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The genetic identification of skeletal remains from Chinese People's Volunteers (CPVs) of the Korean War has been challenging because of the degraded DNA samples and the lack of living close relatives. This study established a workflow for identifying CPVs by combining Y-chromosome short tandem repeats (Y-STRs), mitochondrial DNA (mtDNA) hypervariable regions I and II, autosomal STRs (aSTRs), and identity-informative SNPs (iiSNPs). A total of 20 skeletal remains of CPVs and 46 samples from their alleged relatives were collected. The success rate of DNA extraction from human remains was 100%. Based on Y-STRs, six remains shared the same male lineages with their alleged relatives. Meanwhile, mtDNA genotyping supports two remains sharing the same maternal lineages with their alleged relatives. Likelihood ratios (LRs) were further obtained from 27 aSTRs and 94 iiSNPs or 1936 iiSNPs to confirm their relationship. All joint pedigree LRs were >100. Finally, six remains were successfully identified. This pilot study for the systematic genetic identification of CPVs from the Korean War can be applied for the large-scale identification of CPVs in the future.
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The abuse of illicit drugs poses serious threats to the physical and mental health of users, as well as to the overall safety and welfare of society. In this work, we present a newly developed technique for drug detection based on mass spectrometry. This technique combines Leidenfrost desorption with low-temperature arc plasma ionization mass spectrometry. This method is applicable for detecting furanyl fentanyl in complex matrices. Key advantages of this technique include minimal sample fragmentation and high sensitivity for detection. The Leidenfrost desorption plays a pivotal role in this methodology, as it spontaneously concentrates analyte molecules during the gradual evaporation of the solvent. Eventually, these concentrated molecules are redistributed at their highest concentrations, resulting in exceptionally high sensitivity. In the course of our investigation, we achieved a remarkable detection limit of 10 pg mL-1 for furanyl fentanyl in pure water. Moreover, the characteristic ion peaks of furanyl fentanyl can be distinctly identified within complex matrices such as wine, beverages, urine, and lake water. This innovative drug detection technology offers several advantages, including a simple setup, cost-effectiveness, rapid detection, high sensitivity, and minimal sample pretreatment.
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Fentanila , Fentanila/análogos & derivados , Furanos , Limite de Detecção , Fentanila/análise , Fentanila/urina , Humanos , Espectrometria de Massas/métodos , Drogas Ilícitas/análise , Detecção do Abuso de Substâncias/métodos , Lagos/análise , Lagos/químicaRESUMO
The ABO blood group plays an important role in blood transfusion, linkage analysis, individual identification, etc. Serologic methods of blood typing are gold standards for the time being, which require stable typing antisera and fresh blood samples and are labor intensive. At present, reliable determination of ABO blood group genotypes based on single-nucleotide polymorphisms (SNPs) among A, B, and O alleles remains necessary. Thus, in this work, CRISPR/Cas13a-mediated genotyping for the ABO blood group by detecting SNPs between different alleles was proposed. The ABO*O.01.01(c.261delG) allele (G for the A/B allele and del for the O allele) and ABO*B.01(c.796C > A) allele (C for the A/O allele and A for the B allele) were selected to determine the six genotypes (AA, AO, BB, BO, OO, and AB) of the ABO blood group. Multiplex PCR was adapted to simultaneously amplify the two loci. CRISPR/Cas13a was then used to specifically differentiate ABO*O.01.01(c.261delG) and ABO*B.01(c.796C > A) of A, B, and O alleles. Highly accurate determination of different genotypes was achieved with a limit of detection of 50 pg per reaction within 60 min. The reliability of this method was further validated based on its applicability in detecting buccal swab samples with six genotypes. The results were compared with those of serological and sequencing methods, with 100% accuracy. Thus, the CRISPR/Cas13a-mediated assay shows great application potential in the reliable identification of ABO blood group genotypes in a wide range of samples, eliminating the need to collect fresh blood samples in the traditional method.
