Publications by authors named "Xiaoyang Sun"

96 Publications

ITPRIP promotes glioma progression by linking MYL9 to DAPK1 inhibition.

Cell Signal 2021 Jun 7:110062. Epub 2021 Jun 7.

Department of Neurosurgery, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, 1 Huanghe West Road, Huaian 223300, China. Electronic address:

Epigenetic gene silencing of the tumor suppressor death-associated protein kinase 1 (DAPK1) is implicated in the progression of malignant gliomas. However, the mechanism underlying the repression of DAPK1 in gliomas remains elusive. In this study, we identified the existence of DAPK1-inositol 1,4,5-trisphosphate receptor (IPR)-interacting protein (ITPRIP) -myosin regulatory light polypeptide 9 (MYL9) complex in malignant glioma cells. Lentivirus co-infection and coimmunoprecipitation showed that ITPRIP bound with the death domain (DD) of DAPK1 in vitro. Further, dissociating ITPRIP-DAPK1 interaction inhibited glioma tumor growth in vitro but not in vivo. Moreover, knockdown of ITPRIP or DAPK1 impaired the ternary complex formation, whereas MYL9 knockdown did not affect ITPRIP-DAPK1 association. We further found that ITPRIP recruited MYL9 to the kinase domain (KD) of DAPK1, and in turn impeded the phosphorylation of MYL9. Accordingly, interference of ITPRIP enhanced the suppressive effects of DAPK1-KD on glioma progression both in vitro and in vivo. Our results demonstrate that ITPRIP plays a crucial role in the inhibition of DAPK1 and enhancement of tumorigenic properties of malignant glioma cells.
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http://dx.doi.org/10.1016/j.cellsig.2021.110062DOI Listing
June 2021

MABAN: Multi-Agent Boundary-Aware Network for Natural Language Moment Retrieval.

IEEE Trans Image Process 2021 16;30:5589-5599. Epub 2021 Jun 16.

The amount of videos over the Internet and electronic surveillant cameras is growing dramatically, meanwhile paired sentence descriptions are significant clues to select attentional contents from videos. The task of natural language moment retrieval (NLMR) has drawn great interests from both academia and industry, which aims to associate specific video moments with the text descriptions figuring complex scenarios and multiple activities. In general, NLMR requires temporal context to be properly comprehended, and the existing studies suffer from two problems: (1) limited moment selection and (2) insufficient comprehension of structural context. To address these issues, a multi-agent boundary-aware network (MABAN) is proposed in this work. To guarantee flexible and goal-oriented moment selection, MABAN utilizes multi-agent reinforcement learning to decompose NLMR into localizing the two temporal boundary points for each moment. Specially, MABAN employs a two-phase cross-modal interaction to exploit the rich contextual semantic information. Moreover, temporal distance regression is considered to deduce the temporal boundaries, with which the agents can enhance the comprehension of structural context. Extensive experiments are carried out on two challenging benchmark datasets of ActivityNet Captions and Charades-STA, which demonstrate the effectiveness of the proposed approach as compared to state-of-the-art methods. The project page can be found in https://mic.tongji.edu.cn/e5/23/c9778a189731/page.htm.
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http://dx.doi.org/10.1109/TIP.2021.3086591DOI Listing
June 2021

Performance of liver stiffness measurements obtained with FibroScan is affected by glucose metabolism in patients with nonalcoholic fatty liver disease.

Lipids Health Dis 2021 Mar 23;20(1):27. Epub 2021 Mar 23.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: The performance of liver stiffness measurements (LSMs) obtained using FibroScan can be affected by several factors, and cut-off values are different for fibrosis caused by various aetiologies. The study aims to evaluate the diagnostic accuracy of LSM in nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism and investigate whether the LSM value would be affected by metabolic indicators.

Methods: The study involved 91 NAFLD patients with abnormal glucose metabolism who underwent liver biopsy. The diagnostic accuracy of LSM value was evaluated by the receiver operator characteristic (ROC) curves, with the biopsy results taken as the gold standard. Multivariate linear regression and subgroup analysis were performed to determine the correlated indicators.

Results: The areas under the ROC curves (AUROCs) of LSM values for detecting fibrosis stage ≥1, 2, 3 and 4 were 0.793 (95% confidence interval [CI]: 0.695-0.871), 0.764 (95% CI: 0.663-0.846), 0.837 (95% CI: 0.744-0.906) and 0.902 (95% CI: 0.822-0.955), with cut-off values of 6.3, 7.6, 8.3 and 13.8 kPa, respectively. Multivariate linear regression demonstrated that haemoglobin A1c (HbA1c, β = 0.205, P = 0.026) and alanine aminotransferase (ALT, β = 0.192, P = 0.047) were independently associated with the LSM value after adjustment for fibrosis stage, ballooning and inflammation grade from liver biopsy. Subgroup analysis demonstrated that LSM values were slightly higher in patients with HbA1c ≥7% than in those with HbA1c < 7% and in patients with body mass index (BMI) ≥30 kg/m than in those with BMI < 30 kg/m.

Conclusions: FibroScan was valuable for the evaluation of liver fibrosis in NAFLD patients with abnormal glucose metabolism. FibroScan is recommended to evaluate severe fibrosis, especially to exclude advanced fibrosis. Glucose metabolism state may affect LSM values.
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http://dx.doi.org/10.1186/s12944-021-01453-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986416PMC
March 2021

Diagnosis of Fibrosis Using Blood Markers and Logistic Regression in Southeast Asian Patients With Non-alcoholic Fatty Liver Disease.

Front Med (Lausanne) 2021 23;8:637652. Epub 2021 Feb 23.

Human Metabolomics Institute, Inc., Shenzhen, China.

Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of fibrosis. Liver biopsy remains the gold standard for the confirmation of fibrosis in NAFLD patients. Effective and non-invasive diagnosis of advanced fibrosis is essential to disease surveillance and treatment decisions. Herein we used routine medical test markers and logistic regression to differentiate early and advanced fibrosis in NAFLD patients from China, Malaysia, and India ( = 540, = 147, and = 97) who were confirmed by liver biopsy. Nine parameters, including age, body mass index, fasting blood glucose, presence of diabetes or impaired fasting glycemia, alanine aminotransferase, γ-glutamyl transferase, triglyceride, and aspartate transaminase/platelet count ratio, were selected by stepwise logistic regression, receiver operating characteristic curve (ROC), and hypothesis testing and were used for model construction. The area under the ROC curve (auROC) of the model was 0.82 for differentiating early and advanced fibrosis (sensitivity = 0.69, when specificity = 0.80) in the discovery set. Its diagnostic ability remained good in the two independent validation sets (auROC = 0.89 and 0.71) and was consistently superior to existing panels such as the FIB-4 and NAFLD fibrosis score. A web-based tool, LiveFbr, was developed for fast access to our model. The new model may serve as an attractive tool for fibrosis classification in NAFLD patients.
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http://dx.doi.org/10.3389/fmed.2021.637652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940822PMC
February 2021

Deficiency for Lcn8 causes epididymal sperm maturation defects in mice.

