Publications by authors named "Jing Zheng"

824 Publications

Mesenchymal stem cells enhance the impact of KIR receptor-ligand mismatching on acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia but not in those with acute lymphocytic leukemia.

Hematol Oncol 2021 Apr 13. Epub 2021 Apr 13.

Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.

Killer cell immunoglobulin-like receptor (KIR) receptor-ligand mismatch has been shown to be protective for acute and chronic graft-versus-host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia. Mesenchymal stem cells (MSC) have been considered as one of the most promising prophylaxis for severe GVHD. However, there are no prospective or retrospective studies determining whether they can work synergistically on GVHD. To investigate the potential influence of KIR matching and MSCs, and their synergism on aGVHD and cGVHD after allo-HSCT in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. Data from 104 patients with AML and 50 patients with ALL treated with allo-HSCT in the transplantation unit were retrospectively analyzed. KIR genotyping was performed by the PCR-SSO method. The amplicons were quantified on the Luminex 200 flow analyzer and analyzed using the Quick-Type for Lifecodes software to generate KIR data. Cox proportional hazards models were used in multivariate analyses. KIR receptor-ligand matching was associated with an increased risk of grade II-IV aGVHD compared to KIR receptor-ligand mismatching (p < 0.001) in AML patients, but KIR ligand-mismatching had no significant effect on aGVHD or cGVHD in ALL patients. In contrast, MSCs reduced the incidence of grade II-IV aGVHD in both AML and ALL patients (AML: p = 0.006; ALL: p = 0.008) regardless of KIR mismatching. The combination of KIR receptor-ligand mismatch and MSC transplantation significantly suppressed grade II-IV aGVHD occurrence in AML patients (p = 0.039). In the KIR mismatch group, the incidence of aGVHD was 2.8% in patients receiving MSC compared to 14.6% in those who did not (p = 0.047). KIR receptor-ligand mismatch, MSC transplantation and their combined use significantly reduced the risk of aGVHD after allo-HSCT. These data provide a clinically applicable strategy to reduce aGVHD, thus improving allo-HSCT outcome.
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http://dx.doi.org/10.1002/hon.2867DOI Listing
April 2021

Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs.

Front Cell Dev Biol 2021 25;9:637248. Epub 2021 Mar 25.

Department of Neonatology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Premature infants have a high risk of bronchopulmonary dysplasia (BPD), which is characterized by abnormal development of alveoli and pulmonary vessels. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid are involved in the development of BPD and might serve as predictive biomarkers for BPD. However, the roles of exosomes and EXO-miRNAs from umbilical cord blood of BPD infants in regulating angiogenesis are yet to be elucidated. In this study, we showed that umbilical cord blood-derived exosomes from BPD infants impaired angiogenesis Next-generation sequencing of EXO-miRNAs from preterm infants without (NBPD group) or with BPD (BPD group) uncovered a total of 418 differentially expressed (DE) EXO-miRNAs. These DE EXO-miRNAs were primarily enriched in cellular function-associated pathways including the PI3K/Akt and angiogenesis-related signaling pathways. Among those EXO-miRNAs which are associated with PI3K/Akt and angiogenesis-related signaling pathways, BPD reduced the expression of hsa-miR-103a-3p and hsa-miR-185-5p exhibiting the most significant reduction (14.3% and 23.1% of NBPD group, respectively); BPD increased hsa-miR-200a-3p expression by 2.64 folds of the NBPD group. Furthermore, overexpression of hsa-miR-103a-3p and hsa-miR-185-5p in normal human umbilical vein endothelial cells (HUVECs) significantly enhanced endothelial cell proliferation, tube formation, and cell migration, whereas overexpressing hsa-miR-200a-3p inhibited these cellular responses. This study demonstrates that exosomes derived from umbilical cord blood of BPD infants impair angiogenesis, possibly via DE EXO-miRNAs, which might contribute to the development of BPD.
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http://dx.doi.org/10.3389/fcell.2021.637248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027316PMC
March 2021

Genetic Variations May Modulate Risk of Parkinson's Disease in Han Chinese Population.

Front Neurosci 2021 19;15:620929. Epub 2021 Mar 19.

Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, China.

Studies in animal models have suggested that aldehyde dehydrogenase 1 (encoded by ) protects against Parkinson's disease (PD) by reducing toxic metabolites of dopamine. Herein we aimed to investigate whether was genetically associated with PD susceptibility in humans. A Han Chinese population of 1,039 subjects was recruited to analyze six tag-single nucleotide polymorphisms (SNPs), followed by haplotype analyses and variants interaction analyses. Real-time PCR was used to analyze mRNA levels of in peripheral blood of 42 subjects. The tag-SNP rs7043217 of was significantly associated with PD susceptibility with the T serving as a risk allele (genotype frequency, = 0.030; allele frequency, = 0.013, OR = 1.258, 95% CI = 1.050-1.508). Multiple haplotypes were linked to abnormalities of PD risk, topped by a 4-SNP GGTA module in the order of rs4646547, rs1888202, rs7043217, and rs647880 ( = 9.610 × 10, OR = 6.420, 95% CI = 2.944-13.998). Interaction analyses showed that a simultaneous presence of the CC genotype of rs7043217 and the TT genotype of variant rs4767944 conferred an elevated protection against PD ( = 4.68 × 10, OR = 0.378, 95% CI = 0.219-0.652). The mRNA expression of showed a trend of reduction ( = 0.084) in PD patients compared to the controls. Our results provide novel genetic insights into the role of ALDH1 in PD pathogenesis.
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http://dx.doi.org/10.3389/fnins.2021.620929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017280PMC
March 2021

Longitudinal dynamics of antibody responses in recovered COVID-19 patients.

Signal Transduct Target Ther 2021 03 31;6(1):137. Epub 2021 Mar 31.

Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China.

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http://dx.doi.org/10.1038/s41392-021-00559-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009921PMC
March 2021

Efficacy and Safety of Sacubitril/Valsartan Therapy for Acute Decompensated Heart Failure with Reduced Ejection Fraction during the Vulnerable Phase: A Multicenter, Assessor-Blinded, Prospective, Observational, Cohort Study.