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Sistema ABO de Grupos Sanguíneos , Polimorfismo de Nucleotídeo Único , Sistema ABO de Grupos Sanguíneos/genética , Reprodutibilidade dos Testes , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Genótipo , Reação em Cadeia da Polimerase MultiplexRESUMO
Environmentally persistent free radicals (EPFRs) can pose exposure risks by inducing the generation of reactive oxygen species. As a new class of pollutants, EPFRs have been frequently detected in atmospheric particulate matters. In this study, the seasonal variations and sources of EPFRs in a severe cold region in Northeastern China were comprehensively investigated, especially for the high pollution events. The geomean concentration of EPFRs in the total suspended particle was 6.58 × 1013 spins/m3 and the mean level in winter was one order of magnitude higher than summer and autumn. The correlation network analysis showed that EPFRs had significantly positive correlation with carbon component, K+ and PAHs, indicating that EPFRs were primarily emitted from combustion and pyrolysis process. The source appointment by the Positive Matrix Factorization (PMF) model indicated that the dominant sources in the heating season were coal combustion (48.4%), vehicle emission (23.1%) and biomass burning (19.4%), while the top three sources in the non-heating season were others (41.4%), coal combustion (23.7%) and vehicle emissions (21.2%). It was found that the high EPFRs in cold season can be ascribed to the extensive use of fossil fuel for heating demand; while the high EPFRs occurred in early spring were caused by the large-scale opening combustion of biomass. In summary, this study provided important basic information for better understanding the pollution characteristics of EPFRs, which suggested that the implementation of energy transformation and straw utilization was benefit for the control of EPFRs in severe cold region.
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Poluentes Atmosféricos , Carvão Mineral , Monitoramento Ambiental , Estações do Ano , Poluentes Atmosféricos/análise , Carvão Mineral/análise , China , Radicais Livres/análise , Biomassa , Material Particulado/análise , Cidades , Poluição do Ar/análiseRESUMO
In this paper, the responses of assembled behaviors of block polyelectrolytes (PEs) to the strength of electrostatic interactions are studied through molecular dynamic simulations. The results show that the assembled structures closely depend on the electrostatic strength. It should be noted that PE coacervation can outweigh the nucleation of hydrophobic blocks and invert the micelle structures at strong electrostatic strengths, leading to the formation of inverted micelles of PE cores and hydrophobic coronas. In the poor solvent condition for neutral block, diverse anisotropic micelles are presented; candy-like conventional micelles of hydrophobic cores and PE patches coexist with inverted candy-like micelles of PE cores and hydrophobic patches and with Janus micelles of semi-neutral aggregate and semi-PE cluster in the presence of divalent and trivalent counterions. The formation of conventional or inverted micelle is largely determined by the type of micellar fusion, which results from the nucleation competition between electrostatic correlation and hydrophobic interaction. The merge of micelles mediated by hydrophobic attraction leads to conventional hydrophobic cores, and the fusion induced by electrostatic correlations results in PE cores micelles. At strong electrostatic strengths, the PE chains exhibit rich conformations at trivalent counterions, ranging from a fully collapsed state to a rod-like state, and parallel alignment of PE chains is found.
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BACKGROUND: The attrition rate of Chinese medical students is high. This study utilizes a nomogram technique to develop a predictive model for dropout intention among Chinese medical undergraduates based on 19 individual and work-related characteristics. METHOD: A repeated cross-sectional study was conducted, enrolling 3536 medical undergraduates in T1 (August 2020-April 2021) and 969 participants in T2 (October 2022) through snowball sampling. Demographics (age, sex, study phase, income, relationship status, history of mental illness) and mental health factors (including depression, anxiety, stress, burnout, alcohol use disorder, sleepiness, quality of life, fatigue, history of suicidal attempts (SA), and somatic symptoms), as well as work-related variables (career choice regret and reasons, workplace violence experience, and overall satisfaction with the Chinese healthcare environment), were gathered via questionnaires. Data from T1 was split into a training cohort and an internal validation cohort, while T2 data served as an external validation cohort. The nomogram's performance was evaluated for discrimination, calibration, clinical applicability, and generalization using receiver operating characteristic curves (ROC), area under the curve (AUC), calibration curves, and decision curve analysis (DCA). RESULT: From 19 individual and work-related factors, five were identified as significant predictors for the construction of the nomogram: history of SA, career choice regret, experience of workplace violence, depressive symptoms, and burnout. The AUC values for the training, internal validation, and external validation cohorts were 0.762, 0.761, and 0.817, respectively. The nomogram demonstrated reliable prediction and discrimination, with adequate calibration and generalization across both the training and validation cohorts. CONCLUSION: This nomogram exhibits reasonable accuracy in foreseeing dropout intentions among Chinese medical undergraduates. It could guide colleges, hospitals, and policymakers in pinpointing students at risk, thus informing targeted interventions. Addressing underlying factors such as depressive symptoms, burnout, career choice regret, and workplace violence may help reduce the attrition of medical undergraduates. TRIAL REGISTRATION: This is an observational study. There is no Clinical Trial Number associated with this manuscript.
