mixed infection on second-line drug resistance during the recommended 2-year MDR-TB treatment.

Methods: Individuals with MDR-TB were enrolled between 2013 and 2016 in a multicentre prospective observational cohort study and were followed up for 2 years until treatment completion. Whole-genome sequencing (WGS) was applied for serial Mycobacterium tuberculosis isolates from study participants throughout the treatment, to study the role of microevolution, exogenous reinfection and mixed infection in the development of second-line drug resistance.

Results: Of the 286 enrolled patients with MDR-TB, 63 (22.0%) M. tuberculosis isolates developed additional drug resistance during the MDR-TB treatment, including 5 that fulfilled the criteria of extensively drug-resistant TB. By comparing WGS data of serial isolates retrieved from the patients throughout treatment, 41 (65.1%) of the cases of additional second-line drug resistance were the result of exogenous reinfection, 18 (28.6%) were caused by acquired drug resistance, i.e. microevolution, while the remaining 4 (6.3%) were caused by mixed infections with drug-resistant and drug-susceptible strains. In multivariate analysis, previous TB treatment (adjusted hazard ratio (aHR) 2.51, 95% CI 1.51-4.18), extensive disease on chest X-ray (aHR 3.39, 95% CI 2.03-5.66) and type 2 diabetes mellitus (aHR 4.00, 95% CI 2.22-7.21) were independent risk factors associated with the development of additional second-line drug resistance.

Conclusions: A large proportion of additional second-line drug resistance emerging during MDR-TB treatment was attributed to exogenous reinfection, indicating the urgency of infection control in health facilities as well as the need for repeated drug susceptibility testing throughout MDR-TB treatment.
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http://dx.doi.org/10.1016/j.cmi.2021.04.001DOI Listing
April 2021

Aeration of the Human Prussak's Space: A 3D Synchrotron Imaging Study.

Otol Neurotol 2021 08;42(7):e894-e904

Department of Surgical Sciences, Otorhinolaryngology and Head and Neck Surgery, Uppsala University.

Objectives: Prussak's space (PS) is an intricate middle ear region which may play an essential role in the development of middle ear disease. The three-dimensional (3D) anatomy of the human PS and its drainage routes remain relatively unknown. Earlier studies have histologically analyzed PS, by micro-dissection and endoscopy. Here, we used synchrotron-radiation phase-contrast imaging (SR-PCI), 3D reconstructions, and modeling to study the framework of the human PS, including aeration pathways. It may lead to increased understanding of development of middle ear pathology.

Design: Nine human temporal bone specimens underwent in-line SR-PCI at the Canadian Light Source in Saskatoon, Saskatchewan, Canada. Data were processed with volume-rendering software to create 3D reconstructions using scalar opacity mapping and segmentations to visualize its walls in fixed, undecalcified human temporal bones.

Results: The PS was found to be an irregular, variably shaped chamber with different aeration systems. Three different drainage pathways were found: 1) via the posterior malleolar pouch of von Tröltsch in seven of nine ears; 2) directly posterior-inferior into the mesotympanum medial to the posterior malleolar pouch in one ear; and 3) anteriorly in another. The posterior-inferior communications depended on the anatomy of the posterior malleolar fold. In one bilateral case, the aeration differed between the ears. Earlier descriptions of upper ventilation routes between the PS and the epitympanic spaces could not be substantiated.

Conclusions: The 3D anatomy of the membrane folds organizing the PS in humans was demonstrated for the first time using in-line SR-PCI. The PS was always aerated into the mesotympanum, suggesting its relative independence of attic ventilation. The impact of its various drainage routes on middle ear ventilation and disease were discussed.
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http://dx.doi.org/10.1097/MAO.0000000000003127DOI Listing
August 2021

Timing of Mouse Molar Formation Is Independent of Jaw Length Including Retromolar Space.

J Dev Biol 2021 Mar 12;9(1). Epub 2021 Mar 12.

Department of Anatomy, Physiology & Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.

