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1.
J Magn Reson Imaging ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38655903

ABSTRACT

BACKGROUND: MRI-based placental analyses have been used to improve fetal growth restriction (FGR) assessment by complementing ultrasound-based measurements. However, these are still limited by time-consuming manual annotation in MRI data and the lack of mother-based information. PURPOSE: To develop and validate a hybrid model for accurate FGR assessment by automatic placental radiomics on T2-weighted imaging (T2WI) and multifeature fusion. STUDY TYPE: Retrospective. POPULATION: 274 pregnant women (29.5 ± $$ \pm $$ 4.0 years) from two centers were included and randomly divided into training (N = 119), internal test (N = 40), time-independent validation (N = 43), and external validation (N = 72) sets. FIELD STRENGTH/SEQUENCE: 1.5-T, T2WI half-Fourier acquisition single-shot turbo spin-echo pulse sequence. ASSESSMENT: First, the placentas on T2WI were manually annotated, and a deep learning model was developed to automatically segment the placentas. Then, the radiomic features were extracted from the placentas and selected by three-step feature selection. In addition, fetus-based measurement features and mother-based clinical features were obtained from ultrasound examinations and medical records, respectively. Finally, a hybrid model based on random forest was constructed by fusing these features, and further compared with models based on other machine learning methods and different feature combinations. STATISTICAL TESTS: The performances of placenta segmentation and FGR assessment were evaluated by Dice similarity coefficient (DSC) and the area under the receiver operating characteristic curve (AUROC), respectively. A P-value <0.05 was considered statistically significant. RESULTS: The placentas were automatically segmented with an average DSC of 90.0%. The hybrid model achieved an AUROC of 0.923, 0.931, and 0.880 on the internal test, time-independent validation, and external validation sets, respectively. The mother-based clinical features resulted in significant performance improvements for FGR assessment. DATA CONCLUSION: The proposed hybrid model may be able to assess FGR with high accuracy. Furthermore, information complementation based on placental, fetal, and maternal features could also lead to better FGR assessment performance. TECHNICAL EFFICACY: Stage 2.

2.
Anticancer Drugs ; 35(1): 46-54, 2024 01 01.
Article in English | MEDLINE | ID: mdl-37449977

ABSTRACT

Protein degraders are currently under rapid development as a promising modality for drug discovery. They are compounds that orchestrate interactions between a target protein and an E3 ubiquitin ligase, prompting intracellular protein degradation through proteasomal pathway. More protein degraders identification will greatly promote the development of this field. BAG3 is widely recognized as an excellent therapeutic target in cancer treatments. Exploring protein degraders that target BAG3 degradation has profound implications. Herein, molecular docking was applied to assess binding energy between 81 clinical phase I kinase inhibitors and BAG3. BAG3 protein and mRNA level were detected by western blot and quantitative real-time PCR. CCK8 assay and colony formation assay were applied to detect the cell viability and proliferation rate. Cell death was accessed using flow cytometry combined with PI and Annexin V double staining. AZD7762, a Chk1 kinase inhibitor, was identified to induce BAG3 degradation in a ubiquitin-proteasome pathway. AZD7762-induced BAG3 degradation was not dependent on Chk1 expression or activity. CRBN, an E3 ligase, was identified to bind to BAG3 and mediated BAG3 ubiquitination in the presence of AZD7762. By targeting Chk1 and BAG3, two ideal therapeutic targets in cancer treatment, AZD7762 would be a powerful chemotherapy agent in the future.


Subject(s)
Proteasome Endopeptidase Complex , Ubiquitin-Protein Ligases , Humans , Proteasome Endopeptidase Complex/metabolism , Cell Line, Tumor , Molecular Docking Simulation , Ubiquitin-Protein Ligases/metabolism , Ubiquitins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Apoptosis Regulatory Proteins/metabolism
3.
BMC Psychiatry ; 24(1): 313, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658896

ABSTRACT

BACKGROUND: Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients. METHODS: The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands. RESULTS: Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups. CONCLUSIONS: Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.