Biochem Biophys Res Commun 2021 Apr 22;548:7-13. Epub 2021 Feb 22.

School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, PR China. Electronic address:

Lipocalin family members, LCN8 and LCN9, are specifically expressed in the initial segment of mouse caput epididymis. However, the biological functions of the molecules in vivo are yet to be clarified. In this study, CRISPR/Cas9 technology was used to generate Lcn8 and Lcn9 knockout mice, respectively. Lcn8 and Lcn9 male mice showed normal spermatogenesis and fertility. In the cauda epididymis of Lcn8 male mice, morphologically abnormal sperm was increased significantly, the proportion of progressive motility sperm was decreased, the proportion of immobilized sperm was elevated, and the sperm spontaneous acrosome reaction (AR) frequency was increased. Conversely, the knockout of Lcn9 did not have any effect on the ratio of morphologically abnormal sperm, sperm motility, and sperm spontaneous AR frequencies. These results demonstrated the role of LCN8 in maintaining the sperm quality in the epididymis, and suggested that the deficiency of LCN8 leads to epididymal sperm maturation defects.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.052DOI Listing
April 2021

Assessment of differences in morphological and physiological leaf lodging characteristics between two cultivars of Hippeastrum rutilum.

BMC Plant Biol 2020 Dec 14;20(1):565. Epub 2020 Dec 14.

College of Horticulture & Landscape Architecture, Northeast Agricultural University, Harbin, 150030, China.

Background: Environmental lodging stress, which is a result of numerous factors, is characterized by uncertainty. However, several studies related to lodging in cereal crops have reported that lodging in the Hippeastrum rutilum environment is very rare. Hippeastrum rutilum is a garden flower with high ornamental value and abundant germplasm resources. Under past cultivation practices, it was found that the plant types of 'Red Lion', with red flowers, and 'Apple Blossom', with pink flowers, are quite different. The leaves of 'Red Lion' are upright, while the leaves of 'Apple Blossom' show lodging, which seriously affects its ornamental value. The aims of this study were to compare the differences between the two varieties with leaf lodging and upright leaves according to morphological and physiological attributes. In this study, karyotype analysis and phenotypic morphological and physiological characteristics were compared to explore the differences between the two plant types.

Results: The karyotype analysis of the two cultivars showed that their chromosome types were both tetraploid plants. The results showed that the lignin content in the leaves of 'Red Lion' was high, the cross-sectional structure of the leaf vascular bundle was more stable, and the chlorophyll content was high. In addition, significantly less energy was transferred to the electron transport chain (ETR) during the photoreaction. Similarly, the results regarding the maximum photosynthetic rate (Fv/Fm), nonphotochemical quenching (NPQ) and effective quantum yield of photosystem II photochemistry (△F/Fm') all indicated that the photosynthetic capacity of "Red Lion" was greater than that of "Apple Blossom", which was affected by leaf lodging. The size of the leaves was significantly smaller, and the leaf sag angle, leaf width, and leaf tip angle presented significantly lower values in 'Red Lion' than in 'Apple Blossom', which exhibits leaf sag. The difference in these factors may be the reason for the different phenotypes of the two cultivars.

Conclusion: The results of this study proved that lodging affects the photosynthetic capacity of Hippeastrum rutilum and revealed some indexes that might be related to leaf lodging, laying a theoretical foundation for cultivating and improving new varieties.
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http://dx.doi.org/10.1186/s12870-020-02784-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737282PMC
December 2020

Gut Microbiome Components Predict Response to Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Prospective, Longitudinal Study.

Clin Cancer Res 2021 Mar 9;27(5):1329-1340. Epub 2020 Dec 9.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.

Purpose: The gut microbiome is involved in antitumor immunotherapy and chemotherapy responses; however, evidence-based research on the role of gut microbiome in predicting response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) remains scarce. This prospective, longitudinal study aimed to evaluate the feasibility of the gut microbiome in predicting nCRT responses.

Experimental Design: We collected 167 fecal samples from 84 patients with LARC before and after nCRT and 31 specimens from healthy individuals for 16S rRNA sequencing. Patients were divided into responders and nonresponders according to pathologic response to nCRT. After identifying microbial biomarkers related to nCRT responses, we constructed a random forest classifier for nCRT response prediction of a training cohort of baseline samples from 37 patients and validated the classifier in another cohort of 47 patients.

Results: We observed significant microbiome alterations represented by a decrease in LARC-related pathogens and an increase in and during nCRT. Furthermore, a prominent microbiota difference between responders and nonresponders was noticed in the baseline samples. Microbes related with butyrate production, including , and , were overrepresented in responders, whereas and were overrepresented in nonresponders. Ten biomarkers were selected for the response-prediction classifier, including , and , which yielded an area under the curve value of 93.57% [95% confidence interval (CI), 85.76%-100%] in the training cohort and 73.53% (95% CI, 58.96%-88.11%) in the validation cohort.

Conclusions: The gut microbiome offers novel potential biomarkers for predicting nCRT responses, which has important manifestations in the clinical management of these patients.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3445DOI Listing
March 2021

Angio-associated migratory cell protein (AAMP) interacts with cell division cycle 42 (CDC42) and enhances migration and invasion in human non-small cell lung cancer cells.

Cancer Lett 2021 Apr 3;502:1-8. Epub 2020 Dec 3.

Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China; Shandong Provincial Collaborative Innovation Center of Cell Biology, School of Life Sciences, Shandong Normal University, Jinan, China. Electronic address:

Angio-associated migratory cell protein (AAMP) is considered a pro-tumor protein, which contributes to angiogenesis, proliferation, adhesion, and other biological activities. Although AAMP is known to facilitate the motility of breast cancer cells and smooth muscle cells by regulating ras homolog family member A (RHOA) activity, the function of AAMP in the metastasis of non-small cell lung cancer (NSCLC) cells still remains unknown. In the present study, AAMP was upregulated in non-small cell lung carcinoma, and was found to promote migration and invasion in NSCLC cells. Further experiments demonstrated that AAMP interacted with cell division cycle 42 (CDC42) and promoted its activation, resulting in the formation of cellular protrusions. Subsequently, we found that AAMP enhanced CDC42 activation by impairing the combination of rho GTPase activating protein 1 (ARHGAP1) and CDC42. Taken together, we revealed and elucidated the critical role of AAMP in the migration and invasion of NSCLC cells and presented a new potential target for lung cancer therapy.
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http://dx.doi.org/10.1016/j.canlet.2020.11.050DOI Listing
April 2021

Osteocalcin and Non-Alcoholic Fatty Liver Disease: Lessons From Two Population-Based Cohorts and Animal Models.

J Bone Miner Res 2021 Apr 21;36(4):712-728. Epub 2020 Dec 21.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.

