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1.
J Natl Cancer Inst ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702830

RESUMO

BACKGROUND: TP53 alterations are common in certain pediatric cancers, making identification of putative germline variants through tumor genomic profiling crucial for patient management. METHODS: We analyzed TP53 alterations in 3123 tumors from 2788 pediatric patients sequenced using tumor-only or tumor-normal paired panels. Germline confirmatory testing was performed when indicated. Somatic and germline variants were classified following published guidelines. RESULTS: In 248 tumors from 222 patients, 284 Tier 1/2 TP53 sequence and small copy number variants were detected. Following germline classification, 73.9% of 142 unique variants were pathogenic/likely pathogenic (P/LP). Confirmatory testing on 118 patients revealed germline TP53 variants in 28 patients (23 P/LP and 5 uncertain significance), suggesting a minimum Li-Fraumeni syndrome (LFS) incidence of 0.8% (23/2788) in this cohort, 10.4% (23/222) in patients with TP53 variant-carrying tumors, and 19.5% (23/118) with available normal samples. About 25% (7/28) of patients with germline TP53 variants did not meet LFS diagnostic/testing criteria while 20.9% (28/134) with confirmed or inferred somatic origins did. TP53 biallelic inactivation occurred in 75% of germline carrier tumors and was also prevalent in other groups, causing an elevated tumor-observed variant allelic fraction (VAF). However, somatic evidence including low VAF correctly identified only 27.8% (25/90) of patients with confirmed somatic TP53 variants. CONCLUSION: The high incidence and variable phenotype of LFS in this cohort highlights the importance of assessing germline status of TP53 variants identified in all pediatric tumors. Without clear somatic evidence, distinguishing somatic from germline origins is challenging. Classifying germline and somatic variants should follow appropriate guidelines.

3.
Chemosphere ; 352: 141391, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325615

RESUMO

Zero-valent iron (ZVI), as an effective medium, is widely used to eliminate heavy metal ions in filter tanks. However, it will react with Cr(VI) to generate Fe-Cr precipitates with low conductivity on its surface, resulting in slow iron corrosion and low Cr(VI) removal efficiency. In this study, three oxidants (KMnO4, NaClO, and Na2S2O8) were employed to promote iron corrosion in ZVI systems for enhanced Cr(VI) removal at a concentration of 5 mg/L through batch tests and column experiments. The ZVI/KMnO4, ZVI/NaClO, and ZVI/Na2S2O8 systems achieved significantly higher Cr(VI) removal rates of 31.5%, 52.8%, and 65.9% than the ZVI system (9.8%). Solid phase characterization confirmed that these improvements were attributed to promoted iron corrosion and secondary mineral formation (e.g., lepidocrocite, ferrihydrite, and magnetite) by oxidants. Those minerals offered more reaction sites for Cr(VI) reduction, adsorption, and sequestration. Cycle experiments indicated that ZVI/oxidant systems could stably remove Cr(VI). In long-term column experiment, the ZVI/NaClO column showed a much longer life-span and exhibited a 34.8 times higher Cr(VI) removal capacity than that of the ZVI column. These findings demonstrated that ZVI in combination with a reasonable amount of oxidants was a promising method for removing Cr(VI) in practical filter tanks and provided a new insight to enhance Cr(VI) removal.


Assuntos
Ferro , Poluentes Químicos da Água , Oxidantes , Corrosão , Cromo/análise
4.
STAR Protoc ; 5(1): 102850, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38285735

RESUMO

Circular dichroism (CD) spectrometry is a rapid technique for detecting protein secondary structure, particularly helicity. DMSO is used to ensure optimal solubility of peptides/peptidomimetics; however, its background absorbance hinders effective CD analysis. Here, we present a protocol for reconstituting peptides/peptidomimetics from DMSO to aqueous buffers for CD analyses. We describe steps for identifying chemicals that induce DMSO evaporation, extracting peptides/peptidomimetics from DMSO, and CD spectrometer setup and analysis. We then detail procedures for secondary structure analyses of reconstituted peptides/peptidomimetics. For complete details on the use and execution of this protocol, please refer to Gao et al. (2023).1.


