Publications by authors named "Weiwei Zhang"

958 Publications

Serum creatinine levels and risk of nonalcohol fatty liver disease in a middle-aged and older Chinese population: a cross-sectional analysis.

Diabetes Metab Res Rev 2021 Aug 3:e3489. Epub 2021 Aug 3.

Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Non-alcoholic fatty liver disease (NAFLD) is now regarded as the hepatic manifestation of metabolic syndrome (MetS). Recent research has suggested that serum creatinine (SCr) may be an indicator of MetS and its related diseases. We aimed to investigate the association between serum creatinine and NAFLD in Chinese adults.

Methods: A cross-sectional sample of 8862 subjects aged 40 yrs or older (40-73 yrs) from China were analyzed in this study. The anthropometric measurements, laboratory tests, and hepatic ultrasonography were conducted. NAFLD presence was defined by hepatic ultrasound in the absence of other liver diseases.

Results: NAFLD subjects had higher serum creatinine than those without NAFLD (66.8 µmol/L vs. 65.6 µmol/L, p<0.001). Moreover, Scr levels were correlated with alanine aminotransferase (β=0.099, p<0.001), aspartate aminotransferase (β=0.135, p<0.001), γ-glutamyltransferase (β=0.039, p<0.001) and insulin resistance (β=0.027, p=0.014) after adjusted for potential covariates. In the multivariable-adjusted logistic regression analyses, compared to the 1 SCr quintile, the odds ratio for NAFLD was 1.35 (95% CI 1.14-1.60, p<0.001) for the 5 quintile after adjusting multiple measured confounders.

Conclusion: Serum creatinine concentration is independently associated with NAFLD in a middle aged and older Chinese population. Elevated SCr levels, even within normal ranges, were associated with higher risk of NAFLD. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/dmrr.3489DOI Listing
August 2021

Comparisons of Vitreal Angiogenic, Inflammatory, Profibrotic Cytokines, and Chemokines Profile between Patients with Epiretinal Membrane and Macular Hole.

J Ophthalmol 2021 13;2021:9947250. Epub 2021 Jul 13.

Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.

Objectives: Idiopathic epiretinal membrane (iERM) or idiopathic macular hole (iMH) is frequently used as a "healthy" control in comparison of vitreous cytokines with other vitreoretinal diseases. This study aimed to investigate if there is a difference in vitreal cytokines expression between patients with iERM and iMH.

Methods: In this prospective study, all subjects received standard pars plana vitrectomy surgery, and 0.5 ml of native vitreous sample was extracted during the vitrectomy. Luminex technology and enzyme-linked immunosorbent assay were used to profile the concentration of 52 classic angiogenic, inflammatory, and profibrotic cytokines and chemokines. Statistical analyses were performed by the Mann-Whitney U test, followed by multiple comparisons by the Bonferroni correction.

Results: Vitreal samples from 13 iERM and 24 iMH were studied. Of the 52 tested cytokines, 41 were similar in expression, and 5 were under the detection limit, while 6 cytokines (MMP-8, Eotaxin, MIP-1a, RANTES, TGF-2, and IL-4) were differently expressed between two groups ( < 0.05). Nevertheless, these significances disappeared after the adjustment of Bonferroni correction.

Conclusion: The tested cytokines showed similar expression between iERM and iMH patients. This indicates that eyes with iERM or iMH can be together served as "healthy" controls.
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http://dx.doi.org/10.1155/2021/9947250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294982PMC
July 2021

Catalpol enhanced physical exercise-mediated brain functional improvement in post-traumatic stress disorder model via promoting adult hippocampal neurogenesis.

Aging (Albany NY) 2021 Jul 29;13(undefined). Epub 2021 Jul 29.

School of Life Science, Beijing Normal University, Beijing, China.

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder characterized by hyper-response to environmental cues as well as the associated depressive and cognitive dysfunctions. According to the key roles of hippocampus for cognitive and emotional regulation, improving hippocampal functions, particularly hippocampal neural plasticity, is the necessary pathway to attenuate the core symptoms of PTSD. The effects of the alternative therapies such as exercise and natural compounds to reduce PTSD symptoms and promote adult hippocampal neurogenesis have been widely demonstrated. However, what is the effect of combining the exercise with traditional Chinese medical compounds remains unknown. In current study, we evaluated the effects of catalpol, which showed the pro-neurogenic effects in previous report, in regulating exercise-mediated PTSD therapeutic effects. With behavioral tests, we found that catalpol treatment promoted the effects of exercise to reduce the response of mice to dangerous cues, and simultaneously enhanced the antidepressant and cognitive protection effects. Moreover, by immunofluorescence we identified that catalpol promoted exercise-mediated hippocampal neurogenesis by enhancing the neural differentiation and mature neuronal survive. We further found that the promote effects of catalpol to exercise-induced environmental hyper-response, antidepressant effects and cognitive protective effects were all compromised by blocking neurogenesis with temozolomide (TMZ). This result indicates that hippocampal neurogenesis is prerequisite for catalpol to promote exercise-mediated brain functional improvement in PTSD model. In conclusion, our research identified the new function of natural compounds catalpol to promote the exercise-mediated brain functional changes in PTSD model, which depend on its effect promoting adult hippocampal neurogenesis.
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http://dx.doi.org/10.18632/aging.203313DOI Listing
July 2021

Self-Supervised Joint Learning Fault Diagnosis Method Based on Three-Channel Vibration Images.

Sensors (Basel) 2021 Jul 13;21(14). Epub 2021 Jul 13.

Key Laboratory of Embedded System and Service Computing, Tongji University, Shanghai 201804, China.