For humans and other mammals to eat effectively, teeth must develop properly inside the jaw. Deciphering craniodental integration is central to explaining the timely formation of permanent molars, including third molars which are often impacted in humans, and to clarifying how teeth and jaws fit, function and evolve together. A factor long-posited to influence molar onset time is the jaw space available for each molar organ to form within. Here, we tested whether each successive molar initiates only after a minimum threshold of space is created via jaw growth. We used synchrotron-based micro-CT scanning to assess developing molars in situ within jaws of C57BL/6J mice aged E10 to P32, encompassing molar onset to emergence. We compared total jaw, retromolar and molar lengths, and molar onset times, between upper and lower jaws. Initiation time and developmental duration were comparable between molar upper and lower counterparts despite shorter, slower-growing retromolar space in the upper jaw, and despite size differences between upper and lower molars. Timing of molar formation appears unmoved by jaw length including space. Conditions within the dental lamina likely influence molar onset much more than surrounding jaw tissues. We theorize that molar initiation is contingent on sufficient surface area for the physical reorganization of dental epithelium and its invagination of underlying mesenchyme.
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http://dx.doi.org/10.3390/jdb9010008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006249PMC
March 2021

Sodium Selenite Attenuates Balloon Injury-Induced and Monocrotaline-Induced Vascular Remodeling in Rats.

Front Pharmacol 2021 15;12:618493. Epub 2021 Mar 15.

Department of Cardiology, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Municipal Central Hospital, Lishui, China.

Vascular remodeling (VR), induced by the massive proliferation and reduced apoptosis of vascular smooth muscle cells (VSMCs), is primarily responsible for many cardiovascular conditions, such as restenosis and pulmonary arterial hypertension. Sodium selenite (SSE) is an inorganic selenium, which can block proliferation and stimulate apoptosis of tumor cells; still, its protective effects on VR remains unknown. In this study, we established rat models with carotid artery balloon injury and monocrotaline induced pulmonary arterial hypertension and administered them SSE (0.25, 0.5, or 1 mg/kg/day) orally by feeding tube for 14 consecutive days. We found that SSE treatment greatly ameliorated the development of VR as evidenced by an improvement of its characteristic features, including elevation of the ratio of carotid artery intimal area to medial area, right ventricular hypertrophy, pulmonary arterial wall hypertrophy and right ventricular systolic pressure. Furthermore, PCNA and TUNEL staining of the arteries showed that SSE suppressed proliferation and enhanced apoptosis of VSMCs in both models. Compared with the untreated VR rats, lower expression of PCNA and CyclinD1, but higher levels of Cleaved Caspase-3 and Bax/Bcl-2 were observed in the SSE-treated rats. Moreover, the increased protein expression of MMP2, MMP9, p-AKT, p-ERK, p-GSK3β and β-catenin that occurred in the VR rats were significantly inhibited by SSE. Collectively, treatment with SSE remarkably attenuates the pathogenesis of VR, and this protection may be associated with the inhibition of AKT and ERK signaling and prevention of VSMC's dysfunction. Our study suggest that SSE is a potential agent for treatment of VR-related diseases.
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http://dx.doi.org/10.3389/fphar.2021.618493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005533PMC
March 2021

MiR-877 suppresses tumor metastasis via regulating FOXM1 in ovarian cancer.

J BUON 2021 Jan-Feb;26(1):229-234

Department of Oncology, Dongda Hospital, Shanxian, Heze, China.

Purpose: Ovarian cancer (OC) is a serious threat to women's life. OC is insidious and lacks early diagnosis and effective treatment. Therefore, it is vital to look for new therapeutic targets and biomarkers.

Methods: MicroRNA-877 (miR-877) expression level in OC was accessed via quantitative real-time polymerase chain reaction (qRT-PCR). Transwell assay, Matrigel assay and wound healing assay were used to analyze the ability of miR-877 on cell migration and invasion. Luciferase reporter assay was employed for verification the target of miR-877. Western blotting was taken in for the determination of the expression level of FOXM1.

Results: MiR-877 had low expression level in OC tissues and cell lines. MiR-877 over-expression induced inhibition of cell migration and invasion. FOXM1 was a direct target of miR-877. MiR-877 restrained cell migration and invasion by negatively regulating FOXM1 expression in OC.

Conclusions: Our research elucidated that miR-877 played a role of tumor suppressor in OC by negatively regulating FOXM1 which may bring a novel insight into new molecular therapeutic targets and biomarkers for OC.
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March 2021

Copper-catalyzed regioselective [3+2] annulation of malonate-tethered acyl oximes with isatins.

