Publications by authors named "Bin Xu"

2,177 Publications

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Lung adenocarcinoma patients with KEAP1 mutation harboring low immune cell infiltration and low activity of immune environment.

Thorac Cancer 2021 Jul 30. Epub 2021 Jul 30.

Department of Respiratory Medicine, Nanjing Chest Hospital, The Affiliated Brain Hospital of Nanjing Medical University, 215 Guangzhou Road, Nanjing, Jiangsu, 210029, China.

Background: Kelch-like ECH-associated protein 1 (KEAP1) has been identified as a cancer driver gene in lung adenocarcinoma (LUAD), and increased evidence has given us clues about the association of KEAP1 mutation and immune characteristics. We assessed the association between KEAP1 mutation and tumor microenvironment in LUAD systematically.

Methods: With the data collected from The Cancer Genome Atlas (TCGA), we evaluated the association of KEAP1 mutation with tumor infiltrating leukocytes (TILs), including dendritic cell, CD8 T cell, CD4 T cell, neutrophil, B cells, and macrophage. Expression differences of the markers of those immune cells were also measured. We further compared the expression of antigen presentation genes and chemokines and the enrichment score of immune-related pathways.

Results: KEAP1 mutation had significant association with lower TILs and cytotoxic T lymphocyte. Strikingly, almost all of antigen presentation genes and chemokine showed lower expression in KEAP1-mutated tumors. Moreover, most of immune-related pathways were less active in KEAP1-mutated tumors. As expected, KEAP1-wild type LUADs favored better overall survival after immunotherapy. Finally, one patient harboring KEAP1 mutation along with a lack of immune cells infiltration in tumor microenvironment failed to respond to checkpoint inhibitor despite high tumor mutational burden (TMB).

Conclusions: KEAP1 mutation has a significant effect on the tumor immune milieu of LUAD and may play as a predictive biomarker of immunotherapy for LUAD patients.
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http://dx.doi.org/10.1111/1759-7714.14089DOI Listing
July 2021

The Role of Androgen Receptor Splicing Variant 7 in Predicting the Prognosis of Metastatic Castration-Resistant Prostate Cancer: Systematic Review and Meta-Analysis.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211035260

Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu, China.

Objective: The purpose of this meta-analysis was to study the prognostic effects of androgen receptor splicing variant 7 (AR-V7) on metastatic castration-resistant prostate cancer (mCRPC) under different treatment options (chemotherapy, hormone therapy).

Methods: We conducted a systematic search of PubMed, EMBASE and Cochrane databases for clinical studies up to June 4, 2021, and used prostate-specific antigen (PSA) progression free-survival (PSA-PFS), radiologic PFS (r-PFS), overall survival (OS) and PSA response rate (PSA RR) as the main endpoints. Subgroup analyses were conducted based on the source of the specimens. STATA v.15 software was used for data analysis.

Results: Twenty-one studies were included in this meta-analysis, with a total of 1578 samples. In the abiraterone (AA)/enzalutamide (E) treatment group, AR-V7 positive patients had worse PSA-PFS (hazard ratio [HR] = 3.40; 95% confidence interval [95%CI] 2.56-4.51; < 0.05) and worse r-PFS (HR = 2.69; 95%CI 1.70-4.24; < 0.05) and OS (HR = 3.02; 95%CI 1.73-5.30; < 0.05). Multivariate Cox regression results showed that AR-V7 positive status was an independent risk factor for OS in the AA/E treatment group. In the taxane treatment group, AR-V7-positive and negative patients had similar PSA-PFS (HR = 0.87; 95%CI 0.46-1.63; = 0.657), r-PFS (HR = 1.01; 95%CI 0.53-1.96; = 0.965) and OS (HR = 1.50; 95%CI 0.89-2.52; = 0.127). For AR-V7-positive patients, the difference in OS between taxane and AA/E treatment was not statistically significant (HR = 1.03; 95%CI 0.52-2.06; = 0.930). However, multivariate Cox regression results suggested that for AR-V7-positive patients, taxane therapy was a protective factor for OS (HR = 0.35; 95%CI 0.20-0.60; < 0.05).

Conclusion: The expression of AR-V7 indicates a poor prognosis and is an independent risk factor for OS in AA/E-treated mCRPC patients. However, AR-V7 positive status does not play the same role in taxane-treated patients. In addition, compared to AA/E, taxane treatment is a protective factor for OS in AR-V7-positive patients. AR-V7 may thus be an effective biomarker for treatment prognosis in patients with mCRPC.
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http://dx.doi.org/10.1177/15330338211035260DOI Listing
July 2021

Cumulative effects of ambient particulate matter pollution on deaths: A multicity analysis of mortality displacement.

Chemosphere 2021 Jul 20;286(Pt 1):131615. Epub 2021 Jul 20.

Jiangsu Provincial Center for Disease Control and Prevention, Jiangsu Road 172, 210009, Nanjing, PR China. Electronic address:

Background: Systematic evaluations of the cumulative effects and mortality displacement of ambient particulate matter (PM) pollution on deaths are lacking. We aimed to discern the cumulative effect profile of PM exposure, and investigate the presence of mortality displacement in a large-scale population.

Methods: We conducted a time-series analysis with different exposure-lag models on 13 cities in Jiangsu, China, to estimate the effects of PM pollution on non-accidental, cardiovascular, and respiratory mortality (2015-2019). Over-dispersed Poisson generalized additive models were integrated with distributed lag models to estimate cumulative exposure effects, and assess mortality displacement.

Results: Pooled cumulative effect estimates with lags of 0-7 and 0-14 days were substantially larger than those with single-day and 2-day moving average lags. For each 10 μg/m increment in PM concentration with a cumulative lag of 0-7 days, we estimated an increase of 0.50 % (95 % CI: 0.29, 0.72), 0.63 % (95 % CI: 0.38, 0.88), and 0.50 % (95 % CI: 0.01, 1.01) in pooled estimates of non-accidental, cardiovascular, and respiratory mortality, respectively. Both PM and PM were associated with significant increases in non-accidental and cardiovascular mortality with a cumulative lag of 0-14 days. We observed mortality displacement within 30 days for non-accidental, cardiovascular, and respiratory deaths.

Conclusions: Our findings suggest that risk assessment based on single-day or 2-day moving average lag structures may underestimate the adverse effects of PM pollution. The cumulative effects of PM exposure on non-accidental and cardiovascular mortality can last up to 14 days. Evidence of mortality displacement for non-accidental, cardiovascular, and respiratory deaths was found.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131615DOI Listing
July 2021

Preparation of Colored Microcapsule Phase Change Materials with Colored SiO Shell for Thermal Energy Storage and Their Application in Latex Paint Coating.

