Publications by authors named "Wei Qian"

884 Publications

Integrative analysis of GWAS and transcriptome to reveal novel loci regulation flowering time in semi-winter rapeseed.

Plant Sci 2021 Sep 17;310:110980. Epub 2021 Jun 17.

Collaborative Innovation Center of Grain and Oil Crops in South China, Hunan Agricultural University, Changsha, 410128, China. Electronic address:

Flowering is an important turning point from vegetative growth to reproductive growth, and vernalization is an essential condition for the flowering of annual winter plants. To investigate the genetic architecture of flowering time in rapeseed, we used the 60 K Brassica Infinium SNP array to perform a genome-wide analysis of haplotype blocks associated with flowering time in 203 Chinese semi-winter rapeseed inbred lines. Twenty-one haplotype regions carrying one or more candidate genes showed a significant association with flowering time. Interestingly, we detected a SNP (Bn-scaff_22728_1-p285715) located in exon 3 of the BnVIN3-C03 gene that showed a significant association with flowering time on chromosome C03. Based on the SNP alleles A and G, two groups of accessions with early and late flowering time phenotypes were selected, respectively, and PCR amplification and gene expression analysis were combined to reveal the structural variation of the BnVIN3-C03 gene that affected flowering time. Moreover, we found that BnVIN3-C03 inhibited the expression of BnFLC-A02, BnFLC-A03.1, BnFLC-A10 and BnFLC-C03.1, thus modulating the flowering time of Brassica napus. This result provides insight into the genetic improvement of flowering time in B. napus.
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http://dx.doi.org/10.1016/j.plantsci.2021.110980DOI Listing
September 2021

Depression of Pyroptosis by Inhibiting Caspase-1 Activation Improves Neurological Outcomes of Kernicterus Model Rats.

ACS Chem Neurosci 2021 Jul 23. Epub 2021 Jul 23.

Department of Neonatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China.

Kernicterus is a severe complication of extreme neonatal hyperbilirubinemia. Prolonged exposure to high-level unconjugated bilirubin (UCB) directly damages brain tissue. Neuroinflammation is believed to contribute to UCB-induced neurotoxicity. Pyroptosis has been as a highly inflammatory form of programmed cell death. Therefore, this study aimed to explore whether pyroptosis was involved in the pathogenesis of UCB neurotoxicity in kernicterus model rats. VX-765, a specific inhibitor of caspase-1, was intraperitoneally administered to the model rats to observe its effects on the short-term and long-term outcomes of the model animals at the molecular, cellular, morphological, and behavioral levels. The results indicated that UCB significantly induced the activation of caspase-1 and gasdermin D(GSDMD), and VX-765 inhibited caspase-1-GSDMD pathway. Compared with those of the UCB group and the vehicle+UCB group, VX-765-treated rats released lower levels of IL-1β and IL-18. Furthermore, H&E and TUNEL staining showed that nerve cells in the VX-765-treated group were better preserved and had less DNA fragmentation. Most importantly, VX-765 improved both the short-term and long-term neurological functions of kernicterus model rats. This study demonstrated that pyroptosis was involved in the pathogenesis of kernicterus through caspase-1 activation, which could be inhibited by VX-765, exerting a neuroprotective effect in kernicterus model rats.
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http://dx.doi.org/10.1021/acschemneuro.1c00287DOI Listing
July 2021

Predictive Radiomic Models for the Chemotherapy Response in Non-Small-Cell Lung Cancer based on Computerized-Tomography Images.

Front Oncol 2021 7;11:646190. Epub 2021 Jul 7.

Department of Electrical and Computer Engineering, University of Texas at El Paso, El Paso, TX, United States.

The heterogeneity and complexity of non-small cell lung cancer (NSCLC) tumors mean that NSCLC patients at the same stage can have different chemotherapy prognoses. Accurate predictive models could recognize NSCLC patients likely to respond to chemotherapy so that they can be given personalized and effective treatment. We propose to identify predictive imaging biomarkers from pre-treatment CT images and construct a radiomic model that can predict the chemotherapy response in NSCLC. This single-center cohort study included 280 NSCLC patients who received first-line chemotherapy treatment. Non-contrast CT images were taken before and after the chemotherapy, and clinical information were collected. Based on the Response Evaluation Criteria in Solid Tumors and clinical criteria, the responses were classified into two categories: response (n = 145) and progression (n = 135), then all data were divided into two cohorts: training cohort (224 patients) and independent test cohort (56 patients). In total, 1629 features characterizing the tumor phenotype were extracted from a cube containing the tumor lesion cropped from the pre-chemotherapy CT images. After dimensionality reduction, predictive models of the chemotherapy response of NSCLC with different feature selection methods and different machine-learning classifiers (support vector machine, random forest, and logistic regression) were constructed. For the independent test cohort, the predictive model based on a random-forest classifier with 20 radiomic features achieved the best performance, with an accuracy of 85.7% and an area under the receiver operating characteristic curve of 0.941 (95% confidence interval, 0.898-0.982). Of the 20 selected features, four were first-order statistics of image intensity and the others were texture features. For nine features, there were significant differences between the response and progression groups ( < 0.001). In the response group, three features, indicating heterogeneity, were overrepresented and one feature indicating homogeneity was underrepresented. The proposed radiomic model with pre-chemotherapy CT features can predict the chemotherapy response of patients with non-small cell lung cancer. This radiomic model can help to stratify patients with NSCLC, thereby offering the prospect of better treatment.
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http://dx.doi.org/10.3389/fonc.2021.646190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293296PMC
July 2021

Comparing ameliorative effects of biomass ash and alkaline slag on an acidic Ultisol under artificial Masson pine: A field experiment.

J Environ Manage 2021 Jul 16;297:113306. Epub 2021 Jul 16.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, P.O. Box 821, Nanjing, 210008, PR China.

Forest soil acidification caused by acid deposition is a serious threat to the forest ecosystem. To investigate the liming effects of biomass ash (BA) and alkaline slag (AS) on the acidic topsoil and subsoil, a three-year field experiment under artificial Masson pine was conducted at Langxi, Anhui province in Southern China. The surface application of BA and AS significantly increased the soil pH, and thus decreased exchangeable acidity and active Al in the topsoil. Soil exchangeable Ca and Mg in topsoil were significantly increased by the surface application of BA and AS, while an increase in soil exchangeable K was only observed in BA treatments. The soil acidity and active Al in subsoil were decreased by the surface application of AS. Compared with the control, soluble monomeric and exchangeable Al in the subsoil was decreased by 38.0% and 29.4% after 3 years of AS surface application. There was a minimal effect on soluble monomeric and exchangeable Al after the application of BA. The soil exchangeable Ca and Mg in the subsoil increased respectively by 54% and 141% after surface application of 10 t ha AS. The decrease of soil active Al and increase of base cations in subsoil were mainly attributed to the high migration capacity of base cations in AS. In conclusion, the effect of surface application of AS was superior to BA in ameliorating soil acidity and alleviating soil Al toxicity in the subsoil of this Ultisol.
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http://dx.doi.org/10.1016/j.jenvman.2021.113306DOI Listing
July 2021

Development of a Novel Prognostic Signature Based on Antigen Processing and Presentation in Patients with Breast Cancer.