Assuntos
Dimetil Sulfóxido , Peptidomiméticos , Dicroísmo Circular , Dimetil Sulfóxido/química , Peptídeos/química , Proteínas , Água
5.
J Mol Diagn ; 26(3): 191-201, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38103590

RESUMO

Inherited bone marrow failure syndromes (IBMFS) are a group of heterogeneous disorders that account for ∼30% of pediatric cases of bone marrow failure and are often associated with developmental abnormalities and cancer predisposition. This article reports the laboratory validation and clinical utility of a large-scale, custom-designed next-generation sequencing panel, Children's Hospital of Philadelphia (CHOP) IBMFS panel, for the diagnosis of IBMFS in a cohort of pediatric patients. This panel demonstrated excellent analytic accuracy, with 100% sensitivity, ≥99.99% specificity, and 100% reproducibility on validation samples. In 269 patients with suspected IBMFS, this next-generation sequencing panel was used for identifying single-nucleotide variants, small insertions/deletions, and copy number variations in mosaic or nonmosaic status. Sixty-one pathogenic/likely pathogenic variants (54 single-nucleotide variants/insertions/deletions and 7 copy number variations) and 24 hypomorphic variants were identified, resulting in the molecular diagnosis of IBMFS in 21 cases (7.8%) and exclusion of IBMFS with a diagnosis of a blood disorder in 10 cases (3.7%). Secondary findings, including evidence of early hematologic malignancies and other hereditary cancer-predisposition syndromes, were observed in 9 cases (3.3%). The CHOP IBMFS panel was highly sensitive and specific, with a significant increase in the diagnostic yield of IBMFS. These findings suggest that next-generation sequencing-based panel testing should be a part of routine diagnostics in patients with suspected IBMFS.


Assuntos
Anemia Aplástica , Doenças da Medula Óssea , Hemoglobinúria Paroxística , Humanos , Criança , Anemia Aplástica/diagnóstico , Anemia Aplástica/genética , Doenças da Medula Óssea/diagnóstico , Doenças da Medula Óssea/genética , Síndrome Congênita de Insuficiência da Medula Óssea , Variações do Número de Cópias de DNA/genética , Reprodutibilidade dos Testes , Hemoglobinúria Paroxística/diagnóstico , Hemoglobinúria Paroxística/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Nucleotídeos
6.
Chemosphere ; 341: 140066, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37673180

RESUMO

Zero-valent iron (Fe0) is restricted in phosphate removal due to the formation of a passive P-Fe layer on its surface. A micro-electric field (0.20 mA cm-2) was employed in Fe0 column to facilitate iron corrosion for enhanced phosphate removal with a Fe0 column as the control. The performance of two columns was compared by batch experiment at a Fe0 filling rate of 10 vol% with quartz sand as dispersing media. The stability and reusability of micro-electric field driven Fe0 (MFD-Fe0) column was estimated by cyclic test. Solid phase analysis showed promoted iron corrosion, iron ion generation, and secondary mineral production such as lepidocrocite and magnetite in the MFD-Fe0 column. Since iron ions tended to precipitate with phosphate, and iron minerals provided reaction sites for phosphate adsorption, the MFD-Fe0 column achieved an enhanced phosphate removal of 94.1%, 2.8 times higher than that of the Fe0 column. The increase of current density from 0 to 0.20 mA cm-2 significantly improved phosphate removal from 24.5% to 94.1%, further demonstrating the promoting effect of micro-electric field on iron corrosion. The MFD-Fe0 column also possessed excellent stability and reusability. It only showed a slight decrease of phosphate removal from 94.1% to 89.7% in eight cycles. It restored a phosphate removal capacity of 97.4% as compared to the initial MFD-Fe0 column by eluting iron (hydro)oxides on Fe0 and quartz sand surfaces with sulfuric acid. This study indicated that MFD-Fe0 is a promising method to remove phosphate from water and an alternative strategy for overcoming Fe0 passivation.