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Intenção , Nomogramas , Evasão Escolar , Estudantes de Medicina , Humanos , Masculino , Feminino , Estudos Transversais , China , Estudantes de Medicina/psicologia , Evasão Escolar/psicologia , Adulto Jovem , Escolha da Profissão , Adulto , Inquéritos e QuestionáriosRESUMO
Pharmaceutical compounds (PhCs) pose a growing concern with potential environmental impacts, commonly introduced into the environment via wastewater treatment plants (WWTPs). The occurrence, removal, and season variations of 60 different classes of PhCs were investigated in the baffled bioreactor (BBR) wastewater treatment process during summer and winter. The concentrations of 60 PhCs were 3400 ± 1600 ng/L in the influent, 2700 ± 930 ng/L in the effluent, and 2400 ± 120 ng/g dw in sludge. Valsartan (Val, 1800 ng/L) was the main contaminant found in the influent, declining to 520 ng/L in the effluent. The grit chamber and BBR tank were substantially conducive to the removal of VAL. Nonetheless, the BBR process showcased variable removal efficiencies across different PhC classes. Sulfadimidine had the highest removal efficiency of 87 ± 17% in the final effluent (water plus solid phase). Contrasting seasonal patterns were observed among PhC classes within BBR process units. The concentrations of many PhCs were higher in summer than in winter, while some macrolide antibiotics exhibited opposing seasonal fluctuations. A thorough mass balance analysis revealed quinolone and sulfonamide antibiotics were primarily eliminated through degradation and transformation in the BBR process. Conversely, 40.2 g/d of macrolide antibiotics was released to the natural aquatic environment via effluent discharge. Gastric acid and anticoagulants, as well as cardiovascular PhCs, primarily experienced removal through sludge adsorption. This study provides valuable insights into the intricate dynamics of PhCs in wastewater treatment, emphasizing the need for tailored strategies to effectively mitigate their release and potential environmental risks.
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Poluentes Químicos da Água , Purificação da Água , Águas Residuárias , Esgotos/análise , Eliminação de Resíduos Líquidos , Estações do Ano , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Antibacterianos/análise , Medição de Risco , Macrolídeos/análise , Preparações FarmacêuticasRESUMO
Dendrobium sinense, an endemic medicinal herb in Hainan Island, is rich in bibenzyl compounds. However, few studies have explored the molecular mechanisms of bibenzyl biosynthesis. This study presents a comprehensive analysis of DsBBS1 and DsBBS2 function in D. sinense. A molecular docking simulation revealed high-resolution three-dimensional structural models with minor domain orientation differences. Expression analyses of DsBBS1 and DsBBS2 across various tissues indicated a consistent pattern, with the highest expression being found in the roots, implying that they play a pivotal role in bibenzyl biosynthesis. Protein expression studies identified optimal conditions for DsBBS2-HisTag expression and purification, resulting in a soluble protein with a molecular weight of approximately 45 kDa. Enzyme activity assays confirmed DsBBS2's capacity to synthesize resveratrol, exhibiting higher Vmax and lower Km values than DsBBS1. Functional analyses in transgenic Arabidopsis demonstrated that both DsBBS1 and DsBBS2 could complement the Atchs mutant phenotype. The total flavonoid content in the DsBBS1 and DsBBS2 transgenic lines was restored to wild-type levels, while the total bibenzyl content increased. DsBBS1 and DsBBS2 are capable of catalyzing both bibenzyl and flavonoid biosynthesis in Arabidopsis. This study provides valuable insights into the molecular mechanisms underlying the biosynthesis of bibenzyl compounds in D. sinense.