Subject(s)
Depressive Disorder, Major , Magnetic Resonance Imaging , Schizophrenia , Humans , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/diagnostic imaging , Male , Female , Adult , Schizophrenia/physiopathology , Schizophrenia/diagnostic imaging , Schizophrenia/complications , Cognition/physiology , Brain/physiopathology , Brain/diagnostic imaging , Neuropsychological Tests/statistics & numerical data , Middle Aged , Young Adult , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnostic imaging
4.
Ann Hum Genet ; 87(5): 232-240, 2023 09.
Article in English | MEDLINE | ID: mdl-37337755

ABSTRACT

BACKGROUND: X chromosomeshort tandem repeat (X-STR) loci are playing an increasingly important role inforensic work, identifying female traces in male contamination and explainingcomplex kinship analyses. METHODS: In this study, we analyzed thegenetic polymorphism of 19 X-STR loci in the Guangdong Hakka, Teochew and Cantonese groups, respectively, aswell as in the Guangdong Hakka, Teochew andCantonese pooled Han. The genetic diversity and forensic characteristics of the19 X-STRs and 7 linkage groups were investigated, respectively. RESULTS: The experiments showed that the genetic diversity (GD) and polymorphism information content (PIC) in the pooledGuangdong Han ranged from 0.5320 to 0.9234 and 0.4369 to 0.9171, respectively, and the cumulative power of discrimination for males (PDM), power of discrimination for females (PDF) and mean paternity exclusion chance (MEC) were higher than 0.9999999, indicating that the 19 X-STRs had high geneticpolymorphism and discriminatory power. Genetic differences among Chinese Hansubgroups and among different Chinese populations were investigated byphylogenetic reconstruction and principal component analysis (PCA), respectively. Genetic analyses based on neighbor-joining (NJ) tree and principal component analysis plot showed that Cantonese, Teochew and Hakka were closely genetically related, and different populations with closer linguistic components had more genetic affinity. CONCLUSIONS: This study adds to the forensic X-STR database and demonstrates the forensic efficiency of 19 X-STRs for the Hakka, Teochewand Cantonese populations in Guangdong, and the pooled Han of Hakka, Teochewand Cantonese people in Guangdong.


Subject(s)
Chromosomes, Human, X , Microsatellite Repeats , Polymorphism, Genetic , Female , Humans , Male , Asian People/genetics , China , Gene Frequency , Genetics, Population , Principal Component Analysis , Chromosomes, Human, X/genetics
5.
Clin Sci (Lond) ; 137(3): 265-279, 2023 02 14.
Article in English | MEDLINE | ID: mdl-36645190

ABSTRACT

Pre-eclampsia (PE) is a major hypertensive disorder of pregnancy. Widespread differentially methylated cytosines (DMCs) with modest changes in methylation level are associated with PE, whereas their cause and biological significance remain unknown. We aimed to clarify DNA methylation patterns around DMCs in 103 placentas using MethylCap targeted bisulfite re-sequencing (MethylCap-seq) assays of 690 selected DMCs. We verified the MethylCap-seq method, then validated 677 (98.1%) of DMCs (vDMCs) in an independent cohort. The validated DMCs were strongly enriched in active placenta-specific enhancers and showed highly dynamic methylation levels. We found high epigenetic heterogeneity between vDMCs and adjacent CpG sites (r2 < 0.2) and a significant decrease in PE in the discovery and replication cohorts (P = 2.00 × 10-24 and 6.43 × 10-9, respectively). We replicated the methylation changes in a hypoxia/reoxygenation cell model. We constructed 112 methylation haplotype blocks and found that the frequencies of unmethylated haplotypes (UMHs) were dynamic with gestational age (GA) and were altered in maternal plasma of patients with PE. Our results uncovered additional DNA methylation features in PE placentas and suggested a model of skewed DNA methylation balance of enhancers in PE.