Cardiology 2021 Mar 29:1-10. Epub 2021 Mar 29.

Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Background: The 3-month period after hospitalization for acute cardiac failure is a vulnerable phase with the highest risk of mortality and rehospitalization. Safety and efficacy of early initiation of sacubitril/valsartan during the index hospitalization for acute decompensated heart failure (ADHF) is unclear. Therefore, we tested whether sacubitril/valsartan could result in a lower rate of a composite outcome of first hospitalization for heart failure and death from cardiovascular causes compared to inhibition of the renin-angiotensin system alone.

Methods: We enrolled patients hospitalized for ADHF and reduced ejection fraction at 4 sites; patients were divided into a sacubitril/valsartan group or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) group. All patients were followed up for 3 months after discharge. The primary endpoint was outcomes as a composite of death from cardiovascular causes and rehospitalization for heart failure.

Results: In total, 251 patients who received sacubitril/valsartan and 251 patients who received ACEIs/ARBs had similar propensity scores and were included and compared. The primary endpoint was reached in 40 patients (15.9%) treated with sacubitril/valsartan and in 59 patients (23.5%) managed by ACEI/ARB (HR, 0.650; 95% CI: 0.435-0.971; p = 0.035). The NYHA class improved in 72.1% of patients in the sacubitril/valsartan group and in 59.8% of patients in the ACEI/ARB group (HR, 1.303; 95% CI: 1.097-1.548, p = 0.004). The key safety outcomes endpoints did not significantly differ.

Conclusions: Among patients hospitalized with ADHF and reduced left ventricular ejection fraction, we observed that sacubitril/valsartan therapy led to reduction in death from cardiovascular causes and rehospitalizations for heart failure when compared to ACEI/ARB therapy alone during the vulnerable phase. Our results support that sacubitril/valsartan may be administered early in the vulnerable phase after ADHF and improves NYHA class.
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http://dx.doi.org/10.1159/000512418DOI Listing
March 2021

[Effect of EDTA and hyaluronic acid on the activity of periodontal ligament fibroblasts and the expression of cytokines].

Shanghai Kou Qiang Yi Xue 2020 Dec;29(6):606-610

Department of Stomatology, The Fourth Hospital of Hebei Medical University. Shijiazhuang 050011,Hebei Province, China.

Purpose: To investigate the effect of ethylenediaminetetraacetic acid (EDTA) and hyaluronic acid (HA) on the activity of periodontal ligament fibroblasts (PDLFs) and the expression of cytokines.

Methods: Twelve wisdom teeth extracted due to orthodontics treatment were selected and prepared into 5 mm×4 mm root pieces, then divided into EDTA group, HA group, EDTA+HA group and untreated group according to different treatment methods. They were placed in the well plate and PDLFs inoculated on the root piece. After 24 and 48 h of inoculation, the cell proliferation of each group was detected by MTT assay. The adhesion of PDLFs was observed under microscope. The inflammatory cytokines (IL-6, IL-8 and IL-1β and TNF-α) levels produced by PDLFs were determined by ELLISA and Western Blot. SPSS 22.0 software package was used for statistical analysis.

Results: After 24 h and 48 h inoculation, all the treatments promoted cell proliferation and adhesion of PDLFs compared with the untreated group, and the combined treatment promoted cell proliferation and adhesion significantly better than single treatment (P<0.05). The cell proliferation and adhesion effect of EDTA group and HA group increased with the inoculation time, without significant difference between the groups (P>0.05). The results of ELLISA and Western blot showed that compared with the untreated group, the treatment groups inhibited the expression of inflammatory factors IL-6, IL-1β and TNF-α, and promoted the expression of IL-8, and the effect of EDTA+HA group was much more significant(P<0.05).

Conclusions: EDTA+HA can significantly promote the growth of periodontal ligament fibroblasts and inhibit the expression of inflammatory cytokines, which may be related to its ability to enhance the adhesion of fibroblasts and then improve their viability.
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December 2020

Two-stage Cox-nnet: biologically interpretable neural-network model for prognosis prediction and its application in liver cancer survival using histopathology and transcriptomic data.

NAR Genom Bioinform 2021 Mar 22;3(1):lqab015. Epub 2021 Mar 22.

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48104, USA.

Pathological images are easily accessible data with the potential of prognostic biomarkers. Moreover, integration of heterogeneous data types from multi-modality, such as pathological image and gene expression data, is invaluable to help predicting cancer patient survival. However, the analytical challenges are significant. Here, we take the hepatocellular carcinoma (HCC) pathological image features extracted by CellProfiler, and apply them as the input for Cox-nnet, a neural network-based prognosis prediction model. We compare this model with the conventional Cox proportional hazards (Cox-PH) model, CoxBoost, Random Survival Forests and DeepSurv, using -index and log-rank -values. The results show that Cox-nnet is significantly more accurate than Cox-PH and Random Survival Forests models and comparable with CoxBoost and DeepSurv models, on pathological image features. Further, to integrate pathological image and gene expression data of the same patients, we innovatively construct a two-stage Cox-nnet model, and compare it with another complex neural-network model called PAGE-Net. The two-stage Cox-nnet complex model combining histopathology image and transcriptomic RNA-seq data achieves much better prognosis prediction, with a median -index of 0.75 and log-rank -value of 6e-7 in the testing datasets, compared to PAGE-Net (median -index of 0.68 and log-rank -value of 0.03). Imaging features present additional predictive information to gene expression features, as the combined model is more accurate than the model with gene expression alone (median -index 0.70). Pathological image features are correlated with gene expression, as genes correlated to top imaging features present known associations with HCC patient survival and morphogenesis of liver tissue. This work proposes two-stage Cox-nnet, a new class of biologically relevant and interpretable models, to integrate multiple types of heterogenous data for survival prediction.
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http://dx.doi.org/10.1093/nargab/lqab015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985035PMC
March 2021

Larger than expected variation range in the real part of the refractive index for ambient aerosols in China.