The accuracy of bearing fault diagnosis is of great significance for the reliable operation of rotating machinery. In recent years, increasing attention has been paid to intelligent fault diagnosis techniques based on deep learning. However, most of these methods are based on supervised learning with a large amount of labeled data, which is a challenge for industrial applications. To reduce the dependence on labeled data, a self-supervised joint learning (SSJL) fault diagnosis method based on three-channel vibration images is proposed. The method combines self-supervised learning with supervised learning, makes full use of unlabeled data to learn fault features, and further improves the feature recognition rate by transforming the data into three-channel vibration images. The validity of the method was verified using two typical data sets from a motor bearing. Experimental results show that this method has higher diagnostic accuracy for small quantities of labeled data and is superior to the existing methods.
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http://dx.doi.org/10.3390/s21144774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309779PMC
July 2021

β-Catenin/LEF-1 transcription complex is responsible for the transcriptional activation of LINC01278.

Cancer Cell Int 2021 Jul 17;21(1):380. Epub 2021 Jul 17.

Department of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, No. 107 of Yanjiangxi Road, Guangzhou, 510120, Guangdong, People's Republic of China.

Background: Our previous study shows that LINC01278 inhibits the malignant proliferation and invasion of papillary thyroid carcinoma (PTC) cells by regulating the miR-376c-3p/DNM3 axis. However, the regulation mechanism of LINC01278 expression in PTC cells is still unclear.

Methods: The luciferase reporter and ChIP assays were used to confirm the binding of LEF-1 to the putative promoter site of LINC01278 gene. The RNA immunoprecipitation and RNA pulldown were used to determine the enrichment of LINC01278 in β-catenin protein. The proteasome inhibitors (MG132) was used for detecting the β-catenin ubiquitination-proteasome degradation. Wnt/β-catenin specific agonists (LiCI), inhibitors (WiKI4) and TOP/FOP-flash reporter assay were used for detecting the activation of Wnt/β-catenin signal. Western blot was used to detected the expression of target proteins.

Results: The online PROMO algorithm determines a putative LEF-1 binding site on LINC01278 promoter, the LEF-1 binds to the putative promoter site of LINC01278 gene, and β-catenin enhances the binding of LEF-1 to the LINC01278 gene promoter. Furthermore, LINC01278 negatively regulated the protein accumulation of β-catenin in the cytoplasm, into nucleus, and ultimately inhibited the transcription of downstream target genes activated by Wnt/β-catenin signal. The results of RNA immunoprecipitation and RNA pulldown proved the direct binding of LINC01278 to β-catenin protein. In addition, the combination of LINC01278 and β-catenin promotes the β-catenin ubiquitination-proteasome degradation.

Conclusion: In summary, we found the transcriptional activation of LINC01278 by the β-catenin/LEF-1 transcription factor, and the negative feedback regulation of LINC01278 onβ-catenin signal.
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http://dx.doi.org/10.1186/s12935-021-02082-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285859PMC
July 2021

EBV-positive HIV-associated diffuse large B cell lymphomas are characterized by JAK/STAT (STAT3) pathway mutations and unique clinicopathologic features.

Br J Haematol 2021 Jul 17. Epub 2021 Jul 17.

Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA.

Even in the era of highly active combination antiretroviral therapy (cART), patients with HIV have a disproportionate risk of developing aggressive lymphomas that are frequently Epstein-Barr virus (EBV)-related. Here, we investigate HIV-associated diffuse large B-cell lymphoma (HIV-DLBCL) and compare EBV-positive and EBV-negative cases. HIV-DLBCL were identified from two academic medical centres and characterised by immunohistochemistry, EBV status, fluorescence in situ hybridisation, cell of origin determination by gene expression profiling, and targeted deep sequencing using a custom mutation panel of 334 genes. We also applied the Lymphgen tool to determine the genetic subtype of each case. Thirty HIV-DLBCL were identified, with a median patient age of 46 years and male predominance (5:1). Thirteen cases (48%) were EBV-positive and 14 (52%) EBV-negative. Nine of the 16 tested cases (56%) had MYC rearrangement, three (19%) had BCL6 (two of which were double hit MYC/BCL6) and none had BCL2 rearrangements. Using the Lymphgen tool, half of the cases (15) were classified as other. All HIV-DLBCL showed mutational abnormalities, the most frequent being TP53 (37%), MYC (30%), STAT3 (27%), HIST1H1E (23%), EP300 (20%), TET2 (20%), SOCS1 (17%) and SGK1 (17%). EBV-negative cases were mostly of germinal centre B-cell (GCB) origin (62%), showed more frequent mutations per case (a median of 13·5/case) and significant enrichment of TP53 (57% vs. 15%; P = 0·046), SGK1 (36% vs. 0%; P = 0·04), EP300 (43% vs. 0%; P = 0·02) and histone-modifying gene (e.g. HIST1H1E, HIST1H1D, 79% vs. 31%; P = 0·02) mutations. EBV-positive cases were mostly of non-GCB origin (70%), with fewer mutations per case (median 8/case; P = 0·007), and these tumours were enriched for STAT3 mutations (P = 0·10). EBV-positive cases had a higher frequency of MYC mutations but the difference was not significant (36% vs. 15%; P = 0·38). EBV-association was more frequent in HIV-DLBCLs, arising in patients with lower CD4 counts at diagnosis (median 46·5 vs. 101, P = 0·018). In the era of cART, approximately half of HIV-DLBCL are EBV-related. HIV-DLBCL are enriched for MYC rearrangements, MYC mutations and generally lack BCL2 rearrangements, regardless of EBV status. Among HIV-DLBCL, tumours that are EBV-negative and EBV-positive appear to have important differences, the latter arising in context of lower CD4 count, showing frequent non-GCB origin, lower mutation burden and recurrent STAT3 mutations.
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http://dx.doi.org/10.1111/bjh.17708DOI Listing
July 2021

The utility of a myeloid mutation panel for the diagnosis of myelodysplastic syndrome and myelodysplastic/myeloproliferative neoplasm.

Int J Lab Hematol 2021 Jul 16. Epub 2021 Jul 16.

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.

Introduction: The diagnosis of myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) is based on morphology and cytogenetics/FISH findings per 2017 WHO classification. With rare exceptions, somatic mutations have not been incorporated as the diagnostic criteria.