Materials (Basel) 2021 Jul 18;14(14). Epub 2021 Jul 18.

College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310000, China.

This article reports the design and manufacture of colored microcapsules with specific functions and their application in architectural interior wall coating. Utilizing reactive dyes grafted SiO shell to encapsulate paraffin through interfacial polymerization and chemical grafting methods, this experiment successfully synthesized [email protected] colored microcapsules. The observations of surface morphology demonstrated that the colored microcapsules had a regular spherical morphology and a well-defined core-shell structure. The analysis of XRD and FT-IR confirmed the presence of amorphous SiO shell and the grafting reactive dyes, and the paraffin possessed high crystallinity. Compared with pristine paraffin, the thermal conductivity of [email protected] colored microcapsules was significantly enhanced. The results of DSC revealed that the [email protected] colored microcapsules performed high encapsulation efficiency and desirable latent heat storage capability. Besides, the examinations of UV-vis and TGA showed that the [email protected] colored microcapsules exhibited good thermal reliability, thermal stability, and UV protection property. The analysis of infrared imaging indicated that the prepared latex paint exhibited remarkable temperature-regulated property. Compared with normal interior wall coatings, the temperature was reduced by about 2.5 °C. With such incomparable features, the [email protected] colored microcapsules not only appeared well in their solar thermal energy storage and temperature-regulated property, but also make the colored latex paint coating have superb colored fixing capabilities.
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http://dx.doi.org/10.3390/ma14144012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303270PMC
July 2021

Electroacupuncture Alleviates Diabetic Peripheral Neuropathy by Regulating Glycolipid-Related GLO/AGEs/RAGE Axis.

Front Endocrinol (Lausanne) 2021 6;12:655591. Epub 2021 Jul 6.

Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China.

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus (DM) and affects over one-third of all patients. Neuropathic pain and nerve dysfunction induced by DM is related to the increase of advanced glycation end products (AGEs) produced by reactive dicarbonyl compounds in a hyperglycemia environment. AGEs induce the expression of pro-inflammatory cytokines the main receptor (RAGE), which has been documented to play a crucial role in the pathogenesis of diabetic peripheral neuropathy. Electroacupuncture (EA) has been reported to have a positive effect on paralgesia caused by various diseases, but the mechanism is unclear. In this study, we used high-fat-fed low-dose streptozotocin-induced rats as a model of type 2 diabetes (T2DM). Persistent metabolic disorder led to mechanical and thermal hyperalgesia, as well as intraepidermal nerve fiber density reduction and nerve demyelination. EA improved neurological hyperalgesia, decreased the pro-inflammatory cytokines, reduced the generation of AGEs and RAGE, and regulated the glyoxalase system in the EA group. Taken together, our study suggested that EA plays a role in the treatment of T2DM-induced DPN, and is probably related to the regulation of metabolism and the secondary influence on the GLO/AGE/RAGE axis.
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http://dx.doi.org/10.3389/fendo.2021.655591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290521PMC
July 2021

Effects of Hand Holding on Anxiety and Pain During Prostate Biopsies: A Pilot Randomized Controlled Trial.

Patient Prefer Adherence 2021 16;15:1593-1600. Epub 2021 Jul 16.

Department of Urology, The Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China.

Background: Effective pain management is limited for patients during prostate biopsy (PBx). Touch support, such as hand holding, has stress-buffering benefits and effective analgesic effects. We conducted a prospective, single-center randomized clinical trial to assess whether hand holding can reduce patient anxiety, pain, and dissatisfaction during PBx.

Methods: Between April 2020 and October 2020, 120 male patients were randomized into three groups: a hand holding with relatives (HR) group, a hand holding with strangers (HS) group and a control group. A visual analog scale (VAS) was used for self-assessments of pain and satisfaction. Anxiety levels were quantified according to the State-Trait Anxiety Inventory (STAI). Hemodynamic changes were also measured.

Results: The degree of pain and anxiety in the hand-holding groups was significantly better than that in the control group (<0.001), and the patients were more willing to undergo repeat PBx (=0.017). The anxiety levels in the HR group were significantly lower than those in the HS group (=0.019). During PBx, the changes in systolic blood pressure and heart rate in the hand-holding groups were more stable than those in the control group (<0.01), and the fluctuations in heart rate in the HR group were smaller than those in the HS group (<0.01).

Conclusion: Hand holding, especially with relatives, can promote incremental reductions in anxiety, pain and dissatisfaction in patients during PBx. Hence, we recommend hand holding with relatives as an effective adjunct during PBx.
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http://dx.doi.org/10.2147/PPA.S321175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291963PMC
July 2021

Feasibility of anterior pedicle screw fixation in lumbosacral spine: a radiographic and cadaveric study.

Ann Transl Med 2021 Jun;9(12):968

Department of Orthopaedics, Tongde Hospital of Zhejiang Province, Hangzhou, China.

Background: The anterior pedicle screw (APS) technique for L5 and S1 is crucial for proper anterior lumbar interbody fusion (ALIF). This study aimed to determine the projection, screw trajectory angle, and bone screw passageway length (BSPL), as well as the screw insertion regularity and the operating area within which it is safe to perform insertion.

Methods: Forty patients with low back pain, all of whom had lumbar computed tomography scans available, was included in this retrospective analysis. Radiographic parameters were measured, including: the distances from the projection to the upper endplate, lower endplate, and midline; the transverse and sagittal screw angles; and the BSPL. In addition, 10 fresh adult cadaveric lumbosacral spine segments were selected to determine the safe anatomic area in which to operate. Finally, APSs were inserted in L5 and S1 to determine the regularity of APS insertion.

Results: We measured the anterior projection parameters, including: the distances to the upper endplate (L5: 12.5±1.3 mm; S1: 4.54±0.87 mm), lower endplate (L5: 17.3±1.6 mm), and midline (L5: 6.6±0.7 mm; S1: 6.6±0.6 mm); the screw trajectory angle, including the transverse screw angle (L5: 25.3±2.8°; S1: 25.7±2.6°), sagittal screw angle (L5: 17.1±1.7°; S1: 22.4±1.1°); and the BSPL (L5: 48.6±3.5 mm; S1: 48.0±3.5 mm). The regularity of APS insertion in L5 and S1 was determined. Upon the needle reaching a point in the lateral view, it reached the corresponding point in the anteroposterior (AP) view. The anatomic parameters of the safe operating area were as follows: the distance from the abdominal aortic bifurcation to the L5 lower edge (40.50±9.40 mm); the distance from the common iliac vein confluence to the L5 lower edge (27.80±8.60 mm); and the horizontal distance from the inner edge of the common iliac vein to the L5 lower edge (37.50±1.30 mm). We also determined the distance between S1 holes (29.30±1.30 mm), the L5/S1 intervertebral height (17.20±1.50 mm), and the safe operating area (2,058.20±84.30 mm).

