Publications by authors named "Jing Fu"

456 Publications

Ecotoxicogenomic analysis of zebrafish embryos exposed to triclosan and mixture triclosan and methyl triclosan using suppression subtractive hybridization and next-generation sequencing.

J Hazard Mater 2021 Feb 26;414:125450. Epub 2021 Feb 26.

Department of Civil and Environmental Engineering, National University of Singapore, Singapore. Electronic address:

Triclosan (TCS) and methyl-triclosan (MTCS), an environmental transformation product of biocide of TCS, have been detected in water, sediment, fish, and invertebrates. In this study, the key pathway perturbation in zebrafish (Danio rerio) embryos exposed to TCS (300 μg/L) and TCS/MTCS mixture (300 μg/L TCS + 30 μg/L MTCS) was assessed by integrating the metabolomic and transcriptomic dysregulation. The differential expressed genes (DEGs) were obtained from the subtracted cDNA libraries by using the suppression subtractive hybridization and next-generation sequencing approach. The dysregulation of twenty-eight GO terms and four KEGG pathways, including oxidative phosphorylation and cardiac muscle contraction, were shown in the TCS treatment group, indicating that TCS could disrupt the mitochondrial inner membrane function by downshifting the electrochemical gradient. Meanwhile, the addition of MTCS in the exposure would cause fourteen additional significant KEGG pathway changes, demonstrating the different effects between two exposure. A pathway-based analysis using the identified DEGs and the altered metabolites in zebrafish embryos treated with TCS and TCS/MTCS mixture, collectively, has been applied. This study demonstrated that the integration of SSH-NGS and metabolomics could reveal toxic effects and potential diseases associated with the exposures of TCS and MTCS in aquatic environments.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125450DOI Listing
February 2021

Inhibiting proliferation and metastasis of osteosarcoma cells by downregulation of long non-coding RNA colon cancer-associated transcript 2 targeting microRNA-143.

Oncol Lett 2021 Apr 8;21(4):265. Epub 2021 Feb 8.

Department of Orthopedics, The First Hospital of Qiqihaer, Qiqihaer, Heilongjiang 161005, P.R. China.

Osteosarcoma is a malignant bone tumor, which has a high incidence in children and adolescents. However, the pathogenesis of osteosarcoma remains unclear. Long noncoding RNA (lncRNA) is a new potential therapeutic target and diagnostic biomarker for osteosarcoma. Hence, the present study aimed to explore the effect of lncRNA colon cancer-associated transcript (CCAT2) on osteosarcoma and its potential underlying mechanisms. For this purpose, the proliferation of osteosarcoma cells was measured using the CCK-8 assay. The scratch-wound and cell invasion assays were used to determine the migration and invasion of osteosarcoma cells, respectively. LncRNA CCAT2 and microRNA (miR)-143 binding sites were identified by the dual-luciferase reporter assay. RNA and protein expression levels were detected by reverse-transcription quantitative PCR and western blotting, respectively. Downregulation of lncRNA CCAT2 inhibited the proliferation, migration, and invasion of osteosarcoma cells. The findings also revealed that miR-143 bound directly to lncRNA CCAT2. The expression of miR-143 was upregulated by the knockdown of lncRNA CCAT2. Downregulation of the FOS-like antigen 2 was also observed after knockdown of lncRNA CCAT2. The function of lncRNA CCAT2 in osteosarcoma cells was attenuated by co-transfection with anti-miR-143 oligodeoxyribonucleotide. In conclusion, downregulation of lncRNA CCAT2 inhibited the proliferation and metastasis of osteosarcoma cells by targeting miR-143. lncRNA CCAT2 was identified as a potential target for osteosarcoma treatment.
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http://dx.doi.org/10.3892/ol.2021.12526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882883PMC
April 2021

Difference of refractive status before and after cycloplegic refraction: the Lhasa Childhood Eye Study.

Jpn J Ophthalmol 2021 Mar 3. Epub 2021 Mar 3.

Strabismus and Pediatric Ophthalmology, Beijing Ophthalmology and Visual Sciences Key Laboratory Ophthalmology Department of Beijing Tongren Hospital, Beijing Tongren Eye Center, Capital Medical University, No.1, Dong Jiao Min Xiang Street, Dongcheng District, Beijing, 100730, People's Republic of China.

Purpose: To compare the differences between cycloplegic and noncycloplegic refraction as well as associated factors in grade one students of primary schools, and explore the effectiveness of noncycloplegic refraction for refractive error screening.

Study Design: Cross-sectional study.

Methods: A school-based study of 1856 students was conducted in Lhasa, Tibetan Plateau, China. Cycloplegia was achieved with two drops of 1% cyclopentolate and 1 drop of Mydrin P at a 5-min interval. Autorefraction was performed under both cycloplegic and noncycloplegic conditions. Bland-Altman analysis, receiver operating characteristic curve analysis, univariate and multiple linear regression models were used for analysis.

Results: Of the 1856 children enrolled, 1830 (98.60%) completed all procedures. The average age was 6.83 ± 0.46 years. 965 (52.73%) children were boys and 1737 (94.92%) were Tibetan. Overall, there was a significant difference between cycloplegic and noncycloplegic SE of 0.90 ± 0.76D (P < 0.001). However, the intra-class coefficient correlation (ICC) for cylinder between these two methods was high (ICC = 0.941, 95% CI, 0.935-0.946). Larger differences between cycloplegic and noncycloplegic SE were associated with hyperopic RE and higher cylindrical value (P < 0.001). The prevalence of myopia, emmetropia and hyperopia with and without cycloplegia was (3.93% vs 14.59%), (9.95% vs 45.8%) and (86.21% vs 39.56%), respectively. Myopia, emmetropia and hyperopia based on noncycloplegic refraction was defined as SE ≤ - 0.625D, - 0.625 < SE ≤ 0D, and SE > 0D, respectively.

Conclusions: Lack of cycloplegia leads to underestimation of hyperopia, with overestimation of myopia and emmetropia. Larger hyperopic refraction exhibited greater difference between cycloplegic and noncycloplegic refraction.
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http://dx.doi.org/10.1007/s10384-021-00828-6DOI Listing
March 2021

Testicular and Spermatic Cord Metastases from Gastric Adenocarcinoma: An Unusual Case.

Cancer Manag Res 2021 23;13:1897-1900. Epub 2021 Feb 23.

Department of Urology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People's Republic of China.

The metastasis of gastric cancer to the testis or spermatic cord is very rare; however, simultaneous testicular and spermatic cord metastases are even rarer. Here, we report an unusual case of a 54-year-old male patient who had undergone radical gastrectomy for gastric adenocarcinoma more than two years before. He complained of palpable painful masses in the right scrotum and inguinal area occurring for more than half a year. Enhanced computed tomography (CT) separately showed an enhanced soft tissue mass in the right testicular and spermatic cord areas. Therefore, a right radical orchiectomy was conducted. The pathology was consistent with the metastases of gastric adenocarcinoma.
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http://dx.doi.org/10.2147/CMAR.S286909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914050PMC
February 2021

Hepatitis B-induced IL-8 Promotes Hepatocellular Carcinoma Venous Metastasis and Intrahepatic Treg Accumulation.