Osteocalcin regulates energy metabolism in an active undercarboxylated/uncarboxylated form. However, its role on the development of non-alcoholic fatty liver disease (NAFLD) is still controversial. In the current study, we investigated the causal relationship of circulating osteocalcin with NAFLD in two human cohorts and studied the effect of uncarboxylated osteocalcin on liver lipid metabolism through animal models. We analyzed the correlations of serum total/uncarboxylated osteocalcin with liver steatosis/fibrosis in a liver biopsy cohort of 196 participants, and the causal relationship between serum osteocalcin and the incidence/remission of NAFLD in a prospective community cohort of 2055 subjects from Shanghai Changfeng Study. Serum total osteocalcin was positively correlated with uncarboxylated osteocalcin (r = 0.528, p < .001). Total and uncarboxylated osteocalcin quartiles were inversely associated with liver steatosis, inflammation, ballooning, and fibrosis grades in both male and female participants (all p for trend <.05). After adjustment for confounding glucose, lipid, and bone metabolism parameters, the male and female participants with lowest quartile of osteocalcin still had more severe liver steatosis, with multivariate-adjusted odds ratios (ORs) of 7.25 (1.07-49.30) and 4.44 (1.01-19.41), respectively. In the prospective community cohort, after a median of 4.2-year follow-up, the female but not male participants with lowest quartile of osteocalcin at baseline had higher risk to develop NAFLD (hazard ratio [HR] = 1.90; 95% confidence interval [CI] 1.14-3.16) and lower chance to achieve NAFLD remission (HR = 0.56; 95% CI 0.31-1.00). In wild-type mice fed a Western diet, osteocalcin treatment alleviated hepatic steatosis and reduced hepatic SREBP-1 and its downstream proteins expression. In mice treated with osteocalcin for a short term, hepatic SREBP-1 expression was decreased without changes of glucose level or insulin sensitivity. When SREBP-1c was stably expressed in a human SREBP-1c transgenic rat model, the reduction of lipogenesis induced by osteocalcin treatment was abolished. In conclusion, circulating osteocalcin was inversely associated with NAFLD. Osteocalcin reduces liver lipogenesis via decreasing SREBP-1c expression. © 2020 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4227DOI Listing
April 2021

Investigation of Daily Glucose Profile of Inpatients in Non-endocrinology Departments in Chinese Population.

Front Public Health 2020 5;8:521227. Epub 2020 Nov 5.

Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China.

Inpatient hyperglycemia is associated with poor prognosis and increased hospitalization expenses. China has a large population of inpatients with hyperglycemia, but their glucose monitoring states (including preprandial, postprandial and bedtime glucose) are unknown, especially in non-endocrinology departments. In this cross-sectional study, 5,790 patients with hyperglycemia from 31 non-endocrinology departments were enrolled, and a total of 1,22,032 point-of-care blood glucose (POC-BG) records were collected. The "patient-day" unit of measure was used as a metric for the inpatient glucose. A total of 2,763 patients from endocrinology wards were included for the comparison of the improvement of glycemic management during hospitalization in non-endocrinology wards. A total of 61.16% of patient-days had <4 POC-BG tests. Postprandial POC-BG was tested significantly less frequently than preprandial POC-BG (10.60% vs. 58.85% of all records, < 0.001). The patient-day-weighted mean BG was higher in non-ICU wards than in the ICU (9.72 ± 3.37 vs. 9.00 ± 3.19 mmol/L, < 0.001). The rate of hyperglycemia (BG >10 mmol/L) was 37.60% in all non-endocrinology wards (ICU vs. non-ICU: 33.19% vs. 39.17%, < 0.001). In non-ICU wards, the rate of hyperglycemia (BG >10 mmol/L) was significantly higher in surgical wards than in medical wards (40.30% vs. 36.90%, < 0.001). ICU had a significantly higher rate of achieving the blood glucose target than the non-ICU wards (32.50% vs. 26.38%, < 0.001). In the non-ICU departments, medical wards had higher rate of achieving the blood glucose target than surgical wards (39.70% vs. 19.08%, < 0.001). With increasing days of hospitalization, there was no improvement in glycemic control in non-endocrinology wards. The ICU had a significantly higher rate of hypoglycemia than non-ICU wards (4.62% vs. 3.73%, < 0.05). In non-ICU wards, medical wards had a significantly higher rate of hypoglycemia than surgical wards (5.71% vs. 2.75%, < 0.05). Both the frequency of BG monitoring and the daily glucose profile of inpatients in Chinese non-endocrinology departments were less than ideal and need to be urgently improved.
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http://dx.doi.org/10.3389/fpubh.2020.521227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674397PMC
May 2021

Beneficial Effects of Mixing Kentucky Bluegrass With Red Fescue Plant-Soil Interactions in Black Soil of Northeast China.

Front Microbiol 2020 28;11:556118. Epub 2020 Oct 28.

College of Horticulture and Landscape Architecture, Northeast Agricultural University, Harbin, China.

Continuous monoculture of cool-season turfgrass causes soil degradation, and visual turf quality decline is a major concern in black soil regions of Northeast China. Turf mixtures can enhance turfgrass resistance to biotic and abiotic stresses and increase soil microbial diversity. Understanding mechanism by plant-soil interactions and changes of black soil microbial communities in turf mixture is beneficial to restoring the degradation of urbanized black soils and maintaining sustainable development of urban landscape ecology. In this study, based on the previous research of different sowing models, two schemes of turf monoculture and mixture were conducted in field plots during 2016-2018 in a black soil of Heilongjiang province of Northeast China. The mixture turf was established by mixing 50% Kentucky bluegrass "Midnight" ( L.) with 50% Red fescue "Frigg" ( L.); and the monoculture turf was established by sowing with pure Kentucky bluegrass. Turf performance, soil physiochemical properties, and microbial composition from rhizosphere were investigated. Soil microbial communities and abundance were analyzed by Illumina MiSeq sequencing and quantitative PCR methods. Results showed that turfgrass quality, turfgrass biomass, soil organic matter (SOM), urease, alkaline phosphatase, invertase, and catalase activities increased in PF mixture, but disease percentage and soil pH decreased. The microbial diversity was also significantly enhanced under turf mixture model. The microbial community compositions were significantly different between the two schemes. Turf mixtures obviously increased the abundances of , , , and spp., while remarkably reduced the abundances of and spp. Redundancy analysis showed that the compositions of bacteria and fungi were related to edaphic parameters, such as SOM, pH, and enzyme activities. Since the increasing of turf quality, biomass, and disease resistance were highly correlated with the changes of soil physiochemical parameters and microbial communities in turf mixture, which suggested that turf mixture with two species (i.e., Kentucky blue grass and Red fescue) changed soil microbial communities and enhanced visual turfgrass qualities through positive plant-soil interactions by soil biota.
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http://dx.doi.org/10.3389/fmicb.2020.556118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656059PMC
October 2020

Preoperative Chemoradiotherapy Postoperative Chemoradiotherapy for Patients With Locally Advanced Gastric Cancer: A Retrospective Study Based on Propensity Score Analyses.