Conclusions: This study has determined the projection, screw trajectory angle, and BSPL of APSs in L5 and S1, their insertion regularity, and the area in which the operation can be safely performed.
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http://dx.doi.org/10.21037/atm-21-2143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267288PMC
June 2021

Bioinformatics Analysis of Expression Profiles and Prognostic Values of the Signal Transducer and Activator of Transcription Family Genes in Glioma.

Front Genet 2021 2;12:625234. Epub 2021 Jul 2.

Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.

Signal transducer and activator of transcription () family genes-of which there are seven members: , and -have been associated with the progression of multiple cancers. However, their prognostic values in glioma remain unclear. In this study, we systematically investigated the expression, the prognostic value, and the potential mechanism of the family genes in glioma. The expression of 1/2/3/5A/6 members were significantly higher and positively correlated with mutations, while the expression of was lower and negatively correlated with mutations in glioma. Survival analysis indicated that the upregulation of and downregulation of expression was associated with poorer overall survival in glioma. Joint effects analysis of expression suggested that the prognostic value of the group was more significant than that of each individual gene. Thus, we constructed a risk score model to predict the prognosis of glioma. The receiver operating characteristic curve and calibration curves showed good performance as prognostic indicators in both TCGA (The Cancer Genome Atlas) and the CGGA (Chinese Glioma Genome Atlas) databases. Furthermore, we analyzed the correlation between expression with immune infiltration in glioma. The Protein-protein interaction network and enrichment analysis showed that members and co-expressed genes mainly participated in signal transduction activity, Hepatitis B, the Jak-STAT signaling pathway, transcription factor activity, sequence-specific DNA binding, and the cytokine-mediated signaling pathway in glioma. In summary, our study analyzed the expression, prognostic values, and biological roles of the gene family members in glioma, based on which we developed a new risk score model to predict the prognosis of glioma more precisely.
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http://dx.doi.org/10.3389/fgene.2021.625234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283826PMC
July 2021

Photoinactivation of the oxygen-evolving complex regulates the photosynthetic strategy of the seagrass Zostera marina.

J Photochem Photobiol B 2021 Jul 14;222:112259. Epub 2021 Jul 14.

Ocean School, Yantai University, Yantai 264005, PR China.

Zostera marina, a widespread seagrass, evolved from a freshwater ancestor of terrestrial monocots and successfully transitioned into a completely submerged seagrass. We found that its oxygen-evolving complex (OEC) was partially inactivated in response to light exposure, as evidenced by both the increment of the relative variable fluorescence at the K-step and the downregulation of the OEC genes and proteins. This photosynthetic regulation was further addressed at both proteome and physiology levels by an in vivo study. The unchanged content of the ΔpH sensor PsbS protein and the non-photochemical quenching induction dynamics, described by a single exponential function, verified the absence of the fast qE component. Contents and activities of chlororespiration, Mehler reaction, malic acid synthesis, and photorespiration key enzymes were not upregulated, suggesting that alternative electron flows remained unactivated. Furthermore, neither significant production of singlet oxygen nor increment of total antioxidative capacity indicated that reactive oxygen species were not produced during light exposure. In summary, these low electron consumptions may allow Z. marina to efficiently use the limited electrons caused by partial OEC photoinactivation to maintain a normal carbon assimilation level.
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http://dx.doi.org/10.1016/j.jphotobiol.2021.112259DOI Listing
July 2021

Simulation of portal/hepatic vein associated remnant liver ischemia/congestion by three-dimensional visualization technology based on preoperative CT scan.

Ann Transl Med 2021 May;9(9):756

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Remnant liver hypoperfusion is frequently observed after hepatectomy, and associated with a higher risk of postoperative complications and poorer survival. However, the development of remnant liver hypoperfusion was not fully understood.

Methods: We retrospectively analyzed patients who received hepatectomy and took contrast-enhanced computed tomography (CT) scans before, 1-week (POW1) and 4-week (POW4) after resection in our department from June 2017 to July 2019. We simulated and estimated the occurrence of portal-vein-related remnant liver ischemia (RLI) and hepatic-vein-related remnant liver congestion (RLC) after hepatectomy via three-dimensional visualization technology (3DVT) according to blood vessels ligated in the resection; then we analyzed association between the estimated RLI, RLC, and postoperative clinical outcomes.

Results: A total of 102 eligible patients were analyzed. Remnant liver hypoperfusion was observed in 47 (46%) patients in the POW1 CT scans and shrunk in the POW4 CT scans. RLC had better diagnostic significance than RLI in predicting remnant liver hypoperfusion [area under receiver operating characteristic (ROC) curve: 0.745 0.569, P=0.026]. Multivariate analysis showed that larger RLI [odds ratio (OR), 1.154; 95% confidence interval (CI), 1.075-1.240; P<0.001] was independent risk factor for post-hepatectomy liver failure (PHLF). Besides, larger RLC (OR, 1.114; 95% CI, 1.032-1.204; P=0.006) was independent risk factor for major postoperative complications.

Conclusions: Remnant liver hypoperfusion can be predicted during the preoperative surgical plan by 3DVT. Portal vein related RLI was associated with PHLF, and hepatic vein related RLC was associated with major postoperative complications. Preservation of the hepatic vein and complete removal of the perfusion territory of ligated vessels are essential procedures to reduce RLI/RLC and the risk of PHLF or other surgical complications.
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http://dx.doi.org/10.21037/atm-20-7920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246180PMC
May 2021

IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies: Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome.

Am J Surg Pathol 2021 Jul 15. Epub 2021 Jul 15.

Departments of Neuropathology Pathology, Charité Universitätsmedizin Berlin, Corporate Member of Free University Berlin and Humboldt University Berlin Berlin Institute of Health, Berlin German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ) Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK) Hopp-Children's Cancer Center (KiTZ), Heidelberg Institute of Pathology, University of Luebeck and University Hospital Schleswig-Holstein, Luebeck Department of Neuropathology, Philipps University and University Hospital of Marburg, Marburg Department of Pathology, University Hospital Leipzig, Leipzig Department of Neuropathology, University Medical Center Göttingen, Göttingen Institute of Neuropathology, University Hospital Muenster, Muenster Department of Neuropathology, Justus-Liebig-University and University Hospital of Giessen, Giessen Institute of Pathology, Friedrich-Alexander-University and University Hospital Erlangen-Nürnberg, Erlangen Institute of Neuropathology Department of Pediatric Hematology and Oncology, University Medical Center, Hamburg-Eppendorf Research Institute Children's Cancer Center, Hamburg, Germany Departments of Pathology Medicine, Memorial Sloan Kettering Cancer Center Department of Pathology Laura and Isaac Perlmutter Cancer Center, NYU Langone Health and School of Medicine, New York, NY Bone Tumor Reference Center at the Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel Department of Pathology, University Hospital Basel, Basel, Switzerland.