Pathol Oncol Res 2021 1;27:600727. Epub 2021 Apr 1.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.

Complex antigen processing and presentation processes are involved in the development and progression of breast cancer (BC). A single biomarker is unlikely to adequately reflect the complex interplay between immune cells and cancer; however, there have been few attempts to find a robust antigen processing and presentation-related signature to predict the survival outcome of BC patients with respect to tumor immunology. Therefore, we aimed to develop an accurate gene signature based on immune-related genes for prognosis prediction of BC. Information on BC patients was obtained from The Cancer Genome Atlas. Gene set enrichment analysis was used to confirm the gene set related to antigen processing and presentation that contributed to BC. Cox proportional regression, multivariate Cox regression, and stratified analysis were used to identify the prognostic power of the gene signature. Differentially expressed mRNAs between high- and low-risk groups were determined by KEGG analysis. A three-gene signature comprising HSPA5 (heat shock protein family A member 5), PSME2 (proteasome activator subunit 2), and HLA-F (major histocompatibility complex, class I, F) was significantly associated with OS. HSPA5 and PSME2 were protective (hazard ratio (HR) < 1), and HLA-F was risky (HR > 1). Risk score, estrogen receptor (ER), progesterone receptor (PR) and PD-L1 were independent prognostic indicators. KIT and ACACB may have important roles in the mechanism by which the gene signature regulates prognosis of BC. The proposed three-gene signature is a promising biomarker for estimating survival outcomes in BC patients.
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http://dx.doi.org/10.3389/pore.2021.600727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262234PMC
April 2021

Dendritic/Post-synaptic Tau and Early Pathology of Alzheimer's Disease.

Front Mol Neurosci 2021 25;14:671779. Epub 2021 Jun 25.

Department of Biochemistry and Molecular Biology, Medical School, Nantong University, Nantong, China.

Microtubule-associated protein tau forms insoluble neurofibrillary tangles (NFTs), which is one of the major histopathological hallmarks of Alzheimer's disease (AD). Many studies have demonstrated that tau causes early functional deficits prior to the formation of neurofibrillary aggregates. The redistribution of tau from axons to the somatodendritic compartment of neurons and dendritic spines causes synaptic impairment, and then leads to the loss of synaptic contacts that correlates better with cognitive deficits than amyloid-β (Aβ) aggregates do in AD patients. In this review, we discuss the underlying mechanisms by which tau is mislocalized to dendritic spines and contributes to synaptic dysfunction in AD. We also discuss the synergistic effects of tau and oligomeric forms of Aβ on promoting synaptic dysfunction in AD.
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http://dx.doi.org/10.3389/fnmol.2021.671779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270001PMC
June 2021

The chromosome-scale reference genome of Rubus chingii Hu provides insight into the biosynthetic pathway of hydrolysable tannins.

Plant J 2021 Jun 26. Epub 2021 Jun 26.

Life Science College, Anhui Agricultural University, Hefei, 230036, China.

Rubus chingii Hu (Fu-Pen-Zi), a perennial woody plant in the Rosaceae family, is a characteristic traditional Chinese medicinal plant because of its unique pharmacological effects. There are abundant hydrolysable tannin (HT) components in R. chingii that provide health benefits. Here, an R. chingii chromosome-scale genome and related functional analysis provide insights into the biosynthetic pathway of HTs. Sequence data totaling 231.21 Mb (155 scaffolds with an N50 of 8.2 Mb) were assembled into seven chromosomes with an average length of 31.4 Mb, and 33130 protein-coding genes were predicted, 89.28% of which were functionally annotated. Evolutionary analysis showed that R. chingii was most closely related to R. occidentalis, from which it was predicted to have diverged 22.46 million years ago. Comparative genomic analysis showed that there was a tandem gene cluster of UGT, CXE and SCPL genes on chromosome 02 of R. chingii, including 11 CXE, 8 UGT, and 6 SCPL genes, which may be critical for the synthesis of HTs. In vitro enzyme assays indicated that the proteins encoded by the CXE (LG02.4273) and UGT (LG02.4102) genes have tannin hydrolase and gallic acid glycosyltransferase functions, respectively. The genomic sequence of R. chingii will be a valuable resource for comparative genomic analysis within the Rosaceae family and will be useful for understanding the biosynthesis of HTs.
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http://dx.doi.org/10.1111/tpj.15394DOI Listing
June 2021

Quantitative trait loci (QTL) analysis of leaf related traits in spinach (Spinacia oleracea L.).

BMC Plant Biol 2021 Jun 24;21(1):290. Epub 2021 Jun 24.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.

Background: Spinach (Spinacia oleracea L.) is an important leafy vegetable crop, and leaf-related traits including leaf length, leaf width, and petiole length, are important commercial traits. However, the underlying genes remain unclear. The objective of the study was to conduct QTL mapping of leaf-related traits in spinach.

Results: A BC population was used to construct the linkage map and for QTL mapping of leaf length, leaf width, petiole length, and the ratio of leaf length to width in 2015 and 2019. Two genetic linkage maps were constructed by specific locus amplified fragment sequencing (SLAF-seq), and kompetitive allele specific PCR (KASP) technology, respectively using BC population in 2015. Based on the results of 2015, the specific linkage groups (LG) detected QTLs were generated using BC population in 2019. A total of 13 QTLs were detected for leaf-related traits, only five QTLs being repeatedly detected in multiple years or linkage maps. Interestingly, the major QTLs of leaf length, petiole length, and the ratio of leaf length to width were highly associated with the same SNP markers (KM3102838, KM1360385 and KM2191098). A major QTL of leaf width was mapped on chromosome 1 from 41.470-42.045 Mb. And 44 genes were identified within the region. Based on the GO analysis, these genes were significantly enriched on ribonuclease, lyase activity, phosphodiester bond hydrolysis process, and cell wall component, thus it might change cell size to determine leaves shape.