Cancer Res 2021 Mar 2. Epub 2021 Mar 2.

Chinese Academy of Sciences Key Laboratory of Infection and Immunity,IBP, Institute of Biophysics

Hepatitis B-associated hepatocellular carcinoma (HCC) is often accompanied by severe vascular invasion and portal vein tumor thrombus leading to a poor prognosis. However, the underlying mechanism of this disease remains obscure. In this study, we demonstrate that the hepatitis B virus (HBV)-encoded gene HBx induces high IL-8 production through MEK-ERK signal activation, leading to enhanced endothelial permeability to facilitate tumor vascular invasion. In a vascular metastatic model using a tail vein injection in a transgenic mouse with selective expression of human CXCR1 in the endothelium, activation of the IL-8-CXCR1 cascade by overexpression of IL-8 in tumor cells dramatically enhanced liver metastasis. Mechanistically, IL-8 selectively induced GARP-latent-TGF-β in liver sinusoidal endothelial cells and subsequently provoked preferential regulatory T cell polarization to suppress antitumor immunity. Collectively, these findings reveal a hepatitis B-associated IL-8-CXCR1 signaling axis that mediates vascular invasion and local microenvironmental immune escape of HCC to induce intrahepatic metastasis, which may serve as potential therapeutic targets for HBV-associated HCC.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3453DOI Listing
March 2021

Synchrotron-based X-ray fluorescence microscopy reveals accumulation of polymyxins in single human alveolar epithelial cells.

Antimicrob Agents Chemother 2021 Mar 1. Epub 2021 Mar 1.

Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia.

Intravenous administration of the last-line polymyxins results in poor drug exposure in the lungs and potential nephrotoxicity; while inhalation therapy offers better pharmacokinetics/pharmacodynamics for pulmonary infections by delivering the antibiotic to the infection site directly. However, polymyxin inhalation therapy has not been optimized and adverse effects can occur. This study aimed to quantitatively determine the intracellular accumulation and distribution of polymyxins in single human alveolar epithelial A549 cells. Cells were treated with an iodine-labeled polymyxin probe FADDI-096 (5.0 and 10.0 μM) for 1, 4, and 24 h. Concentrations of FADDI-096 in single A549 cells were determined by synchrotron-based X-ray fluorescence microscopy. Concentration- and time-dependent accumulation of FADDI-096 within A549 cells was observed. The intracellular concentrations (mean ± SEM, n ≥ 189) of FADDI-096 were 1.58 ± 0.11, 2.25 ± 0.10, and 2.46 ± 0.07 mM following 1, 4 and 24 h of treatment at 10 μM, respectively. The corresponding intracellular concentrations following the treatment at 5 μM were 0.05 ± 0.01, 0.24 ± 0.04, and 0.25 ± 0.02 mM (n ≥ 189). FADDI-096 was mainly localized throughout the cytoplasm and nuclear region over 24 h. The intracellular zinc concentration increased in a concentration- and time-dependent manner. This is the first study to quantitatively map the accumulation of polymyxins in human alveolar epithelial cells and provides crucial insights for deciphering the mechanisms of their pulmonary toxicity. Importantly, our results may shed light on the optimization of inhaled polymyxins in patients and the development of new-generation safer polymyxins.
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http://dx.doi.org/10.1128/AAC.02314-20DOI Listing
March 2021

Increased Prolactin is an Adaptive Response to Protect Against Metabolic Disorders in Obesity.

Endocr Pract 2021 Jan 15. Epub 2021 Jan 15.

Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China. Electronic address:

Objective: Prolactin (PRL) is a polypeptide hormone named for its crucial role in lactation. Recently, PRL has been recognized as a metabolic hormone that regulates energy metabolism. The current study aimed to investigate the relationship between circulating PRL and metabolic alterations in overweight/obese patients and the effect of weight loss through bariatric surgery on circulating PRL.

Methods: A total of 448 overweight/obese patients aged between 18 and 40 years and 120 age- and sex-matched healthy controls with normal weight were enrolled. Among all participants, 156 obese patients underwent bariatric surgery.

Results: Circulating PRL levels were significantly increased in the overweight (15.27 ± 9.58 μg/L) and obese (17.75 ± 9.15 μg/L) groups compared with the normal weight (13.57 ± 9.03 μg/L) group. Multiple regression analyses demonstrated that the adipose tissue insulin resistance (adipo-IR) level was an independent predictor for PRL (β = -0.451, P < .01). Despite comparable anthropometric parameters, the overweight/obese patients with a higher PRL tertile had decreased levels of triglycerides, nonesterified fatty acids, homeostasis model assessment of insulin resistance, and adipo-IR compared with the patients in the moderate and lower PRL tertiles. Serum PRL levels were significantly decreased following the alleviation of metabolic parameters after bariatric surgery (from 17.12 ± 8.27 to 13.00 ± 5.78 μg/L, P < .05), and the decrease in PRL levels was significantly greater in the lower adipo-IR group than in the higher adipo-IR group (P < .01).

Conclusion: An increased serum PRL level might be an adaptive response for protecting against metabolic disorders in obesity.
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http://dx.doi.org/10.1016/j.eprac.2021.01.002DOI Listing
January 2021

A novel homozygous variant in ZP2 causes abnormal zona pellucida formation and female infertility.

J Assist Reprod Genet 2021 Feb 18. Epub 2021 Feb 18.

Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.

Purpose: We aimed to identify pathogenic variants in two infertile sisters in a family with a thin zona pellucida (ZP) phenotype.

Methods: Whole-exome sequencing was performed in the two affected sisters, and Sanger sequencing was used to confirm the identified variants. The effects of the identified variant were further investigated in mouse oocytes and Chinese hamster ovary (CHO) cells.

Results: We identified a novel homozygous frameshift variant in ZP2 (c.1235_1236del, p.Q412Rfs*17) in the two affected individuals. Immunoblotting demonstrated that the variant produced a truncated ZP2 protein that was expressed at low levels in CHO cells. Immunofluorescence in mouse oocytes confirmed the decreased protein level of mutant ZP2, although the subcellular localization was not affected. In addition, immunoprecipitation showed that the pathogenic variant reduced the interaction between ZP2 and ZP3.

Conclusion: This study identified a novel pathogenic variant in ZP2 that produces a truncated ZP2 protein. The variant might disrupt the assembly of ZP2-ZP3 dimers, thus resulting in a thin ZP and female infertility.
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http://dx.doi.org/10.1007/s10815-021-02107-2DOI Listing
February 2021

Overexpression of Limb Bud and Heart Alleviates Sepsis-Induced Acute Lung Injury via Inhibiting the NLRP3 Inflammasome.

Biomed Res Int 2021 23;2021:4084371. Epub 2021 Jan 23.

Department of Emergency, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, No. 32, The Second West Section of the First Ring Road, Qingyang District, Chengdu City, Sichuan Province 610000, China.