IDH2 R172 mutations occur in sinonasal undifferentiated carcinoma (SNUC), large-cell neuroendocrine carcinoma (LCNEC), sinonasal adenocarcinomas, and olfactory neuroblastoma (ONB). We performed a clinical, pathologic, and genetic/epigenetic analysis of a large IDH2-mutated sinonasal tumor cohort to explore their distinct features. A total 165 sinonasal/skull base tumors included 40 IDH2 mutants studied by light microscopy, immunohistochemistry, and genome-wide DNA methylation, and 125 IDH2 wild-type tumors used for comparison. Methylation profiles were analyzed by unsupervised hierarchical clustering, t-distributed stochastic neighbor embedding dimensionality reduction and assessed for copy number alterations (CNA). Thirty-nine histologically assessable cases included 25 (64.1%) SNUC, 8 (20.5%) LCNEC, 2 (5.1%) poorly differentiated adenocarcinomas, 1 (2.7%) ONB, and 3 (7.7%) IDH2-mutated tumors with ONB features. All cases were high-grade showing necrosis (82.4%), prominent nucleoli (88.9%), and median 21 mitoses/10 HPFs. AE1/AE3 and/or CAM 5.2 were positive in all and insulinoma-associated protein 1 (INSM1) in 80% cases. All IDH2 mutants formed one distinct group by t-distributed stochastic neighbor embedding dimensionality reduction separating from all IDH2 wild-type tumors. There was no correlation between methylation clusters and histopathologic diagnoses. Recurrent CNA included 1q gain (79.3%), 17p loss (75.9%), and 17q gain (58.6%). No CNA differences were observed between SNUC and LCNEC. IDH2 mutants showed better disease-specific survival than SMARCB1-deficient (P=0.027) and IDH2 wild-type carcinomas overall (P=0.042). IDH2-mutated sinonasal tumors are remarkably homogeneous at the molecular level and distinct from IDH2 wild-type sinonasal malignancies. Biology of IDH2-mutated sinonasal tumors might be primarily defined by their unique molecular fingerprint rather than by their respective histopathologic diagnoses.
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http://dx.doi.org/10.1097/PAS.0000000000001697DOI Listing
July 2021

Factors Associated with Survival From Xp11.2 Translocation Renal Cell Carcinoma Diagnosis-A Systematic Review and Pooled Analysis.

Pathol Oncol Res 2021 30;27:610360. Epub 2021 Mar 30.

Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.

Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a rare subtype of renal cell carcinoma (RCC), characterized by translocations of Xp11.2 breakpoints, involving of the transcription factor three gene (TFE3). The aim of our study was to comprehensively characterize the clinical characteristics and outcomes, and to identify risk factors associated with OS and PFS in Xp11.2 tRCC patients. Literature search on Xp11.2 tRCC was performed using databases such as pubmed EMBASE and Web of Science. Studies were eligible if outcomes data (OS and/or PFS) were reported for patients with a histopathologically confirmed Xp11.2 tRCC. PFS and OS were evaluated using the univariable and multivariable Cox regression model. There were 80 eligible publications, contributing 415 patients. In multivariable analyses, the T stage at presentation was significantly associated with PFS (HR: 3.87; 95% CI: 1.70 to 8.84; = 0.001). The median time of PFS was 72 months. In the multivariable analyses, age at diagnosis (HR: 2.16; 95% CI: 1.03 to 4.50; = 0.041), T stage at presentation (HR: 4.44; 95% CI: 2.16 to 9.09; < 0.001) and metastasis status at presentation (HR: 2.67; 95% CI: 1.12 to 6.41; = 0.027) were all associated with OS, with a median follow-up time of 198 months. T stage at presentation is the only factor that is associated with both PFS and OS in patients with Xp11.2 tRCC. Also, patients over 45 or with metastases are more likely to have poorer OS.
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http://dx.doi.org/10.3389/pore.2021.610360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262176PMC
March 2021

SP1 Expression and the Clinicopathological Features of Tumors: A Meta-Analysis and Bioinformatics Analysis.

Pathol Oncol Res 2021 28;27:581998. Epub 2021 Jan 28.

Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu, China.

Specificity protein 1 (SP1) plays a vital role to promote carcinogenesis in a variety of tumors, and its up-regulated expression is reported to be a hinter of poor prognosis of patients. We conducted this meta-analysis to elucidate the clinical significance and prognostic value of SP1 in malignant tumors. PubMed and Cochrane Library were searched for studies published between January 1, 2000 and June 1, 2020. The combined odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to investigate the correlation of SP1 with clinical behaviors and prognosis in patients with solid tumors. UALCAN was used to conduct bioinformatics analysis. A total of 24 documents involving 2,739 patients were enrolled in our review. The random-effect model was used to perform this analysis due to the high level of heterogeneity. SP1 low expression was not conducive to lymph node metastasis (OR = 0.42; 95% CI: 0.28-0.64; < 0.05), progression of TNM stage (OR = 0.34; 95% CI: 0.20-0.57; < 0.05) and tumor infiltration (OR = 0.33; 95% CI: 0.18-0.60; < 0.05). Elevated SP1 expression was connected with shorter survival time of patients with hepatocellular carcinoma, pancreatic cancer, gastric cancer and esophageal cancer (HR = 1.95; 95% CI: 1.16-3.28; < 0.05). According to UALCAN database, breast cancer, ovarian cancer, colon cancer and lung adenocarcinoma display an elevated SP1 expression in comparison with normal tissues. Kaplan-Meier survival plots indicate SP1 mRNA level has negative effects on prognosis of liver hepatocellular carcinoma and brain lower grade glioma. SP1 was associated with lymph node metastasis, TNM stage and depth of invasion, and indicated poor clinical outcome, which brought new insights on the potential candidacy of SP1 in clinical usage.
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http://dx.doi.org/10.3389/pore.2021.581998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262197PMC
January 2021

Fast and Ultrasensitive Visual Detection of Exosomes in Body Fluids for Point-of-Care Disease Diagnosis.