Sci Total Environ 2021 Mar 14;779:146443. Epub 2021 Mar 14.

Department of Atmospheric and Oceanic Sciences, School of Physics, Peking University, Beijing 100871, China.

The real part of the refractive index (RRI) of ambient aerosol, which is widely used in remote sensing and atmospheric models, is one of the key factors determining its particles' optical properties. The characteristics of ambient aerosol RRI in China have not yet been well studied owing to a lack of observations. For the first time, the properties of aerosol RRI were studied based on field measurements in China at four sites with different atmospheres. The results revealed that the measured ambient aerosol RRI varied significantly between 1.36 and 1.78, increasing with the mass ratio of organic components. The scattering coefficient and direct radiative effects of the aerosols were estimated to increase by factors of 2 and 3, respectively, when RRI increased from 1.36 to 1.78. Our results indicate that variation in ambient aerosol RRI should be considered in aerosol and climate models to achieve an accurate estimation of aerosol's radiative impacts.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146443DOI Listing
March 2021

Development of a Reduced Chemical Reaction Mechanism for -Pentanol Based on Combined Reduction Methods and Genetic Algorithm.

ACS Omega 2021 Mar 26;6(9):6448-6459. Epub 2021 Feb 26.

Key Laboratory of Shaanxi Province for Development and Application of New Transportation Energy, Chang'an University, Xi'an 710064, P. R. China.

To gradually reduce the demand for fossil energy and accelerate energy transformation, alcohol fuels are being vigorously developed and utilized in the world. -Pentanol as a common alcohol fuel has attracted increasing attention in recent years owing to its many advantages. In this study, a reduced mechanism of -pentanol containing 148 species and 575 reactions was established based on combined reduction methods including the direct relationship graph with error propagation, reaction pathway analysis, rate of production analysis, and temperature sensitivity analysis methods. Then, the reaction rate parameters were optimized using the nondominated sorting genetic algorithm II. A verification experiment for the oxidation of -pentanol was conducted in a jet-stirred reactor (JSR) with gas chromatography-mass spectrometry. The main species mole fractions were quantitatively analyzed in the temperature range 700-1100 K, equivalence ratios of 0.5-2.0, and a pressure of 1 atm. Extensive validations were performed over wide experimental conditions by comparing the experimental data of the ignition delay time, species concentration profiles in the JSR, and laminar flame speed. It was found that the predicted values were in good agreement with the experimental values. Therefore, the reduced mechanism developed in this study can accurately predict the experimental results, which is capable of reasonably applying to the simulation of combustion behaviors of -pentanol in internal combustion engines.
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http://dx.doi.org/10.1021/acsomega.1c00147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948435PMC
March 2021

Association of homocysteine with ankylosing spondylitis: a systematic review and meta-analysis.

Adv Rheumatol 2021 Mar 10;61(1):17. Epub 2021 Mar 10.

Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI, 53715, USA.

Background: Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS.

Methods: Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software.

Results: Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = - 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype.

Conclusion: This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings.

Trial Registration: This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426 .
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http://dx.doi.org/10.1186/s42358-021-00175-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944467PMC
March 2021

Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice.

Mol Metab 2021 Mar 3;49:101202. Epub 2021 Mar 3.

Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan. Electronic address:

Objective: Impaired circadian clocks can cause obesity, but their pathophysiological role in brown adipose tissue (BAT), a major tissue regulating energy metabolism, remains unclear. To address this issue, we investigated the effects of complete disruption of the BAT clock on thermogenesis and energy expenditure.

Methods: Mice with brown adipocyte-specific knockout of the core clock gene Bmal1 (BA-Bmal1 KO) were generated and analyzed.

Results: The BA-Bmal1 KO mice maintained normal core body temperatures by increasing shivering and locomotor activity despite the elevated expression of thermogenic uncoupling protein 1 in BAT. BA-Bmal1 KO disrupted 24 h rhythmicity of fatty acid utilization in BAT and mildly reduced both BAT thermogenesis and whole-body energy expenditure. The impact of BA-Bmal1 KO on the development of obesity became obvious when the mice were fed a high-fat diet.

Conclusions: These results reveal the importance of the BAT clock for maintaining energy homeostasis and preventing obesity.
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http://dx.doi.org/10.1016/j.molmet.2021.101202DOI Listing
March 2021

Breviscapine Pretreatment Inhibits Myocardial Inflammation and Apoptosis in Rats After Coronary Microembolization by Activating the PI3K/Akt/GSK-3β Signaling Pathway.

Drug Des Devel Ther 2021 25;15:843-855. Epub 2021 Feb 25.

Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People's Republic of China.

Purpose: Coronary microembolization (CME) can cause myocardial inflammation, apoptosis and progressive cardiac dysfunction. On the other hand, breviscapine exerts a significant cardioprotective effect in many cardiac diseases although its role and the potential mechanisms in CME remain unclear. Therefore, the present study aimed to ascertain whether pretreatment with breviscapine could improve CME-induced myocardial injury by alleviating myocardial inflammation and apoptosis. The possible underlying mechanisms were also explored.

Methods: In this study, 48 Sprague-Dawley (SD) rats were randomly assigned to the CME, CME + breviscapine (CME + BE), CME + breviscapine + LY294002 (CME + BE + LY) and sham groups (12 rats per group). In addition, the CME model was successfully established by injecting 42 μm inert plastic microspheres into the left ventricle of rats. Rats in the CME + BE and CME + BE + LY groups received 40 mg/kg/d of breviscapine for 7 days before inducing CME. Moreover, rats in the CME + BE + LY group were intraperitoneally injected with the phosphoinositide 3-kinase (PI3K) specific inhibitor, LY294002 (10 mg/kg) 30 minutes before CME modeling. 12 h after surgery, the study measured cardiac function, the serum levels of markers of myocardial injury, myocardial inflammation-associated mRNAs and proteins, myocardial apoptosis-associated mRNAs and proteins and conducted myocardial histopathology.