Conclusions: Five QTLs for leaf-related traits were repeatedly detected at least two years or linkage maps. The major QTLs of leaf length, petiole length, and the ratio of leaf length to width were mapped on the same loci. And three genes (Spo10792, Spo21018, and Spo21019) were identified as important candidate genes for leaf width.
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http://dx.doi.org/10.1186/s12870-021-03092-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223354PMC
June 2021

Mining the evolutionary patterns of pit mud microbiome and driving factors under the impact of long-term strong-flavor production.

Appl Environ Microbiol 2021 Jun 23:AEM0088521. Epub 2021 Jun 23.

Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, P.R. China.

Mud cellar creates a unique microenvironment for the fermentation of strong-flavor (SFB). Recent researches and long-term practice have highlighted the key roles of microbes inhabiting pit mud in the formation of SFB's characteristic flavor. A positive correlation between the quality of SFB and cellar age was extracted from practice, however, the evolutionary patterns of pit mud microbiome and driving factors remain unclear. Here, based on the variation regularity analysis of microbial community structure and metabolites of samples from cellars of different ages (∼30/100/300 years), we further investigated the effects of lactate and acetate (main microbial metabolites in fermented grains) on modulating pit mud microbiome. Esters (50.3%-64.5%) dominated the volatile compounds identified in pit mud, and contents of the four typical acids (lactate, hexanoate, acetate and butyrate) increased with cellar age. Bacteria (9.5-10.4 lg copies/g) and archaea (8.3-9.1 lg copies/g) mainly constituted pit mud microbiota, respectively dominated by Clostridia (39.7%-81.2%) and Methanomicrobia (32.8%-92.9%). An upward trend with cellar age characterized the relative and absolute abundance of the most predominant bacterial/archaeal genus, /. Correlation analysis revealed significantly ( < 0.05) positive relationships between the two genera and major metabolites. Anaerobic fermentation with acetate and lactate as carbon sources enhanced the enrichment of Clostridia, and furthermore, the relative abundance of (40.9%) significantly increased after 15-day fed-batch fermentation with lactate compared with the initial pit mud (0.22%). This work presents a directional evolutionary pattern of pit mud microbial consortia and provides an alternative way to accelerate the enrichment of functional microbes. The solid-state anaerobic fermentation in a mud cellar is the most typical feature of strong-flavor (SFB). Metabolites produced by microbes inhabiting pit mud are crucial to create the unique flavor of SFB. Accordingly, craftspeople have always highlighted the importance of pit mud microbiome and concluded by centuries of practice that the production rate of high-quality increases with cellar age. To deepen the understanding of pit mud microbiome, we determined the microbial community and metabolites of different-aged pit mud, inferred the main functional groups and explored the forces driving the microbial community evolution through metagenomic, metabolomic and multivariate statistical analyses. The results showed that the microbial consortia of pit mud presented a regular and directional evolutionary pattern under the impact of continuously batch-to-batch brewing activities. This work provides insight into the key roles of pit mud microbiome in SFB production and supports the production optimization of high-quality pit mud.
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http://dx.doi.org/10.1128/AEM.00885-21DOI Listing
June 2021

Exogenous l-fucose protects the intestinal mucosal barrier depending on upregulation of FUT2-mediated fucosylation of intestinal epithelial cells.

FASEB J 2021 07;35(7):e21699

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

FUT2, a protein that uses l-fucose to mediate fucosylation of intestinal epithelial cells, is one of the detected gene variants in IBD patients. We aimed to investigate whether exogenous l-fucose could be an enteral nutritional supplement to protect intestinal barrier function. The effect of l-fucose on the restoration of epithelial barrier function in both the DSS-induced colitis mouse model and LPS-stimulated Caco-2 cells was investigated, and the impact on fucosylation of epithelial cells was examined. The severity of DSS-induced colitis was significantly reduced by l-fucose. Restoration of epithelial barrier function by l-fucose was detected. Direct l-fucose-mediated protection of tight junctions was observed in Caco-2 cells. Moreover, exogenous l-fucose promoted the exogenous metabolic pathway of l-fucose, and fucosylation of epithelial cells both in vivo and in vitro. Moreover, knockout of the FUT2 gene restrained fucosylation and the protective effect of l-fucose on barrier function. The severity of colitis was not improved by l-fucose in Fut2 knockout mice. Therefore we conclude that exogenous l-fucose protects intestinal barrier function and relieves intestinal inflammation via upregulation of FUT2-mediated fucosylation of intestinal epithelial cells.
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http://dx.doi.org/10.1096/fj.202002446RRRRDOI Listing
July 2021

Cancer-Preventive Role of Bone Marrow-Derived Mesenchymal Stem Cells on Colitis-Associated Colorectal Cancer: Roles of Gut Microbiota Involved.

Front Cell Dev Biol 2021 4;9:642948. Epub 2021 Jun 4.

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Mesenchymal stem cells (MSCs) treatment showed promising results in inflammatory bowel disease in both rodent models and patients. Nevertheless, previous studies conducted conflicting results on preclinical tumor models treated with MSCs concerning their influence on tumor initiation and progression. This study is designed to demonstrate the role of bone marrow-derived MSCs and the potential mechanism in the colitis-associated colon cancer (CAC) model.

Methods: Bone marrow-derived MSCs were isolated from green fluorescent protein-transgenic mice, cultured, and identified by flow cytometry. Azoxymethane and dextran sulfate sodium were administrated to establish the CAC mouse model, and MSCs were infused intraperitoneally once per week. The mice were weighed weekly, and colon length, tumor number, and average tumor size were assessed after the mice were killed. MSC localization was detected by immunofluorescence staining; tumor cell proliferation and apoptosis were measured by immunohistochemistry staining of Ki-67 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay, respectively. The colonic tumor tissues were isolated for RNA-seq, and fecal samples were collected for 16S ribosomal RNA sequencing of the microbiome.

Results: After injection intraperitoneally, MSCs migrated to the intestine and inhibited the initiation of colitis-associated colorectal cancer. This inhibition effect was marked by less weight loss, longer colon length, and reduced tumor numbers. Moreover, MSCs reduced tumor cell proliferation and induced tumor cell apoptosis. Furthermore, MSCs could inhibit chronic inflammation assessed by RNA-sequencing and promote gut microbiome normalization detected by 16S ribosomal RNA sequencing.

Conclusion: The results proved that MSCs could migrate to the colon, inhibit chronic inflammation, and regulate gut microbiome dysbiosis to suppress the development of CAC.
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http://dx.doi.org/10.3389/fcell.2021.642948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212064PMC
June 2021

Overexpression of PTPRN Promotes Metastasis of Lung Adenocarcinoma and Suppresses NK Cell Cytotoxicity.