Front Oncol 2020 16;10:560115. Epub 2020 Oct 16.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Purpose: Although adjuvant chemoradiotherapy (CRT) used to be recommended as a standard of care for locally advanced gastric cancer, this suggestion has been strongly challenged recently. However, clear evidence regarding the optimization of radiotherapy is lacking. The purpose of this study was to compare the effectiveness of preoperative CRT that of postoperative CRT for resectable or potentially resectable gastric cancer.

Methods: From January 2005 to December 2017, patients with clinical stage III/IVa (, T3-4aN+M0 or T4bNxM0) locally advanced gastric cancer were retrospectively identified. Survival after preoperative CRT and postoperative CRT was assessed by unadjusted, propensity score matching (PSM) and inverse probability of treatment weight (IPTW) analyses. Moreover, exploratory subgroup analyses were performed, and toxicity and patterns of failure were also investigated.

Results: The median follow-up time was 32.5 months. A total of 82 and 463 patients were enrolled in the preoperative and postoperative CRT groups, respectively. After propensity score matching, preoperative CRT was associated with improved overall survival (OS) and disease-free survival (DFS) compared with postoperative CRT (3-year OS: 72.6 54.4%, log-rank p = 0.0021; 3-year DFS: 61.7 44.7%, log-rank p = 0.002). The unadjusted and IPTW analyses yielded consistent results. A complete pathologic response was achieved in 13.4% of the preoperative CRT group. Although the incidence of grade 3 or 4 adverse effects and surgical complications were similar between the two groups, significantly fewer patients experienced treatment interruptions or dose reductions due to toxic effects in the preoperative CRT setting than in the postoperative CRT setting (3.7 10.6%, p = 0.049).

Conclusions: Compared with postoperative CRT, preoperative CRT was associated with improved OS and DFS, superior treatment compliance and comparable surgical complications for patients with locally advanced gastric cancer. Our findings provide important evidence for the optimal combination modalities of surgery and CRT in the absence of randomized clinical data.
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http://dx.doi.org/10.3389/fonc.2020.560115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596744PMC
October 2020

Determining whether multiple needles are necessary in interstitial brachytherapy for thoracic tumors: A dosimetry analysis.

Indian J Cancer 2020 Oct-Dec;57(4):437-442

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

Background: In interstitial brachytherapy, needles must be inserted in a regular, parallel arrangement to ensure a uniform target dose distribution and conformal distribution to the target. It is generally difficult to achieve this in thoracic tumors because of obstruction by the ribs. Furthermore, insertion of multiple needles may cause the patient considerable harm and could expose him/her to additional risks. Thus, we propose the single-dwell-position method, discuss its applicability, and compare it with the actual multiple-needle method using dosimetry. The aim of this study was to evaluate the necessity for multiple needles with irregular alignment in interstitial brachytherapy for thoracic tumors.

Methods: Twelve patients' interstitial brachytherapy plans were reviewed. The single-dwell-position interstitial brachytherapy plans, wherein one needle was hypothetically inserted, were compared with the actual multiple-needle plans. Dose parameters, including clinical target volume (CTV) and volumes of the lung, spinal cord, heart, and ribs, were compared. We also evaluated the correlation between CTV size and dose difference in the lungs. The nonparametric Wilcoxon test was used.

Results: There were no statistically significant differences in the doses achieved with the single-dwell-position plans and actual multiple-needle plans. The correlation between the CTV size and dose difference in the lungs was weak.

Conclusions: Irregularly arranged multiple-needle interstitial brachytherapy does not provide superior doses to the lung, heart, spinal cord, or ribs compared with single-dwell-position plans. If regular arrangement of multiple needles is difficult to achieve, the multiple-needle scheme is not the only viable option.
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http://dx.doi.org/10.4103/ijc.IJC_693_18DOI Listing
October 2020

Identification of a Novel c-Myc Inhibitor 7594-0037 by Structure-Based Virtual Screening and Investigation of Its Anti-Cancer Effect on Multiple Myeloma.

Drug Des Devel Ther 2020 28;14:3983-3993. Epub 2020 Sep 28.

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.

Introduction: Multiple myeloma (MM) is an extremely malignant and incurable hematological cancer. Increased expression of the c-Myc oncoprotein is closely associated with shorter overall survival of MM patients, implying that c-Myc is a potential therapeutic target.

Main Methods: We identified a potential c-Myc inhibitor 7594-0037 by structure-based virtual screening from the ChemDiv database. CCK8 assay and flow cytometry were used to detect MM cell viability, cell cycle and apoptosis. Q-PCR and Western blot were used to measure corresponding mRNA and protein expression levels. Protein stability assay measured the stability of c-Myc.

Results: Compound 7594-0037 exhibited stronger anti-proliferative activity against MM cells, and induced MM cell cycle G2 phase arrest and apoptosis. More importantly, compound 7594-0037 overcame myeloma resistance to bortezomib and exhibited a synergistic effect with bortezomib, resulting in increased MM cell death. The mechanism consists of compound 7594-0037 facilitating c-Myc protein degradation via decreasing the c-Myc S62 phosphorylation levels mediated by PIM1 kinase. Molecular dynamics simulation with the c-Myc/7594-0037 complex showed that compound 7594-0037 bound tightly to the N-terminus of c-Myc, and blocked the binding interaction of the two termini of c-Myc, which resulted in c-Myc entering into an unstable state.

Conclusion: Overall, our study provides preliminary data for compound 7594-0037, which can be used as a novel c-Myc inhibitor and is a potential candidate therapeutic drug for multiple myeloma.
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http://dx.doi.org/10.2147/DDDT.S264077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532311PMC
September 2020

Effects of enzymatic free fatty acid reduction process on the composition and phytochemicals of rice bran oil.

Food Chem 2021 Feb 5;337:127757. Epub 2020 Aug 5.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, 100048, PR China.

The effects of enzymatic free fatty acid reduction process (EFFARP) on the composition and phytochemicals of dewaxed and degummed rice bran oil (DDRBO) were investigated and compared with the effects observed using internal acyl acceptors. The acid value of DDRBO was effectively decreased from 16.99 mg KOH/g to approximately 0.36 mg KOH/g by EFFARP. EFFARP significantly decreased the moisture content and peroxide value of DDRBO and increased the induction period. The Sn-2 fatty acid comoposition of DDRBO after EFFARP was very reaching the total fatty acid composition. EFFARP significantly increased the triacylglycerol content compared to the control, while the oryzanol content was not obviously affected. The contents of free sterol, and total tocopherol and tocotrienol were increased slightly by EFFARP compared to the control. When conducted under vacuum with added nitrogen, EFFARP shows great application potential in the edible oil industry.
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http://dx.doi.org/10.1016/j.foodchem.2020.127757DOI Listing
February 2021

Effect of ultrasound-assisted extraction on the structure and emulsifying properties of peanut protein isolate.

J Sci Food Agric 2021 Feb 28;101(3):1150-1160. Epub 2020 Aug 28.

National Engineering Laboratory for Wheat & Corn Further Processing, Henan University of Technology, Zhengzhou, China.