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Bibenzilas , Dendrobium , Proteínas de Plantas , Dendrobium/genética , Dendrobium/metabolismo , Dendrobium/química , Bibenzilas/química , Bibenzilas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Simulação de Acoplamento Molecular , Regulação da Expressão Gênica de Plantas , Arabidopsis/genética , Arabidopsis/metabolismo , Plantas Geneticamente Modificadas , Flavonoides/biossíntese , Flavonoides/química , Flavonoides/metabolismoRESUMO
BACKGROUND: The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic variation and breakthrough infection is not well defined among persons with Delta variant SARS-CoV-2 infection. METHODS: In a retrospective cohort, we assessed whether individual nonlineage defining mutations and overall genomic variation (including low-frequency alleles) were associated with breakthrough infection, defined as SARS-CoV-2 infection after coronavirus disease 2019 primary vaccine series. We identified all nonsynonymous single-nucleotide polymorphisms, insertions, and deletions in SARS-CoV-2 genomes with ≥5% allelic frequency and population frequency of ≥5% and ≤95%. Using Poisson regression, we assessed the association with breakthrough infection for each individual mutation and a viral genomic risk score. RESULTS: Thirty-six mutations met our inclusion criteria. Among 12 744 persons infected with Delta variant SARS-CoV-2, 5949 (47%) were vaccinated and 6795 (53%) were unvaccinated. Viruses with a viral genomic risk score in the highest quintile were 9% more likely to be associated with breakthrough infection than viruses in the lowest quintile, but including the risk score improved overall predictive model performance (measured by C statistic) by only +0.0006. CONCLUSIONS: Genomic variation within SARS-CoV-2 Delta variant was weakly associated with breakthrough infection, but several potential nonlineage defining mutations were identified that might contribute to immune evasion by SARS-CoV-2.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Infecções Irruptivas , COVID-19/epidemiologia , Estudos Retrospectivos , Vacinas contra COVID-19 , California/epidemiologia , GenômicaRESUMO
Gastric cancer (GAS) is one of the malignant tumors of the gastrointestinal system. Alterations in metabolite composition can reflect pathological processes of GAS and constitute a basis for diagnosis and treatment improvements. In this study, a total of 301 serum samples from 150 GAS patients at different tumor-node-metastasis (TNM) stages and 151 healthy controls were collected. Mass spectrometry platforms were performed to investigate the changes in GAS-related metabolites and explore the new potential serum biomarkers and the metabolic dysregulation associated with GAS progression. Twelve differential metabolites (ethyl 2,4-dimethyl-1,3-dioxolane-2-acetate, D-urobilinogen, 14-HDoHE, 13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid, 5,6-dihydroxyprostaglandin F1a, 9'-carboxy-gamma-tocotrienol, glutaric acid, alanine, tyrosine, C18:2(FFA), adipic acid, and suberic acid) were identified to establish the diagnosis model for GAS. The defined biomarker panel was also statistically significant for GAS progression with different TNM stages. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment revealed the metabolic dysregulation associated with GAS progression. In conclusion, a diagnostic panel was established and validated, which could be used to further stage the early and advanced GAS patients from healthy controls. These findings may provide useful information for explaining the GAS metabolic alterations and try to facilitate the characterization of GAS patients in the early stage.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metabolômica/métodos , Espectrometria de Massas , BiomarcadoresRESUMO