Anal Chem 2021 Jul 13;93(29):10372-10377. Epub 2021 Jul 13.

Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, Jiangsu, China.

Fast detection of low-concentration exosomes in body fluids is of great significance in understanding the pathogenesis and disease diagnosis but is quite a challenging work due to the complex matrix, tedious pretreatment, and relatively poor sensitivity without the aid of instruments. In this work, by simply using a filter membrane to enrich the exosomes at low concentrations and the use of CuS nanoparticles as labels, we were able to detect exosomes at concentrations as low as 2 × 10 particles/μL in a complex matrix by the naked eye. Due to its high sensitivity, specificity, and simplicity, it can be used for the diagnosis of direct prostate cancer via a 5 mL urine sample within 2 h without the use of any instrument. This method can also be applicable for the detection of other biological nanoparticles, such as viruses, at low concentrations in a complex matrix, offering a promising candidate for point-of-care disease diagnosis with low cost.
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http://dx.doi.org/10.1021/acs.analchem.1c02136DOI Listing
July 2021

Impact of previous Caesarean section on reproductive outcomes after assisted reproductive technology: systematic review and meta-analyses.

Reprod Biomed Online 2021 Apr 22. Epub 2021 Apr 22.

Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha Hunan, China; Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha Hunan, China. Electronic address:

This meta-analysis investigated whether a previous Caesarean section has an impact on the outcomes of treatment with assisted reproductive technology (ART). PubMed, Embase, Cochrane Library, Web of Science and Google Scholar were searched. Clinical trials published in English up to May 2020 were included. Seven studies performed between 2016 and 2020 met all the inclusion criteria. It was found that previous Caesarean section leads to significantly decreased clinical pregnancy rate (CPR) (risk ratio [RR] 0.86; 95% confidence interval [CI], 0.81, 0.92; P < 0.00001) and live birth rate (LBR) (RR 0.80; 95% CI 0.73, 0.86; P < 0.00001). Caesarean section increased the miscarriage rate (RR 1.39; 95% CI 1.18, 1.64; P < 0.0001), and difficult transfer (RR 8.23; 95% CI 4.63, 14.65; P < 0.00001) after ART compared with women who had previous vaginal delivery. The combined results also showed similar endometrial thickness, number of oocytes retrieved, implantation rate, ectopic pregnancy rate, preterm birth and stillbirth between women with previous Caesarean section and women with previous vaginal delivery. In conclusion, Caesarean sections have a detrimental effect on CPR and LBR, and increase the risk of miscarriage and difficult transfer. The indications for Caesarean section should be strictly controlled, and full consultation should be provided to pregnant women. Further studies with stratification analysis of twin and single pregnancies are needed to evaluate the impact of Caesarean section.
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http://dx.doi.org/10.1016/j.rbmo.2021.04.007DOI Listing
April 2021

circ_0005962 functions as an oncogene to aggravate NSCLC progression.

Open Med (Wars) 2021 2;16(1):997-1009. Epub 2021 Jul 2.

Department of Gastrointestinal Surgery, Gong'an County People's Hospital, No. 119, Chan Ling Road, Douhudi Town, Gong'an County, Jingzhou, Hubei 433000, China.

Background: Non-small cell lung cancer (NSCLC) is a leading threat to human lives with high incidence and mortality. Circular RNAs were reported to play important roles in human cancers. The purpose of this study was to investigate the role of circ_0005962 and explore the underlying functional mechanisms.

Methods: The protein levels of Beclin 1, light chain3 (LC3-II/LC3-I), Pyruvate dehydrogenase kinase 4 (PDK4), Cleaved Caspase 3 (C-caspase 3), and proliferating cell nuclear antigen were examined using western blot analysis. Glycolysis was determined according to the levels of glucose consumption and lactate production. Xenograft model was constructed to investigate the role of circ_0005962 .

Result: circ_0005962 expressed with a high level in NSCLC tissues and cells. circ_0005962 knockdown inhibited proliferation, autophagy, and glycolysis but promoted apoptosis in NSCLC cells. miR-382-5p was targeted by circ_0005962, and its inhibition reversed the role of circ_0005962 knockdown. Besides, PDK4, a target of miR-382-5p, was regulated by circ_0005962 through miR-382-5p, and its overexpression abolished the effects of miR-382-5p reintroduction. circ_0005962 knockdown suppressed tumor growth .

Conclusion: circ_0005962 knockdown restrained cell proliferation, autophagy, and glycolysis but stimulated apoptosis through modulating the circ_0005962/miR-382-5p/PDK4 axis. Our study broadened the insights into understanding the mechanism of NSCLC progression.
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http://dx.doi.org/10.1515/med-2021-0255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254573PMC
July 2021

The effects of mTOR or Vps34-mediated autophagy on methylmercury-induced neuronal apoptosis in rat cerebral cortex.

Food Chem Toxicol 2021 Jul 6;155:112386. Epub 2021 Jul 6.

Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, People's Republic of China. Electronic address:

Methylmercury (MeHg) is a environmental contaminant, which can induce neurotoxic effects. So far, the exact molecular mechanisms of autophagy and its effect on apoptosis in MeHg-induced neurotoxicity have not been elucidated. Here, rats were exposed to MeHg (4, 8, or 12 μmol/kg) for 4 weeks to evaluate the dose-effect relationship between MeHg and apoptosis, or autophagy in cerebral cortex. On this basis, rapamycin (Rapa) or 3-methyladenine (3-MA) was administrated to further explore the regulatory mechanisms of autophagy on MeHg-induced neuronal apoptosis. The pathological changes, autophagy or apoptosis levels, expression of autophagic or apoptotic-associated factors such as mTOR, S6K1, 4EBP1, Vps34, Beclin1, p62, LC3, Bcl-2/Bax, caspase, or MAPKs were investigated. Results showed that MeHg dose-dependently induced pathological changes in cerebral cortex, and the levels of autophagy and apoptosis were increased. Furthermore, Rapa pretreatment antagonized MeHg-induced apoptosis, whereas 3-MA further aggravated apoptosis, which were supported by findings that Rapa activated mTOR-mediated autophagy while 3-MA inhibited Vps34-related autophagy, further affect neuronal apoptosis through regulation of apoptotic factors mentioned above. In conclusion, the findings indicated that MeHg dose-dependently induced autophagy or apoptosis, and mTOR or Vps34 may play important roles in mediating autophagy, which further regulated apoptosis through MAPKs or mitochondrial apoptosis pathways.
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http://dx.doi.org/10.1016/j.fct.2021.112386DOI Listing
July 2021

CCCH protein-PvCCCH69 acted as a repressor for leaf senescence through suppressing ABA-signaling pathway.