Background: With an increasing demand for edible protein, research on new extraction methods is attracting more attention. The effects of such methods on functional properties are important. The present study aimed to evaluate the effect of ultrasound-assisted extraction on the extraction efficiency, structure, and the emulsifying properties of peanut protein isolate (PPI).

Results: Ultrasound-assisted extraction significantly improved extraction efficiency and shortened the processing time. The nanostructure, molecular weight distribution, and particle size of PPI were altered by ultrasound-assisted extraction. The emulsifying properties of the PPI from ultrasound-assisted extraction were significantly improved compared with alkaline extraction. Peanut protein isolate had lower molecular weight fractions, higher levels of hydrophobic amino acids, and the highest fluorescence intensity with ultrasound intensity, temperature, and time of 3.17 W cm , 35 °C, and 30 min, respectively. These contributed to the higher emulsifying activity index and emulsifying stability index of the PPI emulsions. The uniform distribution of droplets and smaller particle size of the PPI emulsions was also observed.

Conclusion: The results suggested that ultrasound can be used to induce the conformational changes to modify the interfacial association between protein-oil phases, thereby improving the emulsifying properties of peanut protein. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.10726DOI Listing
February 2021

Association between non-alcoholic fatty liver disease-associated hepatic fibrosis and bone mineral density in postmenopausal women with type 2 diabetes or impaired glucose regulation.

BMJ Open Diabetes Res Care 2020 08;8(1)

Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China

Introduction: To evaluate the association of non-alcoholic fatty liver disease (NAFLD)-associated hepatic fibrosis with bone mineral density (BMD) in postmenopausal women with type 2 diabetes mellitus (T2DM) or impaired glucose regulation (IGR).

Research Design And Methods: Two cohorts including 46 subjects with biopsy-proven NAFLD and 445 subjects with proton magnetic resonance spectrum-proven NAFLD were enrolled in this study. All subjects were postmenopausal women with T2DM or IGR. BMD at the lumbar spine L1-L4 and hip was measured using dual-energy X-ray absorptiometry. NAFLD fibrosis stage and NAFLD fibrosis score were used to evaluate the severity of liver fibrosis.

Results: In subjects with liver biopsy-proven NAFLD, BMD (T-score, Z-score and BMD value) in the advanced fibrosis group were significantly lower than that in the non-advanced fibrosis group (p<0.05). Fibrosis stage was negatively associated with T-score, Z-score and BMD value after adjusting for age, body mass index (BMI) and fasting plasma glucose (FPG). Additionally, fibrosis stage was independently associated with T-score, Z-score and BMD value after adjusting for age, BMI and FPG. These results were validated in a large cohort of 445 subjects. Additionally, bone metabolism-associated factors, including calcium and phosphate, were associated with liver fibrosis, indicating that bone metabolism may play a critical role in the association between liver fibrosis and BMD. Mechanically, parathyroid hormone and biomarkers of bone formation (osteocalcin and procollagen type 1 N-terminal propeptide) and bone resorption (procollagen type I carboxy terminal peptide β special sequence) were increased in subjects with advanced liver fibrosis than in subjects without advanced liver fibrosis, indicating that liver fibrosis decreased BMD probably via increasing bone turnover.

Conclusions: NAFLD-associated hepatic fibrosis was negatively associated with decreased BMD in postmenopausal women with T2DM or IGR. Liver fibrosis decreased BMD probably via increasing bone turnover. Severe liver fibrosis may represent high risk for osteoporosis in postmenopausal women with T2DM or IGR.
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http://dx.doi.org/10.1136/bmjdrc-2019-000999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409963PMC
August 2020

The deubiquitinase USP22 regulates PD-L1 degradation in human cancer cells.

Cell Commun Signal 2020 07 14;18(1):112. Epub 2020 Jul 14.

Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, 72 Binhai Road, Qingdao, 266237, P. R. China.

Background: Many cancers evade immune surveillance by overexpressing PD-L1. PD-L1 interacted with its receptor PD-1, resulting in reduction of T cell proliferation and activation and thereafter cancer cell death mediated by T-lymphocyte. Understanding the mechanisms that regulate PD-L1 was of vital importance for immune checkpoint blockade therapy (ICBT).

Methods: Human non-small cell lung cancer cells and 293FT cells were used to investigate the function of USP22 upon PD-L1 and CSN5 by WB, Immunoprecipitation, Immunofluorescence and Flow cytometry analysis. B16-F10 cells were used to explore the role of USP22 on tumorigenesis and T cell cytotoxicity. The relationship between USP22 and PD-L1 expression was investigated by Immunohistochemistry analysis in human non-small cell lung cancer samples.

Results: Our data showed that USP22 interacted with PD-L1 and promoted its stability. USP22 deubiquitinated PD-L1 and inhibited its proteasome degradation. Moreover, USP22 also interacted with CSN5 and stabilized CSN5 through deubiquitination. Either USP22 or CSN5 could facilitate the interaction of PD-L1 with the other one. Furthermore, USP22 removed K6, K11, K27, K29, K33 and K63-linked ubiquitin chain of both CSN5 and PD-L1. In addition, USP22 depletion inhibited tumorigenesis and promoted T cell cytotoxicity. Besides, USP22 expression positively correlated with PD-L1 expression in human non-small cell lung cancer samples.

Conclusions: Here, we suggested that USP22 is a new regulator for PD-L1. On the one hand, USP22 could directly regulate PD-L1 stability through deubiquitination. On the other hand, USP22 regulated PD-L1 protein level through USP22-CSN5-PD-L1 axis. In addition, USP22 depletion inhibited tumorigenesis and promoted T cell cytotoxicity. Besides, USP22 expression positively correlated with PD-L1 expression in human non-small cell lung cancer samples. Together, we identified a new regulator of PD-L1 and characterized the important role of USP22 in PD-L1 mediated immune evasion. Targeting USP22 might be a new solution to ICBT. Video abstract.
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http://dx.doi.org/10.1186/s12964-020-00612-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362500PMC
July 2020

Thrombospondin 1 improves hepatic steatosis in diet-induced insulin-resistant mice and is associated with hepatic fat content in humans.

EBioMedicine 2020 Jul 21;57:102849. Epub 2020 Jun 21.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China; Fudan Institute for Metabolic Diseases, Shanghai, China. Electronic address:

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with altered production of secreted proteins. Increased understanding of secreted proteins could lead to improved prediction and treatment of NAFLD. Here, we aimed to discover novel secreted proteins in humans that are associated with hepatic fat content using unbiased proteomic profiling strategy, and how the identified Thbs1 modulates lipid metabolism and hepatic steatosis.

Method: NAFLD patients were enrolled and treated with lifestyle intervention. Patients who underwent liver biopsy were enrolled for analyzing the correlation between circulating Thbs1 and liver steatosis. Mice were fed on high-fat, high-sucrose diet and treated with recombinant Thbs1. Primary hepatocytes isolated from CD36 knockout (CD36-/-) mice and their wild-type littermates (controls) were treated with glucose plus insulin for 24 h together with or without recombinant Thbs1.