OBJECTIVE: To separately compare the long-term risk of mortality among bariatric surgical patients undergoing either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) to large, matched, population-based cohorts of patients with severe obesity who did not undergo surgery. BACKGROUND: Bariatric surgery has been associated with reduced long-term mortality compared to usual care for severe obesity which is particularly relevant in the COVID-19 era. Most prior studies involved the RYGB operation and there is less long-term data on the SG. METHODS: In this retrospective, matched cohort study, patients with a body mass index ≥35 kg/m 2 who underwent bariatric surgery from January 2005 to September 2015 in three integrated health systems in the United States were matched to nonsurgical patients on site, age, sex, body mass index, diabetes status, insulin use, race/ethnicity, combined Charlson/Elixhauser comorbidity score, and prior health care utilization, with follow-up through September 2015. Each procedure (RYGB, SG) was compared to its own control group and the two surgical procedures were not directly compared to each other. Multivariable-adjusted Cox regression analysis investigated time to all-cause mortality (primary outcome) comparing each of the bariatric procedures to usual care. Secondary outcomes separately examined the incidence of cardiovascular-related death, cancer related-death, and diabetes related-death. RESULTS: Among 13,900 SG, 17,258 RYGB, and 87,965 nonsurgical patients, the 5-year follow-up rate was 70.9%, 72.0%, and 64.5%, respectively. RYGB and SG were each associated with a significantly lower risk of all-cause mortality compared to nonsurgical patients at 5-years of follow-up (RYGB: HR = 0.43; 95% CI: 0.35,0.54; SG: HR = 0.28; 95% CI: 0.13,0.57) Similarly, RYGB was associated with a significantly lower 5-year risk of cardiovascular-(HR = 0.27; 95% CI: 0.20, 0.37), cancer- (HR = 0.54; 95% CI: 0.39, 0.76), and diabetes-related mortality (HR = 0.23; 95% CI:0.15, 0.36). There was not enough follow-up time to assess 5-year cause-specific mortality in SG patients, but at 3-years follow-up, there was significantly lower risk of cardiovascular- (HR = 0.33; 95% CI:0.19, 0.58), cancer- (HR = 0.26; 95% CI:0.11, 0.59), and diabetes-related (HR = 0.15; 95% CI:0.04, 0.53) mortality for SG patients. CONCLUSION: This study confirms and extends prior findings of an association with better survival following bariatric surgery in RYGB patients compared to controls and separately demonstrates that the SG operation also appears to be associated with lower mortality compared to matched control patients with severe obesity that received usual care. These results help to inform the tradeoffs between long-term benefits and risks of bariatric surgery.
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COVID-19 , Derivação Gástrica , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Estudos de Coortes , Estudos Retrospectivos , GastrectomiaRESUMO
INTRODUCTION: This study investigated the risk of metachronous advanced neoplasia (AN) after colonoscopy in individuals aged 40-49 years compared with that in individuals aged 50-59 years. METHODS: A retrospective cohort study was performed among Kaiser Permanente Northern California members aged 40-59 years who had their first (index) colonoscopy in 2010-2013. Participants were followed up until death, disenrollment, AN on surveillance colonoscopy, or December 31, 2018. The risk for the development of AN was estimated using the Cox regression, adjusted for confounders. RESULTS: The study included 11,374 patients (2,396 aged 40-49 years and 8,978 aged 50-59 years). When comparing the 40-49 years group with the 50-59 years group, AN was detected in 2.2% vs 4.4% ( P = 0.0003) on surveillance colonoscopy after index colonoscopy finding of no adenoma, in 4.6% vs 7.0% ( P = 0.03) after a finding of nonadvanced adenoma (NAA), and in 7.9% vs 11.7% ( P = 0.06) after a finding of advanced adenoma (AA), respectively. Compared with the 50-59 years group, the 40-49 years group had a lower risk of metachronous AN when no adenoma was detected on index colonoscopy (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.39-0.83) and no difference when NAA (HR 0.84; 95% CI 0.54-1.24) or AA (HR 0.83; 95% CI 0.51-1.31) was detected. DISCUSSION: Compared with patients aged 50-59 years, patients aged 40-49 years may have a lower risk of developing metachronous AN when no adenoma is detected on index colonoscopy and a similar risk when NAA or AA is detected. These data suggest current surveillance colonoscopy guidelines may be applicable to patients aged 40-49 years who undergo colonoscopy.