Chem Commun (Camb) 2021 Apr 8;57(27):3379-3382. Epub 2021 Mar 8.

College of Biotechnology and Pharmaceutical Engineering, State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, 30 Puzhu Rd S, Nanjing, 211816, China.

A copper-catalyzed regioselective [3+2] annulation of malonate-tethered acyl oximes with isatins was developed, affording valuable 2,3-dihydrooxazole-spirooxindoles in moderate to good yields with excellent diastereoselectivity. The reaction sequence involves Cu(i) initiated N-O bond cleavage, 1,5-HAT and C-N bond formation. The protocol features mild reaction conditions and broad substrate scope. DFT calculations demonstrated that the [3+2] annulation pathway is more energetically favourable in both kinetics and thermodynamics.
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http://dx.doi.org/10.1039/d0cc07995bDOI Listing
April 2021

Exploratory Investigation of Intestinal Structure and Function after Stroke in Mice.

Mediators Inflamm 2021 15;2021:1315797. Epub 2021 Feb 15.

Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.

Stroke is the second leading cause of death worldwide. Patients who have a stroke are susceptible to many gastrointestinal (GI) complications, such as dysphagia, GI bleeding, and fecal incontinence. However, there are few studies focusing on the GI tract after stroke. The current study is to investigate the changes of intestinal structure and function in mice after ischemic stroke. Ischemic stroke was made as a disease model in mice, in which brain and ileal tissues were collected for experiments on the 1 and 7 day after stroke. Intestinal motility of mice was inhibited, and intestinal permeability was increased after stroke. Hematoxylin-eosin (HE) staining showed the accumulation of leucocytes in the intestinal mucosa. Myeloperoxidase (MPO) activity and inflammatory proteins (nuclear factor kappa-B (NF-B), inducible nitric oxide synthase (iNOS)) in the small intestine were significantly increased in mice after stroke. The expression of tight junction (TJ) proteins (zonula occludens-1 (ZO-1), occludin, and claudin-1) was downregulated, and transmission electron microscopy (TEM) showed broken TJ of the intestinal mucosa after stroke. Glial fibrillary acidic protein (GFAP) and the apoptosis-associated proteins (tumor necrosis factor (TNF-), caspase-3, and cleaved caspase-3) were notably upregulated as well. Ischemic stroke led to negative changes on intestinal structure and function. Inflammatory mediators and TNF--induced death receptor signaling pathways may be involved and disrupt the small intestinal barrier function. These results suggest that stroke patients should pay attention to GI protection.
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http://dx.doi.org/10.1155/2021/1315797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902147PMC
February 2021

Three-dimensional tonotopic mapping of the human cochlea based on synchrotron radiation phase-contrast imaging.

Sci Rep 2021 Feb 24;11(1):4437. Epub 2021 Feb 24.

School of Biomedical Engineering, Western University, 1152 Richmond St, London, ON, N6A 3K7, Canada.

The human cochlea transforms sound waves into electrical signals in the acoustic nerve fibers with high acuity. This transformation occurs via vibrating anisotropic membranes (basilar and tectorial membranes) and frequency-specific hair cell receptors. Frequency-positions can be mapped within the cochlea to create a tonotopic chart which fits an almost-exponential function with lowest frequencies positioned apically and highest frequencies positioned at the cochlear base (Bekesy 1960, Greenwood 1961). To date, models of frequency positions have been based on a two-dimensional analysis with inaccurate representations of the cochlear hook region. In the present study, the first three-dimensional frequency analysis of the cochlea using dendritic mapping to obtain accurate tonotopic maps of the human basilar membrane/organ of Corti and the spiral ganglion was performed. A novel imaging technique, synchrotron radiation phase-contrast imaging, was used and a spiral ganglion frequency function was estimated by nonlinear least squares fitting a Greenwood-like function (F = A (10 - K)) to the data. The three-dimensional tonotopic data presented herein has large implications for validating electrode position and creating customized frequency maps for cochlear implant recipients.
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http://dx.doi.org/10.1038/s41598-021-83225-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904830PMC
February 2021

Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology.