Subject(s)
DNA Methylation , Pre-Eclampsia , Pregnancy , Female , Humans , Pre-Eclampsia/genetics , Sulfites , Promoter Regions, Genetic , CpG Islands/genetics
6.
BMC Musculoskelet Disord ; 24(1): 477, 2023 Jun 10.
Article in English | MEDLINE | ID: mdl-37301961

ABSTRACT

BACKGROUND: Multiple carpometacarpal fractures and dislocations are rare. This case report describes a novel multiple carpometacarpal injury, namely, 'diagonal' carpometacarpal joint fracture and dislocation. CASE PRESENTATION: A 39-year-old male general worker sustained a compression injury to his right hand in the dorsiflexion position. Radiography indicated a Bennett fracture, hamate fracture, and fracture at the base of the second metacarpal. Subsequent computed tomography and intraoperative examination confirmed an injury to the first to fourth carpometacarpal joint along a diagonal line. The normal anatomy of the patient's hand was successfully restored via open reduction combined with Kirschner wire and steel plate fixation. CONCLUSION: Our findings highlight the importance of taking the injury mechanism into account to avoid a missed diagnosis and to choose the best treatment approach. This is the first case of 'diagonal' carpometacarpal joint fracture and dislocation to be reported in the literature.


Subject(s)
Carpometacarpal Joints , Fractures, Bone , Fractures, Multiple , Hand Injuries , Joint Dislocations , Multiple Trauma , Wrist Injuries , Male , Humans , Adult , Carpometacarpal Joints/diagnostic imaging , Carpometacarpal Joints/surgery , Fractures, Bone/complications , Fractures, Bone/diagnostic imaging , Joint Dislocations/complications , Joint Dislocations/diagnostic imaging , Hand Injuries/surgery
7.
Water Sci Technol ; 88(9): 2264-2270, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37966181

ABSTRACT

A highly hydrophobic metal mesh has great potential for its application in oil/water separation due to its special wettability. However, most current oil/water separation devices are simple with limited separation capacity. A separation device based on a highly hydrophobic metal mesh was constructed for different types of oil/water mixtures. Experimental results show that the device not only can be used for the continuous separation of binary oil/water mixtures of any density ratios but also can realize the simultaneous separation of heavy oil/water/light oil ternary mixtures. This achievement is meaningful for practical applications, which will gain great interest in the future.


Subject(s)
Metals , Oils , Oils/chemistry , Hydrophobic and Hydrophilic Interactions , Wettability
8.
Fa Yi Xue Za Zhi ; 39(4): 373-381, 2023 Aug 25.
Article in English, Zh | MEDLINE | ID: mdl-37859476

ABSTRACT

OBJECTIVES: To explore the potential biomarkers for the diagnosis of primary brain stem injury (PBSI) by using metabonomics method to observe the changes of metabolites in rats with PBSI caused death. METHODS: PBSI, non-brain stem brain injury and decapitation rat models were established, and metabolic maps of brain stem were obtained by LC-MS metabonomics method and annotated to the HMDB database. Partial least square-discriminant analysis (PLS-DA) and random forest methods were used to screen potential biomarkers associated with PBSI diagnosis. RESULTS: Eighty-six potential metabolic markers associated with PBSI were screened by PLS-DA. They were modeled and predicted by random forest algorithm with an accuracy rate of 83.3%. The 818 metabolic markers annotated to HMDB database were used for random forest modeling and prediction, and the accuracy rate was 88.9%. According to the importance in the identification of cause of death, the most important metabolic markers that were significantly up-regulated in PBSI group were HMDB0038126 (genipinic acid, GA), HMDB0013272 (N-lauroylglycine), HMDB0005199 [(R)-salsolinol] and HMDB0013645 (N,N-dimethylsphingosine). CONCLUSIONS: GA, N-lauroylglycine, (R)-salsolinol and N,N-dimethylsphingosine are expected to be important metabolite indicators in the diagnosis of PBSI caused death, thus providing clues for forensic medicine practice.