Assuntos
Ferro , Fosfatos , Corrosão , Quartzo , Areia
7.
Structure ; 31(8): 948-957.e3, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37369205

RESUMO

Integrins are ubiquitously expressed cell-adhesion proteins. Activation of integrins is triggered by talin through an inside-out signaling pathway, which can be driven by RAP1-interacting adaptor molecule (RIAM) through its interaction with talin at two distinct sites. A helical talin-binding segment (TBS) in RIAM interacts with both sites in talin, leading to integrin activation. The bispecificity inspires a "double-hit" strategy for inhibiting talin-induced integrin activation. We designed an experimental peptidomimetic inhibitor, S-TBS, derived from TBS and containing a molecular staple, which leads to stronger binding to talin and inhibition of talin:integrin interaction. The crystallographic study validates that S-TBS binds to the talin rod through the same interface as TBS. Moreover, the helical S-TBS exhibits excellent cell permeability and effectively suppresses integrin activation in cells in a talin-dependent manner. Our results shed light on a new class of integrin inhibitors and a novel approach to design multi-specific peptidomimetic inhibitors.


Assuntos
Peptidomiméticos , Talina , Talina/química , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas de Membrana/química , Peptidomiméticos/farmacologia , Integrinas/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo
8.
Int J Womens Health ; 15: 397-410, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36974132

RESUMO

Objective: Regular functional exercise can help recover the functions of upper limb for patients with breast cancer. By finding the influencing factors of functional exercise compliance and constructing a predictive model, patients with a poor functional exercise compliance can be better identified. This study aims to find out the factors influencing the functional exercise compliance of patients with breast cancer and build a predictive model based on decision tree. Methods: Convenience sampling was used at two tertiary hospitals in Shantou from August 2020 to March 2021. Data of patients with breast cancer patient was obtained from questionnaires and based on demographics, Constant-Murley Score, Functional Exercise Compliance Scale for Postoperative Breast Cancer Patients, Champion Health Belief Model Scale, Social Support Rating Scale, Disease Perception Questionnaire and Family Care Index Questionnaire. Possible influencing factors of functional exercise compliance were analyzed using correlation analysis as well as univariate and binary logistic regression analysis through SPSS v25, and a CHAID decision tree was used to construct a predictive model on training, validation and test sets via SPSS Modeler v18 at a ratio of 6:2:2. Prediction accuracy, sensitivity, specificity and AUC were used to analyze the efficacy of the predictive model. Results: A total of 227 valid samples were collected, of which 145 were assessed with a poor compliance (63.9%). According to a logistic regression analysis, perceived benefits, time after surgery and self-efficacy were influencing factors. The prediction accuracy, sensitivity, specificity and AUC of the predictive model, based on a CHAID decision tree analysis, were 70.73%, 57.1%, 77.8% and 0.81 respectively. Conclusion: The predictive model, based on a CHAID decision tree analysis, had a moderate predictive efficacy, which could be used as a clinical auxiliary tool for clinical nurses to predict patients' functional exercise compliance.

9.
Bioresour Technol ; 373: 128744, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36791978

RESUMO

Tetrasphaera-enhanced biological phosphorus removal (T-EBPR) was developed by augmenting conventional EBPR (C-EBPR) with Tetrasphaera to improve phosphorus removal from anaerobic digestate of swine wastewater. At influent total phosphorus (TP) concentrations of 45-55 mg/L, T-EBPR achieved effluent TP concentration of 4.17 ± 1.02 mg/L, 54 % lower than that in C-EBPR (8.98 ± 0.76 mg/L). The enhanced phosphorous removal was presumably due to the synergistic effect of Candidatus Accumulibacter and Tetrasphaera occupying different ecological niches. Bioaugmentation with Tetrasphaera promoted the polyphosphate accumulation metabolism depending more on the glycolysis pathway, as evidenced by an increase in intracellular storage compounds of glycogen and polyhydroxyalkanoates by 0.87 and 0.34 mmol C/L, respectively. The enhanced intracellular storage capacity was coincidentally linked to the increase in phosphorus release and uptake rates by 1.23 and 1.01 times, respectively. These results suggest bioaugmentation with Tetrasphaera could be an efficient way for improved phosphorus removal from high-strength wastewater.