Front Pharmacol 2020 2;11:591337. Epub 2021 Feb 2.

Department of Cardiology, The Third Affiliated Hospital of Shanghai University, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, China.

Vitamin C (ascorbic acid) is a nutrient used to treat cardiovascular disease (CVD). However, the pharmacological targets of vitamin C and the mechanisms underlying the therapeutic effects of vitamin C on CVD remain to be elucidated. In this study, we used network pharmacology approach to investigate the pharmacological mechanisms of vitamin C for the treatment of CVD. The core targets, major hubs, enriched biological processes, and key signaling pathways were identified. A protein-protein interaction network and an interaction diagram of core target-related pathways were constructed. Three core targets were identified, including phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, signal transducer and activator of transcription-3 (STAT3), and prothrombin. The GO and KEGG analyses identified top 20 enriched biological processes and signaling pathways involved in the therapeutic effects of vitamin C on CVD. The JAK-STAT, STAT, PD1, EGFR, FoxO, and chemokines signaling pathways may be highly involved in the protective effects of vitamin C against CVD. In conclusion, our bioinformatics analyses provided evidence on the possible therapeutic mechanisms of vitamin C in CVD treatment, which may contribute to the development of novel drugs for CVD.
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http://dx.doi.org/10.3389/fphar.2020.591337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884818PMC
February 2021

Photonic generation of quadruple bandwidth dual-band dual-chirp microwave waveforms with immunity to power fading.

Opt Lett 2021 Feb;46(4):868-871

A photonic method to generate and transmit quadruple bandwidth dual-band dual-chirp microwave waveforms with immunity to fiber chromatic dispersion induced power fading is proposed and experimentally demonstrated, which is suitable for Doppler blind-speed elimination, small target detection, and multiband detection in multiband radar systems. A dual-polarization dual-parallel Mach-Zehnder modulator is utilized to realize carrier-suppressed harmonic single-sideband modulation of a radio frequency carrier and carrier-suppressed DSB modulation of a baseband single-chirped waveform at two orthogonal polarization states. After photoelectronic conversion, dual-band bandwidth-quadrupling dual-chirp waveforms are generated. Moreover, different from traditional DSB-based dual-chirp signal generation, the generated dual-chirp microwave waveforms can be transmitted over fiber without power fading, which is significant in dual-band radars for one to multiple base station transmissions.
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http://dx.doi.org/10.1364/OL.416984DOI Listing
February 2021

PTPL1 suppresses lung cancer cell migration via inhibiting TGF-β1-induced activation of p38 MAPK and Smad 2/3 pathways and EMT.

Acta Pharmacol Sin 2021 Aug 3;42(8):1280-1287. Epub 2021 Feb 3.

Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Epithelial-mesenchymal transition (EMT) enables dissemination of neoplastic cells and onset of distal metastasis of primary tumors. However, the regulatory mechanisms of EMT by microenvironmental factors such as transforming growth factor-β (TGF-β) remain largely unresolved. Protein tyrosine phosphatase L1 (PTPL1) is a non-receptor protein tyrosine phosphatase that plays a suppressive role in tumorigenesis of diverse tissues. In this study we investigated the role of PTPL1/PTPN13 in metastasis of lung cancer and the signaling pathways regulated by PTPL1 in terms of EMT of non-small cell lung cancer (NSCLC) cells. We showed that the expression of PTPL1 was significantly downregulated in cancerous tissues of 23 patients with NSCLC compared with adjacent normal tissues. PTPL1 expression was positively correlated with overall survival of NSCLC patients. Then we treated A549 cells in vitro with TGF-β1 (10 ng/mL) and assessed EMT. We found that knockdown of PTPL1 enhanced the migration and invasion capabilities of A549 cells, through enhancing TGF-β1-induced EMT. In nude mice bearing A549 cell xenografts, knockdown of PTPL1 significantly promoted homing of cells and formation of tumor loci in the lungs. We further revealed that PTPL1 suppressed TGF-β-induced EMT by counteracting the activation of canonical Smad2/3 and non-canonical p38 MAPK signaling pathways. Using immunoprecipitation assay we demonstrated that PTPL1 could bind to p38 MAPK, suggesting that p38 MAPK might be a direct substrate of PTPL1. In conclusion, these results unravel novel mechanisms underlying the regulation of TGF-β signaling pathway, and have implications for prognostic assessment and targeted therapy of metastatic lung cancer.
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http://dx.doi.org/10.1038/s41401-020-00596-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285377PMC
August 2021

Prognostic factors for postoperative survival in melanoma patients with bone metastasis.

