Publications by authors named "Jinming Zhao"

69 Publications

Score for Predicting Active Cancer in Patients with Ischemic Stroke: A Retrospective Study.

Biomed Res Int 2021 25;2021:5585206. Epub 2021 May 25.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: We aimed to examine the differences of clinical characteristics between patients with ischemic stroke with active cancer and those without cancer to develop a clinical score for predicting the presence of occult cancer in patients with ischemic stroke.

Methods: This retrospective study enrolled consecutive adult patients with acute ischemic stroke who were admitted to our department between December 2017 and January 2019. The demographic, clinical, laboratory, and neuroimaging characteristics were compared between patients with ischemic stroke with active cancer and those without cancer. Multivariate analysis was performed to identify independent factors associated with active cancer. Subsequently, a predictive score was developed using the areas under the receiver operating characteristic curves based on these independent factors. Finally, Bayesian decision theory was applied to calculate the posterior probability of active cancer for finding the best scoring system.

Results: Fifty-three (6.63%) of 799 patients with ischemic stroke had active cancer. The absence of a history of hyperlipidemia (odds ratio (OR) = 0.17, 95% confidence interval (CI): 0.06-0.48, < 0.01), elevated serum fibrinogen (OR = 1.72, 95% CI: 1.33-2.22, < 0.01) and D-dimer levels (OR = 1.43, 95% CI: 1.24-1.64,  <0.01), and stroke of undetermined etiology (OR = 22.87, 95% CI: 9.91-52.78, < 0.01) were independently associated with active cancer. A clinical score based on the absence of hyperlipidemia, serum fibrinogen level of ≥4.00 g/L, and D-dimer level of ≥2.00 g/mL predicted active cancer with an area under the curve of 0.83 (95% CI: 0.77-0.89, < 0.01). The probability of active cancer was 59% at a supposed prevalence of 6.63%, if all three independent factors were present in a patient with ischemic stroke.

Conclusions: We devised a clinical score to predict active cancer in patients with ischemic stroke based on the absence of a history of hyperlipidemia and elevated serum D-dimer and fibrinogen levels. The use of this score may allow for early intervention. Further research is needed to confirm the implementation of this score in clinical settings.
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http://dx.doi.org/10.1155/2021/5585206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169246PMC
May 2021

Atrial reconstruction, distal gastrectomy with Ante-situm liver resection and autotransplantation for hepatocellular carcinoma with atrial tumor thrombus: A case report.

Medicine (Baltimore) 2021 May;100(19):e25780

Department of Liver Transplantation & Laparoscopic Surgery, Center of Organ Transplantation, The 1st Affiliated Hospital of Xinjiang Medical University.

Rationale: Hepatocellular with tumor thrombi extending into 3 hepatic veins (HVs) and right atrium presents as a real clinical challenge. We report the first documented case of surgical resection of an advanced hepatocellular carcinoma (HCC) with extensive invasion to distal stomach, atrium and hepatic vasculatures.

Patient Concerns: We present a case of 48-years old man with abdominal mass accompanying shortness of breath after activities.

Diagnoses: Preoperative examination revealed giant HCC with tumor thrombi extending into portal vein, HVs, inferior vena cava, and atrium.

Interventions: Distal stomach involvement was confirmed at surgery and, distal gastrectomy, atrial reconstruction and ante-situm liver resection and autotransplantation under cardio-pulmonary bypass were performed.

Outcomes: The operation time was 490 minutes, extracorporeal circulation time 124 minutes, and anhepatic time 40 minutes. Postoperative follow-up revealed normal hepatic and cardiac function with no sign of recurrence.

Lessons: This case illustrates that the extensive invasion of HCC to major vasculature and adjacent organs may not necessarily preclude the liver autotransplantation with multi-visceral resection as the treatment option of extremely advanced HCC patients.
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http://dx.doi.org/10.1097/MD.0000000000025780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133267PMC
May 2021

Genome-wide association analysis for yield-related traits at the R6 stage in a Chinese soybean mini core collection.

Genes Genomics 2021 Aug 6;43(8):897-912. Epub 2021 May 6.

National Center for Soybean Improvement, Key Laboratory of Biology and Genetics and Breeding for Soybean, Ministry of Agriculture, State Key Laboratory for Crop Genetics and Germplasm Enhancement, College of Agriculture, Nanjing Agricultural University, Weigang No. 1, Nanjing, 210095, Jiangsu, China.

Background: Soybean (Glycine max (L.) Merr.) is an economically important crop for vegetable oil and protein production, and yield is a critical trait for grain/vegetable uses of soybean. However, our knowledge of the genes controlling the vegetable soybean yield remains limited.

Objective: To better understand the genetic basis of the vegetable soybean yield.

Methods: The 100-pod fresh weight (PFW), 100-seed fresh weight (SFW), kernel percent (KP) and moisture content of fresh seeds (MCFS) at the R6 stage are four yield-related traits for vegetable soybean. We investigated a soybean mini core collection composed of 224 germplasm accessions for four yield-related traits in two consecutive years. Based on 1514 single nucleotide polymorphisms (SNPs), genome-wide association studies (GWAS) were conducted using a mixed linear model (MLM).

Results: Extensive phenotypic variation existed in the soybean mini core collection and significant positive correlations were shown among most of traits. A total of 16 SNP markers for PFW, SFW, KP and MCFS were detected in all environments via GWAS. Nine SNP markers were repeatedly identified in two environments. Among these markers, eight were located in or near regions where yield-related QTLs have been reported in previous studies, and one was a novel genetic locus identified in this study. In addition, we conducted candidate gene analysis to the large-effect SNP markers, a total of twelve genes were proposed as potential candidate genes of soybean yield at the R6 stage.

Conclusion: These results will be beneficial for understanding the genetic basis of soybean yield at the R6 stage and facilitating the pyramiding of favourable alleles for future high-yield breeding by marker-assisted selection in vegetable soybean.
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http://dx.doi.org/10.1007/s13258-021-01109-9DOI Listing
August 2021

Sinonasal manifestations and dynamic profile of RT-PCR results for SARS-CoV-2 in COVID-19 patients.

Ann Palliat Med 2021 Apr 23;10(4):4174-4183. Epub 2021 Mar 23.

Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Key Laboratory of Otorhinolaryngology-Head & Neck Surgery Ministry of Education, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Key Laboratory of Nasal Diseases, Beijing, China.