Subject(s)
Brain Injuries , Metabolomics , Rats , Animals , Metabolomics/methods , Biomarkers/metabolism , Brain Stem/metabolism
9.
J Cell Physiol ; 237(7): 3080-3094, 2022 07.
Article in English | MEDLINE | ID: mdl-35579960

ABSTRACT

Intrahepatic cholestasis of pregnancy (ICP) is a common pregnancy-specific disease, characterized by increased bile acid levels and adverse fetal outcomes. We previously reported excessive bile acids led to dysfunction of placental trophoblasts in ICP. However, the detailed mechanism is still unclear. Autophagy is fundamental process for protecting cell survival against adverse conditions. Here, we evaluated the effect of increased concentration of bile acids on autophagy in trophoblasts in vitro and in vivo. First, we demonstrated that the autophagy substrate p62/sequestosome-1 was accumulated in placental tissues from patients with ICP and in human trophoblasts treated with hydrophobic bile acids, including chenodeoxycholic acid and deoxycholic acid. Furthermore, we found that treatment with hydrophobic bile acids impaired autophagic flux in both time- and concentration-dependent manners, by suppressing the AMP-activated protein kinase/unc-51-like kinase 1 autophagic signaling pathway. Notably, trophoblasts were prone to apoptotic cell death upon starvation along with bile-acids treatment in vitro or in an ICP mouse model in vivo. Additionally, we revealed mitochondrial dysfunction was the predominant biological process in excessive bile acids induced trophoblast impairment under starvation by proteomic assay. Collectively, our study proposed a complex interaction of excessive bile acids induced autophagic flux, mitochondrial dysfunction, and cellular apoptosis in placental trophoblasts may play a critical role in the pathogenesis of ICP.


Subject(s)
Placenta , Trophoblasts , Animals , Apoptosis , Autophagy , Bile Acids and Salts/pharmacology , Cholestasis, Intrahepatic , Female , Humans , Mice , Mitochondria , Placenta/metabolism , Pregnancy , Pregnancy Complications , Proteomics , Trophoblasts/metabolism
10.
BMC Psychiatry ; 22(1): 654, 2022 10 21.
Article in English | MEDLINE | ID: mdl-36271368

ABSTRACT

BACKGROUND: Bipolar disorder (BD) and schizophrenia (SC) have many similarities in clinical manifestations. The acute phase of BD has psychotic symptoms, while SC also has emotional symptoms during the onset, which suggests that there is some uncertainty in distinguishing BD and SC through clinical symptoms. AIM: To explore the characteristics of brain functional activities and cognitive impairment between BD and SC. METHODS: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test was performed on patients in drug-naïve BD and SC (50 subjects in each group), and resting-state functional magnetic resonance imaging (rs-fMRI) scanning was performed meanwhile. Rs-fMRI data were routinely preprocessed, and the value of the fractional amplitude of low-frequency fluctuation (fALFF) was calculated. Then each part of the scores of the RBANS and the characteristics of brain function activities were compared between the two groups. Finally used Pearson correlation to analyze the correlation between cognition and brain function. RESULTS: (1) Compared with BD group, all parts of RBANS scores in SC group decreased; (2) The left inferior occipital gyrus (IOG, peak coordinates - 30, -87, -15; t = 4.78, voxel size = 31, Alphasim correction) and the right superior temporal gyrus (STG, peak coordinates 51, -12, 0; t = 5.08, voxel size = 17, AlphaSim correction) were the brain areas with significant difference in fALFF values between BD and SC. Compared with SC group, the fALFF values of the left IOG and the right STG in BD group were increased (p < 0.05); (3) Pearson correlation analysis showed that the visuospatial construction score was positively correlated with the fALFF values of the left IOG and the right STG (rleft IOG = 0.304, p = 0.003; rright STG = 0.340, p = 0.001); The delayed memory (figure recall) score was positively correlated with the fALFF value of the left IOG (rleft IOG = 0.207, p = 0.044). DISCUSSION: The cognitive impairment of SC was more serious than BD. The abnormal activities of the left IOG and the right STG may be the core brain region to distinguish BD and SC, and are closely related to cognitive impairment, which provide neuroimaging basis for clinical differential diagnosis and explore the pathological mechanism of cognitive impairment.