Objective: Sepsis is a leading cause of acute lung injury (ALI). This study attempted to investigate the effects of limb bud and heart (LBH) on the development of sepsis-induced ALI and its underlying mechanism of action.

Methods: The sepsis-induced ALI mouse model was established by cecal ligation and puncture (CLP). The lung injury score and lung wet/dry weight (W/D) ratio were used to evaluate the lung injury. , ALI was simulated by lipopolysaccharide (LPS) treatment in A549 cells. The mRNA expression of LBH, NLRP3, ASC, and proinflammatory cytokines was measured by qRT-PCR. The viability of LPS-induced A549 cells was analyzed by MTT assay. Furthermore, western blot was performed to detect the protein expression of LBH, NLRP3, and ASC. LPS-induced A549 cells were treated with MCC950 (NLRP3 inflammasome inhibitor) to confirm the effect of LBH on NLRP3 inflammasome.

Results: The mRNA and protein expression of LBH was decreased in sepsis-induced ALI. LBH overexpression reduced the lung injury score, lung W/D ratio, expression of proinflammatory cytokines, and NLRP3 inflammasome activation in sepsis-induced ALI mouse model. Additionally, LBH upregulation increased the viability, while it decreased the proinflammatory cytokine expression and NLRP3 inflammasome activation of LPS-induced A549 cells. Moreover, MCC950 reversed the promoting effects of LBH silencing on proinflammatory cytokine expression and NLRP3 inflammasome activation in LPS-induced A549 cells.

Conclusions: LBH alleviated lung injury in sepsis-induced ALI mouse model by inhibiting inflammation and NLRP3 inflammasome, and restrained the inflammation by inhibiting NLRP3 inflammasome in LPS-induced A549 cells, providing a novel therapeutic target for ALI.
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http://dx.doi.org/10.1155/2021/4084371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847343PMC
January 2021

Effectiveness of laparoscopic tubal anastomosis in tubal occlusion patients after laparoscopic salpingostomy for tubal pregnancy.

Int J Gynaecol Obstet 2021 Feb 4. Epub 2021 Feb 4.

Department of Reproductive Endocrinology, Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

Objective: To evaluate the effectiveness of laparoscopic tubal anastomosis for tubal occlusions associated with infertility in patients with prior laparoscopic salpingostomy for ectopic pregnancy.

Methods: This study is a retrospective analysis of the pregnancy outcomes of 173 infertile patients who underwent hysteroscopy and laparoscopic tubal anastomosis treatment between January 2013 and August 2018 in the Department of Reproductive Endocrinology in West China Second University Hospital of Sichuan University. All patients had a history of laparoscopic salpingostomy for tubal pregnancy. The primary outcomes were intrauterine pregnancy (IUP), ectopic pregnancy (EP), and delivery (DEL) rates. We further studied the associated factors that could influence the chance in pregnancy status.

Results: The 24-month cumulative clinical pregnancy rate of all patients was 107/173 (61.8%). The distribution of outcomes for the entire group of pregnancies was as follows: IUP rate, 76/173 (43.9%); EP rate, 31/173 (17.9%); DEL rate, 68/173 (39.3%); and miscarriage rate, 8/173 (4.6%). Age, type of anastomosis, hydrosalpinx, and endometrial polyp were significant prognostic factors in the multivariate model.

Conclusion: Laparoscopic tubal anastomosis is an effective treatment for tubal-associated infertility due to previous laparoscopic salpingostomy for ectopic pregnancy, especially for patients under 35 years of age.
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http://dx.doi.org/10.1002/ijgo.13637DOI Listing
February 2021

Prevalence of Heterophoria in Tibetan Grade-One Students: The Lhasa Childhood Eye Study.

J Ophthalmol 2020 24;2020:9570908. Epub 2020 Dec 24.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.

Introduction: The study aims to explore the prevalence of heterophoria and associate factors in Tibetan grade-one students.

Methods: The Lhasa Childhood Eye Study (LCES) is a school-based cohort study. 1942 grade-one students from 7 elementary schools were randomly sampled by stratified cluster sampling. Ocular examinations were performed in participants, including ocular motility, distance and near visual acuity, cycloplegic autorefraction, and stereoacuity. The near (33 cm) and distance (6 m) fixation cover test was used to differentiate orthophoria, heterophoria, and heterotropia, and the magnitude of the phoria was measured by the Maddox rod and prisma.

Results: Of 1856 grade-one students completing all the ocular examinations, 1852 participants finished the ocular alignment test. The mean age was 6.82 ± 0.46 years (range 6∼10 years); 981 (52.97%) were males, and 871 (47.03%) were females. The prevalence of phoria was 22.89% ( = 424). At distance fixation, the prevalence of heterophoria, exophoria, and esophoria was 4.64%, 4.21%, and 0.43% separately, while at near fixation, the prevalence was 22.73%, 22.35%, and 0.38%. No vertical phoria was detected. The mean magnitude of heterophoria at near and distance fixation was -7.63 ± 5.15 PD (exo: -7.83 ± 4.91 PD, eso: +5.67 ± 3.61 PD) and -4.84 ± 5.94 PD (exo: -6.26 ± 4.20 PD, eso: +8.13 ± 3.04 PD). The prevalence of esophoria was associated with hyperopia (OR = 6.38, 95% CI: 1.15-35.28,  = 0.03; OR = 5.42, 95% CI: 1.04-28.24,  = 0.04) and amblyopia (OR = 16.02, 95% CI: 1.81∼141.96,  = 0.01; OR = 11.37, 95% CI: 1.34∼96.52,  = 0.03) at near and distance fixation. The prevalence of exophoria was associated with myopia at near fixation (OR = 2.43, 95% CI: 1.47-4.00, <0.01). In the near heterophoria group, the proportion of children with abnormal stereoacuity was 23.26% ( = 97), significantly higher ( = 5.70,  = 0.017) than that in orthophoria (17.99%,  = 244).

Conclusions: In Lhasa, grade-one pupils have a lower prevalence of heterophoria. Near exophoria was associated with myopia, while esophoria was related to hyperopia and amblyopia both near and distance. Heterophoria may be one of the affected factors for reducing stereoacuity.
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http://dx.doi.org/10.1155/2020/9570908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803105PMC
December 2020

circRNA_0005529 facilitates growth and metastasis of gastric cancer via regulating miR-527/Sp1 axis.

BMC Mol Cell Biol 2021 Jan 20;22(1). Epub 2021 Jan 20.

Department of Emergency, Huai'an Hospital Affiliated of Xuzhou Medical University and Huai'an Second People's Hospital, No. 62 Huaihai South Road, Huai 'an City, Jiangsu Province, China.

