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Background: Patients with systemic sclerosis (SSc) are known to have higher incidence of atherosclerosis (AS). Mitochondrial injuries in SSc can cause endothelial dysfunction, leading to AS; thus, mitochondria appear to be hubs linking SSc to AS. This study aimed to identify the mitochondria-related biomarkers of SSc and AS. Methods: We identified common differentially expressed genes (DEGs) in the SSc (GSE58095) and AS (GSE100927) datasets of the Gene Expression Omnibus (GEO) database. Considering the intersection between genes with identical expression trends and mitochondrial genes, we used the least absolute shrinkage and selection operator (LASSO) as well as random forest (RF) algorithms to identify four mitochondria-related hub genes. Diagnostic nomograms were then constructed to predict the likelihood of SSc and AS. Next, we used the CIBERSORT algorithm to evaluate immune infiltration in both disorders, predicted the transcription factors for the hub genes, and validated these genes for the two datasets. Results: A total of 112 genes and 13 mitochondria-related genes were identified; these genes were then significantly enriched for macrophage differentiation, collagen-containing extracellular matrix, collagen binding, antigen processing and presentation, leukocyte transendothelial migration, and apoptosis. Four mitochondria-related hub DEGs (IFI6, FSCN1, GAL, and SGCA) were also identified. The nomograms showed good diagnostic values for GSE58095 (area under the curve (AUC) = 0.903) and GSE100927 (AUC = 0.904). Further, memory B cells, γδT cells, M0 macrophages, and activated mast cells were significantly higher in AS, while the resting memory CD4+ T cells were lower and M1 macrophages were higher in SSc; all of these were closely linked to multiple immune cells. Gene set enrichment analysis (GSEA) showed that IFI6 and FSCN1 were involved in immune-related pathways in both AS and SSc; GAL and SGCA are related to mitochondrial metabolism pathways in both SSc and AS. Twenty transcription factors (TFs) were predicted, where two TFs, namely BRCA1 and PPARγ, were highly expressed in both SSc and AS. Conclusion: Four mitochondria-related biomarkers were identified in both SSc and AS, which have high diagnostic value and are associated with immune cell infiltration in both disorders. Hence, this study provides new insights into the pathological mechanisms underlying SSc and AS. The specific roles and action mechanisms of these genes require further clinical validation in SSc patients with AS.
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The study of facile-synthesis and low-cost X-ray scintillators with high light yield, low detection limit and high X-ray imaging resolution plays a vital role in medical and industrial imaging fields. However, the optimal balance between X-ray absorption, decay lifetime and excitonic utilization efficiency of scintillators to achieve high-resolution imaging is extremely difficult due to the inherent contradiction. Here two thermally activated delayed fluorescence (TADF)-actived coinage-metal clusters M6 S6 L6 (M=Ag or Cu) were synthesized by simple solvothermal reaction, where the cooperation of heavy atom-rich character and TADF mechanism supports strong X-ray absorption and rapid luminescent collection of excitons. Excitingly, Ag6 S6 L6 (SC-Ag) displays a high photoluminescence quantum yield of 91.6 % and scintillating light yield of 17420â photons MeV-1 , as well as a low detection limit of 208.65â nGy s-1 that is 26â times lower than the medical standard (5.5â µGy s-1 ). More importantly, a high X-ray imaging resolution of 16â lp/mm based on SC-Ag screen is demonstrated. Besides, rigid core skeleton reinforced by metallophilicity endows clusters M6 S6 L6 strong resistance to humidity and radiation. This work provides a new view for the design of efficient scintillators and opens the research door for silver clusters in scintillation application.