Subject(s)
Bipolar Disorder , Schizophrenia , Humans , Magnetic Resonance Imaging/methods , Bipolar Disorder/diagnostic imaging , Schizophrenia/diagnostic imaging , Rest , Cognition
11.
BMC Pulm Med ; 22(1): 474, 2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36514015

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, with complex etiology, difficult treatment and poor prognosis. The objective of this study was to investigate the potential biomarkers for PAH based on bioinformatics analysis. METHODS: The GSE117261 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by screening PAH patients and controls. Then the DEGs were analyzed using a Weighted Gene Co-expression Network Analysis (WGCNA) and the key modules were determined, and to further explore their potential biological functions via Gene Ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes Pathway analysis (KEGG), and Gene Set Enrichment Analysis (GSEA). Moreover, Protein-protein interaction (PPI) networks were constructed to identify hub gene candidates in the key modules. Finally, real-time quantitative polymerase chain reaction was supplied to detect the expressions of hub genes in human pulmonary arterial smooth cells treated with cobalt chloride (COCl2) which was used to mimic hypoxia. RESULTS: There were 2299 DEGs identified. WGCNA indicated that yellow module was the key one correlated with PAH. GO and KEGG analysis demonstrated that genes in the yellow module were mainly enriched in 'Pathways in cancer'. GSEA revealed that 'HALLMARK_MYC_TARGETS_V1' was remarkably enriched in PAH. Based on the PPI network, vascular endothelial growth factor A, proto-oncogene receptor tyrosine kinase (KIT), PNN interacting serine and arginine rich protein (PNISR) and heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) were identified as the hub genes. Additionally, the PCR indicated that the elevated expressions of PNISR and HNRNPH1 were in line with the bioinformatics analysis. ROC analysis determined that PNISR and HNRNPH1 may be potential biomarkers to provide better diagnosis of PAH. CONCLUSION: PNISR and HNRNPH1 were potential biomarkers to diagnosis PAH. In summary, the identified DEGs, modules, pathways, and hub genes provide clues and shed light on the potential molecular mechanisms of PAH.


Subject(s)
Gene Regulatory Networks , Pulmonary Arterial Hypertension , Humans , Biomarkers , Gene Expression Profiling , Pulmonary Arterial Hypertension/genetics
12.
Sensors (Basel) ; 22(5)2022 Feb 25.
Article in English | MEDLINE | ID: mdl-35270973

ABSTRACT

The application of agricultural robots can liberate labor. The improvement of robot sensing systems is the premise of making it work. At present, more research is being conducted on weeding and harvesting systems of field robot, but less research is being conducted on crop disease and insect pest perception, nutritional element diagnosis and precision fertilizer spraying systems. In this study, the effects of the nitrogen application rate on the absorption and accumulation of nitrogen, phosphorus and potassium in sweet maize were determined. Firstly, linear, parabolic, exponential and logarithmic diagnostic models of nitrogen, phosphorus and potassium contents were constructed by spectral characteristic variables. Secondly, the partial least squares regression and neural network nonlinear diagnosis model of nitrogen, phosphorus and potassium contents were constructed by the high-frequency wavelet sensitivity coefficient of binary wavelet decomposition. The results show that the neural network nonlinear diagnosis model of nitrogen, phosphorus and potassium content based on the high-frequency wavelet sensitivity coefficient of binary wavelet decomposition is better. The R2, MRE and NRMSE of nn of nitrogen, phosphorus and potassium were 0.974, 1.65% and 0.0198; 0.969, 9.02% and 0.1041; and 0.821, 2.16% and 0.0301, respectively. The model can provide growth monitoring for sweet corn and a perception model for the nutrient element perception system of an agricultural robot, while making preliminary preparations for the realization of intelligent and accurate field fertilization.