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Segunda Neoplasia Primária , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Colonoscopia , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/epidemiologia , Adenoma/diagnóstico , Adenoma/epidemiologiaRESUMO
An increasing number of studies indicate that cancer patients' histidine (HIS) circulating levels have changed. However, the causality between HIS and cancer is still not well established. Thus, to ascertain the causal link between HIS and cancers, we performed a bidirectional Mendelian randomization (MR) analysis. Summary-level data are derived from publicly available genome-wide association studies (GWAS). The causal effects were mainly estimated using the inverse-variance weighted method (IVW). The weighted-median (WM) method and MR-Egger regression were conducted as sensitivity analyses. In the forward-MR, we found malignant neoplasm of respiratory system and intrathoracic organs (OR: 1.020; 95% CI: 1.006-1.035; pIVW = 0.007) genetically associated with circulating HIS. And there was no significant genetic correlation between HIS and another 11 site-specific cancers using IVW method. In the reversed-MR, we did not observe the causal relationship between HIS and 12 site-specific cancers. Our findings help clarify that HIS, as a biomarker for malignant neoplasms of respiratory system and intrathoracic organs, is causal rather than a secondary biomarker of the cancerous progression. The mechanism between histidine and cancer progression deserves further investigation.
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Histidina , Neoplasias , Humanos , Histidina/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Neoplasias/genética , BiomarcadoresRESUMO
Purpose: To evaluate the frequency of LTBP2 mutations and to elaborate on LTBP2-related clinical phenotypes in a Chinese congenital ectopia lentis (CEL) cohort. Methods: In total, 145 Chinese probands with CEL were recruited for this study and underwent ocular and systemic examinations. Whole-exome sequencing was used to identify mutations, and Sanger sequencing and bioinformatics analysis were further performed to verify pathogenic mutations. Results: Overall, biallelic mutations in LTBP2 involving eight novel mutations (c.4370-7_4370-9delTCT, c.4370-5C>G, c.3452G>A, c.2253delG, c.4114T>C, c.1251G>A, c.4760G>A, and c.620G>A) were identified in four CEL probands (4/145, 2.76%). Patients with LTBP2 mutations were characterized by a megalocornea, spherophakia, high myopia, and glaucoma instead of a flat cornea, high corneal astigmatism, cardiovascular and skeletal abnormalities that were reported in other gene mutations. A novel homozygous frameshift mutation was detected, and this type of mutation was found to cause more complicated ocular symptoms than others, ranging from the anterior segment to the fundus. Conclusion: This study reported the mutation frequency of the LTBP2 gene in a Chinese CEL cohort and provided novel insight into LTBP2-related genotype-phenotype associations in CEL.
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Doenças da Córnea , Ectopia do Cristalino , Glaucoma , Proteínas de Ligação a TGF-beta Latente , Humanos , China , Doenças da Córnea/genética , Análise Mutacional de DNA , Ectopia do Cristalino/genética , Ectopia do Cristalino/complicações , Glaucoma/genética , Proteínas de Ligação a TGF-beta Latente/genética , Mutação , Linhagem , FenótipoRESUMO
BACKGROUND: H-type hypertension (HHT) is a disease combined with hyperhomocysteinaemia and hypertension (HT). This study aims to find specific metabolic changes and reveal the pathophysiological mechanism of HHT, which provide the theoretical basis for the early prevention and treatment of HHT. METHODS: Serum samples from three groups including 53 HHT patients, 36 HT patients and 46 healthy controls (HC) were collected. The targeted and untargeted metabolomics analyses were performed to determine the metabolic changes. Based on multivariate statistical analysis, the serum potential metabolites were screened and different metabolic pathways were explored. RESULTS: Our results demonstrated that there were 28 important potential metabolites for distinguishing HT from HHT patients. Metabolic pathway analysis showed that the different metabolic pathways between HHT and HC group were arginine biosynthesis, arginine and proline metabolism, and tyrosine metabolism. The changed metabolic pathway of HT and HC group included linoleic acid metabolism. The specific metabolic pathways of HT-HHT comparison group had phenylalanine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; glycine, serine and threonine metabolism. CONCLUSIONS: Metabolomics analysis by mass spectrometry multi-platform revealed the differences of metabolic profiles between HHT and HT subjects. This work laid the groundwork for understanding the aetiology of HHT, and these findings may provide the useful information for explaining the HHT metabolic alterations and try to prevent HHT.