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Deletional α-thalassemia is characterized by reduced hemoglobin A2 and involves the deletion of a few nucleotides, which is a rare hereditary disease. However, the detection of rare mutations using commonly used genetic tests is highly challenging. In the present study, next-generation sequencing (NGS) was used to identify a novel 7-bp deletion α-thalassemia in one individual from a Chinese family. Hematological parameters of the family members were determined using an automated cell counter, and hemoglobin electrophoresis was performed using a capillary electrophoresis system. Subsequently, NGS was performed on the genomic DNA of the patient and her family members. The 7-bp deletion (named Hb Honghe [HBA1: c.401_407delGCACCGT]) of α-thalassemia in the α-globin gene was confirmed using Sanger sequencing. The patient's father was also a heterozygous carrier of HBA1: c.401_407delGCACCGT deletion, but not her mother or sister. The application of the combined molecular approach is essential for the accurate diagnosis of rare thalassemia. This study reports a novel case of α- thalassemia. The characterization of the mutation might provide new insights into genetic counseling and accurate diagnosis of thalassemia.
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Talasemia alfa , Humanos , Talasemia alfa/diagnóstico , Talasemia alfa/genética , Globinas alfa/genética , Hemoglobina Glucada , Pueblos del Este de Asia , Mutación , Familia de Multigenes , Eliminación de GenRESUMEN
Luminescent metal halides have been exploited as a new class of X-ray scintillators for security checks, nondestructive inspection, and medical imaging. However, the charge traps and hydrolysis vulnerability are always detrimental to the three-dimensional ionic structural scintillators. Here, the two zero-dimensional organic-manganese(II) halide coordination complexes 1-Cl and 2-Br were synthesized for improvements in X-ray scintillation. The introduction of a polarized phosphine oxide can help to increase the stabilities, especially the self-absorption-free merits of these Mn-based hybrids. The X-ray dosage rate detection limits reached up to 3.90 and 0.81 µGyair/s for 1-Cl and 2-Br, respectively, superior to the medical diagnostic standard of 5.50 µGyair/s. The fabricated scintillation films were applied to radioactive imaging with high spatial resolutions of 8.0 and 10.0 lp/mm, respectively, holding promise for use in diagnostic X-ray medical imaging.
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Anisotropic charge transport plays a pivotal role in clarifying the conductivity mechanism in direct X-ray detection to improve the detection sensitivity. However, the anisotropic photoelectric effect of semiconductive single crystal responsive to X-ray is still lacking of theoretical and experimental proof. The semiconductive coordination polymers (CPs) with designable structures, adjustable functions, and high crystallinity provide a suitable platform for exploring the anisotropic conductive mechanism. Here,the study first reveals a 1D conductive transmission path for direct X-ray detection from the perspective of structural chemistry. The semiconductive copper(II)-based CP 1 single crystal detector exhibits unique anisotropic X-ray detection performance. Along the 1D π-π stacking direction, the single crystal device (1-SC-a) shows a superior sensitivity of 2697.15 µCGyair -1 cm-2 and a low detection limit of 1.02 µGyair s-1 among CPs-based X-ray detectors. This study provides beneficial guidance and deep insight for designing high-performance CP-based X-ray detectors.
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Two examples of efficient cathode-ray scintillation coordination polymers with good stability at high voltage were prepared by conjugating luminescent groups with d10 metal ions. The synergistic effect of inorganic metal and organic ligand suppresses the self-quenching of the conjugated luminescent groups and enhances the scintillation performance. This work provides new ideas for the design of new field-emission displays and cathode-ray scintillation materials.
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Chromosomal abnormalities (CAs) can cause spontaneous miscarriage and increase the incidence of subsequent pregnancy loss and other complications. Presently, CAs are detected mainly by array comparative genomic hybridization (CGH) and single nucleotide polymorphism microarrays. The present study developed a lowcoverage nextgeneration sequencing method to detect CAs in spontaneous miscarriage and assess its clinical performance. In total, 1,401 patients who had experienced an abortion were enrolled in the present study and divided into two groups. In group I, 437 samples that had been previously validated by array CGH were used to establish a method to detect CAs using a semiconductor sequencing platform. In group II, 964 samples, which were not verified, were assessed using established methods with respect to clinical significance. Copy number variant (CNV)positive and euploidy samples were verified by array CGH and short tandem repeat profiling, respectively, based on quantitative fluorescent PCR. The lowcoverage sequencing method detected CNVs >1 Mb in length and a total of 3.5 million unique reads. Similar results to array CGH were obtained in group I, except for six CNVs <1 Mb long. In group II, there were 341 aneuploidies, 195 CNVs, 25 mosaicisms and 403 euploidies. Overall, among the 1,401 abortion samples, there were 536 aneuploidies, 263 CNVs, 34 mosaicisms, and 568 euploidies. Trisomies were present in all autosomal chromosomes. The most common aneuploidies were T16, monosomy X, T22, T15, T21 and T13. Furthermore, one tetrasomy 21, one CNV associated with WolfHirschhorn syndrome, one associated with DiGeorge syndrome and one associated with both PraderWilli and Angelman syndromes were identified. These four cases were confirmed by short tandem repeat profiling and array CGH. Quantitative fluorescent PCR revealed nine polyploidy samples. The present method demonstrated equivalent efficacy to that of array CGH in detecting CNVs >1 Mb, with advantages of requiring less input DNA and lower cost.