Background: Circular RNAs (circRNAs) are endogenous non-coding RNAs, which are associated with various biological processes, including microRNA (miRNA) interaction, protein binding and regulatory splicing. circRNA_0005529 (circ_0005529) is derived from vacuolar protein sorting 33 homologue B (VPS33B), and its biological role in gastric cancer (GC) has not been examined. In this study, the expression and location of circ_0005529 and microRNA-527 (miR-527) were determined by qRT-PCR and fluorescence in situ hybridization (FISH). Cell proliferation and cell migration were determined by MTT, EdU incorporation, colony formation, wound scratch and transwell assays. In addition, immunohistochemistry and western blotting were performed to determine the expressions of specificity protein 1 (Sp1), PCNA, c-myc, E-cadherin and N-cadherin. Western blotting and luciferase reporter assay were performed to study the interaction between circ_0005529 and miR-527 or miR-527 and Sp1. The functional effects of circ_0005529 on GC through regulating Sp1 were further evaluated using xenograft and metastatic mouse models in vivo.

Results: Our results showed that circ_0005529 was upregulated in GC tissues and cells, and had promoting effects on cell proliferation and cell migration. Mechanism analysis suggested that circ_0005529 could bind to microRNA-527 (miR-527) and reduce its expression. The interaction between miR-527 and Sp1 in GC was systematically studied. In addition, the results indicated that Sp1 upregulation could rescue the effects on cell proliferation and migration caused by circ_0005529. Moreover, the inhibitory effects of circ_0005529 downregulation on GC growth and metastasis were evaluated in mouse models. These findings suggested that the axis of circ_0005529/miR-527/Sp1 may serve as a promising treatment target for GC diagnosis and treatment.

Conclusions: These findings suggested that the signal axis of circ_0005529/miR-527/Sp1 may has the potential to be explored as a novel therapeutic target for GC diagnosis and treatment. Mechanism diagram: During GC development, overexpressed circ_0005529 sponged miR-527 and then upregulated the expression of Sp1. Subsequently, epithelial-mesenchymal transition (EMT), cell proliferation and cell migration were promoted, which ultimately facilitated the tumor metastasis.
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http://dx.doi.org/10.1186/s12860-020-00340-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816457PMC
January 2021

Stage-Specific PET Radiomic Prediction Model for the Histological Subtype Classification of Non-Small-Cell Lung Cancer.

Cancer Manag Res 2021 12;13:307-317. Epub 2021 Jan 12.

Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, People's Republic of China.

Purpose: To investigate the impact of staging on differences in glucose metabolic heterogeneity between lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) by F-fluorodeoxyglucose positron emission tomography (F-FDG PET) textural analysis and to develop a stage-specific PET radiomic prediction model to distinguish lung ADC from SCC.

Patients And Methods: Patients who were histologically diagnosed with lung ADC or SCC and underwent pretreatment F-FDG PET/CT scans were retrospectively identified. Radiomic features were extracted from a semiautomatically outlined tumor region in the Chang-Gung Image Texture Analysis (CGITA) software package. The differences in radiomic parameters between lung ADC and SCC were compared stage-by-stage in 253 consecutive NSCLC patients with stages I to III disease. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature selection. A radiomic signature for each stage was subsequently constructed and evaluated. Then, an individual nomogram incorporating the radiomic signature and clinical risk factors was established and evaluated. The performance of the constructed models was assessed by receiver operating characteristic (ROC) curve analysis, and the nomogram was further validated by calibration curve analysis.

Results: The performance of the radiomic signature for distinguishing lung ADC and SCC in both the training and validation cohorts was good, with AUCs of 0.883, 0.854, and 0.895 in the training cohort and 0.932, 0.944, and 0.886 in the validation cohort for stages I, II, and III NSCLC, respectively. The radiomic-clinical nomogram integrating radiomic features with independent clinical predictors exhibited more favorable discriminative performance, with AUCs of 0.982, 0.963, and 0.979 in the training cohort and 0.989, 0.984, and 0.978 in the validation cohort for stages I, II, and III, respectively.

Conclusion: Differences in PET radiomic features between lung ADC and SCC varied in different stages. Stage-specific PET radiomic prediction models provided more favorable performance for discriminating the histological subtype of NSCLC.
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http://dx.doi.org/10.2147/CMAR.S287128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811450PMC
January 2021

Clinicopathologic features and clinical outcomes of intravenous leiomyomatosis of the uterus: A case series.

Medicine (Baltimore) 2021 Jan;100(1):e24228

Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University.

Rationale: Intravenous leiomyomatosis (IVL) is a rare and special type of smooth muscle tumor originating in the uterus. It is classified as a benign disease according to its histological features but shows the behavioral characteristics of a malignant tumor. It is easily misdiagnosed and recurrent. The purpose of this study was to retrospectively analyze clinicopathological data of 25 cases of IVL in order to enhance clinicians' understanding of this rare disease.

Patient Concerns: We screened and identified 25 cases of IVL at our hospital from October 2013 to January 2020. Five patients had tumors.

Diagnoses: The diagnosis in each case was pathologically confirmed after surgical treatment.

Interventions: All patients were managed surgically. Although the surgical procedures were different, the surgical approach was geared towards achieving complete excision. Three patients received hormonal therapy with gonadotropinreleasing hormone agonists after surgery.

Outcomes: We retrospectively reviewed all medical records and analyzed the clinicopathologic features and clinical outcomes of this disease as well as the correlations between the clinical features and risk of recurrence. Neither the symptoms nor the preoperative imaging results were suggestive of IVL in any of the cases. Except for two patients who were lost to follow-up, twenty-three patients who were followed up are still alive. Three patients experienced a recurrence.

Lessons: The clinical manifestations and ultrasound images of IVL in the early stages are not typical; thus, IVL is easily misdiagnosed as uterine leiomyoma. Radiologists, pathologists, and surgeons should have a thorough understanding of IVL and a high index of vigilance for IVL in clinical practice. Surgery should always be aimed at achieving complete tumor excision. Patients with large lesions (≥7 cm) and lesions extending to the broad ligament may have an increased risk of recurrence. Early detection, diagnosis, and treatment are very important; once the diagnosis is confirmed, regular follow-ups are crucial.
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http://dx.doi.org/10.1097/MD.0000000000024228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793403PMC
January 2021

Distribution of ocular biometry in young Chinese eyes: The Anyang University Students Eye Study.

Acta Ophthalmol 2020 Dec 16. Epub 2020 Dec 16.

Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Purpose: To investigate the distribution of ocular biometric parameters and its association to refraction in university students in central China.

Methods: Ocular biometric parameters including axial length (AL), central corneal thickness (CCT), keratometry power (K), anterior chamber depth (AQD) and lens thickness (LT) were measured by an optical biometry in a cohort of university students. Corneal radius of curvature (CR), lens position (LP), lens power (P ), vitreous chamber depth (VCD) and AL to corneal radius ratio (AL/CR) were calculated. Cycloplegic refraction was measured using an autorefractor.

Results: A total of 7650 undergraduate students participated in this study, with a mean age of 20.0 ± 1.4 years. The following ocular biometric parameters were measured: AL (24.78 ± 1.21 mm), CCT (539.83 ± 33.03 μm), AQD (3.23 ± 0.25 mm), LT (3.47 ± 0.18 mm), CR (7.79 ± 0.27 mm), LP (4.97 ± 0.23 mm), VCD (17.55 ± 1.15 mm), P (25.00 ± 1.07 dioptres) and AL/CR (3.18 ± 0.15). Male subjects were found to have longer AL, thicker CCT, flatter CR, thinner lens, deeper AQD and VCD than female ones. Myopic subjects were found to have longer AL, thinner CCT, steeper CR, thinner and posterior lens, deeper AQD and VCD, lower P and larger AL/CR than emmetropes and hyperopes. Spherical equivalent (SE) showed a negative correlation with AL/CR (r = -0.914), AL (r = -0.755) and VCD (r = -0.751).