Subject(s)
Robotics , Agriculture/methods , Algorithms , Fertilizers , Phosphorus
13.
Int J Environ Health Res ; 32(11): 2460-2470, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34496690

ABSTRACT

We tested the hypothesis of whether maternal residential proximity to municipal solid waste incinerator (MSWI) sites could significantly affect birth outcomes. This retrospective birth cohort study conducted at the International Peace Maternity and Infant Hospital, Shanghai, China, included 59,606 mothers with singleton live births during 2014-2018. Multivariate generalized linear models were used to examine associations between residential proximity to MSWI sites and birth outcomes. Small for gestational age (SGA) was significantly more common among children with maternal residential proximity to MSWI sites (odds ratio [OR]=1.20, 95% confidence interval [CI]: 1.07-1.34). Maternal prepregnancy body mass index (BMI) influenced this association. Infants of underweight mothers (prepregnancy BMI <18.5 kg/m2) with MSWI exposure (OR=2.00, 95% CI: 1.58-2.52) had higher risks of SGA than their counterparts. Our findings underscore the need to prevent adverse environmental effects of MSWI on birth outcomes; improved exposure assessment measures are warranted in future studies.


Subject(s)
Incineration , Solid Waste , Child , China/epidemiology , Cohort Studies , Female , Humans , Infant , Pregnancy , Retrospective Studies
14.
Entropy (Basel) ; 24(5)2022 May 06.
Article in English | MEDLINE | ID: mdl-35626539

ABSTRACT

The performance evaluation and optimization of an energy conversion system design of an energy intensive drying system applied the method of combining exergy and economy is a theme of global concern. In this study, a gas-type industrial drying system of black tea with a capacity of 100 kg/h is used to investigate the exergetic and economic performance through the exergy and exergoeconomic methodology. The result shows that the drying rate of tea varies from the maximum value of 3.48 gwater/gdry matter h to the minimum 0.18 gwater/gdry matter h. The highest exergy destruction rate is found for the drying chamber (74.92 kW), followed by the combustion chamber (20.42 kW) in the initial drying system, and 51.83 kW and 21.15 kW in the redrying system. Similarly, the highest cost of the exergy destruction rate is found for the drying chamber (18.497 USD/h), followed by the combustion chamber (5.041 USD/h) in the initial drying system, and 12.796 USD/h and 5.222 USD/h in the redrying system. Furthermore, we analyzed the unit exergy rate consumed and the unit exergy cost of water removal in different drying sections of the drying system, and determined the optimal ordering of each component. These results mentioned above indicate that, whether from an energy or economic perspective, the component improvements should prioritize the drying chamber. Accordingly, minimizing exergy destruction and the cost of the exergy destruction rate can be considered as a strategy for improving the performance of energy and economy. Overall, the main results provide a more intuitive judgment for system improvement and optimization, and the exergy and exergoeconomic methodology can be commended as a method for agricultural product industrial drying from the perspective of exergoeconomics.

15.
Electrophoresis ; 42(16): 1578-1593, 2021 08.
Article in English | MEDLINE | ID: mdl-34018209

ABSTRACT

The Y-STR landscape of Coastal Southeastern Han (CSEH) living in Chinese southeast areas (including Guangdong, Fujian, and Zhejiang provinces) is still unclear. We investigated 62 Y-STR markers in a reasonably large number of 1021 unrelated males and 1027 DNA-confirmed father-son pairs to broaden the genetic backgrounds of CSEH. In total, 85 null alleles, 121 off-ladder alleles, and 95 copy number variants were observed, and 1012 distinct haplotypes were determined with the overall HD and DC values of 0.999974 and 0.9912. We observed 369 mutations in 76 099 meiotic transfers, and the average estimated Y-STR mutation rate was 4.85 × 10-3 (95% CI, 4.4 × 10-3 -5.4 × 10-3 ). The Spearman correlation analyses indicated that GD values (R2 = 0.6548) and average allele sizes (R2 = 0.5989) have positive correlations with Y-STR mutation rates. Our RM Y-STR set including 8 candidate RM Y-STRs, of which DYS534, DYS630, and DYS713 are new candidates in CSEH, distinguished 18.52% of father-son pairs. This study also clarified the population structures of CSEH which isolated in population-mixed South China relatively. The strategy, SM Y-STRs for familial searching and RM Y-STRs for individual identification regionally, could be applicable based on enough knowledge of the Y-STR mutability of different populations.