Methods: We analyzed the utility of mutational analysis with a targeted 54-gene or 40-gene next-generation sequencing (NGS) panel in the diagnosis of MDS and MDS/MPN.

Results: We retrospectively collected 92 patients who presented with unexplained cytopenia with or without cytosis, including 32 low-grade MDS (MDS-L), 18 high-grade MDS (MDS-H), 5 therapy-related MDS (MDS-TR), 19 MDS/MPN, and 18 negative cases. Of 92 patients, 197 somatic mutations involving 38 genes were detected and had variant allele frequency (VAF) ranging from 3% to 99%. The most common mutated genes were TET2, ASXL1, RUNX1, TP53, SRSF2, and SF3B1. MDS-L, MDS-H, MDS-TR, and MDS/MPN showed an average number of somatic mutations with a mean VAF of 1.9/33%, 2.6/30%, 2/36%, and 4/41%, respectively. SF3B1 mutations were exclusively observed in MDS-L and MDS/MPN. TP53 gene mutations were more frequently seen in MDS-H and MDS-TR. Among 34 patients with a diagnosis of MDS or MDS/MPN with normal cytogenetics, 31 patients (91%) had at least 1 mutation and 24 patients (71%) had ≥2 mutations with ≥10% VAF.

Conclusion: A myeloid mutational panel provides additional evidence of clonality besides cytogenetics/FISH studies in the diagnosis of cytopenia with or without cytosis. Two or more mutations with ≥10% VAF highly predicts MDS and MDS/MPN with a positive predictive value of 100%.
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http://dx.doi.org/10.1111/ijlh.13659DOI Listing
July 2021

Save China's blue-crowned laughingthrush.

Science 2021 07;373(6551):171

Co-Innovation Center for Sustainable Forestry in Southern China, College of Biology and the Environment, Nanjing Forestry University, Nanjing, Jiangsu, China.

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http://dx.doi.org/10.1126/science.abj4535DOI Listing
July 2021

Effect of Cost-Related Medication Non-adherence Among Older Adults With Medication Therapy Management.

Front Med (Lausanne) 2021 17;8:670034. Epub 2021 Jun 17.

Department of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center, Memphis, TN, United States.

Medication therapy management (MTM) was established by the Center for Medicare and Medicaid Services (CMS) with the aim to improve medication adherence. However, the national prevalence of cost-related medication non-adherence (CRN) is still unknown and there is a literature gap in the association between MTM services and CRN. A cross-sectional study was conducted. A nationally representative study sample from Medicare Current Beneficiary Surveys (MCBS) was used. Survey sampling weights were applied for national estimates of CRN. Weighted multivariable logistic regressions controlling for covariates were conducted to investigate the effect of the MTM on the CRN. The study identified 1,549 MTM-eligible beneficiaries. The prevalence of CRN was higher in MTM-eligible individuals than in non-MTM eligible individuals (24.14 vs. 13.44%; < 0.001). According to the results of multivariable logistic regressions, we found that MTM eligibility was significantly associated with a higher prevalence of CRN (OR: 1.59; 95% CI: 1.28-1.96). Additionally, some other variables such as health status, with or without low-income subsidy are also associated with CRN. Our findings suggest that the prevalence of CRN in MTM-eligible beneficiaries was higher than in non-MTM eligible beneficiaries. Further studies with the longitudinal design are warranted to clarify the relationship between MTM and CRN. Alternative strategies to improve CRN should be considered in future Medicare Part D Enhanced MTM Models.
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http://dx.doi.org/10.3389/fmed.2021.670034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245679PMC
June 2021

A Tale of Two Immune Cells in Rheumatoid Arthritis: The Crosstalk Between Macrophages and T Cells in the Synovium.

Front Immunol 2021 17;12:655477. Epub 2021 Jun 17.

Department of Orthopaedics, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Joint inflammation of RA is closely related to infiltration of immune cells, synovium hyperplasia, and superfluous secretion of proinflammatory cytokines, which lead to cartilage degradation and bone erosion. The joint synovium of RA patients contains a variety of immune cellular types, among which monocytes/macrophages and T cells are two essential cellular components. Monocytes/macrophages can recruit and promote the differentiation of T cells into inflammatory phenotypes in RA synovium. Similarly, different subtypes of T cells can recruit monocytes/macrophages and promote osteoblast differentiation and production of inflammatory cytokines. In this review, we will discuss how T cell-monocyte/macrophage interactions promote the development of RA, which will provide new perspectives on RA pathogenesis and the development of targeted therapy.
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http://dx.doi.org/10.3389/fimmu.2021.655477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248486PMC
June 2021

, , and Variants in Alzheimer's Disease: Systematic Re-evaluation According to ACMG Guidelines.

Front Aging Neurosci 2021 18;13:695808. Epub 2021 Jun 18.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.

The strategies of classifying , , and variants varied substantially in the previous studies. We aimed to re-evaluate these variants systematically according to the American college of medical genetics and genomics and the association for molecular pathology (ACMG-AMP) guidelines. In our study, , , and variants were collected by searching Alzforum and PubMed database with keywords "PSEN1," "PSEN2," and "APP." These variants were re-evaluated based on the ACMG-AMP guidelines. We compared the number of pathogenic/likely pathogenic variants of , , and . In total, 66 variants, 323 variants, and 63 variants were re-evaluated in our study. 94.91% of previously reported pathogenic variants were re-classified as pathogenic/likely pathogenic variants, while 5.09% of them were variants of uncertain significance (VUS). carried the most prevalent pathogenic/likely pathogenic variants, followed by and . Significant statistically difference was identified among these three genes when comparing the number of pathogenic/likely pathogenic variants ( < 2.2 × 10). Most of the previously reported pathogenic variants were re-classified as pathogenic/likely pathogenic variants while the others were re-evaluated as VUS, highlighting the importance of interpreting , , and variants with caution according to ACMG-AMP guidelines.
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http://dx.doi.org/10.3389/fnagi.2021.695808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249733PMC
June 2021

BBNet: A Novel Convolutional Neural Network Structure in Edge-Cloud Collaborative Inference.