Hortic Res 2021 Jul 7;8(1):165. Epub 2021 Jul 7.

Department of Plant Biology and Pathology, Rutgers the State University of New Jersey, New Brunswick, NJ, 08901, USA.

CCCH is a subfamily of zinc finger proteins involved in plant growth, development, and stresses response. The function of CCCH in regulating leaf senescence, especially its roles in abscisic acid (ABA)-mediated leaf senescence is largely unknown. The objective of this study was to determine functions and mechanisms of CCCH gene in regulating leaf senescence in switchgrass (Panicum virgatum). A CCCH gene, PvCCCH69 (PvC3H69), was cloned from switchgrass. Overexpressing PvC3H69 in rice suppressed both natural senescence with leaf aging and dark-induced leaf senescence. Endogenous ABA content, ABA biosynthesis genes (NCED3, NCED5, and AAO3), and ABA signaling-related genes (SnRKs, ABI5, and ABF2/3/4) exhibited significantly lower levels in senescencing leaves of PvC3H69-OE plants than those in WT plants. PvC3H69-suppression of leaf senescence was associated with transcriptional upregulation of genes mainly involved in the light-dependent process of photosynthesis, including light-harvesting complex proteins, PSI proteins, and PSII proteins and downregulation of ABA biosynthesis and signaling genes and senescence-associated genes. PvC3H69 could act as a repressor for leaf senescence via upregulating photosynthetic proteins and repressing ABA synthesis and ABA signaling pathways.
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http://dx.doi.org/10.1038/s41438-021-00604-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263708PMC
July 2021

Does Sex Influence Outcomes in Myocardial Infarction With Nonobstructive Coronary Arteries?

Angiology 2021 Jul 7:33197211028428. Epub 2021 Jul 7.

Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

We examined differences in clinical profiles, predictors, and outcomes among patients with myocardial infarction (MI) with nonobstructive coronary arteries (MINOCAs) by sex. Data of 259 (132 males and 127 females) patients with MINOCA were consecutively collected. The primary clinical end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal MI, stroke, heart failure, and angina rehospitalization. Female patients with MINOCA were likely to be older than male patients with higher non-ST elevation myocardial infarction rate. Total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels were higher in female patients while male patients were more likely to have a smoking history, greater ST elevation myocardial infarction rate, higher diastolic blood pressure, and more alcohol use. During the 2-year follow-up, the incidence of MACE in males and females was similar (18% vs 20.2%, respectively; = .673). The multivariable predictors of MACE in the female group were age, hypertension, and left ventricular ejection fraction (LVEF), whereas diabetes, smoking, and LVEF were multivariable predictors of MACE in the male group. In conclusion, there were differences in the clinical profiles between sexes. Clinical outcome was similar between male and female patients with MINOCA, whereas predictive risk factors varied.
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http://dx.doi.org/10.1177/00033197211028428DOI Listing
July 2021

Highland barley starch (Qingke): Structures, properties, modifications, and applications.

Int J Biol Macromol 2021 Jul 2;185:725-738. Epub 2021 Jul 2.

School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China. Electronic address:

Highland barley (HB) is mainly composed of starch, which may account for up to 65% of the dry weight to the kernel. HB possesses unique physical and chemical properties and has good industrial application potential. It has also been identified as a minor grain crop with excellent nutritional and health functions. Highland barley starch (HBS) features a number of structural and functional properties that render it a useful material for numerous food and non-food applications. This review summarizes the current status of research on the extraction processes, chemical composition, molecular fine structures, granular morphology, physicochemical properties, digestibility, chemical and physical modifications, and potential uses of HBS. The findings provide a comprehensive reference for further research on HBS and its applications in various food and non-food industries.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.204DOI Listing
July 2021

Development and Validation of a Nomogram Based on Perioperative Factors to Predict Post-hepatectomy Liver Failure.

J Clin Transl Hepatol 2021 Jun 15;9(3):291-300. Epub 2021 Mar 15.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Background And Aims: Post-hepatectomy liver failure (PHLF) is a severe complication and main cause of death in patients undergoing hepatectomy. The aim of this study was to build a predictive model of PHLF in patients undergoing hepatectomy.

Methods: We retrospectively analyzed patients undergoing hepatectomy at Zhongshan Hospital, Fudan University from July 2015 to June 2018, and randomly divided them into development and internal validation cohorts. External validation was performed in an independent cohort. Least absolute shrinkage and selection operator (commonly referred to as LASSO) logistic regression was applied to identify predictors of PHLF, and multivariate binary logistic regression analysis was performed to establish the predictive model, which was visualized with a nomogram.

Results: A total of 492 eligible patients were analyzed. LASSO and multivariate analysis identified three preoperative variables, total bilirubin (=0.001), international normalized ratio (<0.001) and platelet count (=0.004), and two intraoperative variables, extent of resection (=0.002) and blood loss (=0.004), as independent predictors of PHLF. The area under receiver operating characteristic curve (referred to as AUROC) of the predictive model was 0.838 and outperformed the model for end-stage liver disease score, albumin-bilirubin score and platelet-albumin-bilirubin score (AUROCs: 0.723, 0.695 and 0.663, respectively; <0.001 for all). The optimal cut-off value of the predictive model was 14.7. External validation showed the model could predict PHLF accurately and distinguish high-risk patients.

Conclusions: PHLF can be accurately predicted by this model in patients undergoing hepatectomy, which may significantly contribute to the postoperative care of these patients.
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http://dx.doi.org/10.14218/JCTH.2021.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237151PMC
June 2021

Electroacupuncture at ST36 Improve the Gastric Motility by Affecting Neurotransmitters in the Enteric Nervous System in Type 2 Diabetic Rats.

Evid Based Complement Alternat Med 2021 16;2021:6666323. Epub 2021 Jun 16.

Nanjing University of Traditional Chinese Medicine, Nanjing 210023, Jiangsu, China.