Subject(s)
Mutation Rate , China , Chromosomes, Human, Y/genetics , Forensic Genetics , Genetics, Population , Haplotypes , Humans , Male , Microsatellite Repeats/genetics , Mutation
16.
Int J Legal Med ; 135(2): 443-444, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32030456

ABSTRACT

The genetic polymorphism of 17 autosomal short tandem repeat (STR) loci included in the PowerPlex® 18D System was evaluated from 638 unrelated healthy Han individuals of Meizhou in Guangdong Province, Southern China. The values of combined power of discrimination (CPD) and the combined probability of exclusion (CPE) were observed as 0.999999999999999 and 0.999999933. Penta E showed the highest values of polymorphism information content (0.9073), expected heterozygosity (0.9147), and observed heterozygosity (0.9373), whereas TPOX showed the lowest (0.5373, 0.6035, and 0.6082). Furthermore, both of the PCA plot and neighbor-joining phylogenetic tree showed that the Meizhou Hakka population has a relatively close genetic relationship with the Guangdong Han population. The results showed that most of these 17 autosomal STR loci were highly informative and can be effective for forensic individual identification and paternity testing in Meizhou Hakka population.


Subject(s)
Asian People/genetics , Ethnicity/genetics , Genetic Variation , Microsatellite Repeats , Polymorphism, Genetic , China/ethnology , Humans
17.
Bioorg Chem ; 114: 105026, 2021 09.
Article in English | MEDLINE | ID: mdl-34186467

ABSTRACT

In this work, two series of cyclic amine-containing benzimidazole carboxamide derivatives were designed and synthesized as potent anticancer agents. PARP1/2 inhibitory activity assays indicated that most of the compounds showed significant activity. The in vitro antiproliferative activity of these compounds was investigated against four human cancer cell lines (MDA-MB-436, MDA-MB-231, MCF-7 and CAPAN-1), and several compounds exhibited strong cytotoxicity to tumor cells. Among them, 2-(1-(4,4-difluorocyclohexyl)piperidin-4-yl)-1H-benzo[d]imidazole-4-carboxamide (17d) was found to be effective PARP1/2 inhibitors (IC50 = 4.30 and 1.58 nM, respectively). In addition, 17d possessed obvious selective antineoplastic activity and noteworthy microsomal metabolic stability. What's more, further studies revealed that 17d was endowed with an excellent ADME profile. These combined results indicated that 17d could be a promising candidate for the treatment of cancer.


Subject(s)
Antineoplastic Agents/pharmacology , Benzimidazoles/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacokinetics , Benzimidazoles/chemical synthesis , Benzimidazoles/metabolism , Benzimidazoles/pharmacokinetics , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Male , Microsomes, Liver/metabolism , Molecular Docking Simulation , Molecular Dynamics Simulation , Poly (ADP-Ribose) Polymerase-1/metabolism , Poly(ADP-ribose) Polymerase Inhibitors/chemical synthesis , Poly(ADP-ribose) Polymerase Inhibitors/metabolism , Poly(ADP-ribose) Polymerase Inhibitors/pharmacokinetics , Poly(ADP-ribose) Polymerases/metabolism , Rats, Sprague-Dawley
18.
Sensors (Basel) ; 21(21)2021 Oct 23.
Article in English | MEDLINE | ID: mdl-34770329