Finding: Serum Thbs1 levels are increased in participants with NAFLD and positively associated with liver steatosis grades. Improvement of liver steatosis after lifestyle intervention was accompanied with significant reduction of serum Thbs1 levels. Pharmacological administration of recombinant human Thbs1 attenuates hepatic steatosis in diet-induced obese mice. Treatment with Thbs1 protein or stably overexpression of Thbs1 causes a significant reduction of lipid accumulation in primary hepatocytes or HepG2 cells exposed to high glucose plus insulin, suggesting that Thbs1 regulates lipid metabolism in a hepatocyte-autonomous manner. Mechanistically, Thbs1 inhibits cleavage and processing of SREBP-1, leading to a reduction of target lipogenic gene expression and hepatic steatosis. Inhibitory effects of Thbs1 on lipogenesis and triglyceride accumulation are abrogated in CD36 deficient primary hepatocytes exposed to high glucose plus insulin. Interestingly, beneficial effects of Thbs1 on lipid accumulation are observed in primary hepatocytes treated with a Thbs1 nonapeptide mimetic ABT-526.

Interpretation: Thbs1 is a biomarker for NAFLD in humans, and pharmacological and genetic approaches for the modulation of Thbs1 activity may have the therapeutic potential for treating hepatic steatosis. FUND: A full list of funding bodies that contributed to this study can be found in the Funding Sources section.
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http://dx.doi.org/10.1016/j.ebiom.2020.102849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317187PMC
July 2020

Regional difference in the susceptibility of non-alcoholic fatty liver disease in China.

BMJ Open Diabetes Res Care 2020 06;8(1)

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute of Metabolic Disease, Fudan University, Shanghai, China

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a global health problem with high geographic heterogeneity. We aimed to investigate regional-specific concomitant rate of NAFLD and quantitative relationship between liver fat content (LFC) and glucose metabolism parameters in representative clinical populations from six provinces/municipalities of China.

Research Design And Methods: A total of 2420 eligible Han Chinese were enrolled consecutively from 10 clinics of obesity, diabetes and metabolic diseases located at six provinces/municipalities of China, and divided into North (Tianjin, Shandong and Heilongjiang) and South (Shanghai, Jiangsu and Henan) groups according to their geographical latitude and proximity of NAFLD concomitant rate. LFC was assessed by a quantitative ultrasound method. Multivariate regression models and analysis of covariance were used to assess the regional difference in the risk of NAFLD.

Results: The concomitant rate of NAFLD was 23.3%, 44.0% and 55.3% in individuals with normal glucose tolerance (NGT), pre-diabetes and diabetes, respectively. A higher concomitant rate of NAFLD was found in the participants from the North comparing with the South group, regardless of glucose metabolism status (34.7% vs 16.2% in NGT, 61.5% vs 34.7% in pre-diabetes and 67.1% vs 48.1% in diabetes). This regional difference remained significant after adjustment for age, gender, alcohol drinking, cigarette smoking, confounding metabolic parameters and liver enzymes. For any given blood glucose, participants from the North had higher LFC than those from the South group.

Conclusions: Half of Han Chinese with pre-diabetes/type 2 diabetes had NAFLD, and the individuals from the North cities were more susceptible to NAFLD.
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http://dx.doi.org/10.1136/bmjdrc-2020-001311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287499PMC
June 2020

Microvascular decompression for hemifacial spasm associated with distinct offending vessels: A retrospective clinical study.

Clin Neurol Neurosurg 2020 07 1;194:105876. Epub 2020 May 1.

Department of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, China. Electronic address:

Objective: To investigate the surgical effects and complications of microvascular decompression (MVD) for hemifacial spasm (HFS) based on different offending vessels, and report our surgical experience of HFS patients related to vertebral artery.

Patients And Methods: MVDs performed in Nanjing Drum Tower Hospital between January 1, 2014 and December 31, 2017 were retrospectively studied, and 1152 patients with HFS were split into two groups in accordance with the offending vessels.

Results: 954 patients with HFS caused by small vascular compression were classified as Group A. 849 patients got cured immediately after MVD, while delayed resolution was identified in 101 patients. 4 patients were not relieved and 4 were relapsed during the follow-up period. We observed 76 cases of delayed facial paralysis, 7 cases of hearing loss, 2 hoarseness and 3 cases of CSF leakage after surgery. In Group B, 198 patients displayed HFS associated with the vertebral artery (VA). 144 cases were spasm free after surgery and 51 patients had a delayed resolution. 3 patients were not significantly ameliorated and 2 were relapsed during the follow-up period. The major postoperative complications included facial paralysis in 28 patients, hearing loss in 4 and hoarseness and dysphagia in 3. The two groups showed no operative death.

Conclusions: For the patients with HFS related to VA, the delayed cure rate and the incidence of postoperative cranial nerve complications were higher than HFS attributed to small vascular compression. And the two groups were not different in the long-term outcome and the incidence of permanent cranial nerve complications.
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http://dx.doi.org/10.1016/j.clineuro.2020.105876DOI Listing
July 2020

Nanovector Assembled from Natural Egg Yolk Lipids for Tumor-Targeted Delivery of Therapeutics.

ACS Appl Mater Interfaces 2020 Feb 5;12(7):7984-7994. Epub 2020 Feb 5.

Department of Central Laboratory, The Affiliated Huaian No.1 People's Hospital , Nanjing Medical University , Huai'an 223300 , China.

Nanomedicine uses nanotechnology-based strategies for precision tumor therapy, including passive and ligand-mediated active tumor targeting by nanocarriers. However, the possible biotoxicity of chemosynthetic nanovectors limits their clinical applications. A novel natural egg yolk lipid nanovector (EYLN) was developed for effective loading and delivery of therapeutic agents. Lipids were extracted from egg yolks and reassembled into nanosized particles. EYLNs' stability, cellular uptake, toxicity, and delivery capacity for therapeutic agents were evaluated in vitro. The systemic toxicity and biodistribution of EYLNs were analyzed in normal mice, and the therapeutic effects of doxorubicin (Dox)-loaded EYLNs were evaluated in mouse breast cancer and hepatoma models. EYLNs had a particle size of ∼40 nm and a surface ζ-potential of -45 mV and were effectively internalized by tumor cells, without showing toxicity and side effects in vitro and in vivo. Importantly, their excellent permeability and retention effect significantly enhanced the distribution of EYLNs at tumor sites, and EYLN-Dox effectively inhibited the tumor growth in both mouse models. Targeted modification with folic acid further promoted vector-mediated drug distribution in tumors. This study demonstrates that lipids with specific proportions in the egg yolk can be used to construct natural drug vectors, providing a new strategy for nano-oncology research.
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http://dx.doi.org/10.1021/acsami.9b22293DOI Listing
February 2020

FoxO3 regulates hepatic triglyceride metabolism via modulation of the expression of sterol regulatory-element binding protein 1c.