Electroacupuncture (EA) can effectively relieve hyperglycemia and gastric emptying disorders in diabetic gastroparesis (DGP). However, the effect of EA on type 2 diabetes mellitus (T2DM) gastroparesis and its mechanism in the enteric nervous system (ENS) are rarely studied. We investigated the therapeutic effect of EA at ST36 and its effect on the main inhibitory and excitatory neurotransmitters in the ENS in DGP rats. Male Sprague-Dawley (SD) rats were fed a high-fat diet for 2 weeks and injected with streptozotocin (STZ) at 35 mg/kg to induce T2DM. T2DM rats were divided into the diabetic mellitus (DM) group and the EA group. The control (CON) group comprised normal rats without any intervention. EA treatment was started 6 weeks after the induction of DM and continued for 5 weeks. The body weight and food intake of the rats were recorded every week. Blood glucose, insulin, glucose tolerance, gastric emptying, and antral motility were measured after treatment. The expression of protein gene product 9.5 (PGP9.5), neuronal nitric oxide synthase (nNOS), and choline acetyltransferase (ChAT) in gastric antrum were quantified by western blotting and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The T2DM gastroparesis model was successfully established. EA treatment reduced the body weight, food intake, and blood glucose; improved glucose intolerance and insulin resistance; increased the gastric emptying rate, the mean antral pressure, and the amplitude of antral motility; and decreased the frequency of antral motility compared with those in the DM group. EA treatment increased the expression level of nNOS, ChAT, and PGP9.5 proteins, and nNOS and ChAT mRNA. The results suggested that EA at ST36 could ameliorate DGP, partly restore the damage to general neurons, and increase nNOS and ChAT in the gastric antrum. EA improved DGP partly via reducing the loss of inhibitory and excitatory neurotransmitters in the ENS.
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http://dx.doi.org/10.1155/2021/6666323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225438PMC
June 2021

SNP-mediated lncRNA-ENTPD3-AS1 upregulation suppresses renal cell carcinoma via miR-155/HIF-1α signaling.

Cell Death Dis 2021 Jul 3;12(7):672. Epub 2021 Jul 3.

Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.

Over the last decade, more than 10 independent SNPs have been discovered to be associated with the risk of renal cell carcinoma among different populations. However, the biological functions of them remain poorly understood. In this study, we performed eQTL analysis, ChIP-PCR, luciferase reporter assay, and Cox regression analysis to identify the functional role and underlying mechanism of rs67311347 in RCC. The ENCORI database, which contains the lncRNA-miRNA-mRNA interactions, was used to explore the possible target miRNA of ENTPD3-AS1. The results showed that the G > A mutation of rs67311347 created a binding motif of ZNF8 and subsequently upregulated ENTPD3-AS1 expression by acting as an enhancer. The TCGA-KIRC and our cohorts both confirmed the downregulation of ENTPD3-AS1 in RCC tissues and demonstrated that increased ENTPD3-AS1 expression was associated with good OS and PFS. Furthermore, ENTPD3-AS1 interacted with miR-155-5p and activated the expression of HIF-1α, which was an important tumor suppressor gene in the development of RCC. The functional experiments revealed that overexpression of ENTPD3-AS1 inhibited cell proliferation in RCC cell lines and the effect could be rescued by knocking down HIF-1α. Our findings reveal that SNP-mediated lncRNA-ENTPD3-AS1 upregulation suppresses renal cell carcinoma via miR-155/HIF-1α signaling.
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http://dx.doi.org/10.1038/s41419-021-03958-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254807PMC
July 2021

Application of a Generative Adversarial Network in Image Reconstruction of Magnetic Induction Tomography.

Sensors (Basel) 2021 Jun 3;21(11). Epub 2021 Jun 3.

Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Shenyang 110819, China.

Image reconstruction of Magnetic induction tomography (MIT) is an ill-posed problem. The non-linear characteristics lead many difficulties to its solution. In this paper, a method based on a Generative Adversarial Network (GAN) is presented to tackle these barriers. Firstly, the principle of MIT is analyzed. Then the process for finding the global optimum of conductivity distribution is described as a training process, and the GAN model is proposed. Finally, the image was reconstructed by a part of the model (the generator). All datasets are obtained from an eight-channel MIT model by COMSOL Multiphysics software. The voltage measurement samples are used as input to the trained network, and its output is an estimate for image reconstruction of the internal conductivity distribution. The results based on the proposed model and the traditional algorithms were compared, which have shown that average root mean squared error of reconstruction results obtained by the proposed method is 0.090, and the average correlation coefficient with original images is 0.940, better than corresponding indicators of BPNN and Tikhonov regularization algorithms. Accordingly, the GAN algorithm was able to fit the non-linear relationship between input and output, and visual images also show that it solved the usual problems of artifact in traditional algorithm and hot pixels in L2 regularization, which is of great significance for other ill-posed or non-linear problems.
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http://dx.doi.org/10.3390/s21113869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199933PMC
June 2021

Elimination of Hole Mouth Burr in Multilayer PCB Micro-Hole by Using Micro-EDM.

Micromachines (Basel) 2021 Jun 12;12(6). Epub 2021 Jun 12.

Shenzhen Jinzhou Precision Technology Corp., Shenzhen 518116, China.

The micro-hole is a key structure in multilayer printed circuit board (PCB), as it enables the effective transmission of electrical signals. At present, the most common way to machine PCB micro-holes is mechanical drilling using micro-bit. However, in the mechanical drilling of micro-holes, these holes are prone to burring at the hole mouth due to the micro-bit failing to cleanly cut through the first layer of copper foil on the PCB. Hole mouth burr can seriously affect the performance of the PCB, resulting in potential short circuiting or even ruining the PCB. To solve the above problems, this paper proposed to machine the first layer of copper foil on the PCB via micro electro-discharge machining (micro-EDM) to eliminate hole mouth burr. Compared with the mechanical drilling, micro-EDM is a form of non-contact machining, and the high temperature generated from the electric spark discharge can erode the first layer of copper foil, thus fully eliminating hole mouth burr. This paper performed a detailed study of the influence of spindle speed, machining voltage, pulse width, and pulse interval on hole mouth quality. After that, the technological parameters for eliminating hole mouth burr were obtained. Finally, under the effects of 20,000 rpm spindle speed, 26 V machining voltage, 4 μs pulse width, and 8 μs pulse interval, a micro-bit with a diameter of 200 μm was used to perform micro-EDM of the first layer of copper foil. From the machining results, it can be known that the PCB micro-hole was possessed of overall good quality, with good hole wall surface quality and almost no visible hole mouth burr.
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http://dx.doi.org/10.3390/mi12060688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231649PMC
June 2021

Identification of Enzalutamide Resistance-Related circRNA-miRNA-mRNA Regulatory Networks in Patients with Prostate Cancer.

Onco Targets Ther 2021 21;14:3833-3848. Epub 2021 Jun 21.

Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People's Republic of China.

Purpose: This study aimed to identify enzalutamide resistant-related (EnzR-related) circRNAs and to characterize and validate circRNA-miRNA-mRNA ceRNA regulatory network and corresponding prognostic signature of prostate cancer patients.