ABSTRACT

Laser-induced graphene (LIG) has been widely used in flexible sensors due to its excellent mechanical properties and high conductivity. In this paper, a flexible pressure sensor prepared by bionic micro/nanostructure design and LIG mass fraction regulation is reported. First, prepared LIG and conductive carbon paste (CCP) solutions were mixed to obtain a conductive polymer. After the taro leaf structure was etched on the surface of the aluminum alloy plate by Nd:YAG laser processing, the conductive polymer was evenly coated on the template. Pressure sensors were packaged with a stencil transfer printing combined with an Ecoflex flexible substrate. Finally, the effects of different laser flux and the proportion of LIG in the composite on the sensitivity of the sensor are discussed. The results show that when the laser flux is 71.66 J·cm-2 and the mass fraction of LIG is 5%, the sensor has the best response characteristics, with a response time and a recovery time of 86 ms and 101 ms, respectively, with a sensitivity of 1.2 kPa-1 over a pressure range of 0-6 kPa, and stability of 650 cycle tests. The LIG/CCP sensor with a bionic structure demonstrates its potential in wearable devices.


Subject(s)
Graphite , Nanostructures , Wearable Electronic Devices , Electric Conductivity , Lasers
19.
J Cell Physiol ; 235(12): 9538-9556, 2020 12.
Article in English | MEDLINE | ID: mdl-32529639

ABSTRACT

Despite the high prevalence of varicose veins, the underlying pathogenesis of this disease remains unclear. The present study aims to explore the role of insulin-like growth factor binding protein 6 (IGFBP6) in vascular smooth muscle cells (VSMCs). Using a protein array approach, we identified several differentially expressed proteins between varicose great saphenous veins and normal great saphenous veins. Bioinformatic analysis showed that IGFBP6 was closely related to cell proliferation. Further validation confirmed that IGFBP6 was one of the most highly expressed proteins in varicose vein tissue. Knocking down IGFBP6 in VSMCs significantly attenuated cell proliferation and induced the S phase arrest during the cell cycle. Further experiments demonstrated that IGFBP6 knockdown increased cyclin E ubiquitination, which reduced expression of cyclin E and phosphorylation of CDK2. Furthermore, IGFBP6 knockdown arrested centrosome replication, which subsequently influenced VSMC morphology. Ultimately, IGFBP6 was validated to be involved in VSMC proliferation in varicose vein tissues. The present study reveals that IGFBP6 is closely correlated with VSMC biological function and provides unprecedented insights into the underlying pathogenesis of varicose veins.


Subject(s)
Cyclin E/genetics , Cyclin-Dependent Kinase 2/genetics , Insulin-Like Growth Factor Binding Proteins/genetics , Proteome/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation/genetics , Gene Knockdown Techniques , Humans , Male , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Protein Array Analysis , Saphenous Vein/metabolism , Varicose Veins/metabolism , Varicose Veins/pathology
20.
J Cell Physiol ; 235(3): 3043-3055, 2020 03.
Article in English | MEDLINE | ID: mdl-31544245

ABSTRACT

Esophageal cancer (EC) is the world's eighth most common malignant neoplasm and is ranked as the sixth leading cause of death related to cancer. Aberrant microRNA (miRNA) expression has been reported to be associated with esophageal squamous cell carcinoma. However, the molecular mechanism of miR-204-5p in esophageal squamous cell carcinoma (ESCC) is not clear. Therefore, the aim of this study was to investigate the potential role of miR-204-5p in ESCC. In the present study, we found that miR-204-5p could affect ESCC proliferation, invasion, apoptosis, and cell cycle in cell and mouse models. A dual-luciferase reporter assay showed that miR-204-5p expression was negatively correlated with interleukin-11 (IL-11) expression. IL-11 overexpression reversed the suppressive effects of miR-204-5p in the cell lines. These results indicated that miR-204-5p functions as a tumor suppressor by directly targeting IL-11 in ESCC.


Subject(s)
Apoptosis/genetics , Cell Proliferation/genetics , Esophageal Squamous Cell Carcinoma/genetics , Interleukin-11/metabolism , MicroRNAs/genetics , Cell Proliferation/physiology , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Squamous Cell Carcinoma/pathology , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Humans , Interleukin-11/genetics , Mouth Neoplasms/genetics , Neoplasm Invasiveness/genetics , Squamous Cell Carcinoma of Head and Neck/genetics
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