Results: The findings demonstrated that pretreatment with breviscapine alleviated myocardial injury following CME by improving cardiac dysfunction, decreasing the serum levels of markers of myocardial injury, reducing the size of myocardial microinfarct and lowering the cardiomyocyte apoptotic index. More importantly, pretreatment with breviscapine resulted to a decrease in the levels of inflammatory and pro-apoptotic mRNAs and proteins in myocardial tissues and there was an increase in the levels of anti-apoptotic mRNAs and proteins. However, these protective effects were eliminated when breviscapine was combined with LY294002.

Conclusion: The findings from this study indicated that breviscapine may inhibit myocardial inflammation and apoptosis by regulating the PI3K/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway, thereby ameliorating CME-induced cardiac dysfunction and reducing myocardial injury.
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http://dx.doi.org/10.2147/DDDT.S293382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920514PMC
February 2021

QTLs and candidate genes analyses for fruit size under domestication and differentiation in melon (Cucumis melo L.) based on high resolution maps.

BMC Plant Biol 2021 Mar 3;21(1):126. Epub 2021 Mar 3.

Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture and Rural Affairs, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, 100081, Beijing, China.

Background: Melon is a very important horticultural crop produced worldwide with high phenotypic diversity. Fruit size is among the most important domestication and differentiation traits in melon. The molecular mechanisms of fruit size in melon are largely unknown.

Results: Two high-density genetic maps were constructed by whole-genome resequencing with two F segregating populations (WAP and MAP) derived from two crosses (cultivated agrestis × wild agrestis and cultivated melo × cultivated agrestis). We obtained 1,871,671 and 1,976,589 high quality SNPs that show differences between parents in WAP and MAP. A total of 5138 and 5839 recombination events generated 954 bins in WAP and 1027 bins in MAP with the average size of 321.3 Kb and 301.4 Kb respectively. All bins were mapped onto 12 linkage groups in WAP and MAP. The total lengths of two linkage maps were 904.4 cM (WAP) and 874.5 cM (MAP), covering 86.6% and 87.4% of the melon genome. Two loci for fruit size were identified on chromosome 11 in WAP and chromosome 5 in MAP, respectively. An auxin response factor and a YABBY transcription factor were inferred to be the candidate genes for both loci.

Conclusion: The high-resolution genetic maps and QTLs analyses for fruit size described here will provide a better understanding the genetic basis of domestication and differentiation, and provide a valuable tool for map-based cloning and molecular marker assisted breeding.
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http://dx.doi.org/10.1186/s12870-021-02904-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931605PMC
March 2021

Multifunctional Programmable DNA Nanotrain for Activatable Hypoxia Imaging and Mitochondrion-Targeted Enhanced Photodynamic Therapy.

ACS Appl Mater Interfaces 2021 Mar 19;13(8):9681-9690. Epub 2021 Feb 19.

School of Chemistry and Biological Engineering, Changsha University of Science and Technology, Changsha 410004, China.

Programmable DNA-based nanostructures (, nanotrains, nanoflowers, and DNA dendrimers) provide new approaches for safe and effective biological imaging and tumor therapy. However, few studies have reported that DNA-based nanostructures respond to the hypoxic microenvironment for activatable imaging and organelle-targeted tumor therapy. Herein, we innovatively report an azoreductase-responsive, mitochondrion-targeted multifunctional programmable DNA nanotrain for activatable hypoxia imaging and enhanced efficacy of photodynamic therapy (PDT). Cyanine structural dye (Cy3) and black hole quencher 2 (BHQ2), which were employed as a fluorescent mitochondrion-targeted molecule and azoreductase-responsive element, respectively, covalently attached to the DNA hairpin monomers. The extended guanine (G)-rich sequence at the end of the DNA hairpin monomer served as a nanocarrier for the photosensitizer 5,10,15,20-tetrakis(4--methylpyridiniumyl) porphyrin (TMPyP4). Upon initiation between the DNA hairpin monomer and initiation probe, the fluorescence of Cy3 and the singlet oxygen (O) generation of TMPyP4 in the programmable nanotrain were effectively quenched by BHQ2 through the fluorescence resonance energy transfer (FRET) process. Once the programmable nanotrain entered cancer cells, the azo bond in BHQ2 will be reduced to amino groups by the high expression of azoreductase under hypoxia conditions; then, the fluorescence of Cy3 and the O generation of TMPyP4 will significantly be restored. Furthermore, due to the mitochondrion-targeting characteristic endowed by Cy3, the TMPyP4-loaded nanotrain would accumulate in the mitochondria of cancer cells and then demonstrate enhanced PDT efficacy under light irradiation. We expect that this programmable DNA nanotrain-based multifunctional nanoplatform could be effectively used for activatable imaging and high performance of PDT in hypoxia-related biomedical field.
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http://dx.doi.org/10.1021/acsami.0c21681DOI Listing
March 2021

Puerarin pretreatment attenuates cardiomyocyte apoptosis induced by coronary microembolization in rats by activating the PI3K/Akt/GSK-3β signaling pathway.

Korean J Physiol Pharmacol 2021 Mar;25(2):147-157

Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrov.

Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 μm microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.
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http://dx.doi.org/10.4196/kjpp.2021.25.2.147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893491PMC
March 2021

Sandwich-type electrochemical immunosensor for CEA detection using magnetic hollow Ni/C@SiO nanomatrix and boronic acid functionalized CPS@PANI@Au probe.

Talanta 2021 Apr 29;225:122006. Epub 2020 Dec 29.

College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, 201620, China.

A sandwich-type electrochemical immunosensor was developed for the detection of CEA where hollow magnetic silica coated nickel/carbon (Ni/C@SiO) nanocomposites was used as an immobilized carrier and gold nanoparticle-coated PANI microsphere (CPS@PANI@Au) as electrochemical transducer. Magnetic assembly of Ni/C@SiO nanocomposites allow easy separation and assembly which eliminates the further modification process. In addition, the prepared CPS@PANI@Au possess good biocompatibility, and electrical conductivity. The fabricated immunosensor show excellent sensing performance including a wide dynamic range from 0.006 to 12.00 ng mL and low detection limit at 1.56 pg mL. Moreover, this sensor shows superior selectivity with excellent reliability and reproducibility which might lead into easier implementation in clinical setting.
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http://dx.doi.org/10.1016/j.talanta.2020.122006DOI Listing
April 2021

Decoding the Evolutionary Response to Ensartinib in Patients With ALK-Positive NSCLC by Dynamic Circulating Tumor DNA Sequencing.