Background: Sinonasal symptoms were usually reported to appear initially, yielding the symptoms important for the early detection of coronavirus disease 2019 (COVID-19). This study was conducted retrospectively to investigate the detailed sinonasal manifestations and dynamic profile of real-time reverse transcription polymerase chain reaction (RT-PCR) results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in COVID-19 patients longitudinally.

Methods: This retrospective study included 11 consecutive patients. The prevalence, timing and severity of sinonasal manifestations were analyzed. Oropharyngeal, nasal, sputum and stool specimens were collected to detect RT-PCR for SARS-CoV-2 over COVID-19 period.

Results: Among the 11 patients, 6 (54.5%) were female, and the median age was 51 (IQR, 36-62) years. Seven patients (63.6%) experienced sinonasal symptoms, with 6 (54.5%) exhibiting sinonasal symptoms on the onset day. Seven patients (63.6%) demonstrated nasal obstruction, 5 (45.5%) had rhinorrhea, and 4 (36.4%) exhibited olfactory dysfunction. All six patients with sinonasal symptoms on the onset day had non-severe infections. Most patients (85.7%) with sinonasal symptoms had non-severe infections. Sinonasal symptoms commonly appeared early. The positive RT-PCR rate for SARS-CoV-2 in various specimens was highest in the first week (73.3%), then gradually decreased over the disease course, but 3 patients (27.3%) had experienced a long-lasting fluctuated positive RT-PCR results since 29 days of illness in both groups, especially for two patients with airway comorbidities.

Conclusions: Sinonasal symptoms were more prevalent in patients with mild or moderate COVID-19 and usually appeared early. In addition, regular nucleic acid testing for SARS-CoV-2 should be considered for COVID-19 patients with certain airway comorbidities.
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http://dx.doi.org/10.21037/apm-20-2493DOI Listing
April 2021

Genome-wide association studies of plant architecture-related traits and 100-seed weight in soybean landraces.

BMC Genom Data 2021 03 6;22(1):10. Epub 2021 Mar 6.

National Center for Soybean Improvement, Key Laboratory of Biology and Genetics and Breeding for Soybean, Ministry of Agriculture, State Key Laboratory for Crop Genetics and Germplasm Enhancement, College of Agriculture, Nanjing Agricultural University, Nanjing, 210095, China.

Background: Plant architecture-related traits (e.g., plant height (PH), number of nodes on main stem (NN), branch number (BN) and stem diameter (DI)) and 100-seed weight (100-SW) are important agronomic traits and are closely related to soybean yield. However, the genetic basis and breeding potential of these important agronomic traits remain largely ambiguous in soybean (Glycine max (L.) Merr.).

Results: In this study, we collected 133 soybean landraces from China, phenotyped them in two years at two locations for the above five traits and conducted a genome-wide association study (GWAS) using 82,187 single nucleotide polymorphisms (SNPs). As a result, we found that a total of 59 SNPs were repeatedly detected in at least two environments. There were 12, 12, 4, 4 and 27 SNPs associated with PH, NN, BN, DI and 100-SW, respectively. Among these markers, seven SNPs (AX-90380587, AX-90406013, AX-90387160, AX-90317160, AX-90449770, AX-90460927 and AX-90520043) were large-effect markers for PH, NN, BN, DI and 100-SW, and 15 potential candidate genes were predicted to be in linkage disequilibrium (LD) decay distance or LD block. In addition, real-time quantitative PCR (qRT-PCR) analysis was performed on four 100-SW potential candidate genes, three of them showed significantly different expression levels between the extreme materials at the seed development stage. Therefore, Glyma.05 g127900, Glyma.05 g128000 and Glyma.05 g129000 were considered as candidate genes with 100-SW in soybean.

Conclusions: These findings shed light on the genetic basis of plant architecture-related traits and 100-SW in soybean, and candidate genes could be used for further positional cloning.
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http://dx.doi.org/10.1186/s12863-021-00964-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937308PMC
March 2021

Is routine abdominal drainage necessary for patients undergoing elective hepatectomy? A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Feb;100(6):e24689

Department of Liver Transplantation & Laparoscopic Surgery, Digestive & Vascular Surgery Centre, the 1 Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Objectives: To evaluate comparative outcomes of routine abdominal drainage (RAD) and non-routine abdominal drainage (NRAD) during elective hepatic resection for hepatic neoplasms.

Materials And Methods: We systematically searched MEDLINE, EMBASE, The Cochrane Library, Web of Science. The searching phrases included "liver resection," "hepatic resection," "hepatectomy," "abdominal drainage," "surgical drainage," "prophylactic drainage," "intraperitoneal drainage," "drainage tube," "hepatectomy," "abdominal drainage" and "drainage tube." Two independent reviewers critically screened literature, extracted data and assessed the risk of bias. Post-operative morbidity and mortality were the outcome parameters. Combined overall effect sizes were calculated using fixed-effect or random-effect model.

Results: We have identified 9 RCTs and 3 comparative studies reporting total of 5726 patients undergoing elective hepatectomy under RAD (n = 3084) or NRAD (NRAD group, n = 2642). RAD was associated with significantly higher overall complication rate [odds risk  = 1.79, 95% CI (1.10, 2.93), P = .02] and biliary leakage rate [odds risk  = 2.41, 95% CI (1.48, 3.91), P = .0004] compared with NRAD. Moreover, it significantly increased hospital stays [mean difference  = 0.95, 95% CI (0.02, 1.87), P = .04] compared with NRAD. RAD showed no difference regarding intra-abdominal hemorrhage, wound complications, liver failure, subphrenic complications, pulmonary complications, infectious complications, reoperation and mortality compared with NRAD.

Conclusions: Although routine abdominal drainage may help surgeons to observe post-operative complication, it seems to be associated with increased post-operative morbidity and longer hospital stays. Non-routine abdominal drainage may be an appropriate option in selected patients undergoing hepatic resection. Higher level of evidence is needed.
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http://dx.doi.org/10.1097/MD.0000000000024689DOI Listing
February 2021

Generation and identification of a conditional knockout allele for the PSMD11 gene in mice.

BMC Dev Biol 2021 02 1;21(1). Epub 2021 Feb 1.

Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China.

Background: Our previous study have shown that the PSMD11 protein was an important survival factor for cancer cells except for its key role in regulation of assembly and activity of the 26S proteasome. To further investigate the role of PSMD11 in carcinogenesis, we constructed a conditional exon 5 floxed allele of PSMD11 (PSMD11) in mice.