Conclusions: This study provided a range of reference values for the main ocular biometric parameters in young adults and reported their distributions based on gender and refractive status. Our study indicates that SE has a strong correlation with AL/CR ratio, AL and VCD.
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http://dx.doi.org/10.1111/aos.14710DOI Listing
December 2020

Prevalence of Amblyopia and Associated Risk Factors in Tibetan Grade One Children.

Ophthalmic Res 2021 4;64(2):280-289. Epub 2020 Dec 4.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.

Introduction: Amblyopia is an important public health problem and standard screening is quite necessary for early diagnosis and treatment especially for the remote areas. As the place of the largest Tibetan population, the Tibetan Plateau has special geographical characteristics such as high altitude, time zone, and ethnic composition, where very little information is available about the prevalence of amblyopia and other ocular diseases. The article aims to determine the prevalence of amblyopia and associated factors in grade 1 Tibetan children, living in Lhasa, Tibet Autonomous Region.

Methods: A cross-sectional study was conducted. All the participants were scheduled for comprehensive eye examinations including visual acuity testing, ocular deviation and movement evaluation, cycloplegic refraction and examinations of the external eye, anterior segment, media, and fundus. Amblyopia was assessed in the children according to the standard definition.

Results: A total of 1,856 students participated in the examinations (97.58% response rate). 1,852 students completed all the related examinations, and 34 of them were diagnosed as amblyopia with the prevalence of 1.84% (95% confidence interval [CI]: 1.22-2.45%). Unilateral amblyopia was diagnosed in 23 students (1.24%, 95% CI: 0.74-1.75%), including 16 anisometropic, 4 strabismic, 1 visual deprivational, and 2 mixed. Other 11 students were diagnosed as bilateral amblyopia (0.59%, 95% CI: 0.24-0.94%), including 9 ametropic, 1 deprivational, and 1 with nystagmus. The mean cylinder refraction and absolute value of the spherical equivalent refraction of amblyopic eyes was respectively -2.15 ± 1.52 D and 2.70 ± 2.33 D. Amblyopia was significantly associated with hyperopia (≥+2.00 D, odds ratio [OR] 8.22, 95% CI 3.42-19.72), astigmatism (≤-2.00 D, OR 6.76, 95% CI 2.56-17.85), and anisometropia (≥+0.50 to <+1.00 D, OR 3.95, 95% CI 1.44-10.79; ≥+1.00 D, OR 21.90, 95% CI 8.24-58.18).

Conclusions: The prevalence of amblyopia in grade 1 students of Lhasa is relatively higher than that of many other ethnic populations in China previously reported. Refractive errors including anisometropia, hyperopia, and astigmatism are the major risk factors of amblyopia.
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http://dx.doi.org/10.1159/000511264DOI Listing
December 2020

Efficient degradation of bisphenol A via peroxydisulfate activation using in-situ N-doped carbon nanoparticles: Structure-function relationship and reaction mechanism.

J Colloid Interface Sci 2021 Mar 29;586:551-562. Epub 2020 Oct 29.

College of Environmental Science and Engineering, Hunan University, Changsha 410082, PR China; Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha 410082, PR China. Electronic address:

A novel in-situ N-doped carbon nanoparticles (NCNs) was prepared through direct pyrolysis of N-rich polyaniline (PANI) without using external N-containing precursor and the as-prepared materials were employed as metal-free peroxydisulfate (PDS) activator for bisphenol A (BPA) degradation. The catalyst derived from PANI carbonization at 900 °C (NCNs-9) displayed the excellent catalytic activity to activate PDS, resulting in 96.0% BPA degradation efficiency within 20 min. The catalytic activity of NCNs was closely related to their structure-composition, and higher graphitic N content and larger BET surface area were beneficial to the generation of reactive oxygen species (ROS). The quenching tests and electron paramagnetic resonance (EPR) demonstrated that BPA degradation in PDS/NCNs system was accomplished via non-radical (O) and radical ( ·OH, SO·, and O·) pathways, in which O· was the main ROS. The origin of O· was the conversion of dissolved oxygen and the activation of PDS. The possible degradation pathways of BPA were also proposed. This study might provide inspirations to design in-situ N-doped carbon nanoparticles as the PDS activator for efficient degradation of persistent organic compound via advanced oxidation processes (AOPs).
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http://dx.doi.org/10.1016/j.jcis.2020.10.120DOI Listing
March 2021

Retinal and circumpapillary nerve fiber layer thickness and associated factors in children.

Eye (Lond) 2020 Nov 25. Epub 2020 Nov 25.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology & Visual Sciences, Beijing, China.

Objective: To evaluate the distribution of macula and circumpapillary retina nerve fiber layer (cpRNFL) thickness and other associated factors among grade-1 primary school children in Lhasa using spectral-domain optical coherence tomography (SD-OCT).

Methodology: OCT assessment was conducted on 1856 grade-1 students from 7 primary schools in Lhasa, Tibet following a successful random stratified sampling of the students. Each child underwent comprehensive general and ocular examinations as well as an SD-OCT detection (12 × 9 mm, 3D wide scan mode, Topcon 3D OCT-1) to assess the thickness of the macula, ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex (GCC), and cpRNFL. Multivariate and correlation analyses were performed to evaluate the association of the demographic and ocular variables.

Results: The average age of the 1762 (94.43%) students who underwent OCT assessment was 6.83 ± 0.46 years. Among them, 984 (53.02%) were boys. The number of students who had macular, cpRNFL, and optic disc scans completed and with adequate image quality were 1412 (82.2%), 1277 (74.4%), and 1243 (72.4%), respectively. The average macula full retinal thickness (FRT), GCIPL, GCC, and cpRNFL thickness of the students was 279.19 ± 10.61 μm, 76.41 ± 4.70 μm, 108.15 ± 6.15  μm, and 112.33 ± 13.5 μm, respectively. Multivariate regression and correlation analysis further revealed that boys and girls had significant differences in their average cpRNFL thickness. Moreover, GCC and GCIPL thickness was negatively correlated with IOP but positively correlated with the body mass index. The thickness of all the layers of the macula and cpRNFL were positively correlated with spherical equivalent. Further to this, the average macular FRT, GCIPL, and GCC thicknesses were positively correlated with cpRNFL global thickness.

Conclusion: This study describes the normal distribution of macular retina, cpRNFL, and optic disc parameters in grade-1 Tibetan children in Lhasa. It contributes to the establishment of a normative ophthalmology database of Tibetan children, and advances the ability of OCT in ophthalmic disorder diagnosis during long-term monitoring in plateau.
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http://dx.doi.org/10.1038/s41433-020-01313-zDOI Listing
November 2020

Prevalence and associated risk factors for childhood strabismus in Lhasa, Tibet, China: a cross-sectional, school-based study.