J Thorac Oncol 2021 Feb 13. Epub 2021 Feb 13.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China. Electronic address:

Introduction: By implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC.

Methods: In a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel.

Results: A total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p < 0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p < 0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation.

Conclusions: Our study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.
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http://dx.doi.org/10.1016/j.jtho.2021.01.1615DOI Listing
February 2021

Investigation of the Cytotoxic Activity of Emodin 35 Derivative on Multiple Myeloma Cell Lines.

Evid Based Complement Alternat Med 2021 25;2021:6682787. Epub 2021 Jan 25.

Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China.

Background: Bortezomib is used for treating multiple myeloma (MM); however, it has considerable adverse effects. Emodin has been reported to exhibit inhibitory effects on MM cell lines. We investigated the efficacy of emodin 35 (E35), an emodin derivative, using U266 and MM1s cell lines in treating MM and the efficacy of combining bortezomib and E35.

Methods: MTT assays were used to observe the effects of E35 on MM cell growth. The effects on cellular apoptosis were then observed using Annexin V/propidium iodide (PI) staining assay. The expression of apoptosis-related genes, including the caspase family, was examined. The efficacy of combining bortezomib and E35 was investigated by examining the expression of the Akt/mTOR/4EBP1 signaling pathway-related proteins.

Results: We report that E35 inhibited the growth of U266 and MM1s cells by inducing cellular apoptosis. Moreover, E35 downregulated the expression of apoptosis-related genes and suppressed the phosphorylation of Akt/mTOR/4EBP1 signaling pathway-related genes, thus exhibiting synergistic effects with bortezomib. All observed effects were dose-dependent.

Conclusion: The results showed that E35 exhibited cytotoxic effects in MM cell lines in protein levels. Thus, E35, particularly in combination with bortezomib, may be considered as a promising treatment for MM; however, this requires further investigation .
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http://dx.doi.org/10.1155/2021/6682787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850823PMC
January 2021

Mitigation of acute radiation-induced brain injury in a mouse model using anlotinib.

Ann Palliat Med 2021 Jan;10(1):312-322

Department of Oncology, Binzhou Medical University Hospital, Binzhou, China. Email:

Background: With the development of radiological technologies, radiotherapy has been gradually widely used in the clinic to intracranial tumours and become standardised. However, the related central nervous system disorders are still the most obvious complications after radiotherapy. This study aims to quantify the effectiveness of anlotinib, a small molecule inhibitor of multiple receptor tyrosine kinases, in mitigating acute phase of radiation-induced brain injury (RBI) in a mouse model.

Methods: The onset and progression of RBI were investigated in vivo. All mice, (except for the sham group) were irradiated at a single-fraction of 20 Gy and treated with different doses of anlotinib (0, 0.2 and 0.8 mg/kg, respectively). The expression levels of glial fibrillary acidic protein (GFAP), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and phosphorylated vascular endothelial growth factor receptor-2 (p-VEGFR2) were assessed by western blot. Histological changes were identified by luxol fast blue (LFB) staining.

Results: The expression levels of GFAP, HIF-1α, and VEGF were downregulated following treatment with anlotinib. However, anlotinib failed to inhibit the development of demyelination. Cerebral edema [as measured by brain water content (BWC)] was also mitigated following treatment with anlotinib.

Conclusions: In summary, treatment with anlotinib significantly mitigated the adverse effects of acute RBI in a dose-dependent manner by downregulating the activation of astrocytes, improving brain hypoxia, and alleviating cerebral edema.
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http://dx.doi.org/10.21037/apm-20-2284DOI Listing
January 2021

[Expression and clinical significance of Spindly and Bub3 in oral squamous cell carcinoma].

Shanghai Kou Qiang Yi Xue 2020 Oct;29(5):528-532

Department of Stomatology, The Fourth Hospital of Hebei Medical University.Shijiazhuang 050011, Hebei Province, China.

Purpose: To investigate the expression and significance of Spindly and Bub3 in oral squamous cell carcinoma(OSCC).

Methods: Sixty-five patients with OSCC admitted to the Fourth Hospital of Hebei Medical University from March 2017 to March 2019 were enrolled. RT-PCR was used to detect the expression of Spindly and Bub3 mRNA in oral squamous cell carcinoma and adjacent normal tissues from the patients. OSCC cell line was cultured. After siRNA transfection interference with the expression of Spindly and Bub3 genes, cell viability was detected by MTT assay, and the cell migration ability was detected by scratch test. Statistical analysis was performed with SPSS 22.0 software package RESULTS: The expression levels of Spindly and Bub3 mRNA in OSCC were significantly higher in adjacent tissues(P<0.05). The expression of Spindly and Bub3 mRNA was related to TNM staging, clinical staging and lymph node metastasis (P<0.05). The 5-year survival rate of patients with high expression of Spindly, Bub3, Spindly/Bub3 were significantly higher than the counterparts with low expression, and the 5-year survival rate of patients with high expression of Spindly/Bub3 was significantly lower than that of patients with high expression of Spindly and Bub3(P<0.05). The expression level of Spindly in siRNA-Spindly group was significantly lower than that in Spindly negative control group and blank control group, and the expression level of Bub3 in siRNA-Bub3 group was also significantly lower than that in Bub3 negative control group and blank control group. The expression level of Spindly in siRNA-Spindly group was significantly lower than that in Spindly negative control group and blank control group, and the expression level of Bub3 in siRNA-Bub3 group was also lower than that in Bub3 negative control group and blank control group. The migration ability of cells in siRNA-Spindly group at 24 and 48 hours was significantly lower than that in Spindly negative control group and blank control group; the migration ability at 24 and 48 hours was significantly lower than that of Bub3 negative control group and blank control group(P<0.05).