Front Cell Dev Biol 2021 2;9:622018. Epub 2021 Jun 2.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.

Background: Lung adenocarcinoma (LUAD) is the most common diagnostic histologic subtype of non-small cell lung cancer, but the role of receptor-type tyrosine-protein phosphatase-like N (PTPRN) in LUAD has not been studied.

Methods: We conducted a bioinformatic analysis to identify the expression of PTPRN on LUAD data from the Cancer Genome Atlas (TCGA) and the relationship between PTPRN and overall survival of LUAD patients. The effects of PTPRN on the migration ability of LUAD cells and the underlying mechanisms were investigated by and assays (i.e., wound healing assay, transwell assay, western blotting, xenograft model, and immunohistochemistry). Gene-set enrichment analysis and computational resource were used to analyze the correlation between PTPRN and different tumor-infiltrating immune cells (TIICs). Lactate dehydrogenase assay and Enzyme-linked immunosorbent assay were conducted to examine natural killer (NK) cell cytotoxicity.

Results: In our study, we found that PTPRN was up-regulated in LUAD and related to metastasis of LUAD patients. Besides, PTPRN was correlated with poor prognosis in the TCGA-LUAD dataset. PTPRN overexpression promoted LUAD cell migration and the expression of EMT markers by influencing MEK/ERK and PI3K/AKT signaling. Moreover, PTPRN expression was significantly associated with TIICs, especially NK cells. A549 and H1299 cells overexpressed PTPRN inhibited NK cell cytotoxicity.

Conclusion: Taken together, these findings demonstrated that PTPRN might be a potential and novel therapeutic target modulating antitumor immune response in treatment of LUAD.
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http://dx.doi.org/10.3389/fcell.2021.622018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207963PMC
June 2021

Hemorheological responses to an acute bout of maximal exercise in Veterans with Gulf War Illness.

Life Sci 2021 Sep 16;280:119714. Epub 2021 Jun 16.

New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ, USA; Surgical Services, Veterans Affairs New Jersey Health Care System, East Orange, NJ, USA.

Background: Altered red blood cell (RBC) deformability has been reported in Veterans with Gulf War Illness (GWI) who endorse exercise-induced symptom exacerbation and fatigue. However, it is unknown whether altered RBC deformability is worsened secondary to exercise.

Objective: To evaluate RBC deformability in response to maximal exercise in individuals with and without GWI.

Methods: Seventeen Veterans with GWI and 11 controls performed maximal exercise and provided blood samples (pre-, immediately post- and 60-min post-exercise). We calculated RBC deformation at infinite stress (EI), shear stress for half-deformation (SS) and their ratio (SS/EI) via repeated measures ANOVA with group and time as factors.

Results: A moderate interaction effect (p = 0.08, η = 0.10), large main effect for group (p = 0.02, η = 0.19) and moderate main effect for time (p = 0.20, η = 0.06) were observed for EI, but only the main effect for group reached statistical significance. Changes in SS and SS/EI over time were similar between cases and controls as were main effects.

Conclusions: Veterans with GWI had more deformable RBCs in comparison to controls that was unaffected by maximal exercise. Future studies to confirm our findings and identify associated mechanisms are warranted.
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http://dx.doi.org/10.1016/j.lfs.2021.119714DOI Listing
September 2021

Combined toxicity of nano-TiO and Cd to Scenedesmus obliquus: Effects at different concentration ratios.

J Hazard Mater 2021 Jun 9;418:126354. Epub 2021 Jun 9.

Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.

The continuous release of manufactured nanomaterials (MNMs) to environments raised concerns on their combined toxicological risks with co-existing contaminants, since MNMs might severely alter the environmental behavior and fate of the contaminants. In this study, the combined toxicity of nano-sized titanium dioxide (nTiO) and cadmium (Cd) to the green alga Scenedesmus obliquus and the underlying physicochemical mechanisms were investigated for the first time at different concentration ratios of Cd to nTiO to closely mimic the realistic environment scenarios where the concentration ratios of nTiO to other contaminants are constantly changing. Our results suggested that under the co-exposure to different concentration ratios of Cd to nTiO, the co-exposure contaminants exhibited three different combined toxicity modes (antagonistic, partially additive, and synergistic). Specifically, antagonistic combined toxicity was observed under co-exposure to a low concentration ratio of nTiO to Cd as the absorption by nTiO decreased the bioavailability of Cd. However, the partially additive and synergistic combined toxicity occurred when the proportion of nTiO in the co-exposure system was relatively high, which would mechanically and/or oxidatively damage the alga cell structures. Even worse, as a carrier of Cd, nTiO enhanced the amount of Cd entering cells, which significantly enhanced the toxicity of Cd to algae. Overall, we demonstrated that concentration ratios of nTiO to Cd play an important role in determining the combined toxicity mode, which would provide a novel reference to environmental and health risk assessment of co-exposure to conventional pollutants and MNMs.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126354DOI Listing
June 2021

A Conditional Process Model to Explain Somatization During Coronavirus Disease 2019 Epidemic: The Interaction Among Resilience, Perceived Stress, and Sex.

Front Psychol 2021 20;12:633433. Epub 2021 May 20.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

Background: More than 15% of Chinese respondents reported somatic symptoms in the last week of January 2020. Promoting resilience is a possible target in crisis intervention that can alleviate somatization.

Objectives: This study aims to investigate the relationship between resilience and somatization, as well as the underlying possible mediating and moderating mechanism, in a large sample of Chinese participants receiving a crisis intervention during the coronavirus disease 2019 epidemic.

Methods: Participants were invited online to complete demographic information and questionnaires. The Symptom Checklist-90 somatization subscale, 10-item Connor-Davidson resilience scale, and 10-item Perceived Stress Scale were measured.

Results: A total of 2,557 participants were included. Spearman correlation analysis revealed that lower resilience was associated with more somatic symptoms ( < 0.001). The conditional process model was proved (indirect effect = -0.01, 95% confidence interval = [-0.015, -0.002]). The interaction effects between perceived stress and sex predicted somatization ( = 0.05, = 0.006).

Conclusion: Resilience is a key predictor of somatization. The mediating effects of perceived stress between resilience and somatization work in the context of sex difference. Sex-specific intervention by enhancing resilience is of implication for alleviating somatization during the coronavirus disease 2019 epidemic.
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http://dx.doi.org/10.3389/fpsyg.2021.633433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172608PMC
May 2021

Do weight perception and bullying victimization account for links between weight status and mental health among adolescents?