Sensors (Basel) 2021 Jun 30;21(13). Epub 2021 Jun 30.

College of Engineering, Huaqiao University, Quanzhou 362021, China.

Edge-cloud collaborative inference can significantly reduce the delay of a deep neural network (DNN) by dividing the network between mobile edge and cloud. However, the in-layer data size of DNN is usually larger than the original data, so the communication time to send intermediate data to the cloud will also increase end-to-end latency. To cope with these challenges, this paper proposes a novel convolutional neural network structure-BBNet-that accelerates collaborative inference from two levels: (1) through channel-pruning: reducing the number of calculations and parameters of the original network; (2) through compressing the feature map at the split point to further reduce the size of the data transmitted. In addition, This paper implemented the BBNet structure based on NVIDIA Nano and the server. Compared with the original network, BBNet's FLOPs and parameter achieve up to 5.67× and 11.57× on the compression rate, respectively. In the best case, the feature compression layer can reach a bit-compression rate of 512×. Compared with the better bandwidth conditions, BBNet has a more obvious inference delay when the network conditions are poor. For example, when the upload bandwidth is only 20 kb/s, the end-to-end latency of BBNet is increased by 38.89× compared with the cloud-only approach.
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http://dx.doi.org/10.3390/s21134494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272083PMC
June 2021

Mixed plantations of and change soil fungal and archaeal communities and enhance soil phosphorus availability in Shanghai, China.

Ecol Evol 2021 Jun 27;11(12):7239-7249. Epub 2021 May 27.

Shanghai Chenshan Botanical Garden Shanghai China.

Soil degradation has been found in urban forests in Shanghai, especially in the pure plantations. Mixed plantations are considered to improve soil quality because they can stimulate organic matter cycling and increase soil carbon and nutrient content. Although soil microbes play crucial roles in regulating soil biogeochemical processes, little is known about how mixed plantations affect soil microbial communities, including bacteria, archaea, and fungi. Here, we evaluated soil chemical properties, abundances and compositions of soil bacterial, archaeal, and fungal communities, and enzyme activities in pure and mixed and plantations, located in Shanghai, China. The results showed that soil available phosphorus content in the mixed plantation of and was significantly higher than that in pure plantations, while no significant difference was observed in the content of soil organic carbon, total and available nitrogen, total and available potassium among the three studied plantations. We found higher fungal abundance in the mixed plantation, when compared to both pure plantations. Moreover, fungal abundance was positively correlated with the content of soil available phosphorus. No significant difference was found in the abundance and diversity of bacterial and archaeal community among the three studied plantations. A similarity analysis (ANOSIM) showed that mixed plantation significantly altered the community composition of archaea and fungi, accompanied with an increase of alkaline phosphatase activity. However, ANOSIM analysis of bacterial communities showed that there was no significant group separation among different plantations. Overall, results from this study indicated that fungal and archaeal communities were more sensitive to aboveground tree species than bacterial community. Moreover, mixed plantations significantly increased the activity of alkaline phosphatase and the content of soil available phosphorus, suggesting that afforestation with and is an effective way to alleviate phosphorus deficiency in urban forests in Shanghai, China.
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http://dx.doi.org/10.1002/ece3.7532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216939PMC
June 2021

Unraveling the Regulatory Mechanism of Color Diversity in Petals by Integrative Transcriptome and Metabolome Analysis.

Front Plant Sci 2021 11;12:685136. Epub 2021 Jun 11.

College of Horticulture and Gardening, Yangtze University, Jingzhou, China.

petals are colorful, rich in anthocyanins, and possess important ornamental, edible, and medicinal value. However, the regulatory mechanism of anthocyanin accumulation in is still unclear. In this study, an integrative analysis of the metabolome and transcriptome was conducted in five cultivars with different petal colors. Overall, a total of 187 flavonoids were identified (including 25 anthocyanins), and 11 anthocyanins were markedly differentially accumulated among these petals, contributing to the different petal colors in . Moreover, cyanidin-3-(6-malonyl) glucoside was confirmed as the main contributor to the red petal phenotype, while cyanidin-3-rutinoside, peonidin-3-glucoside, cyanidin-3-glucoside, and pelargonidin-3-glucoside were responsible for the deep coloration of the petals. Furthermore, a total of 12,531 differentially expressed genes (DEGs) and overlapping DEGs (634 DEGs) were identified by RNA sequencing, and the correlation between the expression level of the DEGs and the anthocyanin content was explored. The candidate genes regulating anthocyanin accumulation in the petals were identified and included 37 structural genes (especially and ), 18 keys differentially expressed transcription factors (such as , , , , and ), and 16 other regulators (mainly including transporter proteins, zinc-finger proteins, and others). Our results provide new insights for elucidating the function of anthocyanins in petal color expression.
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http://dx.doi.org/10.3389/fpls.2021.685136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226227PMC
June 2021

The role of frontotemporal dementia associated genes in patients with Alzheimer's disease.

Neurobiol Aging 2021 May 30. Epub 2021 May 30.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, China; Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China; Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China. Electronic address:

Alzheimer's disease (AD) and frontotemporal dementia (FTD) overlap clinically and pathologically. However, the role of FTD-associated genes in patients with AD remained unclear. To explore the relationship between FTD-associated genes and AD risk, we investigated 14 FTD-associated genes via targeted next-generation sequencing panel or whole-genome sequencing in a total of 721 AD patients and 1391 controls. Common variant-based association analysis and gene-based association test of rare variants were performed by PLINK 1.9 and Sequence Kernel Association Test-Optimal (SKAT-O test) respectively. As a result, 2 common variants, UBQLN1 rs1044175 (p value = 2.76 × 10) and MAPT rs2258689 (p value = 5.71 × 10), differed significantly between AD patients and controls. Additionally, gene-based analysis aggregating rare variants demonstrated that HNRNPA1 reached statistical significance in the SKAT-O test (p value = 2.24 × 10). Protein-protein interaction analysis showed that UBQLN1, MAPT, and HNRNPA1 interacted with proteins encoded by well-recognized AD-associated genes. Our study indicated that UBQLN1, MAPT, and HNRNPA1 are implicated in the pathogenesis of AD in the mainland Chinese population.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.05.016DOI Listing
May 2021

miRNA-31 increases radiosensitivity through targeting STK40 in colorectal cancer cells.