Medicine (Baltimore) 2021 Jan;100(4):e24558

Department of Orthopedics, Taizhou University Affiliated Municipal Hospital, Taizhou, Zhejiang.

Abstract: Melanoma can spread to the bone by metastasis and is relevant to a poor outcome. However, because of the rarity of melanoma patients with bone metastasis, the prognostic postoperative survival factors of them have not been elucidated. The aim of this special population-based cohort was to elucidate the prognostic factors associated with postoperative survival. The Surveillance, Epidemiology, and End Results database was used to extract postoperative survival data relating to patients with melanoma and bone metastasis at diagnosis between 2010 and 2016, along with data on a range of potential postoperative prognostic factors. We then investigated the potential postoperative prognostic roles of these factors using a Cox regression model and the Kaplan-Meier analysis. In all, the Surveillance, Epidemiology, and End Results database included 186 cases. Regarding overall survival, the 1-, 3-, and 5-year overall survival rates for the entire cohort were 36.2%, 15.4%, and 9.5%, respectively. Regarding cancer-specific survival, the 1-, 3-, and 5-year cancer-specific survival rates were 42.0%, 23.2%, and 16.6%, respectively. Within a cohort of melanoma patients with bone metastasis after surgery, our analysis showed that a smaller tumor size and the lack of metastases at other sites were predictors of survival.
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http://dx.doi.org/10.1097/MD.0000000000024558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850704PMC
January 2021

Facial Expression Recognition With Machine Learning and Assessment of Distress in Patients With Cancer.

Oncol Nurs Forum 2021 01;48(1):81-93

West China Hospital.

Objectives: To estimate the effectiveness of combining facial expression recognition and machine learning for better detection of distress.

Sample & Setting: 232 patients with cancer in Sichuan University West China Hospital in Chengdu, China.

Methods & Variables: The Distress Thermometer (DT) and Hospital Anxiety and Depression Scale (HADS) were used as instruments. The HADS included scores for anxiety (HADS-A), depression (HADS-D), and total score (HADS-T). Distressed patients were defined by the DT cutoff score of 4, the HADS-A cutoff score of 8 or 9, the HADS-D cutoff score of 8 or 9, or the HADS-T cutoff score of 14 or 15. The authors applied histogram of oriented gradients to extract facial expression features from face images, and used a support vector machine as the classifier.

Results: The facial expression features showed feasible differentiation ability on cases classified by DT and HADS.

Implications For Nursing: Facial expression recognition could serve as a supplementary screening tool for improving the accuracy of distress assessment and guide strategies for treatment and nursing.
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http://dx.doi.org/10.1188/21.ONF.81-93DOI Listing
January 2021

Establishment and validation of a risk model for prediction of in-hospital mortality in patients with acute ST-elevation myocardial infarction after primary PCI.

BMC Cardiovasc Disord 2020 12 9;20(1):513. Epub 2020 Dec 9.

Department of Cardiology, Cangzhou Central Hospital, Cangzhou, Hebei, China.

Background: Currently, how to accurately determine the patient prognosis after a percutaneous coronary intervention (PCI) remains unclear and may vary among populations, hospitals, and datasets. The aim of this study was to establish a prediction model of in-hospital mortality risk after primary PCI in patients with acute ST-elevated myocardial infarction (STEMI).

Methods: This was a multicenter, observational study of patients with acute STEMI who underwent primary PCI. The outcome was in-hospital mortality. The least absolute shrinkage and selection operator (LASSO) method was used to select the features that were the most significantly associated with the outcome. A regression model was built using the selected variables to select the significant predictors of mortality. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the performance of the nomogram.