Lipids Health Dis 2019 Nov 15;18(1):197. Epub 2019 Nov 15.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Background: Excessive intrahepatic lipid accumulation is the major characteristic of nonalcoholic fatty liver disease (NAFLD). We sought to identify the mechanisms involved in hepatic triglyceride (TG) homeostasis. Forkhead box class O (FoxO) transcription factors have been shown to play an important role in hepatic metabolism. However, little is known about the effect of FoxO3 on hepatic TG metabolism.

Methods: Liver biopsy samples from patients with NALFD and liver tissues from high glucose and high sucrose (HFHS) fed mice, ob/ob mice and db/db mice were collected for protein and mRNA analysis. HepG2 cells were transfected with small interfering RNA to mediate FoxO3 knockdown, or adenovirus and plasmid to mediate FoxO3 overexpression. FoxO3-cDNA was delivered by adenovirus to the liver of C57BL/6 J male mice on a chow diet or on a high-fat diet, followed by determination of hepatic lipid metabolism. Sterol regulatory element-binding protein 1c (SREBP1c) luciferase reporter gene plasmid was co-transfected into HepG2 cells with FoxO3 overexpression plasmid.

Results: FoxO3 expression was increased in the livers of HFHS mice, ob/ob mice, db/db mice and patients with NAFLD. Knockdown of FoxO3 reduced whereas overexpression of FoxO3 increased cellular TG concentrations in HepG2 cells. FoxO3 gain-of-function caused hepatic TG deposition in C57BL/6 J mice on a chow diet and aggravated hepatic steatosis when fed a high-fat diet. Analysis of the transcripts established the increased expression of genes related to TG synthesis, including SREBP1c, SCD1, FAS, ACC1, GPAM and DGAT2 in mouse liver. Mechanistically, overexpression of FoxO3 stimulated the expression of SREBP1c, whereas knockdown of FoxO3 inhibited the expression of SREBP1c. Luciferase reporter assays showed that SREBP1c regulated the transcriptional activity of the SREBP1c promoter.

Conclusions: FoxO3 promotes the transcriptional activity of the SREBP1c promoter, thus leading to increased TG synthesis and hepatic TG accumulation.
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http://dx.doi.org/10.1186/s12944-019-1132-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857156PMC
November 2019

Novel Triazole Derivatives Containing Different Ester Skeleton: Design, Synthesis, Biological Evaluation and Molecular Docking.

Chem Pharm Bull (Tokyo) 2020 Jan 8;68(1):64-69. Epub 2019 Nov 8.

Laboratory of Clinical Pharmacy, Ordos School of Clinical Medicine, Inner Mongolia Medical University.

Invasive fungal disease constitutes a growing health problem and development of novel antifungal drugs with high potency and selectivity are in an urgent need. In this study, a novel series of triazole derivatives containing different ester skeleton were designed and synthesized. Microdilution broth method was used to investigate antifungal activity. Significant inhibitory activity of compounds 5c, 5d, 5e, 5f, 5m and 5n was evaluated against the Candida albicans (I), Candida albicans clinical isolate (II), Candida glabrata clinical isolate (I), and Candida glabrata (II) with minimum inhibitory concentrations (MIC) values ranging from 2 to 16 µg/mL. Notably, compounds 5e and 5n showed the best inhibition against Candida albicans (II), Candida glabrata (I), and Candida glabrata (II) at the concentrations of 2 and 8 µg/mL, respectively. Molecular docking study revealed that the target compounds interacted with CYP51 mainly through hydrophobic and van der Waals interactions. The results indicated that these novel triazole derivatives could serve as promising leads for development of antifungal agents.
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http://dx.doi.org/10.1248/cpb.c19-00624DOI Listing
January 2020

Calcium permeation property and firmness change of cherry tomatoes under ultrasound combined with calcium lactate treatment.

Ultrason Sonochem 2020 Jan 9;60:104784. Epub 2019 Sep 9.

Department of Food Science & Technology, National University of Singapore, Singapore 117543, Singapore; National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Suzhou, Jiangsu 215123, PR China. Electronic address:

This study aimed to investigate the effect of ultrasound combined with calcium lactate (2%, w/v) treatment (U + Ca) on calcium permeation and firmness of cherry tomatoes. Calcium distribution and fruit pectin nanostructure were also analysed by transmission electron microscope (TEM) and atomic force microscopy (AFM), respectively. The firmness (31.45 N) was maintained when ultrasound energy density was 20 W/L for 15 min at 15 °C. The Ca content increased in U + Ca treated fruit. Meanwhile, the Peleg's model could be used to express the change of solid gain in cherry tomatoes under ultrasound treatment at 15, 20, and 25 °C. According to the AFM results, the width (≥40 nm) and length (≥2 μm) of chelate-soluble pectin (CSP) and sodium carbonate-soluble pectin (SSP) chains with large frequency was observed in U + Ca treated fruit. Under desirable conditions (15 °C, 15 min, 20 W/L), ultrasound combined with calcium lactate could maintain the quality of cherry tomatoes.
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http://dx.doi.org/10.1016/j.ultsonch.2019.104784DOI Listing
January 2020

Hypofractionated Ir source stereotactic ablative brachytherapy with coplanar template assistance in the primary treatment of peripheral lung cancer.

J Contemp Brachytherapy 2019 Aug 29;11(4):370-378. Epub 2019 Aug 29.

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

Purpose: In this study, we reported the safety and efficacy of hypofractionated Ir source stereotactic ablative brachytherapy (SABT) with coplanar template assistance for peripheral lung cancer, and compared the dosimetric parameters between SABT and stereotactic body radiotherapy (SBRT).

Material And Methods: Thirty-three peripheral lung cancer patients, with the gross lung tumor volume (GTVL) < 5 cm in diameter were enrolled in this study. We assessed the safety and efficacy of SABT, and compared the dosimetric parameters between SABT and SBRT.

Results: Chest computed tomography (CT) of post-SABT revealed mild pneumothorax in 2 of 33 patients. Complete response (CR) plus partial response (PR) rate for GTVL at 6-month was 100%. Local control (LC) rate for GTVL at 1-year was 96.9%. For organs at risk (OARs), D1000 cm, and D1500 cm for lung in 1, 3, and 5 fractions were not statistically different between SABT and SBRT (all > 0.05); the remaining dosimetric parameters were significantly lower in SABT than in SBRT (all < 0.01).

Conclusions: SABT can provide safe and effective treatment, and warrant generalization for peripheral lung cancer.
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http://dx.doi.org/10.5114/jcb.2019.87218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737569PMC
August 2019

Increased lymph node yield indicates improved survival in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

Cancer Med 2019 08 28;8(10):4615-4625. Epub 2019 Jun 28.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, PR China.

Purpose: It is recommended for colorectal cancer to harvest at least 12 lymph nodes (LNs) during surgery to avoid understaging of the disease. However, it is still controversial whether it is necessary to harvest from locally advanced rectal cancer (LARC) patients who underwent neoadjuvant chemoradiotherapy (neo-CRT). The impact of lymph node yield (LNY) on prognosis in LARC patients was analyzed.