Asia Pac J Clin Oncol 2021 Jun 25. Epub 2021 Jun 25.

Peking University Third Hospital, Beijing, China.

Objective: To propose and verify that miRNA-31 increases the radiosensitivity of colorectal cancer and explore its potential mechanism.

Method: A bioinformatics analysis was performed to confirm that the expression of miRNA-31 was higher in colorectal cancer than in normal colorectal tissue. The expression of miRNA-31 was detected to verify the change in its expression in a radiotherapy-resistant cell line. Methylation was detected to explore the cause of the decrease in miRNA-31 expression. Overexpression or inhibition of miRNA-31 further confirmed the change in its expression in colorectal cancer cell lines. Bioinformatics methods were used to screen the downstream target genes and for experimental verification. A luciferase assay was performed to determine the miRNA-31 binding site in STK40. Overexpression or inhibition of STK40 in colorectal cancer cell lines further confirmed the change in STK40 expression in vitro.

Results: The bioinformatics results showed higher expression of miRNA-31 in tumors than in normal tissue, and miRNA-31 mainly participated in the pathway related to cell replication. Next, we observed the same phenomenon: miRNA-31 was expressed at higher levels in colorectal tumors than in normal colorectal tissue and its expression decreased in radiation-resistant cell lines after radiation, implying that miRNA-31 increased the radiosensitivity of colorectal cancer cell lines. No significant change in upstream methylation was observed. miRNA-31 regulated the radiosensitivity of colorectal cancer cell lines by inhibiting STK40. Notably, miRNA-31 played a role by binding to the 3' untranslated region of SK40. STK40 negatively regulated the radiosensitivity of colorectal cancer cells.

Conclusions: miRNA-31 increases the radiosensitivity of colorectal cancer cells by targeting STK40; miRNA-31 and STK40 are expected to become potential biomarkers for increasing the sensitivity of tumor radiotherapy in clinical treatment.
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http://dx.doi.org/10.1111/ajco.13602DOI Listing
June 2021

Supporting Learner Success: Revisiting Strategic Competence Through Developing an Inventory for Computer-Assisted Speaking Assessment.

Front Psychol 2021 7;12:689581. Epub 2021 Jun 7.

School of Curriculum and Pedagogy, Faculty of Education and Social Work, The University of Auckland, Auckland, New Zealand.

This study investigated English-as-a-foreign-language (EFL) learners' strategic competence in the computer-assisted integrated speaking tests (CAIST) through the development and validation of the (SCICASA). Based on our review of the literature on the CAIST, strategic competence, and available instruments for measuring the construct, we defined EFL learners' strategic competence in the CAIST as learners' use of four metacognitive strategies: Planning, problem-solving, monitoring, and evaluating, with each of them consisting of various components. These metacognitive strategies formulated the four factors and scale items of the SCICASA under validation. An exploratory factor analysis of responses from 254 EFL students and the subsequent confirmatory factor analysis of data collected on another sample of 242 students generated 23 items under the four factors. The high validity and reliability of the SCICASA reveal that EFL learners' strategic competence operates in the forms of the four metacognitive strategies in the CAIST. This will lend some new supporting evidence for Bachman and Palmer's (2010) strategic competence model while providing implications for metacognitive instructions and test development. Concomitantly, the findings show the inventory as a valid instrument for measuring strategic competence in computer-assisted foreign/second language (L2) speaking assessment and relevant research arenas and beyond.
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http://dx.doi.org/10.3389/fpsyg.2021.689581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215541PMC
June 2021

Isolation and identification of a 2,3,7,8-Tetrachlorodibenzo-P-dioxin degrading strain and its biochemical degradation pathway.

J Environ Health Sci Eng 2021 Jun 24;19(1):541-551. Epub 2021 Feb 24.

School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083 People's Republic of China.

This study aims to find a high-efficiency degradation strain which can biodegrade the 2,3,7,8-Tetrachlorodibenzo-P-dioxin (2,3,7,8-TCDD). In this paper, a new fungus strain was isolated from activated sludge of Dagu Drainage River in Tianjin which was able to degrade 2,3,7,8-TCDD in the medium. Based on its morphology and phylogenetic analysis of its 18S rDNA sequence, the strain was identified as sp. QI-1. Response surface methodology using central composite rotatable design of cultural conditions was successfully employed for optimization resulting in 87.9 % degradation of 2,3,7,8-TCDD (1 µg/mL) within 6 days. The optimum condition for degrading 2,3,7,8-TCDD was at 31℃ and pH 7.4. The biodegradation process was fitted to a first-order kinetic model. The kinetic equation was C=0.939e and its half-life was 5.21d. The fungus strain degraded 2,3,7,8-TCDD to form intermediates, they were 4,5-Dichloro-1,2-benzoquinone, 4,5-Dichlorocatechol, 2-Hydrooxy-1,4-benzoquinone, 1,2,4-Trihydroxybenzene and β-ketoadipic acid. A novel degradation pathway for 2,3,7,8-TCDD was proposed based on analysis of these metabolites. The results suggest that sp. QI-1 may be an ideal microorganism for biodegradation of the 2,3,7,8-TCDD-contaminated environments.
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http://dx.doi.org/10.1007/s40201-021-00626-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172717PMC
June 2021

Carrier Diffusion and Recombination Anisotropy in the MAPbI Single Crystal.

ACS Appl Mater Interfaces 2021 Jun 18;13(25):29827-29834. Epub 2021 Jun 18.

Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China.