Results: Totally, 1169 and 316 patients were enrolled in the training and validation sets, respectively. Fourteen predictors were identified by the LASSO analysis: sex, Killip classification, left main coronary artery disease (LMCAD), grading of thrombus, TIMI classification, slow flow, application of IABP, administration of β-blocker, ACEI/ARB, symptom-to-door time (SDT), symptom-to-balloon time (SBT), syntax score, left ventricular ejection fraction (LVEF), and CK-MB peak. The mortality risk prediction nomogram achieved good discrimination for in-hospital mortality (training set: C-statistic = 0.987; model calibration: P = 0.722; validation set: C-statistic = 0.984, model calibration: P = 0.669). Area under the curve (AUC) values for the training and validation sets are 0.987 (95% CI: 0.981-0.994, P = 0.003) and 0.990 (95% CI: 0.987-0.998, P = 0.007), respectively. DCA shows that the nomogram can achieve good net benefit.

Conclusions: A novel nomogram was developed and is a simple and accurate tool for predicting the risk of in-hospital mortality in patients with acute STEMI who underwent primary PCI.
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http://dx.doi.org/10.1186/s12872-020-01804-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727168PMC
December 2020

Application of artificial neural networks to predict multiple quality of dry-cured ham based on protein degradation.

Food Chem 2021 May 9;344:128586. Epub 2020 Nov 9.

China Meat Research Center, Beijing 100068, China; Beijing Key Laboratory of Meat Processing Technology, Beijing 100068, China. Electronic address:

This study investigated protein degradation and quality changes during the processing of dry-cured ham, and then established the multiple quality prediction model based on protein degradation. From the raw material to the curing period, proteolysis index of external samples were higher than that of internal samples, however, the difference gradually decreased from the drying period to the maturing period. Protein degradation can be used as indicators for controlling quality of the hams. With protein degradation index as input variables, the back propagation-artificial neural networks (BP-ANN) models were optimized, with training function of trainlm, transfer function of logsig in input-hidden layer and tansig in hidden-output layer, and 20 hidden layer neurons. Furthermore, the relative errors of predictive data and experimental data of 12 samples were approximately 0 with the BP-ANN model. Results indicated that the BP-ANN has great potential in predicting multiple quality of dry-cured ham based on protein degradation.
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http://dx.doi.org/10.1016/j.foodchem.2020.128586DOI Listing
May 2021

Primary pulmonary lymphoepithelioma-like carcinoma accompanied by hypertrophic pulmonary osteoarthropathy in a non-epidemic region: a case report and literature review.

J Int Med Res 2020 Nov;48(11):300060520965816

Department of Respiratory and Critical Care Medicine, Ningbo First Hospital, Ningbo, China.

Pulmonary lymphatic epithelioma-like carcinoma (LELC) is a rare and unique subtype, accounting for 0.9% of all lung cancers. To date, just over 200 cases have been reported worldwide. The Epstein-Barr virus plays a role in the pathogenesis of LELC. Most patients are from East Asia, especially southeastern China. Chest computed tomography mainly shows a single lump or nodule around the lung. In this article, we report a 49-year-old male patient from a non-epidemic area who was hospitalized for "intermittent blood in his phlegm for more than 4 months". Imaging revealed two nodules in the left lower lobe of his lung. Transbronchial lung biopsy was performed on one of the nodules, and he was diagnosed with primary LELC. Single-photon emission computed tomography revealed that he had hypertrophic pulmonary osteoarthropathy, which is a rare symptom of paraneoplastic syndrome. Because the preoperative evaluation considered early-stage disease, video-assisted thoracoscopic surgery for the left lower lobe and mediastinal lymph node dissection were performed. Both lesions were eventually diagnosed as LELC. Fortunately, lymph node metastasis did not occur, and he did not receive other postoperative treatments. He was followed up for 1 year, and no recurrence was found.
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http://dx.doi.org/10.1177/0300060520965816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658514PMC
November 2020

Fruquintinib effectively controlled the advanced small bowel adenocarcinoma progressed after multiple lines of palliative treatment: a case report and literature review.

Cancer Biol Ther 2020 12 5;21(12):1105-1108. Epub 2020 Nov 5.

Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital Zhejiang ,University School of Medicine, Hangzhou, Zhejiang, China.