Results: It was found that homozygous PSMD11 mice showed normal and exhibited a normal life span and fertility, and showed roughly equivalent expression of PSMD11 in various tissues, suggesting that the floxed allele maintained the wild-type function. Cre recombinase could induce efficient knockout of the floxed PSMD11 allele both in vitro and in vivo. Mice with constitutive single allele deletion of PSMD11 derived from intercrossing between PSMD11 and CMV-Cre mice were all viable and fertile, and showed apparent growth retardation, suggesting that PSMD11 played a significant role in the development of mice pre- or postnatally. No whole-body PSMD11 deficient embryos (PSMD11) were identified in E7.5-8.5 embryos in uteros, indicating that double allele knockout of PSMD11 leads to early embryonic lethality. To avoid embryonic lethality produced by whole-body PSMD11 deletion, we further developed conditional PSMD11 global knockout mice with genotype Flp;FSF-R26; PSMD11 , and demonstrated that PSMD11 could be depleted in a temporal and tissue-specific manner. Meanwhile, it was found that depletion of PSMD11 could induce massive apoptosis in MEFs.

Conclusions: In summary, our data demonstrated that we have successfully generated a conditional knockout allele of PSMD11 in mice, and found that PSMD11 played a key role in early and postnatal development in mice, the PSMD11 mice will be an invaluable tool to explore the functions of PSMD11 in development and diseases.
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http://dx.doi.org/10.1186/s12861-020-00233-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849139PMC
February 2021

A Nomogram Combing Peripheral Parameters for Estimation of CRSwNP Recurrence.

Am J Rhinol Allergy 2020 Dec 6:1945892420978957. Epub 2020 Dec 6.

Department of Otorhinolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Background: The preoperative prediction of the recurrence of chronic rhinosinusitis with nasal polyps (CRSwNP) remains difficult in clinical practice.

Objective: We aimed to develop a nomogram that combined peripheral risk factors to clinically predict the recurrence of CRSwNP.

Methods: Data from 158 CRSwNP patients who underwent endoscopic sinus surgery (ESS) from January 2012 to December 2016 were collected, and the patients were followed up for 3 years. Of these, 96 patients who underwent ESS in an earlier period formed the training cohort for nomogram development, and 62 patients who underwent ESS thereafter formed the validation cohort to confirm the model's performance. Risk factors for recurrence identified by univariate and multivariate logistic regression were used to create a nomogram.

Results: The recurrence rate was 29.2% (28/96) for the training cohort and 35.5% (22/62) for the validation cohort. Univariate analysis identified blood eosinophils (Eos), serum IgE level, asthma comorbidity, and the number of previous ESSs as risk factors for recurrence. Among those four parameters, serum IgE level and a previous ESS surgery were identified as two independent risk factors. A nomogram consisting of blood Eos, total serum IgE level, asthma comorbidity, and the number of previous ESSs was constructed, demonstrating a C index of 0.81 (95% CI, 0.79-0.83) and 0.80 (95% CI, 0.77-0.83) for predicting recurrence in the training and validation cohorts, respectively. The nomogram had well-fitted calibration curves.

Conclusion: The nomogram might be able to preoperatively predict the recurrence of CRSwNP by using currently available and objective parameters. Further studies are required to validate its reliability and effectiveness.
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http://dx.doi.org/10.1177/1945892420978957DOI Listing
December 2020

SPOCK2 Serves as a Potential Prognostic Marker and Correlates With Immune Infiltration in Lung Adenocarcinoma.

Front Genet 2020 10;11:588499. Epub 2020 Nov 10.

Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.

Lung adenocarcinoma (LUAD) is one of the major types of lung cancer. Tumor-infiltrating immune cells (TIICs) are positively associated with overall survival (OS) in LUAD. The SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 2 (SPOCK2) is a complex type of secreted proteoglycan involved in forming a protective barrier against viral infection. The purpose of this study was to investigate the relationship between SPOCK2 and TIICs and the prognostic role of SPOCK2 in LUAD. The GEPIA2, GEO, CPTAC, and HPA databases were analyzed to examine both the mRNA and protein expression of SPOCK2 in LUAD. GEPIA2 and the Kaplan-Meier Plotter (KM Plotter) were used to evaluate the prognostic value of SPOCK2 in LUAD patients. TCGA data were examined for a correlation between SPOCK2 expression and clinical characteristics. Gene enrichment analyses were performed to explore the underlying mechanism of SPOCK2 based on LinkedOmics. RegNetwork was used to predict the regulators of SPOCK2. The correlation between SPOCK2 and TIICs, including immune infiltration level and relative proportion was investigated via TIMER. KM Plotter was also used to evaluate the prognostic role of SPOCK2 expression in LUAD with enriched and decreased TIIC subgroups. We found SPOCK2 was significantly downregulated in LUAD compared with that in non-tumor controls and was correlated with clinical parameters. Moreover, a high SPOCK2 expression level predicted better survival. The SPOCK2-associated regulatory network was constructed. SPOCK2 influenced the TIIC infiltration level and relative proportion in LUAD. Furthermore, a high SPOCK2 expression level was associated with a favorable prognosis in enriched CD4 + T cells and macrophage subgroups in LUAD. In conclusion, a high level of SPOCK2 expression predicted favorable prognosis and was significantly correlated with TIICs in LUAD. Therefore, the expression of SPOCK2 may affect the prognosis of LUAD partly due to TIICs.
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http://dx.doi.org/10.3389/fgene.2020.588499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683796PMC
November 2020

Repeat hepatic resection VS radiofrequency ablation for the treatment of recurrent hepatocellular carcinoma: an updated meta-analysis.

Minim Invasive Ther Allied Technol 2020 Nov 4:1-10. Epub 2020 Nov 4.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Background: This paper evaluates the efficacy and safety of repeat hepatic resection and radiofrequency ablation in the treatment of recurrent hepatocellular carcinoma.

Material And Methods: We retrieved and collected all relevant articles from the inception to 8 March 2020. After data extraction, we conducted meta-analysis and carried out the heterogeneity test, sensitivity analysis, and publication bias test to evaluate reliability.

Results: A total of 12 studies with 1746 patients (rHR 837, RFA 909) were included. rHR was similar to RFA in a one-year overall survival rate (OS), while rHR was superior to RFA in 3- and 5-year OS and 1-, 3-, and 5-year disease-free survival rates (DFS), but the procedure-related complications of RFA were significantly less than those of rHR. Among the subgroups with Milan criteria, rHR was similar to RFA in 1-, 3-, and 5-year OS and 1-year DFS, but superior to RFA in 3- and 5-year DFS.