Assuntos
Actinomycetales , Águas Residuárias , Animais , Suínos , Fósforo/metabolismo , Anaerobiose , Polifosfatos/metabolismo , Reatores Biológicos , Actinomycetales/metabolismo , Esgotos
10.
Histopathology ; 82(6): 946-952, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36648026

RESUMO

AIMS: Ossifying fibromyxoid tumor (OFMT) is a rare enigmatic tumor of uncertain differentiation that can be classified as typical, atypical, and malignant subtypes based on cellularity, nuclear grade, and mitotic activity. The majority of OFMTs, regardless of the risk of malignancy, harbor genetic translocations. We report two malignant OFMTs, including one with evidence of dedifferentiation, with novel genefusions. METHODS AND RESULTS: Case 1 was a 63-year-old male with a dedifferentiated OFMT arising in the right wrist, while case 2 was a 41-year-old male with a malignant OFMT presenting as a posterior mediastinal mass. Case 2 showed multifocal expression with EMA and synaptophysin, while desmin and S100 were absent in both tumors. NGS sequencing studies detected PHF1::FOXR1 and PHF1::FOXR2 gene fusions in cases 1 and 2, respectively. Despite aggressive regimens, both progressed with wide spread metastases resulting in death within six years of diagnosis. CONCLUSIONS: We expand the genetic spectrum of OFMTs with two novel gene fusions, PHF1::FOXR1 and PHF1::FOXR2. These cases confirm the previously reported tendencies for OFMTs with rare variant fusions to demonstrate malignant behavior, unusual morphology, and non-specific immunophenotype.


Assuntos
Fibroma Ossificante , Fibroma , Neoplasias de Tecidos Moles , Masculino , Humanos , Pessoa de Meia-Idade , Adulto , Fibroma Ossificante/patologia , Neoplasias de Tecidos Moles/patologia , Fibroma/patologia , Fusão Gênica , Proteínas de Ligação a DNA/genética , Proteínas do Grupo Polycomb/genética , Proteínas do Grupo Polycomb/metabolismo , Fatores de Transcrição Forkhead/genética
11.
Chemosphere ; 310: 136915, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36270520

RESUMO

In this work, zero-valent iron (ZVI) combined with anaerobic bacteria was used in the remediation of Cd(II)-polluted soil under the mediation of sulfate (SO42-). Owing to hydrogen-autotrophic sulfate reduction, serious corrosion occurred on sulfate-mediated biotic ZVI in terms of solid phase characterization as massive corrosive products (e.g., goethite, magnetite and green rust) were formed, which were crucial in the immobilization of Cd(II). Thus, this integrated system achieved a 4.9-fold increase in aqueous Cd(II) removal and converted more than 53% of easily available Cd(II)-fractions (acid-extractable and reducible) to stable forms (oxidizable and residual) based on the sequential extraction results as compared to the sulfate-mediated ZVI system. Increasing SO42- concentration and ZVI dosage both demonstrated positive correlation to Cd(II) immobilization, which further reflected that hydrogenotrophic desulfuration acted an essential role in improving Cd(II) immobilization. It indicated that hydrogenotrophic desulfuration could accelerate iron corrosion and promote reactive mineral formation through biomineralization, as well as generate cadmium sulfide precipitates (CdS) to achieve excellent immobilization performance for Cd(II). Besides, this reaction was favorable under neutral pH condition. Our results highlighted the promoted effect of hydrogen-autotrophic desulfuration on ZVI corrosion to immobilize Cd(II) and offered a practicable technique in Cd(II)-polluted soil remediation.


Assuntos
Ferro , Solo , Ferro/química , Sulfatos , Cádmio/análise , Hidrogênio
12.
J Hazard Mater ; 441: 129833, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36084458