Conclusions: Spindly and Bub3 are highly expressed in OSCC. Specific inhibition of Spindly and Bub3 gene expression can reduce the proliferation and migration of cancer cells, which might be used as one of the targets for the treatment of OSCC.
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October 2020

Resveratrol protects against myocardial ischemic injury via the inhibition of NF‑κB‑dependent inflammation and the enhancement of antioxidant defenses.

Int J Mol Med 2021 Mar 4;47(3). Epub 2021 Feb 4.

Laboratory of Cardiovascular Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China.

Resveratrol (RES) is a natural phenol which possesses multiple pharmacological actions. The present study aimed to determine whether RES protects against myocardial ischemic injury in association with the inhibition of NF‑κB‑dependent inflammation and the enhancement of antioxidant defenses in mice following acute myocardial infarction (AMI). Male C57/BL mice were randomly assigned to 3 groups as follows: The sham‑operated (sham) group, AMI + vehicle group and AMI + RES group. Rat H9C2 cells were also used to examine the effects of RES on hypoxia‑induced oxidative injury . Redox homeostasis in the mouse myocardium and rat H9C2 cells was determined post‑treatment. The mRNA and protein levels of phosphorylated (p‑)IκB kinase (p‑IKK), p‑nuclear factor (NF)‑κB p65, interleukin (IL)‑1β, IL‑6, nerve growth factor (NGF) and insulin‑like growth factor‑1 (IGF‑1) were measured by RT‑qPCR and western blot analysis. It was found that RES slightly protected the myocardium against ischemic injury in mice, while it prevented the hypoxia‑induced apoptosis of H9C2 cells. RES decreased the production of reactive oxygen species (ROS) and enhanced the activities of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GPx). RES also downregulated the protein and/or mRNA levels of p‑IKK, p‑NF‑κB p65, IL‑1β, IL‑6, NGF and IGF‑1 at 7 and 28 days after infarction. On the whole, these data indicate that RES protects the myocardium against ischemic injury in association with the inhibition of oxidative stress and inflammatory responses. Thus, RES has the potential to be used as an adjunctive therapeutic drug for heart diseases.
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http://dx.doi.org/10.3892/ijmm.2021.4862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895514PMC
March 2021

A Correlative Study Between IVIM-DWI Parameters and the Expression Levels of Ang-2 and TKT in Hepatocellular Carcinoma.

Front Oncol 2020 15;10:594366. Epub 2021 Jan 15.

Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Background: Noninvasive evaluation of the expression of angiopoietin-2 (Ang-2) and transketolase (TKT) in hepatocellular carcinoma (HCC) is of great significance for the clinical development of individualized treatment plans. However, the correlation between intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and the expression of Ang-2 and TKT has not been reported. We sought to investigate the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs.

Methods: Conventional non-enhanced magnetic resonance imaging (MRI) and IVIM-DWI and dynamic contrast MRI were performed for 61 patients with HCC before surgical treatment. Various IVIM-DWI parameters, such as apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D) and fraction of fast apparent diffusion coefficient (f), were calculated using Function-MADC software. Expression levels of Ang-2 and TKT in HCC were detected immunohistochemical staining and classified into two grades. Independent sample tests were used to compare differences in parameters between the two groups. The Spearman rank correlation test was used to analyze the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs.

Results: The D and f values were significantly higher in the high Ang-2 group than in the low Ang-2 group; there were no obvious between-group differences in ADC and D. Ang-2 expression was positively correlated with D* and f but not with ADC and D. The ADC and D values were significantly lower in the high TKT group than in the low TKT group, whereas the between-group differences for D* and f were not significant. TKT expression was negatively correlated with ADC and D but not with D* and f.

Conclusions: IVIM-DWI can be used to evaluate Ang-2 and TKT expression in HCC.
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http://dx.doi.org/10.3389/fonc.2020.594366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845759PMC
January 2021

Association of changes in nursing work environment, non-professional tasks, and nursing care left undone with nurse job outcomes and quality of care: A panel study.

Int J Nurs Stud 2021 Mar 29;115:103860. Epub 2020 Dec 29.

School of Nursing, Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: Strengthening quality of care without compromising nurse job outcomes by building a safer health care system is a common concern worldwide including in China. Most of the current evidence comes from cross-sectional studies conducted in western countries, which limits inferences of causality and generalization.

Objective: The objectives of this longitudinal study were to compare changes in quality of care, nurse job outcomes, nursing work environment, non-professional tasks, and nursing care left undone in acute hospitals in China between 2014 and 2018. Secondly, we wanted to determine the association of changes in nursing work environment, non-professional tasks, and nursing care left undone with nurse job outcomes and quality of care.

Design, Settings, And Participants: A prospective two-stage panel study conducted in 108 adult medical and surgical units from 23 hospitals in Guangdong province, China in 2014 and repeated in 2018.

Methods: Work environment was measured by the Practice Environment Scale of the Nursing Work Index. Non-professional tasks were measured with a seven-item scale surveying the performance of and time spent on non-professional tasks. Nursing care left undone was measured by 12 items addressing necessary nursing activities. Nurse job outcomes included burnout, dissatisfaction, and retention. Quality of care was measured by four items indicating overall quality of care as assessed by nurses (three items) and patients (one item). Generalized estimating equations with linear regression were employed to analyze data.

Results: In 2018, compared with 2014, the nursing work environment had improved, and non-professional workloads had decreased minimally. The average number of the 12 nursing care tasks left undone had increased to 6.5 from 5.6 in 2014. Fewer nurses reported job dissatisfaction or intention to leave. Quality of care was improved slightly as assessed by nurses and patients. As for the changes of hospital organizational factors on quality of care, a better nursing work environment was related to better nurse job outcomes and quality of care. More non-professional tasks were related to higher levels of nurse job burnout. Less nursing care left undone was associated with better nurse-assessed quality of care. Units with more nurses experiencing job burnout and dissatisfaction were likely to have poorer nurse-assessed quality of care.