Conclusions: RFA is the first choice for recurrent HCC meeting Milan criteria. When it does not meet the Milan criteria, minimally invasive treatment should not be carried out at the cost of survival, and rHR should be the first choice.
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http://dx.doi.org/10.1080/13645706.2020.1839775DOI Listing
November 2020

Sirtuin 5 regulates the proliferation, invasion and migration of prostate cancer cells through acetyl-CoA acetyltransferase 1.

J Cell Mol Med 2020 12 26;24(23):14039-14049. Epub 2020 Oct 26.

Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.

Sirtuin 5 (SIRT5) is a NAD -dependent class III protein deacetylase, and its role in prostate cancer has not yet been reported. Therefore, to explore the diagnosis and treatment of prostate cancer, we investigated the effect of SIRT5 on prostate cancer. Sirtuin 5 was assessed by immunohistochemistry in 57 normal and cancerous prostate tissues. We found that the tissue expression levels of SIRT5 in patients with Gleason scores ≥7 were significantly different from those in patients with Gleason scores <7 (P < .05, R > 0). Further, mass spectrometry and pathway screening experiments showed that SIRT5 regulated the activity of the mitogen-activated protein kinase (MAPK) pathway, which in turn modulated the expression of MMP9 and cyclin D1. Being a substrate of SIRT5, acetyl-CoA acetyltransferase 1 (ACAT1) was regulated by SIRT5. SIRT5 also regulated MAPK pathway activity through ACAT1. These results revealed that SIRT5 promoted the activity of the MAPK pathway through ACAT1, increasing the ability of prostate cancer cells to proliferate, migrate and invade. Overall, these results indicate that SIRT5 expression is closely associated with prostate cancer progression. Understanding the underlying mechanism may provide new targets and methods for the diagnosis and treatment of the disease.
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http://dx.doi.org/10.1111/jcmm.16016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753991PMC
December 2020

LINC00657 knockdown suppresses hepatocellular carcinoma progression by sponging miR-424 to regulate PD-L1 expression.

Genes Genomics 2020 11 29;42(11):1361-1368. Epub 2020 Sep 29.

Department of Liver & Laparoscopic Surgery, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan South Road, Xinshi District, Ürümqi, 830054, Xinjiang Uyghur Autonomous Region, China.

Background: Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed malignant tumor and the fourth leading cause of cancer-related deaths worldwide. As a novel non-coding RNA, LINC00657 was firstly identified as an oncogenic role in breast cancer. However, few research focus on the effect of LINC00657 on the progression of HCC.

Objectives: The purpose of this study was to investigate the effect of LINC00657 on HCC tissues and cells, and further explore the potential mechanism.

Methods: We first measured the expression of LINC00657 in HCC tissues and cell lines using qRT-PCR. Next we established LINC00657 knockdown in HCC cells. CCK-8 assay, cell invasion assay, flow cytometry analysis, qRT-PCR and western blotting were applied to assess the role of LINC00657 knockdown in the biological behavior of HCC cells. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism.

Results: LINC00657 was remarkably overexpressed in HCC tissues and cell lines, associated with poor prognosis. LINC00657 knockdown repressed cell proliferation and invasion, promoted cell apoptosis of HCC cell lines. The bioinformatics analysis showed LINC00657 sponged miR-424 as a ceRNA. Besides, PD-L1 mimic rescued the suppression of si-LINC00657 in the biological behavior of HCC cells.

Conclusion: In a word, we observed LINC00657 regulated PD-L1 expression by sponging miR-424, thus affecting the developments of hepatocellular carcinoma. These findings LINC00657 may provide new evidence for therapeutic application in hepatocellular carcinoma.
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http://dx.doi.org/10.1007/s13258-020-01001-yDOI Listing
November 2020

Impaired small airway function in non-asthmatic chronic rhinosinusitis with nasal polyps.

Clin Exp Allergy 2020 12 12;50(12):1362-1371. Epub 2020 Oct 12.

Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium.

Background: There is clinical evidence for impaired lung function in chronic rhinosinusitis with nasal polyps (CRSwNP) patients, which may be due to a high incidence of asthma comorbidity. The lung function characteristics of non-asthmatic CRSwNP patients are not known. Small airway dysfunction (SAD) is involved in the pathogenesis of asthma. However, whether SAD is detected in non-asthmatic patients with CRSwNPs remains unclear.

Objective: This study analysed the lung function of non-asthmatic patients with CRSwNPs and evaluated its clinical relevance in CRSwNPs.

Methods: The clinical data for 191 consecutive CRSwNP patients (73 asthmatic and 118 non-asthmatic) and 30 control subjects were prospectively collected. The patients were followed up for at least 3 years (mean [standard deviation], 42.47 ± 8.38 months). Serum and tissue total IgE levels were measured in 95 and 93 patients, respectively. Tissue eosinophil counts were documented in 63 patients.

Results: Non-asthmatic CRSwNP patients had decreased forced expiratory flow at 75% of the FVC (FEF ) and FEF compared to the control subjects, and this difference was related to the severity of CRSwNP. The risk factors for impaired lung function in asthmatic and non-asthmatic patients were duration of asthma and smoking. A multivariate logistic analysis showed that decreased FEF was associated with the recurrence of non-asthmatic CRSwNPs. The lung function of CRSwNP patients negatively correlated with the degree of type-2 inflammation, which was defined by the levels of Eos and IgE in polyp tissues and blood. The SAD of non-asthmatic CRSwNP patients was related to serum IgE levels.

Conclusions And Clinical Relevance: This study provides evidence that non-asthmatic CRSwNP patients may have SAD, which correlated with the severity and recurrence of CRSwNP. The decreased lung function of patients with CRSwNP was related to the degree of type-2 inflammation.
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http://dx.doi.org/10.1111/cea.13747DOI Listing
December 2020

Expression of IFN-induced 2'-5'-oligoadenylate synthetases correlates with immune infiltration, revealing potential targets and new biomarkers for basal-like breast cancer prognosis.

Int Immunopharmacol 2020 Nov 1;88:106916. Epub 2020 Sep 1.

Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning Province, China; Department of Pathology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China. Electronic address:

Triple-negative breast cancer has been classified as basal-like immune activated (BLIA), basal-like immune-suppressed (BLIS), and two other subtypes, suggesting potential immune therapeutic targets for basal-like breast cancer (BLBC). 2'-5'-Oligoadenylate synthetases (OASs), identified from differentially expressed genes (DEGs) between BLIA and BLIS breast cancers (GSE76124), are involved in antiviral activity induced by interferons. However, the association between the four OASs and prognosis or tumor-infiltrating immune cells (TIICs) remains unclear. Expression, survival data, and immune correlations for OASs in BLBC were assessed using bioinformatics tools. We found that OASs were highly expressed in BLIA breast cancer. Survival analysis suggested that high transcriptional levels of OASs were associated with better overall survival, relapse-free survival, and distant metastasis-free survival in patients with BLBC. Moreover, the prognostic value of OASs with respect to different clinicopathological factors, and especially according to lymph node metastasis, in patients with BLBC was further assessed. Our findings elucidated the expression, prognostic role, and effect of OASs in TIICs on BLBC, which might promote the development of OAS-targeted immunotherapy for BLBC.
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http://dx.doi.org/10.1016/j.intimp.2020.106916DOI Listing
November 2020

High prevalence of Clonorchis sinensis infections and coinfection with hepatitis virus in riverside villages in northeast China.

Sci Rep 2020 07 16;10(1):11749. Epub 2020 Jul 16.

Department of Hepatology, The First Hospital of Jilin University, Jilin University, No. 71 Xinmin Street, Changchun, 130021, China.

In China, the prevalence of Clonorchis sinensis (C. sinensis) infections is only evaluated at the provincial level by national sampling surveys, and data from villages and counties are still lacking. In this study, we conducted a cross-sectional survey in 10 villages located along the Lalin River in northeast China. Clonorchiasis was diagnosed using a modified Kato-Katz method that detects the C. sinensis egg in stools. A total of 3,068 persons were screened and 2,911 were recruited for the study. Overall, the prevalence of C. sinensis infection was 29.3%. Among 175 participants who were cured after antiparasitic treatment, 54 (30.86%) were re-infected in this survey. After calibration of potential confounders, male gender, occupation as a farmer, smoking, and occasionally or frequently eating raw fish were independent risk factors for C. sinensis infection. The results of laboratory examinations in the C. sinensis/hepatitis B or C virus co-infection group were similar to those in the hepatitis B or C virus mono-infection groups. In conclusion, C. sinensis is highly endemic in villages along the Lalin River, and the primary route of infection is the consumption of raw freshwater fish. Co-infection with C. sinensis did't aggravate the clinical manifestations of viral hepatitis in this cross-sectional study.
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http://dx.doi.org/10.1038/s41598-020-68684-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366707PMC
July 2020

Comprehensive Identification of Drought Tolerance QTL-Allele and Candidate Gene Systems in Chinese Cultivated Soybean Population.

Int J Mol Sci 2020 Jul 8;21(14). Epub 2020 Jul 8.

Soybean Research Institute, Nanjing Agricultural University, Nanjing 210095, China.

Drought is one of the most important factors affecting plant growth and productivity. The previous results on drought tolerance (DT) genetic system in soybean indicated a complex of genes not only few ones were involved in the trait. This study is featured with a relatively thorough identification of QTL-allele/candidate-gene system using an efficient restricted two-stage multi-locus multi-allele genome-wide association study, on two comprehensive DT indicators, membership index values of relative plant weight (MPW) and height (MPH), instead of a single biological characteristic, in a large sample (564 accessions) of the Chinese cultivated soybean population (CCSP). Based on 24,694 multi-allele markers, 75 and 64 QTL with 261 and 207 alleles (2-12/locus) were detected for MPW and MPH, explaining 54.7% and 47.1% of phenotypic variance, respectively. The detected QTL-alleles were organized into a QTL-allele matrix for each indicator, indicating DT is a super-trait conferred by two (even more) QTL-allele systems of sub-traits. Each CCSP matrix was separated into landrace (LR) and released cultivar (RC) sub-matrices, which showed significant differentiation in QTL-allele constitutions, with 58 LR alleles excluded and 16 new ones emerged in RC. Using the matrices, optimal crosses with great DT transgressive recombinants were predicted. From the detected QTL, 177 candidate genes were annotated and validated with quantitative Real-time PCR, and grouped into nine categories, with ABA and stress responders as the major parts. The key point of the above results is the establishment of relatively full QTL-allele matrices composed of numerous gene functions jointly conferring DT, therefore, demonstrates the complexity of DT genetic system and potential of CCSP in DT breeding.
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http://dx.doi.org/10.3390/ijms21144830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402128PMC
July 2020

Interleukin-22 Inhibits Respiratory Syncytial Virus Production by Blocking Virus-Mediated Subversion of Cellular Autophagy.

iScience 2020 Jul 10;23(7):101256. Epub 2020 Jun 10.

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue, MUH 628 NW, Pittsburgh, PA 15213, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address:

Respiratory syncytial virus (RSV) infection can cause severe bronchiolitis in infants requiring hospitalization, whereas the elderly and immunocompromised are prone to RSV-induced pneumonia. RSV primarily infects lung epithelial cells. Given that no vaccine against RSV is currently available, we tested the ability of the epithelial-barrier protective cytokine interleukin-22 (IL-22) to control RSV production. When used in a therapeutic modality, IL-22 efficiently blunted RSV production from infected human airway and alveolar epithelial cells and IL-22 administration drastically reduced virus titer in the lungs of infected newborn mice. RSV infection resulted in increased expression of LC3B, a key component of the cellular autophagic machinery, and knockdown of LC3B ablated virus production. RSV subverted LC3B with evidence of co-localization and caused a significant reduction in autophagic flux, both reversed by IL-22 treatment. Our findings inform a previously unrecognized anti-viral effect of IL-22 that can be harnessed to prevent RSV-induced severe respiratory disease.
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http://dx.doi.org/10.1016/j.isci.2020.101256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317237PMC
July 2020

FNDC5/irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction.

Stem Cell Res Ther 2020 06 10;11(1):228. Epub 2020 Jun 10.

Department of Cardiology, PLA Rocket Force Characteristic Medical Center, Beijing, 100088, China.

Background: The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cell survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed to be involved in a cardioprotective effect, but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI.

Methods: BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc-eGFP) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and overexpression of FNDC5 (FNDC5-OV) in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5-OV.