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Hipertensão , Metabolômica , Humanos , Metabolômica/métodos , Espectrometria de Massas , Tirosina , Fenilalanina , Arginina , BiomarcadoresRESUMO
Weill-Marchesani syndrome (WMS) manifests as ectopia lentis (EL), microspherophakia and short stature, which is caused by ADAMTS10, LTBP2, or ADAMTS17 gene defects. This study aims to investigate the characteristics and genotype-phenotype correlations of WMS with ADAMTS17 mutations. WMS patients with ADAMTS17 variants were identified by whole-exome sequencing from 185 patients with EL. All the included patients underwent comprehensive ocular and systemic examinations. ADAMTS17 variants were reviewed from included patients, published literature, and public databases. Bioinformatics analysis, co-segregation analysis, species sequence analysis, and protein silico modeling were used to verify the pathogenic mutations. A total of six novel ADAMTS17 mutations (c.1297C > T, c.2948C > T, c.1322+2T > C, c.1716C > G, c.1630G > A, and c.1669C > T) were identified in four WMS probands in our EL cohort (4/185, 2.16%). All probands and their biological parents presented with apparent short stature compared with the standard value. In particular, one child was detected with valvular heart disease, which has not previously been reported in patients with ADAMTS17 mutations. Conserved residues were greatly affected by the substitution of amino acids caused by these six mutations. Short stature could be considered a clue for EL patients with ADAMTS17 mutations, and much more attention needs to be paid to heart disorders among these patients. This study not only reported the characteristics of ADAMTS17 mutation-related WMS but also helped to recognize the genotype-phenotype correlations in these patients.
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Ectopia do Cristalino , Glaucoma , Síndrome de Weill-Marchesani , Humanos , Síndrome de Weill-Marchesani/genética , Mutação , Ectopia do Cristalino/genética , Estudos de Associação Genética , Proteínas ADAMTS/genética , Proteínas de Ligação a TGF-beta Latente/genéticaRESUMO
BACKGROUND: Insertion and deletion (InDel) polymorphisms have considerable potential in the field of forensic genetics because of their low mutation rate and small amplicons. At present, InDel polymorphisms detection based on the technique of capillary electrophoresis is the main technique used in forensic DNA laboratory. However, this method is complicated and time-consuming, and is not suitable for rapid on-site paternity and personal identification. Next-generation sequencing analysis of InDels polymorphisms requires expensive instruments, large upfront reagent and supply costs, computational requirements and complex bioinformatics, increased the time to obtain results. Thus, there is an urgent need to establish a method to provide reliable, rapid, sensitive and economical genotyping for InDels. METHOD: A rapid InDels (32 InDels) panel was established using fluorogenic probes-based multiplex real-time PCR with microfluidic test cartridge and portable real-time PCR instrument. Then, we performed several validation studies including concordance, accuracy, sensitivity, stability, species specificity. RESULTS: It showed that the complete genotypes could be obtained from ≥100 pg of input DNA and from a series of challenging samples with high accuracy and specificity within 90 min. CONCLUSION: This method provides a rapid and cost-effective solution for InDels genotyping and personal identification in portable format.