BMC Ophthalmol 2020 Nov 25;20(1):463. Epub 2020 Nov 25.

Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.

Background: To estimate the prevalence of strabismus and associated risk factors among grade one school children in Lhasa, Tibet, China.

Methods: The Lhasa Childhood Eye Study (LCES) was a cross-sectional, school-based childhood study conducted in Grade one students from primary schools in Lhasa, Tibet, China. Comprehensive ophthalmic examinations and basic systemic examinations were evaluated. A questionnaire survey containing information about children, as well as parents' information, was sent to the corresponding parents of eligible children. The prevalence of strabismus and its 95% confidence interval was estimated. Univariate and multivariate logistic regression analyses were conducted to determine the associated risk factors.

Results: A total of 1942 eligible grade one students were enrolled, of which 1856 participants completed all examinations. The average age was 6.83 ± 0.46 years, 53% of participants were boys and 1762 were the Tibetan Minority. Over all, the prevalence of strabismus was 68/1856 (3.7%) (95%CI: 2.81,4.52), with no difference between the ages, genders, ethnicities and body mass index, while tilting one's head when writing may be a risk factor for strabismus (P = 0.004). Strabismus students had mean best corrected visual acuity of 0.16 ± 0.28(LogMAR), over 50% patients with esotropia were hyperopic, and participants who had stereopsis impairments showed a significant difference between esotropia and exotropia (P = 0.026).

Conclusions: The prevalence of strabismus in LCES was 3.7%, which is higher than previous reports from Chinese childhood epidemiology studies. Strabismus is a common contributing factor to amblyopia. Tilting one's head when writing may be a risk factor. Esotropia is more likely to affect stereopsis and be associated with the refractive state of hyperopia.

Trial Registration: The study has finished the clinical registration on Chinese Clinical Trial Registry. ( http://www.chictr.org.cn , ChiCTR1900026693 ).
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http://dx.doi.org/10.1186/s12886-020-01732-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687812PMC
November 2020

Conventional ICSI improves the euploid embryo rate in male reciprocal translocation carriers.

J Assist Reprod Genet 2021 Jan 23;38(1):129-138. Epub 2020 Nov 23.

Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.

Purpose: To evaluate whether the morphologically normal spermatozoa selected for intracytoplasmic sperm injection (ICSI) under microscope had a higher rate of normal/balanced chromosome contents than that in the whole unselected sperm from reciprocal translocation carriers.

Methods: Five hundred unselected spermatozoa from each of 40 male translocation carriers were performed with fluorescence in situ hybridization (FISH), to determine the rates of gametes with different meiotic contents of translocated chromosomes. Meanwhile, 3030 biopsied blastocysts from 239 male and 293 female reciprocal translocation carriers were detected with the microarray technique to analyze the rates of embryos with different translocated chromosome contents.

Results: The D3 embryo rate, blastocyst formation rate, and euploid rate of blastocysts were remarkably higher in male carriers than those in female (p = 0.001, p = 0.004, and p = 0.035, respectively). In addition, the percentages of alternate products, which contained normal/balanced chromosome contents, in embryos from male carriers were markedly higher than those in sperm FISH (p = 2.48 × 10 and p = 2.88 × 10), while the percentages of adjacent-2 and 3:1 products were lower than those in sperm FISH (p = 0.003 and p = 5.28 × 10). Moreover, consistent results were obtained when comparing the rates of products in embryos between male and female carriers. Specifically, the incidence of alternate products in male carriers was higher than those in female carriers (p = 0.022). However, no similar differences were seen between sperm and embryos of female carriers.

Conclusion: ICSI facilitates the selection of spermatozoa with normal/balanced chromosome contents and improves the D3 embryo rate, blastocyst formation rate, and the euploid embryo rate in male carriers.
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http://dx.doi.org/10.1007/s10815-020-02013-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822975PMC
January 2021

d-Orbital steered active sites through ligand editing on heterometal imidazole frameworks for rechargeable zinc-air battery.

Nat Commun 2020 Nov 17;11(1):5858. Epub 2020 Nov 17.

Department of Chemical Engineering, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON, N2L 3G1, Canada.

The implementation of pristine metal-organic frameworks as air electrode may spark fresh vitality to rechargeable zinc-air batteries, but successful employment is rare due to the challenges in regulating their electronic states and structural porosity. Here we conquer these issues by incorporating ligand vacancies and hierarchical pores into cobalt-zinc heterometal imidazole frameworks. Systematic characterization and theoretical modeling disclose that the ligand editing eases surmountable energy barrier for *OH deprotonation by its efficacy to steer metal d-orbital electron occupancy. As a stride forward, the selected cobalt-zinc heterometallic alliance lifts the energy level of unsaturated d-orbitals and optimizes their adsorption/desorption process with oxygenated intermediates. With these merits, cobalt-zinc heterometal imidazole frameworks, as a conceptually unique electrode, empowers zinc-air battery with a discharge-charge voltage gap of 0.8 V and a cyclability of 1250 h at 15 mA cm, outperforming the noble-metal benchmarks.
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http://dx.doi.org/10.1038/s41467-020-19709-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673988PMC
November 2020

Disseminated Nocardia infection with a lesion occupying the intracranial space complicated with coma: a case report.

BMC Infect Dis 2020 Nov 17;20(1):856. Epub 2020 Nov 17.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Background: Disseminated Nocardia infection is a disease that is easily overlooked in patients with lesions occupying the intracranial space complicated with coma. Early diagnosis and treatment are crucial.

Case Presentation: A 65-year-old man was admitted to the First Affiliated Hospital of Zhejiang University in October 2018 with weakness in the right limbs for 3 days and altered consciousness for 1 day. Five months earlier, he had been diagnosed with membranous kidney disease and had received cyclophosphamide and prednisone. At admission, the white blood cell count was 1.37 × 10/L (with 86.4% neutrophils), and C-reactive protein was 115.60 mg/L. Imaging examinations revealed a lesion occupying the intracranial space, lung infection, and multiple abscesses in the rhomboid muscle. The abscesses were drained. Pus culture confirmed Nocardia cyriacigeorgica infection. With antibiotics and vacuum-sealed drainage of the back wound, the patient improved and was discharged from the hospital.

Conclusions: This case report shows that infection should be considered during the differential diagnosis of lesions in the intracranial space, especially in patients receiving immunosuppressive treatment. In patients with disseminated N. cyriacigeorgica infection, combination antibiotic therapy and surgical drainage of localised abscesses can be effective.
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http://dx.doi.org/10.1186/s12879-020-05569-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672916PMC
November 2020

Application of chromosome microarray analysis in prenatal diagnosis.

BMC Pregnancy Childbirth 2020 Nov 16;20(1):696. Epub 2020 Nov 16.

Department of Obstetrics, Weihai Maternal and Child Health Hospital, the Affiliated Weihai Second Municipal Hospital of Qingdao University, Weihai, China.

Background: To explore the application value of chromosomal microarray analysis (CMA) in prenatal diagnosis.