Materials/methods: In total, 495 LARC patients who underwent neo-CRT in 2006-2015 were analyzed. After examining clinicopathological distribution differences between the LNY subgroups (with the threshold of 12), univariate and multivariate Cox survival analyses were performed. Survival plots were obtained from Kaplan-Meier analyses. Similar subgroup analyses were performed according to the tumor regression grade (TRG) and metastatic status of post-operational LNs.

Results: Of the 495 patients, 287 (57.98%) had an LNY of less than 12. Nearly no significant clinicopathological difference was found between the LNY subgroups, including the TRG scores. Multivariate survival analysis demonstrated that at least 12 LNs examined was an independent prognostic feature of good overall survival (OS), disease-free survival (DFS), and distant metastasis free survival (DMFS), but not local recurrence free survival (LRFS). However, in the subgroup analyses, no association was found between LNY and prognosis in patients with good TRG scores (0-1) or negative LNs.

Conclusions: For LARC patients treated with neo-CRT, an LNY of at least 12 indicated an improved survival. Decreased LNY was not related to better tumor regression. It suggests that a sufficiently high LNY is still required, especially in those with a potentially poor tumor response.
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http://dx.doi.org/10.1002/cam4.2372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712464PMC
August 2019

Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway.

Free Radic Biol Med 2019 09 18;141:192-204. Epub 2019 Jun 18.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, 200032, China; Fudan Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China.

Background: Berberine (BBR), a natural compound extracted from Chinese herb, has been shown to effectively attenuate nonalcoholic fatty liver disease (NAFLD) in clinic. However, the mechanism underlying the effect of BBR is not fully understood. Stearyl-coenzyme A desaturase 1 (SCD1) mediates lipid metabolism in liver. Therefore, we hypothesized that SCD1 mediated the beneficial effect of BBR on NAFLD.

Methods: The expression of SCD1 was measured in the liver of NAFLD patients and ob/ob mice. The effect of BBR on NAFLD was evaluated in C57BL/6 J mice on high fat diet (HFD). The effect of BBR was also investigated in HepG2 and AML12 cells exposed to high glucose and palmitic acid. Oil red O staining was performed to detect triglyceride (TG) level. Quantitative real-time polymerase chain reaction and Western blot were used to detect the messenger ribonucleic acid (mRNA) and protein expression of target genes. The activity of SCD1 promoter was measured by dual-luciferase reporter assay.

Results: The expression of SCD1 was increased in the liver of NAFLD patients and ob/ob mice. BBR reduced hepatic TG accumulation and decreased the expressions of hepatic SCD1 and other TG synthesis related genes both in vivo and in vitro. Knockdown of SCD1 expression mimicked the effect of BBR decreasing TG level in steatotic hepatocytes, whereas overexpression of SCD1 attenuated the effect of BBR. Mechanistically, BBR promoted the phosphorylation of AMP-activated protein kinase (AMPK) and sterol regulatory element-binding protein-1c (SREBP-1c) in HepG2 cells and the liver of HFD-fed mice. Activation of the AMPK-SREBP-1c pathway and sterol regulatory element (SRE) motif in SCD1 promoter (-920/-550) was responsible for the BBR-induced suppression of SCD1.

Conclusion: BBR reduces liver TG synthesis and attenuates hepatic steatosis through the activation of AMPK-SREBP-1c-SCD1 pathway.
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http://dx.doi.org/10.1016/j.freeradbiomed.2019.06.019DOI Listing
September 2019

A novel LARCassigner3 classification predicts outcomes in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy: a retrospective training and validation analysis.

Cancer Manag Res 2019 7;11:4153-4170. Epub 2019 May 7.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People's Republic of China.

To build and validate a predictive model of outcome for patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy. We developed a LARCassigner3 classifier based on tumor and paired normal tissues of patients treated with neoadjuvant chemoradiation and surgery from January 2007 to December 2012 in Fudan University Shanghai Cancer Center. Excluding 23 pairs of tissues failed in the RNA quality test, rested 197 patients were divided into discovery (n=98) and validation (n=99) cohorts randomly. Median follow-up time was 58 months. We used the Kaplan-Meier method to estimate disease-free survival (DFS), overall survival (OS), local recurrent, and distant metastatic rate We constructed a multivariate Cox model to identify the variables independently associated with progression-free and OS. We identified three classifier genes related to relevant colorectal cancer features (CXCL9, SFRP2, and CD44) that formed the LARCassigner3 classifier assay. In the discovery set, the median DFS was 48.1 months (95% confidence interval (CI) 47.3-49.5) in the low-risk group and 23.4 months (95% CI 22.1-24.8) in the high-risk group (=0.0134); the median OS was 39.2 months (95% CI 38.4-40.3) in the high-risk group and 19.1 months (95% CI 18.3-20.7) in the low-risk group (=0.0134); 5-year distant metastasis was 13.9% (95% CI 9.0-21.3) in the low-risk group and 49.8% (95% CI 38.7-60.9) in the high-risk group (=0.0072). Additionally, the different responses to neoadjuvant chemoradiotherapy and the LARCassigner3 low-risk and high-risk groups was statistically significant (=0.004) in the discovery cohort. Similar results were obtained in the internal evaluation cohort. Patients with LARCassigner3 low-risk tumors were associated with a good prognosis. The clinical utility of using LARCassigner3 subtyping for the identification of patients for neoadjuvant chemoradiotherapy requires validation in dependent clinical trial cohorts.
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http://dx.doi.org/10.2147/CMAR.S196662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511254PMC
May 2019

Angio-associated migratory cell protein interacts with epidermal growth factor receptor and enhances proliferation and drug resistance in human non-small cell lung cancer cells.

Cell Signal 2019 09 7;61:10-19. Epub 2019 May 7.

Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China; Shandong Provincial Collaborative Innovation Center of Cell Biology, School of Life Sciences, Shandong Normal University, Jinan, China. Electronic address:

Angio-associated migratory cell protein (AAMP) is expressed in some human cancer cells. Previous studies have shown AAMP high expression predicted poor prognosis. But its biological role in non-small cell lung cancer (NSCLC) cells is still unknown. In our present study, we attempted to explore the functions of AAMP in NSCLC cells. According to our findings, AAMP knockdown inhibited lung cancer cell proliferation and inhibited lung cancer cell tumorigenesis in the mouse xenograft model. Epidermal growth factor receptor (EGFR) is a primary receptor tyrosine kinase (RTK) that promotes proliferation and plays an important role in cancer pathology. We found AAMP interacted with EGFR and enhanced its dimerization and phosphorylation at tyrosine 1173 which activated ERK1/2 in NSCLC cells. In addition, we showed AAMP conferred the lung cancer cells resistance to chemotherapeutic agents such as icotinib and doxorubicin. Taken together, our data indicate that loss of AAMP from NSCLC inhibits tumor growth and elevates drug sensitivity, and these findings have clinical implications to treat NSCLC cancers.
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http://dx.doi.org/10.1016/j.cellsig.2019.05.004DOI Listing
September 2019