RESUMO

In this study, an integrated system of Fe0 and hydrogenotrophic microbes mediated by nitrate (nitrate-mediated bio-Fe0, NMB-Fe0) was established to remediate Cd(II)-contaminated sediment. Solid phase characterization confirmed that aqueous Cd(II) (Cd(II)aq) was successfully immobilized and enriched on iron surface due to promoted iron corrosion driven by hydrogenotrophic denitrification and subsequent greater biomineral production such as magnetite, lepidocrocite and green rust. Compared to a Cd(II)aq removal of 21.1% in overlying water of the nitrate-mediated Fe0 (NM-Fe0) system, the NMB-Fe0 system obtained a much higher Cd(II)aq removal of 83.1% after 7 d remediation. The leaching test and sequential extraction results also showed that the leachability of Cd(II) decreased by 75.9% while the residual fraction of Cd(II) increased by 185.7% in comparison with untreated sediment. Besides, the Cd(II)aq removal raised with the increase of nitrate concentration and Fe0 dosage, further revealing the promotion effect of nitrate on Cd(II) removal by bio-Fe0. This study highlighted the involvement of bio-denitrification in the remediation of Cd(II)-contaminated sediment by Fe0 and provided a new insight to enhance its reactivity and applicability for Cd(II) immobilization.


Assuntos
Ferro , Nitratos , Cádmio/farmacologia , Desnitrificação , Óxido Ferroso-Férrico/farmacologia , Ferro/farmacologia , Água/farmacologia
13.
Sci Rep ; 12(1): 22265, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564420

RESUMO

We investigated the associations of plasma cystatin C with all-cause and cause-specific mortality risk and identified potential modifying factors affecting these associations in middle-aged and elderly people (≥ 50 years). This community-based prospective cohort study included 13,913 individuals aged ≥ 50 years from the Health and Retirement Study. Cox proportional hazard models were used to estimate the associations between cystatin C concentrations and the risk of all-cause and cardiovascular and cancer mortality after adjustment for sociodemographic characteristics, lifestyle factors, self-reported medical history, and other potential confounding factors. During a total of 71,988 person-years of follow-up (median: 5.8 years; interquartile range 3.3-7.6 years), 1893 all-cause deaths were documented, including 714 cardiovascular-related and 406 cancer-related deaths. The comparisons of the groups with the highest (quartile 4) and lowest (quartile 1) cystatin C concentrations revealed that the adjusted hazard ratios and 95% confidence intervals were 1.92 (1.62-2.28) for all-cause mortality, 1.98 (1.48-2.65) for cardiovascular mortality, and 1.62 (1.13-2.32) for cancer mortality. The associations of cystatin C concentrations with all-cause, cardiovascular and cancer mortality did not differ substantially when participants were stratified by sex, age, BMI, current smoking status, current alcohol consumption, and regular exercise (all P for interactions > 0.05). Our study indicates that an elevated plasma cystatin C concentration is associated with an increased risk of all-cause, cardiovascular and cancer mortality both men and women among the middle-aged and elderly individuals.


Assuntos
Doenças Cardiovasculares , Neoplasias , Masculino , Idoso , Pessoa de Meia-Idade , Humanos , Feminino , Estudos Prospectivos , Cistatina C , Estudos de Coortes , Causas de Morte , Doenças Cardiovasculares/etiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Mortalidade
14.
Clin Lab Med ; 42(3): 423-434, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36150821

RESUMO

Because the clinical impact of cancer genomics is being increasingly recognized, tumor sequencing will likely continue to expand in breadth and scope. Therefore, it is vital for laboratory professionals to adopt the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists guidelines and create a standardized system of classification and nomenclature for somatic variants. Combining robust bioinformatics pipelines with thorough data analysis is necessary to efficiently and reproducibly identify and assess the impact of clinically relevant variants.


Assuntos
Testes Genéticos , Neoplasias , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Patologia Molecular
15.
Cell Mol Biol (Noisy-le-grand) ; 67(6): 68-73, 2022 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-35818212