Results: Hypoxic stress contributed to increased apoptosis, decreased cell viability, and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging and immunofluorescence results illustrated that BM-MSCs with overexpression of FNDC5 treatment (FNDC5-MSCs) improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Interestingly, FNDC5-OV elevated the secretion of exosomes in BM-MSCs. Furthermore, FNDC5-MSC therapy significantly reduced fibrosis and alleviated injured heart function.

Conclusions: The present study indicated that irisin or FNDC5 improved BM-MSC engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.
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http://dx.doi.org/10.1186/s13287-020-01746-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288492PMC
June 2020

PEBP1 acts as a rheostat between prosurvival autophagy and ferroptotic death in asthmatic epithelial cells.

Proc Natl Acad Sci U S A 2020 06 8;117(25):14376-14385. Epub 2020 Jun 8.

Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260;

Temporally harmonized elimination of damaged or unnecessary organelles and cells is a prerequisite of health. Under Type 2 inflammatory conditions, human airway epithelial cells (HAECs) generate proferroptotic hydroperoxy-arachidonoyl-phosphatidylethanolamines (HpETE-PEs) as proximate death signals. Production of 15-HpETE-PE depends on activation of 15-lipoxygenase-1 (15LO1) in complex with PE-binding protein-1 (PEBP1). We hypothesized that cellular membrane damage induced by these proferroptotic phospholipids triggers compensatory prosurvival pathways, and in particular autophagic pathways, to prevent cell elimination through programmed death. We discovered that PEBP1 is pivotal to driving dynamic interactions with both proferroptotic 15LO1 and the autophagic protein microtubule-associated light chain-3 (LC3). Further, the 15LO1-PEBP1-generated ferroptotic phospholipid, 15-HpETE-PE, promoted LC3-I lipidation to stimulate autophagy. This concurrent activation of autophagy protects cells from ferroptotic death and release of mitochondrial DNA. Similar findings are observed in Type 2 Hi asthma, where high levels of both 15LO1-PEBP1 and LC3-II are seen in HAECs, in association with low bronchoalveolar lavage fluid mitochondrial DNA and more severe disease. The concomitant activation of ferroptosis and autophagy by 15LO1-PEBP1 complexes and their hydroperoxy-phospholipids reveals a pathobiologic pathway relevant to asthma and amenable to therapeutic targeting.
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http://dx.doi.org/10.1073/pnas.1921618117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321965PMC
June 2020

Comparative Proteomics Analysis Reveals That Lignin Biosynthesis Contributes to Brassinosteroid-Mediated Response to in Soybeans.

J Agric Food Chem 2020 May 29;68(19):5496-5506. Epub 2020 Apr 29.

National Center for Soybean Improvement, Key Laboratory of Biology and Genetics and Breeding for Soybean, Ministry of Agriculture, State Key Laboratory for Crop Genetics and Germplasm Enhancement, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.

Brassinosteroids (BRs) are a group of steroid plant hormones regulating normal growth, development, and stress response in plants. However, the mechanisms by which BRs interfere with the resistance of soybean to () remain largely unknown. The present study analyzed the role of BRs in soybean response against by comparative proteomic approaches. A total of 52,381 peptides were obtained by trypsin digestion of 9,680 proteins, among which 6,640 proteins were quantified, and 402 proteins were identified as differentially expressed proteins (DEPs). Further analysis revealed that DEPs were significantly involved in the lignin biosynthesis pathway. The expression of the majority of key enzymes involved in lignin biosynthesis was upregulated by BR-pretreatment and infection, and lignin accumulation was faster in BR-pretreated soybeans than in untreated controls. Additionally, accumulation of lignin was consistent with these enzyme expressions levels and resistance phenotype. These findings advance the understanding of the role of BRs in the interaction between soybeans and .
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http://dx.doi.org/10.1021/acs.jafc.0c00848DOI Listing
May 2020

GmNAC8 acts as a positive regulator in soybean drought stress.

Plant Sci 2020 Apr 9;293:110442. Epub 2020 Feb 9.

MOA Key Laboratory of Biology and Genetic Improvement of Soybean (General), National Center for Soybean Improvement, State Key Laboratory for Crop Genetics and Germplasm Enhancement, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China. Electronic address:

NAC proteins represent one of the largest transcription factor (TF) families involved in the regulation of plant development and the response to abiotic stress. In the present study, we elucidated the detailed role of GmNAC8 in the regulation of drought stress tolerance in soybean. The GmNAC8 protein was localized in the nucleus, and expression of the GmNAC8 gene was significantly induced in response to drought, abscisic acid (ABA), ethylene (ETH) and salicylic acid (SA) treatments. Thus, we generated GmNAC8 overexpression (OE1 and OE2) and GmNAC8 knockout (KO1 and KO2) lines to determine the role of GmNAC8 in drought stress tolerance. Our results revealed that, compared with the wild type (WT) plant, GmNAC8 overexpression and GmNAC8 knockout lines exhibited significantly higher and lower drought tolerance, respectively. Furthermore, the SOD activity and proline content were significantly higher in the GmNAC8 overexpression lines and significantly lower in the GmNAC8 knockout lines than in the WT plants under drought stress. In addition, GmNAC8 protein was found to physically interact with the drought-induced protein GmDi19-3 in the nucleus. Moreover, the GmDi19-3 expression pattern showed the same trend as the GmNAC8 gene did under drought and hormone (ABA, ETH and SA) treatments, and GmDi19-3 overexpression lines (GmDi19-3-OE9, GmDi19-3-OE10 and GmDi19-3-OE31) showed enhanced drought tolerance compared to that of the WT plants. Hence, the above results indicated that GmNAC8 acts as a positive regulator of drought tolerance in soybean and inferred that GmNAC8 probably functions by interacting with another positive regulatory protein, GmDi19-3.
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http://dx.doi.org/10.1016/j.plantsci.2020.110442DOI Listing
April 2020

Genetic dynamics of earlier maturity group emergence in south-to-north extension of Northeast China soybeans.

Theor Appl Genet 2020 Jun 6;133(6):1839-1857. Epub 2020 Feb 6.

Soybean Research Institute; MARA National Center for Soybean Improvement; MARA Key Laboratory of Biology and Genetic Improvement of Soybean; National Key Laboratory for Crop Genetics and Germplasm Enhancement; Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China.