BMC Public Health 2021 06 4;21(1):1062. Epub 2021 Jun 4.

School of Public Health and Health Systems, University of Waterloo, 200 University Ave, Waterloo, Ontario, N2L 3G1, Canada.

Background: The purpose of this study was to explore whether the way youth perceive their weight and their experiences of bullying victimization account for the increased risk of depression and anxiety symptoms, and poor psychosocial well-being, associated with overweight/obesity in a large sample of Canadian secondary school students. We also explored if associations differed by gender.

Methods: We used cross-sectional survey data from year 7 (2018-19) of the COMPASS study. The sample included 57,059 students in grades 9-12 (Secondary III-V in Quebec) at 134 Canadian secondary schools (Alberta, British Columbia, Ontario, Quebec). First, multiple regression models tested associations between body mass index (BMI) classification and mental health outcomes (anxiety [GAD-7] and depression [CESD-10] symptoms, and psychosocial well-being [Diener's Flourishing Scale]). Second, weight perception and bullying victimization were added to the models. Models were stratified by gender and controlled for sociodemographic covariates and school clustering.

Results: When weight perception and bullying victimization were added to the models, obesity BMI status no longer predicted internalizing symptoms and flourishing scores relative to normal-weight BMIs. Students with 'overweight' or 'underweight' perceptions, and experiences of bullying victimization in the past month, reported higher anxiety and depressive symptomatology, and lower flourishing levels, in comparison to students with 'about right' weight perceptions and without experiences of bullying victimization, respectively, controlling for BMI status. Results were largely consistent across boys and girls.

Conclusions: Results suggest perceptions of weight and experiences of bullying independently contribute to differences in mental health outcomes by weight status among youth. Continued efforts targeting weight-based bullying and weight bias, and the promotion of body size acceptance and positive body image, may help reduce the risk of mental illness and poor mental health among adolescents.
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http://dx.doi.org/10.1186/s12889-021-11037-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177253PMC
June 2021

Mendelian randomization studies of brain MRI yield insights into the pathogenesis of neuropsychiatric disorders.

BMC Genomics 2021 Jun 2;22(Suppl 3):342. Epub 2021 Jun 2.

Shanghai Mental Health Center, School of Biomedical Engineering, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 200030, Shanghai, China.

Background: Observational studies have identified various associations between neuroimaging alterations and neuropsychiatric disorders. However, whether such associations could truly reflect causal relations remains still unknown.

Results: Here, we leveraged genome-wide association studies (GWAS) summary statistics for (1) 11 psychiatric disorders (sample sizes varied from n = 9,725 to 1,331,010); (2) 110 diffusion tensor imaging (DTI) measurement (sample size n = 17,706); (3) 101 region-of-interest (ROI) volumes, and investigate the causal relationship between brain structures and neuropsychiatric disorders by two-sample Mendelian randomization. Among all DTI-Disorder combinations, we observed a significant causal association between the superior longitudinal fasciculus (SLF) and the risk of Anorexia nervosa (AN) (Odds Ratio [OR] = 0.62, 95 % confidence interval: 0.50 ~ 0.76, P = 6.4 × 10). Similar significant associations were also observed between the body of the corpus callosum (fractional anisotropy) and Alzheimer's disease (OR = 1.07, 95 % CI: 1.03 ~ 1.11, P = 4.1 × 10). By combining all observations, we found that the overall p-value for DTI - Disorder associations was significantly elevated compared to the null distribution (Kolmogorov-Smirnov P = 0.009, inflation factor λ = 1.37), especially for DTI - Bipolar disorder (BP) (λ = 2.64) and DTI - AN (λ = 1.82). In contrast, for ROI-Disorder combinations, we only found a significant association between the brain region of pars triangularis and Schizophrenia (OR = 0.48, 95 % CI: 0.34 ~ 0.69, P = 5.9 × 10) and no overall p-value elevation for ROI-Disorder analysis compared to the null expectation.

Conclusions: As a whole, we show that SLF degeneration may be a risk factor for AN, while DTI variations could be causally related to some neuropsychiatric disorders, such as BP and AN. Also, the white matter structure might have a larger impact on neuropsychiatric disorders than subregion volumes.
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http://dx.doi.org/10.1186/s12864-021-07661-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171058PMC
June 2021

Profiling of Volatile Compounds and Associated Gene Expression in Two Cultivars and Their F1 Hybrid Progenies.

Molecules 2021 May 13;26(10). Epub 2021 May 13.

Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou 510642, China.

is an important ornamental crop in the world market and its floral scent can enhance its ornamental value. To date, studies of the components and formation mechanism of the floral scent of are relatively few. In this study, the scent profiles of two varieties were measured by gas chromatograph-mass spectrometer (GC-MS). There were 32 volatile organic compounds (VOCs) identified in  ', and the most abundant compound was eucalyptol (57.5%). Extremely small amounts of VOCs were detected in 'Alabama'. Compared with 'Alabama', most genes related to floral scent synthesis exhibited a higher expression in , including , ,  , , and In order to produce new varieties of with fragrance, 454 progenies of two crossbred combinations of  '' and 'Alabama' were obtained. Four F1 generation plants with different floral scent intensities were selected for further study. The major components of floral scent in the progenies were similar to that of the parental plant. The expression patterns of genes related to floral scent synthesis were consistent with the relative contents of different types of VOCs. This study revealed the profiles of volatile compounds and associated gene expression in two cultivars and their F1 hybrids, which provided a basis for the floral scent inheritance of .
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http://dx.doi.org/10.3390/molecules26102902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153298PMC
May 2021

Brain functional network modeling and analysis based on fMRI: a systematic review.

Cogn Neurodyn 2021 Jun 31;15(3):389-403. Epub 2020 Aug 31.

College of Engineering, The University of Texas at El Paso, El Paso, TX USA.

In recent years, the number of patients with neurodegenerative diseases (i.e., Alzheimer's disease, Parkinson's disease, mild cognitive impairment) and mental disorders (i.e., depression, anxiety and schizophrenia) have increased dramatically. Researchers have found that complex network analysis can reveal the topology of brain functional networks, such as small-world, scale-free, etc. In the study of brain diseases, it has been found that these topologies have undergoed abnormal changes in different degrees. Therefore, the research of brain functional networks can not only provide a new perspective for understanding the pathological mechanism of neurological and psychiatric diseases, but also provide assistance for the early diagnosis. Focusing on the study of human brain functional networks, this paper reviews the research results in recent years. First, this paper introduces the background of the study of brain functional networks under complex network theory and the important role of topological properties in the study of brain diseases. Second, the paper describes how to construct a brain functional network using neural image data. Third, the common methods of functional network analysis, including network structure analysis and disease classification, are introduced. Fourth, the role of brain functional networks in pathological study, analysis and diagnosis of brain functional diseases is studied. Finally, the paper summarizes the existing studies of brain functional networks and points out the problems and future research directions.
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http://dx.doi.org/10.1007/s11571-020-09630-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131458PMC
June 2021

Association of Stress-Related Factors With Anxiety Among Chinese Pregnant Participants in an Online Crisis Intervention During COVID-19 Epidemic.