Conclusions: Improving nursing work environment and supporting nurses to engage in professional and direct patient care as opposed to non-professional work may be beneficial to nurse job outcomes and promote quality of care.
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http://dx.doi.org/10.1016/j.ijnurstu.2020.103860DOI Listing
March 2021

Cox-nnet v2.0: improved neural-network based survival prediction extended to large-scale EMR data.

Bioinformatics 2021 Jan 30. Epub 2021 Jan 30.

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI.

Summary: Cox-nnet is a neural-network based prognosis prediction method, originally applied to genomics data. Here we propose the version 2 of Cox-nnet, with significant improvement on efficiency and interpretability, making it suitable to predict prognosis based on large-scale population data, including those electronic medical records (EMR) datasets. We also add permutation-based feature importance scores and the direction of feature coefficients. When applied on a kidney transplantation dataset, Cox-nnet v2.0 reduces the training time of Cox-nnet up to 32 folds (n = 10,000) and achieves better prediction accuracy than Cox-PH (p < 0.05). It also achieves similarly superior performance on a publicly available SUPPORT data (n = 8,000). The high efficiency and accuracy make Cox-nnet v2.0 a desirable method for survival prediction in large-scale EMR data.

Availability And Implementation: Cox-nnet v2.0 is freely available to the public at https://github.com/lanagarmire/Cox-nnet-v2.0.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab046DOI Listing
January 2021

Role of SIRT2 in regulating the dexamethasone-activated autophagy pathway in skeletal muscle atrophy.

Biochem Cell Biol 2021 Jan 22. Epub 2021 Jan 22.

Shanghai University of Traditional Chinese Medicine, 66322, Department of Biochemistry, Shanghai, China, 201203;

The proteolytic autophagy system is involved in a major regulatory pathway in dexamethasone (Dex)-induced muscle atrophy. Sirtuin 2 (SIRT2) is known to participate in modulating autophagy signaling, exerting effects in skeletal muscle atrophy. We aimed to determine the effects of SIRT2 on autophagy in Dex-induced myoatrophy. Mice were randomly divided into the normal, Dex, and sirtinol groups. C2C12 cells were differentiated into myotubes and transfected with short hairpin (sh)-Sirt2-green fluorescent protein (GFP) or Sirt2-GFP lentivirus. To evaluate the mass and function of skeletal muscles, we measured the myofiber cross-sectional area, myotube size, gastrocnemius muscle wet weight/body weight ratio (%), and time-to-exhaustion. The SIRT2, myosin heavy chain (MyHC), LC3, and Beclin-1 expression levels were detected by western blotting and quantitative reverse transcription-polymerase chain reaction. Inhibition of SIRT2 markedly attenuated the muscle mass and endurance capacity. The same phenotype was observed in Sirt2-shRNA-treated myotubes, as evidenced by their decreased size. Conversely, SIRT2 overexpression alleviated Dex-induced myoatrophy in vitro. Moreover, SIRT2 negatively regulated the expression of the LC3b and Beclin-1 in skeletal muscles. These findings suggested that SIRT2 activation protects myotubes against Dex-induced atrophy through the inhibition of the autophagy system; this phenomenon may potentially serve as a target for treating glucocorticoid-induced myopathy.
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http://dx.doi.org/10.1139/bcb-2020-0445DOI Listing
January 2021

Downregulation of miR-96-5p Inhibits mTOR/NF-κb Signaling Pathway via DEPTOR in Allergic Rhinitis.

Int Arch Allergy Immunol 2021 21;182(3):210-219. Epub 2021 Jan 21.

Medical Center, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.

Background: This study aims to investigate the regulatory effect of microRNA-96-5p (miR-96-5p) in the pathophysiological process of allergic rhinitis (AR).

Methods: Nasal mucosal tissue samples were collected from AR patients and healthy controls. An in vitro AR model was established by stimulating human nasal epithelial cells (HNECs) with interleukin (IL)-13. The expressions of target genes and proteins were measured by qPCR, Western blot, or ELISA. Dual-luciferase reporter assay and pull-down assay were performed to confirm the interaction between miR-96-5p and DEP domain-containing mammalian target of rapamycin-interacting protein (DEPTOR).

Results: The level of miR-96-5p was increased while the expression of DEPTOR was decreased in AR patients. The expressions of proinflammatory cytokines were markedly increased and the mammalian target of rapamycin (mTOR)/NF-κB pathway was activated in HNECs following IL-13 stimulation. miR-96-5p downregulation alleviated the stimulated function by IL-13. DEPTOR was the target of miR-96-5p. Knockdown of DEPTOR reversed the function of miR-96-5p inhibitor on IL-13-stimulated HNECs.

Conclusions: The current study showed that miR-96-5p and DEPTOR were aberrantly expressed in AR nasal mucosa. miR-96-5p knockdown inhibited the production of inflammatory cytokines and the activation of mTOR/NF-κB pathway via targeting DEPTOR. These findings suggested that miR-96-5p might be used as a diagnostic marker and therapeutic target for the treatment of AR.
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http://dx.doi.org/10.1159/000509403DOI Listing
January 2021

The transverse diameter of right common femoral vein by ultrasound in the supine position for predicting post-spinal hypotension during cesarean delivery.

BMC Anesthesiol 2021 Jan 20;21(1):22. Epub 2021 Jan 20.

Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.

Background: Post-spinal anesthesia hypotension during cesarean delivery is caused by decreased systemic vascular resistance due to the blockage of the autonomic nerves, which is further worsened by inferior vena cava (IVC) compression by the gravid uterus. This study aimed to assess whether peak velocity and diameter of the IVC below the xiphoid or right common femoral vein (RCFV) in the inguinal region, as measured on ultrasound, could reflect the degree of IVC compression and further identify parturients at risk of post-spinal hypotension.