Key Message: This population genetic study is characterized with direct comparisons of days to flowering QTL-allele matrices between newly evolved and originally old maturity groups of soybeans to explore its evolutionary dynamics using the RTM-GWAS procedure. The Northeast China (NEC) soybeans are the major germplasm source of modern soybean production in Americas (> 80% of the world total). NEC is a relatively new soybean area in China, expanded after its nomadic status in the seventeenth century. At nine sites of four ecoregions in NEC, 361 varieties were tested for their days to flowering (DTF), a geography-sensitive trait as an indicator for maturity groups (MGs). The DTF reduced obviously along with soybeans extended to higher latitudes, ranging in 41-83 days and MG 000-III. Using the RTM-GWAS (restricted two-stage multi-locus model genome-wide association study) procedure, 81 QTLs with 342 alleles were identified, accounting for 77.85% genetic contribution (R = 0.01-7.74%/locus), and other 20.75% (98.60-77.85%, h = 98.60%) genetic variation was due to a collective of unmapped QTLs. With soybeans northward, breeding effort made the original MG I-III evolved to MG 0-00-000. In direct comparisons of QTL-allele matrices among MGs, the genetic dynamics are identified with local exotic introduction/migration (58.48%) as the first and selection against/exclusion of positive alleles causing new recombination (40.64%) as the second, while only a few allele emergence/mutation happened (0.88%, limited in MG 0, not in MG 00-000). In new MG emergence, 24 QTLs with 19 candidate genes are the major sources. A genetic potential of further DTF shortening (13-21 days) is predicted for NEC population. The QTL detection in individual ecoregions showed various ecoregion-specific QTLs-alleles/genes after co-localization treatment (removing the random environment shifting ones).
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http://dx.doi.org/10.1007/s00122-020-03558-4DOI Listing
June 2020

Evaluation of serum MUC5AC in combination with CA19-9 for the diagnosis of pancreatic cancer.

World J Surg Oncol 2020 Feb 7;18(1):31. Epub 2020 Feb 7.

Department of General Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.

Background: Pancreatic cancer (PC) is a highly aggressive tumor with a poor prognosis that lacks specific diagnostic markers. Mucin 5AC (MUC5AC) is a member of the mucin family, a heterogeneous group of high molecular weight, heavily glycosylated proteins that could be either membrane-bound or secreted. This multi-central study is to evaluate the performance of serum MUC5AC in combination with carbohydrate antigen 19-9 (CA19-9) for the diagnosis of PC in Asian.

Methods: Sixty-one patients with PC (comprised of early pancreatic cancer [n = 30] and late pancreatic cancer [n = 31] patients), 29 benign control, 35 choledocholithiasis, 25 chronic pancreatitis, and 34 healthy controls, were recruited from two hospitals. Serum levels of MUC5AC were evaluated by commercial ELISA kits. CA19-9 was measured by chemiluminescence immunoassay. The cutoff value of MUC5AC was determined based on optimal sensitivity and specificity.

Results: Serum MUC5AC in patients with PC (210.1 [100.5-423.8] ng/mL) presented higher levels than those in controls. The combined biomarker panel (MUC5AC and CA19-9) presented better performance and improved specificity to differentiate PC from controls (AUC 0.894; 95% CI (0.844-0.943), sensitivity 0.738, specificity 0.886) than CA19-9 (p = 0.043) or MUC5AC alone (p = 0.010); however, the latter two had no difference (p = 0.824).

Conclusions: Serum MUC5AC is a potential biomarker for PC. The combination with CA19-9 presents improved specificity and better performance.
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http://dx.doi.org/10.1186/s12957-020-1809-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006398PMC
February 2020

GmWRKY40, a member of the WRKY transcription factor genes identified from Glycine max L., enhanced the resistance to Phytophthora sojae.

BMC Plant Biol 2019 Dec 30;19(1):598. Epub 2019 Dec 30.

National Center for Soybean Improvement, Key Laboratory of Biology and Genetics and Breeding for Soybean, Ministry of Agriculture, State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China.

Background: The WRKY proteins are a superfamily of transcription factors and members play essential roles in the modulation of diverse physiological processes, such as growth, development, senescence and response to biotic and abiotic stresses. However, the biological roles of the majority of the WRKY family members remains poorly understood in soybean relative to the research progress in model plants.

Results: In this study, we identified and characterized GmWRKY40, which is a group IIc WRKY gene. Transient expression analysis revealed that the GmWRKY40 protein is located in the nucleus of plant cells. Expression of GmWRKY40 was strongly induced in soybean following infection with Phytophthora sojae, or treatment with methyl jasmonate, ethylene, salicylic acid, and abscisic acid. Furthermore, soybean hairy roots silencing GmWRKY40 enhanced susceptibility to P. sojae infection compared with empty vector transgenic roots. Moreover, suppression of GmWRKY40 decreased the accumulation of reactive oxygen species (ROS) and modified the expression of several oxidation-related genes. Yeast two-hybrid experiment combined with RNA-seq analysis showed that GmWRKY40 interacted with 8 JAZ proteins with or without the WRKY domain or zinc-finger domain of GmWRKY40, suggesting there were different interaction patterns among these interacted proteins.

Conclusions: Collectively, these results suggests that GmWRKY40 functions as a positive regulator in soybean plants response to P. sojae through modulating hydrogen peroxide accumulation and JA signaling pathway.
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http://dx.doi.org/10.1186/s12870-019-2132-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937711PMC
December 2019

Correction to: Molecular mapping of a novel male-sterile gene ms in soybean [Glycine max (L.) Merr.].

Plant Reprod 2020 03;33(1):75

Soybean Research Institute, National Center for Soybean Improvement, MARA Key Laboratory for Biology and Genetic Improvement of Soybean (General), National Key Laboratory for Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, People's Republic of China.

The Acknowledgement section of the original publication gave a wrong grant number. The correct Acknowledgement should read.
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http://dx.doi.org/10.1007/s00497-019-00380-xDOI Listing
March 2020

Molecular mapping of a novel male-sterile gene ms in soybean [Glycine max (L.) Merr.].

Plant Reprod 2019 12 16;32(4):371-380. Epub 2019 Oct 16.

Soybean Research Institute, National Center for Soybean Improvement, MARA Key Laboratory for Biology and Genetic Improvement of Soybean (General), National Key Laboratory for Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, People's Republic of China.