Front Psychol 2021 30;12:633765. Epub 2021 Apr 30.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Bejing, China.

Previous systematic review indicated the prevalence of prenatal anxiety as 14-54%. Pregnant women are a high-risk population for COVID-19. However, the prevalence of anxiety symptoms and related factors is unknown in Chinese pregnant women during COVID-19 outbreak. To investigate the prevalence of anxiety symptoms and the related factors in Chinese pregnant women who were attending crisis intervention during the COVID-19 pandemic. The data of this cross-sectional study were collected in about 2 months (February 28 to April 26, 2020). Data analysis was performed from April to May 2020. Participants completed a set of questionnaires via the Wechat Mini-program before starting the online self-help crisis intervention for COVID-19 epidemic. A total of 2,120 Chinese pregnant women who were attending a self-help crisis intervention participated in this study. A survey was developed to address possible stress-related factors in pregnant women during the COVID-19 outbreak, including demographic, socioeconomic, and pregnancy-related factors, as well as COVID-19 related factors. Generalized Anxiety Disorder-7 (GAD-7) scale and the 10-item perceived stress scale were, respectively, employed to measure anxiety and stress-related factors. A total of 21.7% (459) of pregnant women reported at least mild anxiety (≥5 on the GAD-7 scale), and only 82 women reported moderate to severe anxiety (≥10 on the GAD-7 scale). Factors associated with at least mild anxiety included living in Hubei province ( = 1.68, = 1.32-2.13), nobody providing everyday life support ( = 1.81, = 1.18-2.77), pelvic pain or vaginal bleeding ( = 1.67, = 1.32-2.09), and higher perceived stress ( = 6.87, = 5.42-9.02). Having relatives or neighbors with a diagnosis of COVID-19 was not associated with anxiety ( > 0.05). Our findings indicate that evaluation and intervention for maternal and infant health are necessary in pregnant women with anxiety during COVID-19 epidemic, especially those with higher perceived stress, less everyday life support, or vaginal bleeding. Interactions among these related medical, social and psychological factors need to be investigated in future studies.
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http://dx.doi.org/10.3389/fpsyg.2021.633765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119994PMC
April 2021

Serum Exosomal EphA2 is a Prognostic Biomarker in Patients with Pancreatic Cancer.

Cancer Manag Res 2021 7;13:3675-3683. Epub 2021 May 7.

Department of Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China.

Background: Pancreatic cancer (PC) is one of the worst prognoses amongst all malignant diseases. It is therefore of great significance to identify biomarkers with predictive clinical value for the prognosis and recurrence of PC.

Methods: In our study, enzyme-linked immunosorbent assays (ELISA) were used to detect the expression of Exo-EphA2 in the serum of PC patients and controls. Kaplan-Meier curve and Cox regression analyses were used to evaluate the prognostic value of Exo-EphA2 expression in patients with primary and recurrent PC.

Results: The level of serum Exo-EphA2 was significantly higher in the PC group when compared to that of the control group. High expression of Exo-EphA2 in PC was associated with shorter overall survival (OS) and proved to be a significant negative prognostic factor in the multivariate analysis (HR = 1.04, 95% CI: 1.00-1.09, P <0.001). Additionally, we found that the level of serum Exo-EphA2 in recurrent PC patients (first recurrence < 12 months) was positively correlated with the level of Exo-EphA2 at primary diagnosis. Multivariate analysis showed that a high expression of Exo-EphA2 in recurrent PC was associated with shorter recurrence-free survival (RFS) (HR = 1.41, 95% CI: 1.10-1.70, P < 0.001).

Conclusion: High expression of serum Exo-EphA2 represents a novel biomarker for a poor prognosis in PC patients.
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http://dx.doi.org/10.2147/CMAR.S304719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112875PMC
May 2021

Transferrable protection by gut microbes against STING-associated lung disease.

Cell Rep 2021 May;35(6):109113

Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address:

STING modulates immunity by responding to bacterial and endogenous cyclic dinucleotides (CDNs). Humans and mice with STING gain-of-function mutations develop a syndrome known as STING-associated vasculopathy with onset in infancy (SAVI), which is characterized by inflammatory or fibrosing lung disease. We hypothesized that hyperresponsiveness of gain-of-function STING to bacterial CDNs might explain autoinflammatory lung disease in SAVI mice. We report that depletion of gut microbes with oral antibiotics (vancomycin, neomycin, and ampicillin [VNA]) nearly eliminates lung disease in SAVI mice, implying that gut microbes might promote STING-associated autoinflammation. However, we show that germ-free SAVI mice still develop severe autoinflammatory disease and that transferring gut microbiota from antibiotics-treated mice to germ-free animals eliminates lung inflammation. Depletion of anaerobes with metronidazole abolishes the protective effect of the VNA antibiotics cocktail, and recolonization with the metronidazole-sensitive anaerobe Bacteroides thetaiotaomicron prevents disease, confirming a protective role of a metronidazole-sensitive microbe in a model of SAVI.
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http://dx.doi.org/10.1016/j.celrep.2021.109113DOI Listing
May 2021

Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Facilitate Diabetic Wound Healing Through MiR-17-5p-mediated Enhancement of Angiogenesis.

Stem Cell Rev Rep 2021 May 4. Epub 2021 May 4.

Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and 4th Medical Center of Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China.