MAPbI, one of the archetypical metal halide perovskites, is an exciting semiconductor for a variety of optoelectronic applications. The photoexcited charge-carrier diffusion and recombination are important metrics in optoelectronic devices. Defects in grain interiors and boundaries of MAPbI films cause significant nonradiative recombination energy losses. Besides defect impact, carrier diffusion and recombination anisotropy introduced by structural and electronic discrepancies related to the crystal orientation are vital topics. Here, large-sized MAPbI single crystals (SCs) were grown, with the (110), (112), (100), and (001) crystal planes simultaneously exposed through the adjusting ratios of PbI to methylammonium iodide (MAI). Such MAPbI SCs exhibit a weak n-type semiconductor character, and the Fermi levels of these planes were slightly different, causing a homophylic p-n junction at crystal ledges. Utilizing MAPbI SCs, the photoexcited carrier diffusion and recombination within the crystal planes and around the crystal ledges were investigated through time-resolved fluorescence microscope. It is revealed that both the (110) and (001) planes were facilitated to be exposed with more MAI in the growth solutions, and the photoluminescence (PL) of these planes manifesting a red-shift, longer carrier lifetime, and diffusion length compared with the (100) and (112) planes. A longer carrier diffusion length promoted photorecycling. However, excessive MAI-assisted grown MAPbI SCs could increase the radiative recombination. In addition, it revealed that the carrier excited within the (001) and (112) planes was inclined to diffuse toward each other and was favorable to be extracted out of the grain boundaries or crystal ledges.
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http://dx.doi.org/10.1021/acsami.1c07056DOI Listing
June 2021

Analysis of the application of contrast-enhanced ultrasound-guided prostate biopsy in early diagnosis of prostate cancer.

Minerva Med 2021 Jun 18. Epub 2021 Jun 18.

Department of Ultrasound, The Third Hospital of Hebei Medical University, Shijiazhuang, China -

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http://dx.doi.org/10.23736/S0026-4806.21.07622-9DOI Listing
June 2021

The E3-ligase AoUBR1 in N-end rule pathway is involved in the vegetative growth, secretome, and trap formation in Arthrobotrys oligospora.

Fungal Biol 2021 Jul 23;125(7):532-540. Epub 2021 Feb 23.

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 3 Park 1, Beichen West Rd., Chaoyang District, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

The N-end rule pathway is a regulated protein degradation system. Arthrobotrys oligospora, a typical nematode-trapping fungus, switches its life strategies from saprophytism to carnivorism when capturing free-living nematodes by means of adhesive networks. In this study, a putative E3-ligase AoUBR1 involved in N-end rule pathway was characterized in A. oligospora during vegetative growth and trap formation. Expression of AoUBR1 coding gene was down-regulated during trap formation. Compared with wild type, the AoUBR1 knock-out mutants decreased the vegetative growth, formed less traps, and turned to be sensitive to cold stress, while, AoUBR1 overexpression mutants lost the capacity to produce conidia and also formed less traps. A number of genes differentially expressed by knock-out and overexpression of AoUBR1, which lead to the transcriptional responses associated with plasma membrane, transportation, oxidation, and proteolysis. AoUBR1 knock-out also resulted in the down-regulation of numerous secreted proteins associated with carnivorism and nutrient utilization from nematodes. In addition, AoUBR1 homologs were conserved in nematode-trapping fungi based on the genome searching. Therefore, the results suggested AoUBR1 in A. oligospora and its homologs in other trapping fungi are involved in the lifestyle switch between saprophytism and carnivorism.
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http://dx.doi.org/10.1016/j.funbio.2021.02.003DOI Listing
July 2021

In-depth assessment of the PAM compatibility and editing activities of Cas9 variants.

Nucleic Acids Res 2021 Jun 16. Epub 2021 Jun 16.

The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Center for Life Sciences, Genome Editing Research Center, Peking University, Beijing 100871, China.

A series of Cas9 variants have been developed to improve the editing fidelity or targeting range of CRISPR-Cas9. Here, we employ a high-throughput sequencing approach primer-extension-mediated sequencing to analyze the editing efficiency, specificity and protospacer adjacent motif (PAM) compatibility of a dozen of SpCas9 variants at multiple target sites in depth, and our findings validate the high fidelity or broad editing range of these SpCas9 variants. With regard to the PAM-flexible SpCas9 variants, we detect significantly increased levels of off-target activity and propose a trade-off between targeting range and editing specificity for them, especially for the near-PAM-less SpRY. Moreover, we use a deep learning model to verify the consistency and predictability of SpRY off-target sites. Furthermore, we combine high-fidelity SpCas9 variants with SpRY to generate three new SpCas9 variants with both high fidelity and broad editing range. Finally, we also find that the existing SpCas9 variants are not effective in suppressing genome instability elicited by CRISPR-Cas9 editing, raising an urgent issue to be addressed.
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http://dx.doi.org/10.1093/nar/gkab507DOI Listing
June 2021

Immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications.

Cancer Med 2021 Aug 15;10(15):5358-5374. Epub 2021 Jun 15.

State Key Laboratory of Oncogenes and Related Genes, Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Tumor-infiltrating immune cells participate in the initiation and progression of prostate adenocarcinoma (PRAD). However, it is not fully known how immune infiltration affects the development of PRAD and its clinical presentation.

Methods: Herein, we investigated the immune infiltration phenotypes in PRAD based on transcriptome profiles, methylation profiles, somatic mutation, and copy number variations. We also developed an immune prognostic model (IPM) to identify unfavorable prognosis. To verify this model, immunohistochemistry staining was performed on a cohort of PRAD samples. Moreover, we constructed a nomogram to assess the survival of PRAD incorporating immune infiltration and other clinical features.

Results: We categorized PRAD patients into high and low-level clusters based on immune infiltration phenotypes. The patients in the high-level clusters had worse survival than their low-level counterparts. Gene set enrichment analysis indicated that both anti- and pro-tumor terms were enriched in high-level cluster. Moreover, we identified a positive correlation between anti- and pro-tumor immune cells in PRAD microenvironment. Notably, Somatic mutation analysis showed patients in high-level cluster had a higher somatic mutation burden of KMT2D, HSPA8, CHD7, and MAP1A. In addition, we developed an IPM with robust predictive ability. The model can distinguish high-risk PRAD patients with poor prognosis from low-risk PRAD patients in both training and another three independent validation datasets. Besides, we constructed a nomogram incorporating Gleason score, pathological T stage, and IPM for the prognosis prediction of PRAD patients, which displayed robust predictive ability and might contribute to clinical practice.