Nuclear male sterility (NMS) is a potential characteristic in crop recurrent selection and hybrid breeding. Mapping of nuclear male-sterile genes is key to utilizing NMS. Previously, we discovered a spontaneous soybean (Glycine max [L.] Merr.) male-sterile female-fertile mutant NJS-13H, which was conferred by a single recessive gene, designated ms. In this study, the ms was mapped to Chromosome 10 (LG O), and narrowed down between two SSR (simple sequence repeats) markers, BARCSOYSSR_10_794 and BARCSOYSSR_10_819 using three heterozygote-derived segregating populations, i.e., (NJS-13H × NN1138-2)F, (NJS-13H × N2899)F and (NJS-13H)SPAG (segregating populations in advanced generations). This region spans approximately 1.32 Mb, where 27 genes were annotated according to the soybean reference genome sequence (Wm82.a2.v1). Among them, four genes were recognized as candidate genes for ms. Comparing to the physical locations of all the known male-sterile loci, ms is demonstrated to be a new male-sterile locus. This result may help the utilization and cloning of the gene.
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http://dx.doi.org/10.1007/s00497-019-00377-6DOI Listing
December 2019

SIRT5 Promotes Cisplatin Resistance in Ovarian Cancer by Suppressing DNA Damage in a ROS-Dependent Manner via Regulation of the Nrf2/HO-1 Pathway.

Front Oncol 2019 13;9:754. Epub 2019 Aug 13.

Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.

Sirtuin 5 (SIRT5), a mitochondrial class III NAD-dependent deacetylase, plays controversial roles in tumorigenesis and chemoresistance. Accordingly, its role in ovarian cancer development and drug resistance is not fully understood. Here, we demonstrate that SIRT5 is increased in ovarian cancer tissues compared to its expression in normal tissues and this predicts a poor response to chemotherapy. SIRT5 levels were also found to be higher in cisplatin-resistant SKOV-3 and CAOV-3 ovarian cancer cells than in cisplatin-sensitive A2780 cells. Furthermore, this protein was revealed to facilitate ovarian cancer cell growth and cisplatin-resistance . Mechanistically, we show that SIRT5 contributes to cisplatin resistance in ovarian cancer by suppressing cisplatin-induced DNA damage in a reactive oxygen species (ROS)-dependent manner via regulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway.
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http://dx.doi.org/10.3389/fonc.2019.00754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700301PMC
August 2019

Development of sexual dimorphism in two sympatric skinks with different growth rates.

Ecol Evol 2019 Jul 14;9(13):7752-7760. Epub 2019 Jun 14.

Ministry of Education Key Laboratory for Biodiversity and Ecological Engineering College of Life Sciences Beijing Normal University Beijing China.

Sexual size dimorphism (SSD) is widespread in animals, especially in lizards (Reptilia: Squamata), and is driven by fecundity selection, male-male competition, or other adaptive hypotheses. However, these selective pressures may vary through different life history periods; thus, it is essential to assess the relationship between growth and SSD. In this study, we tracked SSD dynamics between a "fading-tail color skink" (blue tail skink whose tail is only blue during its juvenile stage: ) and a "nonfade color" tail skink (retains a blue tail throughout life: ) under a controlled experimental environment. We fitted growth curves of morphological traits (body mass, SVL, and TL) using three growth models (Logistic, Gompertz, and von Bertalanffy). We found that both skinks have male-biased SSD as adults. Body mass has a higher goodness of fit (as represented by very high values) using the von Bertalanffy model than the other two models. In contrast, SVL and TL for both skinks had higher goodness of fit when using the Gompertz model. Two lizards displayed divergent life history tactics: grows faster, matures earlier (at 65 weeks), and presents an allometric growth rate, whereas grows slower, matures later (at 106 weeks), and presents an isometric growth rate. Our findings imply that species- and sex-specific trade-offs in the allocation of energy to growth and reproduction may cause the growth patterns to diverge, ultimately resulting in the dissimilar patterns of SSD.
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http://dx.doi.org/10.1002/ece3.5358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636199PMC
July 2019

15-Lipoxygenase 1 in nasal polyps promotes CCL26/eotaxin 3 expression through extracellular signal-regulated kinase activation.

J Allergy Clin Immunol 2019 11 11;144(5):1228-1241.e9. Epub 2019 Jul 11.

University of Pittsburgh Asthma [email protected], Department of Environmental and Occupational Health, Graduate School of Public Health, Pittsburgh, Pa. Electronic address:

Background: 15-Lipoxygenase 1 (15LO1) is expressed in airway epithelial cells in patients with type 2-high asthma in association with eosinophilia. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also associated with type 2 inflammation and eosinophilia. CCL26/eotaxin 3 has been reported to be regulated by 15LO1 in lower airway epithelial cells. However, its relation to 15LO1 in patients with CRSwNP or mechanisms for its activation are unclear.

Objective: We sought to evaluate 15LO1 and CCL26 expression in nasal epithelial cells (NECs) from patients with CRSwNP and healthy control subjects (HCs) and determine whether 15LO1 regulates CCL26 in NECs through extracellular signal-regulated kinase (ERK) activation.

Methods: 15LO1, CCL26, and phosphorylated ERK were evaluated in NECs from patients with CRSwNP and HCs. 15LO1/CCL26 and CCL26/cytokeratin 5 were colocalized by means of immunofluorescence. IL-13-stimulated NECs were cultured at an air-liquid interface with or without 15-lipoxygenase 1 gene (ALOX15) Dicer-substrate short interfering RNAs (DsiRNA) transfection, a specific 15LO1 enzymatic inhibitor, and 2 ERK inhibitors. Expression of 15LO1 and CCL26 mRNA and protein was analyzed by using quantitative RT-PCR, Western blotting, and ELISA.

Results: 15LO1 expression was increased in nasal polyp (NP) epithelial cells compared with middle turbinate epithelial cells from patients with CRSwNP and HCs. 15LO1 expression correlated with CCL26 expression and colocalized with CCL26 expression in basal cells of the middle turbinate and NPs from patients with CRSwNP. In primary NECs in vitro, IL-13 induced 15LO1 and CCL26 expression. 15LO1 knockdown and inhibition decreased IL-13-induced ERK phosphorylation and CCL26 expression. ERK inhibition (alone) similarly decreased IL-13-induced CCL26. Phosphorylated ERK expression was increased in NECs from CRSwNP subjects and positively correlated with both 15LO1 and CCL26 expression.

Conclusions: 15LO1 expression is increased in NP epithelial cells and contributes to CCL26 expression through ERK activation. 15LO1 could be considered a novel therapeutic target for CRSwNP.
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http://dx.doi.org/10.1016/j.jaci.2019.06.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842430PMC
November 2019