Methods: The results of chromosome karyotype analysis and CMA of 477 cases undergoing amniocentesis were analyzed. The results of the no ultrasound abnormality group and the ultrasound abnormality group were compared separately. Within the ultrasound abnormality group, the results of the ultrasound structural malformation group, the ultrasound soft index abnormality group, and other ultrasound abnormality (including abnormal amniotic fluid volume and fetal growth restriction) groups were compared.

Results: Abnormal chromosome and CMA results were found in a total of 71 cases (15.88%, 71/447), which can be broken down into a total of 23 karyotype abnormalities (5.15%, 23/447), consisting of 18 cases of aneuploidy (4.03%, 18/447), 2 cases of unbalanced chromosome rearrangements (0.44%, 2/447), and 3 cases of chimerism (0.67%, 3/447); 17 cases with detection of pathogenic copy number variations (pCNVs) (3.80%, 17/447); and 31 cases of detection of clinical variants of unknown significance (VOUS) (6.93%, 31/447). CMA detected 3.8% more genetic abnormalities than karyotype analysis (in addition to the abnormalities detected simultaneously by karyotype analysis). Between the no ultrasound abnormality group and the ultrasound abnormality group, there was an extremely significant difference in the detection rate of an abnormal chromosomal karyotype (P < 0.01) and of VOUS (P < 0.01), but there was no significant difference in the detection rate of pCNV (P > 0.05). Comparing the ultrasound structural malformation group, the ultrasound soft index abnormality group, and the other ultrasound abnormality group, there were no significant differences in the detection rate of abnormal chromosomal karyotypes (P > 0.05), pCNV (P > 0.05) or VOUS (P > 0.05).

Conclusions: The detection rate of chromosomal karyotype abnormalities in prenatal diagnosis in cases with no ultrasound abnormalities was higher. For cases with fetal ultrasound structural abnormalities, when compared with traditional karyotype analysis, CMA can improve the detection rate of fetal genetic abnormalities. However, the no ultrasound abnormality group also had a high VOUS abnormality detection rate, so it is necessary to strictly define the CMA indications.
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http://dx.doi.org/10.1186/s12884-020-03368-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667803PMC
November 2020

4'-O-β-D-glucosyl-5-O-methylvisamminol ameliorates imiquimod-induced psoriasis-like dermatitis and inhibits inflammatory cytokines production by suppressing the NF-κB and MAPK signaling pathways.

Braz J Med Biol Res 2020 30;53(12):e10109. Epub 2020 Oct 30.

Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing, China.

Psoriasis is a chronic inflammatory skin disorder in humans, and the inflammatory reaction plays an important role in development and onset of psoriasis. 4'-O-β-D-glucosyl-5-O-methylvisamminol (4GMV) is one of the major active chromones isolated from Saposhnikoviae divaricata (Turcz.) Schischk, which has been reported to exhibit excellent anti-inflammatory activities. However, the possible therapeutic effect on psoriasis and underlying mechanism has not been reported. Thus, the aim of this study was to investigate the protective effect of 4GMV on the imiquimod (IMQ)-induced psoriasis-like lesions in BALB/c mice and the anti-inflammatory effect on the lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. The results demonstrated that 4GMV decreased IMQ-induced keratinocyte proliferation and inflammatory cell infiltration. Moreover, 4GMV treatment significantly inhibited the production of NO, PEG 2, and cytokines such as interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and IL-22 in LPS-stimulated RAW264.7 macrophages. 4GMV also suppressed the LPS-upregulated protein expressions of iNOS and COX-2 in a dose-dependent manner. Furthermore, qRT-PCR analysis showed that 4GMV down-regulated the mRNA level of IL-1β and IL-6 expression. Further studies by western blot indicated that 4GMV inhibited the activation of upstream mediator NF-κB by suppressing the expression of TLR4 and the phosphorylation of IκBα and p65. The phosphorylation of JNK, p38, and ERK were also markedly reversed by 4GMV in LPS-treated RAW264.7 macrophages. Taken together, these results demonstrated that 4GMV showed a protective effect in IMQ-induced psoriasis-like mice and inhibited inflammation through the NF-κB and MAPK signaling pathways, indicating that 4GMV might be a potential therapeutic drug for psoriasis.
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http://dx.doi.org/10.1590/1414-431X202010109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643925PMC
January 2021

Inhibition of endoplasmic reticulum stress prevents high-fat diet mediated atrial fibrosis and fibrillation.

J Cell Mol Med 2020 Dec 1;24(23):13660-13668. Epub 2020 Nov 1.

Department of General Practice/VIP Medical Service, Beijing Hospital, National Center of Gerontology, Beijing, China.

Obesity is a significant risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia with increased mortality and morbidity. High-fat diet (HFD)-induced obesity is associated with the activation of endoplasmic reticulum stress (ERS). However, the role of ERS in HFD-induced AF remains elusive. Human atrium samples were examined for the ERS activation test. C57BL/6J mice were divided into four groups, including the control group, the HFD group, the 4-phenylbutyric acid (4-PBA) group, and the HFD + 4-PBA group. At the age of 4 weeks, the HFD group and the HFD + 4-PBA group were given HFD to construct the obesity model, while the other two groups were given a normal diet (ND). Transesophageal programmed electrical stimulation was conducted to evaluate the AF inducibility and duration. Atrial fibrosis and ERS activation were also investigated.We found that CHOP and GRP-78 protein were significantly higher in overweight patients than the controls (both P < 0.05). AF inducibility and duration of the HFD group were significantly higher than the other groups (both P < 0.05), while there was no difference between those groups (P > 0.05). The mice of the HFD group had significantly higher collagen volume fraction (CVF%) than the other groups (P < 0.05). ERS marker protein of GRP78, p-PERK, ATF6 and CHOP protein expression level was increased in the HFD group, which were significantly mitigated in the HFD + 4-PBA group. In summary, HFD-induced ERS activation facilitates atrial fibrosis and AF. The inhibition of ERS might alleviate atrial fibrosis and reduce the incidence of AF-associated obesity.
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http://dx.doi.org/10.1111/jcmm.15816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754029PMC
December 2020

New insights into unusual droplets: from mediating the wettability to manipulating the locomotion modes.

Chem Commun (Camb) 2020 Nov;56(94):14757-14788

Ministry of Education Key Laboratory for the Green Preparation and Application of Functional Materials, School of Materials Science & Engineering and Hubei Key Laboratory of Polymer Materials, Hubei University, Wuhan 430062, People's Republic of China. and State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, People's Republic of China.