Endothelial dysfunction caused by persistent hyperglycemia in diabetes is responsible for impaired angiogenesis in diabetic wounds. Extracellular vehicles (EVs) are considered potential therapeutic tools to promote diabetic wound healing. The aim of this study was to investigate the effects of EVs secreted by human umbilical cord mesenchymal stem cells (hucMSC-EVs) on angiogenesis under high glucose (HG) conditions in vivo and in vitro and to explore the underlying mechanisms. In vivo, local application of hucMSC-EVs enhanced wound healing and angiogenesis. In vitro, hucMSC-EVs promoted proliferation, migration, and tube formation by inhibiting phosphatase and tensin homolog (PTEN) expression and activating the AKT/HIF-1α/VEGF pathways. MiR-17-5p was found to be highly enriched in hucMSC-EVs. In vitro, MiR-17-5p agomirs downregulated the expression of PTEN and activated the AKT/HIF-1α/VEGF pathway to promote proliferation, migration, and tube formation in HG-treated HUVECs. In vivo, miR-17-5p agomirs mimicked the effects of hucMSC-EVs on wound healing and angiogenesis, whereas miR-17-5p inhibitors reversed their effects. Our findings suggest that hucMSC-EVs have regenerative and protective effects on HG-induced endothelial cells via transfer of miR-17-5p targeting PTEN/ AKT/HIF-1α/VEGF pathway, thereby accelerating diabetic wound healing. Thus, hucMSC-EVs may be promising therapeutic candidates for improving diabetic wound angiogenesis.
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http://dx.doi.org/10.1007/s12015-021-10176-0DOI Listing
May 2021

The Energy to Smoke: Examining the Longitudinal Association between Beverage Consumption and Smoking and Vaping Behaviours among Youth in the COMPASS Study.

Int J Environ Res Public Health 2021 04 7;18(8). Epub 2021 Apr 7.

Population Physical Activity Laboratory, School of Kinesiology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

This study examined the longitudinal association between changes in sugar-sweetened and/or caffeinated beverage consumption and smoking/vaping behaviour among Canadian adolescents. Using longitudinal data from the COMPASS study (2015/16 to 2017/18), four models were developed to investigate whether beverage consumption explained variability in smoking and vaping behaviour in adolescence: (1) smoking initiation, (2) vaping initiation, (3) current smoking status, and (4) current vaping status. Models were adjusted for demographic factors. Multinomial logit models were used for model 1, 2, and 3. A binary logistic regression model was used for model 4. An association between change in frequency of beverage consumption and smoking/vaping behaviour was identified in all models. A one-day increase in beverage consumption was associated with smoking initiation (OR = 1.38, 95% CI: 1.25, 1.51), vaping initiation (OR = 1.23, 95% CI: 1.14, 1.32), identifying as a current smoker (OR = 1.17, 95% CI: 1.01, 1.35), and currently vaping (OR = 1.08, 95% CI: 1.04, 1.11). Change in high-energy drink consumption was the best predictor of smoking behaviours and vaping initiation but not current vaping status. Given the health consequences of smoking and vaping and their association with high-energy drink and coffee consumption, policy initiatives to prevent smoking/vaping initiation, and to limit youth access to these beverages, warrant consideration.
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http://dx.doi.org/10.3390/ijerph18083864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067730PMC
April 2021

A Cluster-Based Energy Optimization Algorithm in Wireless Sensor Networks with Mobile Sink.

Sensors (Basel) 2021 Apr 4;21(7). Epub 2021 Apr 4.

School of Artificial Intelligence, Henan University, Kaifeng 475004, China.

Aiming at high network energy consumption and data delay induced by mobile sink in wireless sensor networks (WSNs), this paper proposes a cluster-based energy optimization algorithm called Cluster-Based Energy Optimization with Mobile Sink (CEOMS). CEOMS algorithm constructs the energy density function of network nodes firstly and then assigns sensor nodes with higher remaining energy as cluster heads according to energy density function. Meanwhile, the directivity motion performance function of mobile sink is constructed to enhance the probability of remote sensor nodes being assigned as cluster heads. Secondly, based on Low Energy Adaptive Clustering Hierarchy Protocol (LEACH) architecture, the energy density function and the motion performance function are introduced into the cluster head selection process to avoid random assignment of cluster head. Finally, an adaptive adjustment function is designed to improve the adaptability of cluster head selection by percentage of network nodes death and the density of all surviving nodes of the entire network. The simulation results show that the proposed CEOMS algorithm improves the cluster head selection self-adaptability, extends the network life, reduces the data delay, and balances the network load.
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http://dx.doi.org/10.3390/s21072523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038497PMC
April 2021

Maternal insomnia during the COVID-19 pandemic: associations with depression and anxiety.

Soc Psychiatry Psychiatr Epidemiol 2021 Aug 23;56(8):1477-1485. Epub 2021 Apr 23.

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Road, Chaoyang District, Beijing, 100101, China.

Background: The COVID-19 outbreak has made people more prone to depression, anxiety and insomnia, and females are at a high risk of developing these conditions. As a special group, pregnant and lying-in women must pay close attention to their physical and mental health, as both have consequences for the mother and the fetus. However, knowledge regarding the status of depression, anxiety and insomnia among these women is limited.

Aim: This study aimed to examine insomnia and psychological factors among pregnant and lying-in women during the COVID-19 pandemic and provide theoretical support for intervention research.

Methods: In total, 2235 pregnant and lying-in women from 12 provinces in China were surveyed; their average age was 30.25 years (SD = 3.99, range = 19-47 years).

Participants And Setting: The participants completed electronic questionnaires designed to collect demographic information and assess levels of depression, anxiety and insomnia.

Results: The prevalence of insomnia in the sample was 18.9%. Depression and anxiety were significant predictors of insomnia. Participants in high-risk areas, those with a disease history, those with economic losses due to the outbreak, and those in the postpartum period had significantly higher insomnia scores.

Discussion: The incidence of insomnia among pregnant and lying-in women is not serious in the context of the epidemic, which may be related to the sociocultural background and current epidemic situation in China.

Conclusion: Depression and anxiety are more indicative of insomnia than demographic variables.
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http://dx.doi.org/10.1007/s00127-021-02072-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063170PMC
August 2021

ANETT: PhAse II trial of NEoadjuvant TAK-228 plus Tamoxifen in patients with hormone receptor-positive breast cancer.

Breast Cancer Res Treat 2021 Jul 15;188(2):433-439. Epub 2021 Apr 15.

Houston Methodist Cancer Center, Houston, TX, USA.

Introduction: Neoadjuvant endocrine therapy is often utilized to downstage Estrogen Receptor-positive (ER+) breast cancer prior to surgery. However, this approach is sometimes met with endocrine resistance mechanisms within the tumor. This trial examines the safety and efficacy of tamoxifen in combination with an mTORC1/2 inhibitor, TAK-228, in the neoadjuvant treatment of ER+ breast cancer.

Methods: In this single-arm, open-label trial, pre- and post-menopausal women were enrolled to receive neoadjuvant tamoxifen (20 mg daily) with TAK-228 (30 mg weekly) for 16 weeks prior to surgery. Patient had tissue sampling at baseline, week 6, and week 16. The primary endpoint was change in Ki-67 from baseline to 6 weeks. The toxicity, change in tumor size, pathologic complete response rate, PEPI score, and baseline Oncotype Dx score were also assessed.