RESUMO

Prostate cancer is a common clinical disease in men. It is known that prostate cancer ranks 3rd in the incidence of malignant tumors of the male genitourinary system in China, which is able to evaluate the riskiness of life expectancy of male patients. Therefore, we investigated the expression of CD133, recombinant human kallikrein 3 (Klk3), grainy head like 2 (grhl2) in prostate cancer, and correlation with tumor characteristics in the present study. A total of 167 prostate cancer patients who underwent surgical treatment in our hospital from February 2017 to April 2021 were selected. Their cancer and adjacent tissues were resected, and CD133 was detected by double staining using immunohistochemistry, Klk3 and grhl2 were detected by RT-PCR analysis, and CD133, Klk3 were analyzed by Pearson's method in different clinical stages, Gleason grade Correlation of grhl2 with tumor characteristics. The expression of CD133, KLK3, and GRHL2 in cancer tissue was increased compared with adjacent tissue (P < 0.05). The expression of CD133, KLK3, and GRHL2 increased with the aggravation of the clinical stage and Gleason grade (P < 0.05). CD133, KLK3, and GRHL2 showed a positive correlation in prostate cancer. The Pearson method found a positive correlation between CD133, KLK3, GRHL2 and clinical stage, Gleason grade, and lymph node metastasis. In general, high CD133, Klk3, and grhl2 expression was observed in prostate cancer and increased with the disease. They presented a positive correlation in prostate cancer presence, and these three gene products correlated with tumor characteristics.


Assuntos
Antígeno AC133 , Proteínas de Ligação a DNA , Calicreínas , Antígeno Prostático Específico , Neoplasias da Próstata , Fatores de Transcrição , Antígeno AC133/genética , China , Proteínas de Ligação a DNA/genética , Humanos , Imuno-Histoquímica , Calicreínas/genética , Masculino , Gradação de Tumores , Antígeno Prostático Específico/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Fatores de Transcrição/genética
16.
Acta Neuropathol Commun ; 10(1): 102, 2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836290

RESUMO

CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of "CIC-rearranged" sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases.


Assuntos
Sarcoma de Células Pequenas , Sarcoma , Neoplasias de Tecidos Moles , Ataxina-1/genética , Biomarcadores Tumorais/genética , Expressão Gênica , Humanos , Lactente , Metilação , Proteínas de Fusão Oncogênica/genética , Proteínas Repressoras/genética , Estudos Retrospectivos , Sarcoma/genética , Sarcoma/patologia , Sarcoma de Células Pequenas/diagnóstico , Sarcoma de Células Pequenas/genética , Sarcoma de Células Pequenas/patologia , Neoplasias de Tecidos Moles/genética , Fatores de Transcrição/genética
17.
Cytokine ; 155: 155902, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35561585

RESUMO

BACKGROUND: The article aims to study the results of EB virus nucleic acid quantification (EBV-DNA) in whole blood lymphocytes to examine whether serum can diagnose EB virus infection in children. Group A consisted of 65 children admitted to the hospital with a probable EB virus infection between February 2017 and February 2018. In the same period of health check-ups, 65 children were randomly selected as Group B. METHODS: To find out the differences between Group A and Group B, EBV-DNAs in whole blood lymphocyte and serum were detected by quantitative fluorescence assay, and EBV-CA-IgM antibody was detected by enzyme-linked immunosorbent assay. RESULTS: The results demonstrate that Group A had a greater rate of positive EBV-DNAs in whole blood lymphocytes and serum than Group B. EBV-DNA positivity was greater in whole blood lymphocytes of Group A and Group B than in serum. In whole blood lymphocytes from Group A, the positive rate of EBV-DNA and EBV-CA-IgM antibodies was statistically significant. CONCLUSION: The positive rate of EBV-DNA in whole blood lymphocytes of EBV-infected children is higher than in serum, the suitable specimens for diagnosis should be chosen based on the individual condition of children patients.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Anticorpos Antivirais , Criança , DNA Viral , Infecções por Vírus Epstein-Barr/diagnóstico , Humanos , Imunoglobulina M , Linfócitos
18.
Artigo em Inglês | MEDLINE | ID: mdl-35232817