Conclusion: Our work illustrated the immune infiltration phenotypes strongly related to the poor prognosis of PRAD patients, and highlighted the potential of the IPM to identify unfavorable tumor features.
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http://dx.doi.org/10.1002/cam4.4063DOI Listing
August 2021

The membrane-targeting mechanism of host defense peptides inspiring the design of polypeptide-conjugated gold nanoparticles exhibiting effective antibacterial activity against methicillin-resistant .

J Mater Chem B 2021 Jun;9(25):5092-5101

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China. and Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.

Multidrug-resistant bacterial infections are a grand challenge to global medical and health systems. Therefore, it is urgent to develop versatile antibacterial strategies that can combat bacterial resistance without displaying toxicity. Here, we synthesize antibacterial polypeptide-conjugated gold nanoparticles that exhibit potent antibacterial activities against clinically isolated multiple drug resistance Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus, and excellent in vitro and in vivo biocompatibility. The antibacterial mechanism study indicates that over-production of reactive oxygen species results in the killing of bacteria. The overall antibacterial performance of these polypeptide-conjugated gold nanoparticles and the convenient synthesis of these polypeptides via lithium hexamethyldisilazide-initiated fast ring-opening polymerization on α-amino acid N-carboxyanhydride imply the potential application of this strategy in treating bacterial infections.
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http://dx.doi.org/10.1039/d1tb00533bDOI Listing
June 2021

Effects of selenate on Se, flavonoid, and glucosinolate in broccoli florets by combined transcriptome and metabolome analyses.

Food Res Int 2021 08 31;146:110463. Epub 2021 May 31.

College of Horticulture and Gardening, Yangtze University, Jingzhou 434025, China. Electronic address:

Broccoli is a nutritious vegetable popular all over the world. This study investigated the effects of different concentrations of selenate (0, 0.1, 0.2, 0.4, 0.8, and 1.6 mmol/L) on the selenium (Se), glucosinolate, and flavonoid contents of broccoli florets. Results showed that the total Se, selenomethionine, and methyl selenocysteine contents increased following selenate dosage. Interestingly, selenate treatment of 0.4 mmol/L decreased the flavonoid but increased the glucosinolate content. Metabolome analysis revealed changes in the individual contents of glucosinolates and flavonoids. Conjoint analysis of transcriptome and metabolome showed that the glucosinolate and flavonoid compounds were potentially regulated by two sulfate transporter genes (Sultr3;1 and Sultr4;2) and several cytochrome P450 genes (e.g., CYP71B21, CYP72C1, and CYP81F1). These new findings indicated that Se treatment may influence glucosinolate and flavonoid accumulation by regulating the expression of these genes. The results of this study provide some novel insights into the effects of Se on glucosinolates and flavonoids in broccoli florets and deepen our understanding of the regulatory network between some specific genes and these compounds.
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http://dx.doi.org/10.1016/j.foodres.2021.110463DOI Listing
August 2021

Combining MGMT promoter pyrosequencing and protein expression to optimize prognosis stratification in glioblastoma.

Cancer Sci 2021 Jun 11. Epub 2021 Jun 11.

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

Pyrosequencing (PSQ) represents the golden standard for MGMT promoter status determination. Binary interpretation of results based on the threshold from the average of several CpGs tested would neglect the existence of the "gray zone". How to define the gray zone and reclassify patients in this subgroup remains to be elucidated. A consecutive cohort of 312 primary glioblastoma patients were enrolled. CpGs 74-81 in the promoter region of MGMT were tested by PSQ and the protein expression was assessed by immunohistochemistry (IHC). Receiver operating characteristic curves were constructed to calculate the area under the curves (AUC). Kaplan-Meier plots were used to estimate the survival rate of patients compared by the log-rank test. The optimal threshold of each individual CpG differed from 5% to 11%. Patients could be separated into the hypomethylated subgroup (all CpGs tested below the corresponding optimal thresholds, n = 126, 40.4%), hypermethylated subgroup (all CpGs tested above the corresponding optimal thresholds, n = 108, 34.6%), and the gray zone subgroup (remaining patients, n = 78, 25.0%). Patients in the gray zone harbored an intermediate prognosis. The IHC score instead of the average methylation levels could successfully predict the prognosis for the gray zone (AUC for overall survival, 0.653 and 0.519, respectively). Combining PSQ and IHC significantly improved the efficiency of survival prediction (AUC: 0.662, 0.648, and 0.720 for PSQ, IHC, and combined, respectively). Immunohistochemistry is a robust method to predict prognosis for patients in the gray zone defined by PSQ. Combining PSQ and IHC could significantly improve the predictive ability for clinical outcomes.
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http://dx.doi.org/10.1111/cas.15024DOI Listing
June 2021

[Retracted] MicroRNA-200c inhibits the metastasis of non-small cell lung cancer cells by targeting ZEB2, an epithelial-mesenchymal transition regulator.

Mol Med Rep 2021 Aug 10;24(2). Epub 2021 Jun 10.

Department of Chemotherapy, Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell Transwell assay data in the article (featured in Figs. 2C and 4C) were strikingly similar to data appearing in different form in other articles by different authors at different research institutions, which were already under consideration for publication or had already been published elsewhere at the time of the present article's submission [C. Lai , 'MicroRNA‑133a inhibits proliferation and invasion, and induces apoptosis in gastric carcinoma cells via targeting fascin actin‑bundling protein 1', Mol Med Rep 12: 1473‑1478, 2015; and Y. Shi , 'MicroRNA‑204 inhibits proliferation, migration, invasion and epithelial‑mesenchymal transition in osteosarcoma cells via targeting Sirtuin 1', Oncol Rep 34: 399‑406, 2015]. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors did not reply to indicate whether or not they agreed with the retraction of the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in 13: 3349-3355, 2016; DOI: 10.3892/mmr.2016.4901].
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http://dx.doi.org/10.3892/mmr.2021.12212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201453PMC
August 2021

Potential biomarkers for inherited thrombocytopenia 2 identified by plasma proteomics.