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Antropologia Forense , Polimorfismo Genético , Humanos , Genótipo , Reação em Cadeia da Polimerase em Tempo Real , DNA/análiseRESUMO
Multivalent salt plays important roles in polyelectrolyte (PE) systems. Some special effects, such as ion mediated electrostatic correlation and reentrant condensation can be induced in the presence of multivalent salt. In this work, the self-assembly behaviors of diblock PEs in trivalent salt solutions are mainly investigated by molecular dynamics (MD) simulations, and partial results are qualitatively verified by experiments. The electrostatic correlation between PE chains and trivalent counterions is first enhanced with the increase of salt concentration, and then the large complexes of co-ions and trivalent counterions reduce the correlation at the excessive salt regime. Therefore, the electrostatic correlation mediated by trivalent ions shows a non-monotonic dependence on salt content. It should be noted that one-dimensional chain-like and two-dimensional planar network supra-micellar structures are obtained at different concentrations of PEs. It is the strong electrostatic correlation mediated by trivalent counterions that leads to the cross-linking of micelles, and homogeneous spherical micelles rather than anisotropic micelles are used as building blocks. Both of these supra-micellar structures predicted by simulations are qualitatively confirmed by experiments, and a micron sized long polymer chain and planar networks of inter-connected micelles are demonstrated in transmission electron microscopy (TEM) images. Reentrant behavior of the assembled micelles is demonstrated at a lower polymer concentration. The transitions from a dispersed micellar phase to a fully phase separated phase (where all the copolymer chains aggregate into one micelle to precipitate out of the solution) and to the re-dissolution of micelles are displayed with an increase in trivalent salt. The non-monotonic dependence of electrostatic correlation on the salt content is well displayed by the four states of the assembled micelles: (i) dispersed micelles, (ii) a single micelle comprising of all copolymer chains, (iii) micellar complex, and (iv) re-dispersed micelles. Our analysis may provide guidance for cross-linking of isotropic micelles into superstructures.
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PURPOSE: Congenital ectopia lentis (CEL) and heart abnormalities are common clinical symptoms in patients with Marfan syndrome (MFS) and related fibrillinopathies, which is caused by mutations in fibrillin-1 (FBN1) gene. This study aims to explore the ocular and cardiovascular characteristics and their association with genotype in children with MFS and related fibrillinopathies. METHODS: Seventy-nine children diagnosed with CEL and with FBN1 mutations confirmed via whole-exome sequencing were included for genotypes and phenotypes analysis. The axial length (AL), corneal curvature, and refractive status were included for ocular phenotypes analysis. The cardiovascular examination was performed by echocardiography, and aortic root Z score was calculated to evaluate the severity of aortic dilatation. The heart disorders were classified as aortic root dilatation, valvular disorders, and others. Both the ocular and cardiac manifestations were collected for comprehensive analysis and compared among patients with different genotypes, including the mutation involving cysteine substitution or mutation in different regions. RESULTS: In CEL children with FBN1 mutations, 77.2% patients could be diagnosed as MFS. It was observed that children with mutations in exons 22-42 had significant higher aortic root Z score (P = 0.003) and higher incidence of cardiovascular disorders (P = 0.004). Additionally, children with cysteine substitution mutations had significant higher aortic root Z score (P = 0.011), and the aortic root Z score was positively associated with axial length (AL) in children under 6 years old (P = 0.035). Those with long AL (≥ 26 mm) had significant higher incidence of valve disorders (P = 0.023). In addition, nearly half the children with CEL (46.8%) were diagnosed with cardiovascular disease for the first time. CONCLUSIONS: CEL children with FBN1 mutations involving cysteine substitution or mutations in exons 22-42 or with long AL had higher risks of severe cardiovascular complications. Knowing the phenotype may help in anticipating severe cardiovascular disease in CEL patients.
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Mass spectrometry imaging (MSI) is a powerful label-free analysis technique that can provide simultaneous spatial distribution of multiple compounds in a single experiment. By combining the sensitive and rapid screening of high-throughput MS with spatial chemical information, metabolite analysis and morphological characteristics are presented in a single image. MSI can be used for qualitative and quantitative analysis of metabolic profiles and it can provide visual analysis of spatial distribution information of complex biological and microbial systems. Matrix-assisted laser desorption ionization, laser ablation electrospray ionization and desorption electrospray ionization are commonly used in MSI. Here, we summarize and compare these three technologies, as well as the applications and prospects of MSI in metabolomics.