Here we present a case of metastatic small bowel adenocarcinoma, which progressed after sequential treatment with XELOX (capecitabine and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), cetuximab, HER-2 targeted therapy and apatinib and was then effectively controlled by fruquintinib. Genetic testing showed wild-type KRAS/NRAS/BRAF, HER-2 amplification, and microsatellite stable. Then the patient started to receive fruquintinib and has already achieved a 6-month progression-free survival. Till Jun 2019, the treatment with fruquintinib is still ongoing and no severe adverse effect has been seen so far.

Although fruquintinib is not, at present, a standard therapeutic strategy recommended by the treatment guideline for advanced small bowel adenocarcinoma, the significant curative effect has been seen in our clinical practice.
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http://dx.doi.org/10.1080/15384047.2020.1836549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722796PMC
December 2020

Clinical Significance of Serum PGC-1 Alpha Levels in Diabetes Mellitus with Myocardial Infarction Patients and Reduced ROS-Oxidative Stress in Diabetes Mellitus with Myocardial Infarction Model.

Diabetes Metab Syndr Obes 2020 28;13:4041-4049. Epub 2020 Oct 28.

Department 1 of Cardiology, Baoding First Center Hospital, Baoding 071002, Hebei, People's Republic of China.

Background: In this study, we explored the clinical significance of serum peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1) alpha levels in diabetes mellitus with myocardial infarction (DMMI) patients and investigated the possible mechanism.

Materials And Methods: Serum samples were obtained from patients with DMMI or normal volunteer in Baoding First Center Hospital. C57BL/6 mice were induced by a single intraperitoneal (i.p.) injection of 100 mg/kg STZ (streptozocin) for in vivo model. Human myocardial cell lines H9C2 cells were induced with high glucose medium (33 mmol/L glucose) for in vitro model. Western blot was used to analyze the protein expressions in this study.

Results: Serum PGC-1 alpha levels were down-regulated in patients with DMMI. There was negative correlation between serum PGC-1 alpha levels and glycated hemoglobin, blood glucose or glucagon in DMMI patients. Recombination of PGC-1 alpha protein decreased the levels of glycated hemoglobin, blood glucose and glucagon, and inhibited oxidative stress and myocardial damage in mice of DMMI. Over-expression of PGC-1 alpha reduced reactive oxygen species (ROS)-oxidative stress, while down-regulation of PGC-1 alpha promoted ROS-oxidative stress via regulation of hemeoxygenase-1 (HO-1) expression in in vitro model of DMMI. The inhibition of HO-1 expression attenuated the anti-oxidation effects of PGC-1 alpha in vitro.

Conclusion: PGC-1 alpha attenuated ROS-oxidative stress in diabetic cardiomyopathy model, and PGC-1 alpha served as a potential intervention to alleviate DMMI in clinical applications.
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http://dx.doi.org/10.2147/DMSO.S276163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604475PMC
October 2020

Nomogram to predict successful smoking cessation in a Chinese outpatient population.

Tob Induc Dis 2020 16;18:86. Epub 2020 Oct 16.

Department of Traditional Medicine, Ningbo First Hospital, Ningbo, China.

Introduction: The study aimed to establish and internally validate a nomogram to predict successful smoking cessation in a Chinese outpatient population.

Methods: A total of 278 participants were included, and data were collected from March 2016 to December 2018. Predictors for successful smoking cessation were evaluated by 3-month sustained abstinence rates. Least absolute shrinkage and selection operator (LASSO) regression was used to select variables for the model to predict successful smoking cessation, and multivariable logistic regression analysis was performed to establish a novel predictive model. The discriminatory ability, calibration, and clinical usefulness of the nomogram were determined by the concordance index (C-index), calibration plot, and decision curve analysis, respectively. Internal validation with bootstrapping was performed.

Results: The nomogram included living with a smoker or experiencing workplace smoking, number of outpatient department visits, reason for quitting tobacco, and varenicline use. The nomogram demonstrated valuable predictive performance, with a C-index of 0.816 and good calibration. A high C-index of 0.804 was reached with interval validation. Decision curve analysis revealed that the nomogram for predicting successful smoking cessation was clinically significant when intervention was conducted at a successful cessation of smoking possibility threshold of 19%.

Conclusions: This novel nomogram for successful smoking cessation can be conveniently used to predict successful cessation of smoking in outpatients.
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http://dx.doi.org/10.18332/tid/127736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586925PMC
October 2020
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