RESUMO

Li-Fraumeni syndrome (LFS) is one of the most common cancer predisposition syndromes that affects both children and adults. Individuals with LFS are at an increased risk of developing various types of cancer over their lifetime including soft tissue sarcomas, osteosarcomas, breast cancer, leukemia, brain tumors, and adrenocortical carcinoma. Heterozygous germline pathogenic variants in the tumor suppressor gene TP53 are the known causal genetic defect for LFS. Single-nucleotide variants (SNVs) including missense substitutions that occur in the highly conserved DNA binding domain of the protein are the most common alterations, followed by nonsense and splice site variants. Gross copy-number changes in TP53 are rare and account for <1% of all variants. Using next-generation sequencing (NGS) panels, we identified a paternally inherited germline intragenic duplication of TP53 in a child with metastatic osteosarcoma who later developed acute myeloid leukemia (AML). Transcriptome sequencing (RNA-seq) demonstrated the duplication was tandem, encompassing exons 2-6 and 28 nt of the untranslated region (UTR) upstream of the start codon in exon 2. The inclusion of the 28 nt is expected to result in a frameshift with a stop codon 18 codons downstream from the exon 6, leading to a loss-of-function allele. This case highlights the significance of simultaneous identification of both significant copy-number variants as well as SNVs/indels using NGS panels.


Assuntos
Neoplasias do Córtex Suprarrenal , Neoplasias da Mama , Síndrome de Li-Fraumeni , Proteína Supressora de Tumor p53 , Adulto , Neoplasias da Mama/genética , Criança , Feminino , Duplicação Gênica/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa/genética , Humanos , Síndrome de Li-Fraumeni/genética , Proteína Supressora de Tumor p53/genética
19.
Sci Total Environ ; 822: 153538, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35104521

RESUMO

In this study, hydrogen-autotrophic microorganisms and zero-valent iron (Fe0) were filled into columns to investigate hydrogenotrophic denitrification effect on cadmium (Cd(II)) removal and column life-span with sand, microorganisms, Fe0 and bio-Fe0 columns as controls. In terms of the experiment results, the nitrate-mediated bio-Fe0 column showed a slow Cd(II) migration rate of 0.04 cm/PV, while the values in the bio-Fe0 and Fe0 columns were 0.06 cm/PV and 0.14 cm/PV respectively, indicating much higher Cd(II) removal efficiency and longer service life of the nitrate-mediated bio-Fe0 column. The XRD and SEM-EDX results implied that this improvement was attributed to hydrogenotrophic denitrification that caused more serious iron corrosion and larger amount of secondary mineral generation (e.g., green rust, lepidocrocite and goethite). These active minerals provided more reaction sites for Cd(II) adsorption and further immobilization. In addition, the decrease of Cd(II) migration front and the increase of removal capacity along the bio-Fe0 column mediated by nitrate presented an uneven distribution in reactive zone. The latter half part was identified to be a more active region for Cd(II) immobilization. The above results indicate that the introduction of nitrate and microorganisms will improve the performance of iron-based permeable reactive barriers for the remediation of Cd(II)-containing groundwater.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Anaerobiose , Cádmio , Ferro , Nitratos/análise , Poluentes Químicos da Água/análise
20.
J Environ Manage ; 301: 113894, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34638045

RESUMO

A biotic iron (Fe0) treatment system combined with mixed microorganisms was applied to remediate cadmium (Cd)-contaminated groundwater under the intervention of sulfate. Due to hydrogenotrophic desulfuration effect, severe iron corrosion was observed in this microbe-collaborative Fe0 system according to surface morphology analysis as lots of secondary minerals (e.g. magnetite, green rust and lepidocrocite) were generated, which was essential for Cd(II) adsorption and immobilization. The sulfate-mediated biotic Fe0 system thereafter achieved a significantly enhanced Cd(II) removal efficiency of 86.1%, over 3.3 times than that in the abiotic Fe0 system. Increasing initial sulfate concentration could improve the removal of cadmium, which further proved that hydrogenotrophic desulfuration played a key role for enhanced Cd removal. According to the experimental results and current reports, the mechanism of Cd(II) removal was revealed into three pathways including adsorption to secondary iron minerals, co-precipitation with iron (hydr)oxides and formation of cadmium sulfide precipitation. Increasing Fe0 dosages showed positive correlation to Cd(II) removal and neutral pH was preferred to sulfate-mediated biotic Fe0 corrosion. These results indicated that sulfate-mediated biotic Fe0 corrosion could greatly relieve the limitation of Fe0 in Cd(II) immobilization, which could be a promising method to eliminate Cd(II) pollution from groundwater.


Assuntos
Cádmio , Água Subterrânea , Cádmio/análise , Corrosão , Ferro , Sulfatos
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