The ability to manipulate droplets can be utilized to develop various smart sensors or actuators, endowing them with fascinating applications for drug delivery, detection of target analytes, environmental monitoring, intelligent control, and so on. However, the stimuli-responsive superhydrophobic/superhydrophilic materials for normal water droplets cannot satisfy the requirements from some certain circumstances, i.e., liquid lenses and biosensors (detection of various additives in water/blood droplets). Stimuli-responsive wetting/dewetting behaviors of exceptional droplets are open issues and are attracting much attention from across the world. In this perspective article, the unconventional droplets are divided into three categories: ionic or surfactant additives in water droplets, oil droplets, and bubble droplets. We first introduce several classical wettability models of droplets and some methods to achieve wettability transition. The unusual droplet motion is also introduced in detail. There are four main types of locomotion modes, which are vertical rebound motion, lateral motion, self-propulsion motion, and anisotropic wettability controlled sliding behavior. The driving mechanism for the droplet motion is briefly introduced as well. Some approaches to achieve this manipulation goal, such as light irradiation, electronic, magnetic, acid-base, thermal, and mechanical ways will be taken into consideration. Finally, the current researches on unconventional droplets extending to polymer droplets and liquid metal droplets on the surface of special wettability materials are summarized and the prospect of unconventional droplet research directions in the field of on-demand transport application will be proposed.
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http://dx.doi.org/10.1039/d0cc05801gDOI Listing
November 2020

Novel Regulators of Sugar-Mediated Lateral Root Development in .

Genes (Basel) 2020 Oct 25;11(11). Epub 2020 Oct 25.

State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University, Yangling, Xianyang 712100, Shaanxi, China.

Lateral root development is a complex process regulated by numerous factors. An important role for sugar in lateral root development has been known for a while, but the underlying molecular basis still remains unclear. In this study, we first showed that WOX7, a sugar-inducible negative regulator of lateral root development, acts downstream of the glucose sensor HXK1. Using a transgenic line homozygous for a transgene expressing GFP under the control of the promoter, we next performed a genetic screen to identify additional genes in this development pathway. A number of mutants with altered level of expression were recovered, and two with increased expression, named and (for ), were further characterized. Both mutants manifest delayed lateral root development, and genetic analysis indicates that single recessive mutations are responsible for the observed phenotypes. The mutations were then located to similar regions on chromosome 2 by marker-assisted analyses, and candidate genes were identified through whole genome sequencing. The significance and limitations of this work are discussed.
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http://dx.doi.org/10.3390/genes11111257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716218PMC
October 2020

[Expression and significance of chemokines CCL21, E-selectins and Hsp90 in periodontal tissues of rats with experimental periodontitis].

Shanghai Kou Qiang Yi Xue 2020 Aug;29(4):350-354

Department of Orthodontics, Affiliated Hospital of Qingdao University. Qingdao 266500, Shandong Province, China.

Purpose: To investigate the expression and significance of chemokines CCL21, E-selectins and heat shock protein 90 (Hsp90) in periodontal tissues of rats with experimental periodontitis.

Methods: Forty 10-week-old male Wistar rats were significantly randomly divided into 4 groups with 10 rats in each group. Periodontitis models were established in groups A, B and C, and the rest were 10 blank control groups. Rats in group A, B and C were sacrificed at 4, 8 and 12 weeks after basic periodontal treatment, and the periodontal tissues of the first and second molars were taken for CCL21, E-selectins and Hsp90 protein expression detection. SPSS 25.0 software package was used to analyze the data.

Results: The levels of periodontal attachment in group A, B and C were higher than those in the control group(P<0.05). The levels of periodontal attachment, CCL21, E-selectins, Hsp90 mRNA and protein expression in periodontal tissues increased first and then decreased(P<0.05). The levels of periodontal attachment, CCL21, E-selectins, Hsp90 mRNA and protein expression in group B and C were significantly higher than those in group A(P<0.05). The levels of periodontal attachment, CCL21, E-selectins, Hsp90 and relative protein expression in periodontal tissues of group C were significantly lower than those of group B(P<0.05).

Conclusions: The expression of CCL21, E-selectins and Hsp90 is up-regulated in periodontitis tissues. With local periodontal treatment, the expression level of CCL21, E-selectins and Hsp90 gradually decreases.
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August 2020

Oocyte Vitrification Temporarily Turns on Oxidation-Reduction Process Genes in Mouse Preimplantation Embryos.

Reprod Sci 2020 Oct 16. Epub 2020 Oct 16.

Shanghai Ji Ai Genetics & IVF Institute, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, China.

We aim to understand how oocyte vitrification impacts subsequent mouse preimplantation embryo development at molecular level. We profiled transcriptomics of fertilized preimplantation embryos derived from mouse vitrified-warmed oocytes. Concomitantly, we evaluated epigenetic markers in fertilized preimplantation embryos. We found that oocyte vitrification did not affect the fertilization and cleavage process but delayed embryo development until blastocyst stage. RNA sequencing revealed that 1575 genes were profoundly altered in the 2-cell stage embryos developed from vitrified oocytes. The most significantly altered biological pathway was "oxidation-reduction process." Such profound transcriptomics change was associated with decreased level of oocyte-specific histone H1FOO in zygote and 2-cell stage. Transcriptome alteration due to oocyte vitrification was less pronounced as embryos develop into the morula stage. Oocyte vitrification temporarily changes transcriptomics in early preimplantation embryos. Targeting oxidation-reduction pathway might be a potential therapeutic strategy to improve embryo quality and long-term embryo survival.
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http://dx.doi.org/10.1007/s43032-020-00337-wDOI Listing
October 2020

Targeting GCK pathway: a novel and selective therapeutic strategy against RAS mutated multiple myeloma.

Blood 2020 Oct 9. Epub 2020 Oct 9.

Columbia University Medical Center, New York, New York, United States.

In multiple myeloma (MM), frequent mutations of NRAS, KRAS, or BRAF are found in up to 50% of newly diagnosed patients. The majority of the NRAS, KRAS, and BRAF mutations occur in hotspots causing constitutive activation of the corresponding proteins. Thus targeting RAS mutation in MM will increase therapeutic efficiency and potentially overcome drug-resistance. We identified Germinal Center Kinase (GCK) as a novel therapeutic target in MM with RAS mutation. GCK knockdown in MM cells demonstrated in vitro and in vivo that silencing of GCK induces MM cell growth inhibition, associated with blocked MKK4/7-JNK phosphorylation and impaired degradation of IKZF1/3, BCL-6, and c-MYC. These effects were rescued by overexpression of an shRNA-resistant GCK, thereby excluding the potential off-target effects of GCK knockdown. In contrast, overexpression of shRNA-resistant GCK kinase-dead mutant (K45A) inhibited MM cell proliferation and failed to rescue the effects of GCK knockdown on MM growth inhibition, indicating that GCK kinase activity is critical for regulating MM cell proliferation and survival. Importantly, the higher sensitivity to GCK knockdown in RASMut cells suggests that targeting GCK is effective in multiple myeloma which harbors RAS mutations. In accordance with the effects of GCK knockdown, the GCK inhibitor TL4-12 dose-dependently downregulated IKZF1 and BCL-6 and led to MM cell proliferation inhibition accompanied by induction of apoptosis. Hereby our data identify GCK as a novel target in RASMut MM cells, providing a rationale to treat RAS mutations in MM. Furthermore, GCK inhibitors might represent an alternative therapy to overcome IMiD-resistance in MM.
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http://dx.doi.org/10.1182/blood.2020006334DOI Listing
October 2020