Results: Twenty-eight women were enrolled on the trial, and 25 completed the entire study course. The combination of tamoxifen and TAK-228 resulted in a significant reduction in Ki-67 from 18.3 to 15.2% (p = 0.0023). The drug was also found to be safe and tolerable. While nausea and hyperglycemia were common side effects, these were manageable. The tumor size also significantly decreased with the treatment, with a median decrease of 0.75 cm (p < 0.0001). There were no pathologic complete responses.

Conclusion: Tamoxifen and TAK-228 was safe and well tolerated neoadjuvant treatment for ER+ breast cancer, preliminary evidence of activity with significant reduction in both Ki-67 and tumor size, warranting further evaluation in a larger study.
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http://dx.doi.org/10.1007/s10549-021-06214-7DOI Listing
July 2021

Spatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development.

Sci Rep 2021 Apr 15;11(1):8246. Epub 2021 Apr 15.

Shanghai Mental Health Center,' Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.

Recurrent deletions and duplications of chromosome 7q11.23 copy number variants (CNVs) are associated with several psychiatric disorders. Although phenotypic abnormalities have been observed in patients, causal genes responsible for CNV-associated diagnoses and traits are still poorly understood. Furthermore, the targeted human brain regions, developmental stages, protein networks, and signaling pathways, influenced by this CNV remain unclear. Previous works showed GTF2I involved in Williams-Beuren syndrome, but pathways affected by GTF2I are indistinct. We first constructed dynamic spatiotemporal networks of 7q11.23 genes by combining data from the brain developmental transcriptome with physical interactions of 7q11.23 proteins. Topological changes were observed in protein-protein interaction (PPI) networks throughout different stages of brain development. Early and late fetal periods of development in the cortex, striatum, hippocampus, and amygdale were observed as the vital periods and regions for 7q11.23 CNV proteins. CNV proteins and their partners are significantly enriched in DNA repair pathway. As a driver gene, GTF2I interacted with PRKDC and BRCA1 to involve in DNA repair pathway. The physical interaction between GTF2I with PRKDC was confirmed experimentally by the liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified that early and late fetal periods are crucial for 7q11.23 genes to affect brain development. Our results implicate that 7q11.23 CNV genes converge on the DNA repair pathway to contribute to the pathogenesis of psychiatric diseases.
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http://dx.doi.org/10.1038/s41598-021-87632-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050238PMC
April 2021

PIVKA-II serves as a potential biomarker that complements AFP for the diagnosis of hepatocellular carcinoma.

BMC Cancer 2021 Apr 13;21(1):401. Epub 2021 Apr 13.

Department of Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin, 300060, China.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system and has high morbidity and mortality rates. It is essential to search new biomarkers to improve the accuracy of early HCC diagnosis. Therefore, we evaluated the diagnostic value of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) as a potential biomarker that complements α-fetoprotein (AFP) in HCC by detecting the serum PIVKA-II levels.

Methods: Serum PIVKA-II levels were compared in 168 HCC patients, 150 benign liver disease patients and 153 healthy controls to investigate the PIVKA-II potential to be a HCC biomarker. Receiver operating characteristic curve (ROC) analysis was used to evaluate the value of PIVKA-II in the diagnosis of HCC and its complementary role of AFP. The correlation between serum PIVKA-II levels and clinicopathological characteristics was analyzed to study the value of PIVKA-II in assessing HCC progression and prognosis. Finally, the ability of PIVKA-II in assessing the surgical treatment effects of HCC was studied by comparing the pre- and post-operative serum PIVKA-II levels in 89 HCC patients.

Results: Serum PIVKA-II levels in HCC patients were significantly higher than that in patients with benign liver disease and healthy controls. The PIVKA-II performance in the diagnosing HCC as an individual biomarker was remarkable. The combined detection of PIVKA-II and AFP improved the diagnostic efficiency of HCC. PIVKA-II retained significant diagnosis capabilities for AFP-negative HCC patients. Significant correlations were found between PIVKA-II expression levels and some clinicopathological characteristics, including tumor size, tumor stage, tumor metastasis, differentiation degree and complications. PIVKA-II expression obviously decreased after surgical resection.

Conclusions: PIVKA-II is a promising serum biomarker for the HCC diagnosis that can be used as a supplement for AFP. The combined diagnosis of the two markers greatly improved the diagnostic efficiency of HCC. The PIVKA-II levels in HCC patients were widely associated with clinicopathological characteristics representing tumor cell dissemination and/or poor prognosis. PIVKA-II can be used to evaluate the curative effects of HCC resection.
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http://dx.doi.org/10.1186/s12885-021-08138-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045263PMC
April 2021

Dynamic estimation of epidemiological parameters of COVID-19 outbreak and effects of interventions on its spread.

J Public Health Res 2021 Mar 10;10(1). Epub 2021 Mar 10.

Institute for Financial Services Analytics Lerner College of Business and Economics, University of Delaware, Newark, DE.

Background: A key challenge in estimating epidemiological parameters for a pandemic such as the initial COVID-19 outbreak in Wuhan is the discrepancy between the officially reported number of infections and the true number of infections. A common approach to tackling the challenge is to use the number of infections exported from the originating city to infer the true number. This approach can only provide a static estimate of the epidemiological parameters before city lockdown because there are almost no exported cases thereafter.

Methods: We propose a Bayesian estimation method that dynamically estimates the epidemiological parameters by recovering true numbers of infections from day-to-day official numbers. To illustrate the use of this method, we provide a comprehensive retrospection on how the COVID-19 had progressed in Wuhan from January 19 to March 5, 2020. Particularly, we estimate that the outbreak sizes by January 23 and March 5 were 11,239 [95% CI 4,794-22,372] and 124,506 [95% CI 69,526-265,113], respectively.

Results: The effective reproduction number attained its maximum on January 24 (3.42 [95% CI 3.34-3.50]) and became less than 1 from February 7 (0.76 [95% CI 0.65-0.92]). We also estimate the effects of two major government interventions on the spread of COVID-19 in Wuhan.

Conclusions: This case study by our proposed method affirms the believed importance and effectiveness of imposing tight non-essential travel restrictions and affirm the importance and effectiveness of government interventions (e.g., transportation suspension and large scale hospitalization) for effective mitigation of COVID-19 community spread.
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http://dx.doi.org/10.4081/jphr.2021.1906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967497PMC
March 2021
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