Methods: We obtained circRNA expression microarray from the Gene Expression Omnibus (GEO) database and performed differential expression analysis to identify EnzR-related circRNAs using the limma package. The miRNA and mRNA expression profiling were downloaded and performed differential expression analysis, then overlapped with predicted candidates. Next, we established circRNA-miRNA-mRNA ceRNA network and PPI network utilized Cytoscape software and STRING database, respectively. In addition, univariate and Lasso Cox regression analyses were applied to generate a prognostic signature. Receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to evaluate the reliability and sensitivity of the signature. Ultimately, we chose hsa_circ_0047641 to validate the feasibility of the EnzR-related ceRNA regulatory pathway using qRT-PCR, CCK8 and Transwell assays.

Results: We identified 13 EnzR-related circRNAs and constructed a ceRNA regulatory network that contained two downregulated circRNAs (has-circ-00000919 and has-circ-0000036) and two upregulated circRNAs (has-circ-0047641 and has-circ-0068697), and their sponged 6 miRNAs and 167 targeted mRNAs. Subsequently, these targeted mRNAs were performed to implement PPI analysis and to identify 10 Hub genes. Functional enrichment analysis provided new ways to seek potential biological functions. Besides, we established a prognostic signature of PCa patients based on 8 prognostic-associated mRNAs. We confirmed that the survival rates of PCa patients with high-risk subgroup were slightly lower than those with low-risk subgroup in the TCGA dataset (p<0.001), and ROC curves revealed that the AUC value for prognostic signature was 0.816. Finally, the functional analysis suggested that knockdown of hsa_circ_0047641 could inhibit the progression of PCa and could reverse Enz-resistance in vitro.

Conclusion: We identified 13 EnzR-related circRNAs, and constructed and confirmed that EnzR-related circRNA-miRNA-mRNA ceRNA network and corresponding prognostic signature could be a useful prognostic biomarker and therapeutic target.
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http://dx.doi.org/10.2147/OTT.S309917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232970PMC
June 2021

The Roles of Oxidative Stress in Regulating Autophagy in Methylmercury-induced Neurotoxicity.

Neuroscience 2021 08 24;469:175-190. Epub 2021 Jun 24.

Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning, China. Electronic address:

Methylmercury (MeHg) is a potential neurotoxin that is highly toxic to the human central nervous system. Although MeHg neurotoxicity has been widely studied, the mechanism of MeHg neurotoxicity has not yet been fully elucidated. Some research evidence suggests that oxidative stress and autophagy are important molecular mechanisms of MeHg-induced neurotoxicity. Researchers have widely accepted that oxidative stress regulates the autophagy pathway. The current study reviews the activation of Nuclear factor-erythroid-2-related factor (Nrf2)-related oxidative stress pathways and autophagy signaling pathways in the case of MeHg neurotoxicity. In addition, autophagy mainly plays a role in the neurotoxicity of MeHg through mTOR-dependent and mTOR-independent autophagy signaling pathways. Finally, the regulation of autophagy by reactive oxygen species (ROS) and Nrf2 in MeHg neurotoxicity was explored in this review, providing a new concept for the study of the neurotoxicity mechanism of MeHg.
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http://dx.doi.org/10.1016/j.neuroscience.2021.06.026DOI Listing
August 2021

Allergen-Specific Treg Cells Upregulated by Lung-Stage Infection Alleviates Allergic Airway Inflammation.

Front Cell Dev Biol 2021 8;9:678377. Epub 2021 Jun 8.

NHC Key Laboratory of Parasite and Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention), Shanghai, China.

infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of the helminth infection and the underlying mechanisms. Most previous studies focused on understanding the preventive effect of infection on asthma (infection before allergen sensitization), whereas the protective effects of infection (allergen sensitization before infection) on asthma were rarely investigated. In this study, we investigated the protective effects of infection on AAI using a mouse model of OVA-induced asthma. To explore how the timing of infection influences its protective effect, the mice were percutaneously infected with cercaria of at either 1 day (infection at lung-stage during AAI) or 14 days before ovalbumin (OVA) challenge (infection at post-lung-stage during AAI). We found that lung-stage infection significantly ameliorated OVA-induced AAI, whereas post-lung-stage infection did not. Mechanistically, lung-stage infection significantly upregulated the frequency of regulatory T cells (Treg cells), especially OVA-specific Treg cells, in lung tissue, which negatively correlated with the level of OVA-specific immunoglobulin E (IgE). Depletion of Treg cells partially counteracted the protective effect of lung-stage infection on asthma. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage infection could relieve OVA-induced asthma in a mouse model. The protective effect was mediated by the upregulated OVA-specific Treg cells, which suppressed IgE production. Our results may facilitate the discovery of a novel therapy for AAI.
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http://dx.doi.org/10.3389/fcell.2021.678377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217774PMC
June 2021

The impact of MYC amplification on clinicopathologic features and prognosis of radiation-associated angiosarcomas of the breast.

Histopathology 2021 Jun 24. Epub 2021 Jun 24.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Aims: Radiation-associated angiosarcomas (RT-AS) of the breast are rare tumours with poor prognosis. MYC amplification is considered the hallmark of RT-AS and is sometimes used as a diagnostic tool to distinguish from other radiation-associated vascular lesions. However, a small subset of RT-AS lacks MYC amplification, which may be associated with better outcome. Loss of H3K27me3 expression by immunohistochemistry (IHC) has been recently postulated as an additional diagnostic marker for RT-AS. This study aimed to evaluate the impact of MYC amplification as detected by fluorescence in situ hybridization and/or next-generation sequencing on clinicopathologic features and outcome in a large cohort of RT-AS, compare outcome with radiation-associated sarcomas of the breast (RT-S) other than angiosarcoma, and evaluate expression of H3K27me3 IHC in these groups.

Methods And Results: Eighty-one RT-AS were identified, including 73 MYC amplified and 8 (10%) non-amplified. MYC amplified RT-AS were diagnosed in older patients (median age 69 vs 61 years). The 5-year disease specific survival and overall survival were 56% and 47%, respectively. Older age, larger tumour size, positive margin and MYC amplification were associated with worse prognosis. None of the RT-AS showed complete loss of H3K27me3 IHC expression. All 18 RT-S were MYC non-amplified, and complete loss of H3K27me3 expression was seen in 2. We found no difference in prognosis between RT-AS and RT-S.

Conclusions: RT-AS is associated with a poor prognosis. Older age at diagnosis, larger tumour size, positive margin at excision and MYC amplification are associated with worse prognosis.
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http://dx.doi.org/10.1111/his.14433DOI Listing
June 2021
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