Methods: Fifty-six parturients who underwent elective cesarean section with spinal anesthesia were included in this study; peak velocities and anteroposterior diameters of the IVC and peak velocities and transverse diameters of the RCFV were measured using ultrasound before anesthesia. The primary outcome was the ultrasound measurements of IVC and RCFV acquired before spinal anesthesia and their association with post-spinal hypotension. Hypotension was defined as a drop in systolic arterial pressure by > 20% from the baseline. Multinomial logistic regression analysis was used to identify the association between the measurements of IVC, RCFV, and post-spinal hypotension during cesarean delivery. Receiver operating characteristic curves were used to test the abilities of the identified parameters to predict post-spinal hypotension; the areas under the curve and optimum cut-off values for the predictive parameters were calculated.

Results: A longer transverse diameter of the RCFV was associated with the occurrence of post-spinal hypotension (odds ratio = 2.022, 95% confidence interval [CI] 1.261-3.243). The area under the receiver operating characteristics curve for the prediction of post-spinal hypotension was 0.759 (95% CI 0.628-0.890, P = 0.001). A transverse diameter of > 12.2 mm of the RCFV could predict post-spinal hypotension during cesarean delivery.

Conclusions: A longer transverse diameter of RCFV was associated with hypotension and could predict parturients at a major risk of hypotension before anesthesia.

Trial Registration: This study was registered at http://www.chictr.org.cn on 16, May, 2018. No. ChiCTR1800016163 .
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http://dx.doi.org/10.1186/s12871-021-01242-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816508PMC
January 2021

Application of Diffusion Weighted Imaging in Prostate Cancer Bone Metas tasis: Detection and Therapy Evaluation.

Anticancer Agents Med Chem 2021 Jan 17. Epub 2021 Jan 17.

Medical Imaging Key Laboratory of Sichuan Province; Medical Research Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000. China.

Background: Bone metastasis is one of the most common complications of Prostate cancer (PCa). The detection of distal bone metastasis at the time of initial PCa diagnosis is valuable for the determination of therapeutic methods and for the prognosis of PCa. Many current therapeutic methods target PCa bone metastasis, but no uniform evaluation standard for therapeutic efficacy has been established; in addition, traditional therapeutic evaluation standards that rely on changes in the measured tumor volume are quite controversial. In clinical practice, the volumes of some tumors often change nonsignificantly at the early stage of therapy (especially targeted therapy),while the volumes of other tumors, such as metastatic bone lesions, are difficult to measure. Diffusion-weighted imaging (DWI) not only reflects the diffusion characteristics of tissues but can also allow the analysis of microstructural and functional changes in tissues. Therefore, DWI is suitable for evaluations of early responses to tumor therapy.

Objective: This study mainly reviews the principle of DWI and its progress in the detection and therapy evaluation of PCa bone metastasis.

Methods: PubMed was searched to identify eligible articles up to December 26, 2020. The keywords of the analysis included DWI, PCa, bone metastasis, therapeutic response, targeted therapy, bone scintigraphy (BS), positron emission tomography/computed tomography (PET/CT) and metastatic castration-resistant prostate cancer (mCRPC).

Results: This review based on collected articles achieved an imaging biomarker for detection and therapy evaluation of PCa bone metastasis.

Conclusion: DWI is a promising imaging method for the detection and therapeutic evaluation of PCa bone metastases.
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http://dx.doi.org/10.2174/1871520621666210118092641DOI Listing
January 2021

A novel electrochemical assay for chymosin determination using a label-free peptide as a substrate.

J Dairy Sci 2021 Mar 15;104(3):2511-2519. Epub 2021 Jan 15.

State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, 2 North Cuihu Road, Kunming 650091, People's Republic of China. Electronic address:

Chymosin is a predominant enzyme in rennet and is used in cheese production because of its excellent milk-clotting activity. Herein, we proposed a facile and label-free electrochemical method for determining chymosin activity based on a peptide-based enzyme substrate. The synthesized substrate peptide for chymosin was assembled onto the surface of the Au-deposited grassy carbon electrode. The current was proportional to chymosin activity, and thus chymosin activity could be determined. The detection ranges of chymosin activity were 2.5 to 25 U mL. The detection limit of chymosin activity was 0.8 U mL. The sensing platform was used to quantify chymosin activity in commercial rennet with high selectivity, excellent stability, and satisfactory reproducibility. We developed a facile, fast, and effective electrochemical assay for detecting chymosin activity, which has potential applications in cheesemaking.
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http://dx.doi.org/10.3168/jds.2020-19282DOI Listing
March 2021

Surface Hardening Behavior of Enamel by Masticatory Loading: Occurrence Mechanism and Antiwear Effect.

ACS Biomater Sci Eng 2020 08 30;6(8):4454-4461. Epub 2020 Jul 30.

Tribology Research Institute, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu 610031, China.

Previous studies have suggested that surface hardening occurs in human tooth enamel under certain loading conditions. However, the occurrence mechanism and significance remain unclear. In this study, the surface hardening behavior of enamel under masticatory loading was studied in vitro using impact treatment and the nanoindentation/scratch technique to identify the mechanism and antiwear effect. The fundamental block of enamel is made of hydroxyapatite (HAP) nanofibers, which consist of fine nanoparticles held together by protein. These fibers respond to masticatory loading in two ways: bending deflection at low loads and fragmentation at high loads. When the contact pressure exceeds the bonding strength between the nanoparticles, the HAP fibers split into fine nanoparticles and then form a surface layer consisting of tightly packed nanoparticles. This results in surface hardening dominated by an increased hardness and elastic modulus. The maximum degree and depth of surface hardening were determined as approximately 60% and 100 nm, respectively. With the occurrence of surface hardening, the wear resistance of the enamel is enhanced, which is manifested by a reduced friction coefficient and wear volume. In summary, the surface hardening of enamel induced by masticatory loading is a result of HAP nanoparticle rearrangement as a response of the enamel hierarchical structure to high chewing loads. It is adaptive overload protection derived from the enamel hierarchical structure and plays a critical role in resisting excessive wear induced by high chewing loads.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00740DOI Listing
August 2020