Platelets 2021 Jun 8:1-8. Epub 2021 Jun 8.

Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Army Medical University, Chongqing, China.

Inherited thrombocytopenia 2 (THC2) is difficult to diagnose due to the lack of specific clinical characteristics and diagnostic methods. To identify potential plasma protein biomarkers for THC2, we collected the plasma samples from a THC2 family (9 THC2 and 15 non-THC2 members), enriched the medium and low abundant proteins using Proteominer and analyzed the protein profiles using the liquid chromatography-mass spectrometry in data independent acquisition mode. Initially, we detected 784 proteins in the plasma samples of this family and identified 27 up-regulated and 36 down-regulated in the THC2 group compared to the non-THC2 group (|log ratio| >1 and -value <0.05). To improve the predictive power, top eight dysregulated proteins (B7Z2B4, LTF, HP, ERN1, IGHV1-8, A0A0X9V9C4, VH6DJ, and D3JV41) were selected by an area under the curve-based random forest process to construct a clinical model. Multivariate analysis with random forest and support vector machine showed that the prediction model provided high discrimination ability for THC2 diagnosis (AUC: 1.000 and 0.967, respectively). The potential plasma protein biomarkers will be tested in more THC2 patients and other thrombocytopenia patients to further validate their specificity and sensitivity.
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http://dx.doi.org/10.1080/09537104.2021.1937594DOI Listing
June 2021

Aggregative Perivascular Tumor Cell Growth Pattern of Primary Central Nervous System Lymphomas Is Associated with Hypoxia-Related Endoplasmic Reticulum Stress.

J Cancer 2021 5;12(13):3841-3852. Epub 2021 May 5.

Department of Hematology, Changhai Hospital, Shanghai 200433, China.

Primary central nervous system lymphomas (PCNSLs) often present a unique histopathological feature of aggregative perivascular tumor cells (APVT). Our previous studies showed that patients of PCNSL with APVTs exhibited poor long-term outcomes and increased expression of the endoplasmic reticulum stress (ERS) factor X-box-binding protein (XBP1). However, very little is known about molecular mechanism of the APVT formation in PCNSLs. The aim of this study is to determine if hypoxia-induced ERS is related to the APVT formation in PCNSLs. In this study, cell culture was used to observe the interplay between diffuse large B cell lymphoma (DLBCL) tumor cells and human brain microvascular endothelial cells (HBMECs) in different oxygen conditions. The expression of XBP1, CXCR and CD44 was manipulated by molecular cloning and siRNA technology. Mouse experiments and clinical studies were conducted to confirm our hypothesis. Our results showed that activated B-cell type-DLBCL cells easily migrated and invaded, and expressed high levels of XBP1 and stromal molecules CXCR4 and CD44 during hypoxia-induced ERS and dithiothreitol unfolded protein response (UPR). The gene upregulation (using overexpression vector) and downregulation (siRNA gene knock-out) in cultured cells and in mouse models further confirmed a close relation of the expression of XBP1, CXCR4, and CD44 with APVT formation, which is coincided with our clinical observation that increased expression of XBP1, CXCR4, and CD44 in the APVT cells in PCNSLs were associated with poor clinical outcomes. The results suggest that hypoxia-induced ERS and UPR might be associated with APVTs formation in PCNSL and its poor clinical outcomes. The results will help us better understand the progression of PCNSL with APVTs feature in daily pathological work and could be valuable for future target treatment of PCNSLs.
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http://dx.doi.org/10.7150/jca.54952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176238PMC
May 2021

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Levels and Cardiometabolic Risk Factors: A Population-Based Cohort Study.

Front Cardiovasc Med 2021 10;8:664583. Epub 2021 May 10.

Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

To evaluate the prospective association of circulating PCSK9 levels with the cardiometabolic risk profiles (high LDL-cholesterol, high triglycerides, low HDL-cholesterol, hypertension, type 2 diabetes, and metabolic syndrome). A population-based prospective study was conducted among 7,104 Chinese individuals (age 56.2 ± 7.5 years; 32.0% men). Circulating PCSK9 levels were measured using ELISA. Circulating PCSK9 levels were higher in women than men (286.7 ± 90.1 vs. 276.1 ± 86.4 ng/ml, < 0.001). And circulating PCSK9 was positively correlated with LDL-cholesterol, total cholesterol, and triglycerides both in men and women (all < 0.001). The positive correlation between PCSK9 and waist circumference, fasting glucose, insulin resistance, systolic blood pressure, diastolic blood pressure and C-reactive protein (all < 0.01) was observed in women only. According to Cox regression analysis, circulating PCSK9 was positively associated with incidence of high LDL-cholesterol both in men (HR 1.33, 95% CI 1.09-1.65, < 0.001) and women (HR 1.36, 95% CI 1.12-1.69, < 0.001). Moreover, PCSK9 was significantly associated with incident high triglycerides (HR 1.31, 95% CI 1.13-1.72, < 0.001), hypertension (HR 1.28, 95% CI 1.08-1.53, = 0.011), type 2 diabetes (HR 1.34, 95% CI 1.09-1.76, = 0.005), and metabolic syndrome (HR 1.30, 95% CI 1.11-1.65, = 0.009) per SD change in women only. No statistically significant association was observed between circulating PCSK9 and incidence of low HDL-cholesterol ( > 0.1). Elevated circulating PCSK9 was significantly associated with cardiometabolic risk factors and independently contributed to the prediction of cardiometabolic risks in women.
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http://dx.doi.org/10.3389/fcvm.2021.664583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141620PMC
May 2021
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