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Aborto Espontáneo , Aberraciones Cromosómicas , Trastornos de los Cromosomas/diagnóstico , Hibridación Genómica Comparativa/métodos , Variaciones en el Número de Copia de ADN , Aborto Espontáneo/diagnóstico , Aborto Espontáneo/genética , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Persona de Mediana Edad , Embarazo , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
Rare autosomal aneuploidies (RAAs) can cause miscarriage or other pregnancy complications and lead to inconsistent results of noninvasive prenatal testing (NIPT), but many NIPT providers have not yet started to provide related services. Our aim was to develop a semiconductor sequencing platform (SSP)-based method for detecting RAAs when pregnant women performed NIPT. Fifty-three aneuploidy samples with verified karyotyping or array comparative genomic hybridization (aCGH) results were collected and subjected to RAAs detection using an SSP to develop a method by genomic sequencing. Various trisomies on all chromosomes other than chromosomes 17 and 19, four multiple aneusomies, one monosomy and five sex chromosome abnormalities were got by our method which can directly identify RAAs via a z-score. Then, artificial mixtures of 10% and 5% DNA were created by adding fragmented fifty-three tissue samples and used in an NIPT simulation to develop a bioinformatics analysis method which can use in NIPT. And the results were in accordance with those of karyotyping and aCGH. Therefore, our method has potential for use in NIPT. Finally, 23,823 clinical plasma samples were tested to verify the performance of our approach. Karyotyping or aCGH was performed on the positive clinical samples. In total, 188 of 23,823 clinical samples were positive (T2, n = 1; T7, n = 1; T13, n = 15; T18, n = 45; T21, n = 125; and multiple aneusomies, n = 1) and verified by karyotyping or aCGH; no sample was a false negative. Several false positives were detected, one of which showed maternal copy number variation (CNV). One case of multiple aneusomies was caused by a maternal tumor. The method developed enables detection of RAAs without increasing costs.
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Aneuploidia , Trastornos de los Cromosomas/diagnóstico , Pruebas de Detección del Suero Materno/métodos , Aborto Espontáneo/genética , Adulto , Trastornos de los Cromosomas/genética , Hibridación Genómica Comparativa , Femenino , Humanos , Cariotipificación/métodos , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Embarazo , Semiconductores , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
Emodin, a natural anthraquinone isolated from the traditional Chinese medicine Radix rhizoma Rhei, can induce apoptosis in many kinds of cancer cells. This study demonstrated that emodin induces apoptosis in human colon cancer HCT116 cells by provoking oxidative stress, which subsequently triggers a p53-mitochondrial apoptotic pathway. Emodin induced mitochondrial transmembrane potential loss, increase in Bax and decrease in Bcl-2 expression and mitochondrial translocation and release of cytochrome c to cytosol in HCT116 cells. In response to emodin-treatment, ROS increased rapidly, and subsequently p53 was overexpressed. Pretreatment with the antioxidant NAC diminished apoptosis and p53 overexpression induced by emodin. Transfecting p53 siRNA also attenuated apoptosis induced by emodin, Bax expression and mitochondrial translocation being reduced compared to treatment with emodin alone. Taken together, these results indicate that ROS is a trigger of emodin-induced apoptosis in HCT116 cells, and p53 expression increases under oxidative stress, leading to Bax-mediated mitochondrial apoptosis.