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Background: Anxiety disorders have emerged as one of the most prevalent mental health problems and health concerns. However, previous research has paid limited attention to measuring public anxiety from a broader perspective. Furthermore, while we know many factors that influence anxiety disorders, we still have an incomplete understanding of how these factors affect public anxiety. We aimed to quantify public anxiety from the perspective of Internet searches, and to analyze its spatiotemporal changing characteristics and influencing factors. Methods: This study collected Baidu Index from 2014 to 2022 in 31 provinces in mainland China to measure the degree of public anxiety based on the Baidu Index from 2014 to 2022. The spatial autocorrelation analysis method was used to study the changing trends and spatial distribution characteristics of public anxiety. The influencing factors of public anxiety were studied using spatial statistical modeling methods. Results: Empirical analysis shows that the level of public anxiety in my country has continued to rise in recent years, with significant spatial clustering characteristics, especially in the eastern and central-southern regions. In addition, we constructed ordinary least squares (OLS) and geographically weighted regression (GWR) spatial statistical models to examine the relationship between social, economic, and environmental factors and public anxiety levels. We found that the GWR model that considers spatial correlation and dependence is significantly better than the OLS model in terms of fitting accuracy. Factors such as the number of college graduates, Internet traffic, and urbanization rate are significantly positively correlated with the level of public anxiety. Conclusion: Our research results draw attention to public anxiety among policymakers, highlighting the necessity for a more extensive examination of anxiety issues, especially among university graduates, by the public and relevant authorities.
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Ansiedade , Humanos , China/epidemiologia , Ansiedade/epidemiologia , Feminino , Masculino , Transtornos de Ansiedade/epidemiologia , Adulto , Internet/estatística & dados numéricosRESUMO
Osteosarcoma is a highly aggressive cancer prevalent among adolescents and young adults, notorious for its tendency to metastasize to the lungs. This research delves into the molecular foundations of osteosarcoma by examining the role of the Hippo signaling pathway and its interaction with the tumor immune microenvironment (TME). Through analysis of transcriptomic data from the TARGET-OS dataset and control samples from GTEx, we identified a set of 131 genes that link high expression profiles in osteosarcoma with the Hippo pathway. A focused examination through univariate Cox regression analysis revealed eight key genes (DLG5, WNT11, TGFB2, DLG4, WNT16, ID2, WNT10B, and WNT10A) with a significant correlation to patient outcomes. Hierarchical clustering of these genes delineated two distinct patient groups with significantly different survival rates, a finding supported by Kaplan-Meier survival analysis. Further investigation into immune cell infiltration and expression profiles of immunoregulatory factors uncovered a notable pattern of immune evasion in the group with poorer prognosis, marked by reduced effector immune cell activity and lower levels of immunostimulatory factors. Single-cell sequencing highlighted the cellular diversity within osteosarcoma samples and identified markers differentiating malignant from nonmalignant cells, correlating these markers with prognostic risk scores. Our results emphasize the critical prognostic value of Hippo pathway genes and the TME in osteosarcoma, shedding light on new avenues for therapeutic intervention and patient-specific treatment strategies.
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Objective: To compare the efficacy and safety of venetoclax (VEN) in combination with chemotherapy (chemo) versus chemo alone in the treatment of acute myeloid leukemia (AML). Method: To compare the efficacy and/or safety of VEN+chemo versus chemotherapy alone for AML, PubMed, Embase, Web of Science, and the Cochrane Library were used to searching up to June 2023. Comparisons included complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), overall response rate (ORR), and adverse events (AEs). Result: A total of 9 articles were included, including 3124 patients. The baseline characteristics between two patient groups were similar. The combined analysis showed that compared with the group receiving chemo alone, the VEN+chemo group exhibited higher rates of CR, CRi, MLFS and ORR. Additionally, the VEN+chemo group had longer event-free survival (EFS) and overall survival (OS) durations. The incidence rates of AEs and serious AEs (SAEs) were similar between the two groups, but the early 30-day mortality rate was lower in the VEN+chemo group than in the chemo alone group. Conclusion: The VEN+chemo therapy demonstrates significant efficacy and safety profile in AML patients. However, more prospective studies are needed in the future to provide more accurate and robust evidence for treatment selection in patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439288, identifier CRD42023439288.
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Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease, and it is a multifactorial disease of the intestinal mucosa. Oxidative stress damage and inflammation are major risk factors for IBD. Vitamin E has powerful antioxidant and anti-inflammatory effects. Our previous work and other investigations have shown that vitamin E has a positive effect on the prevention and treatment of IBD. In this paper, the source and structure of vitamin E and the potential mechanism of vitamin E's role in IBD were summarized, and we also analyzed the status of vitamin E deficiency in patients with IBD and the effect of vitamin E supplementation on IBD. The potential mechanisms by which vitamin E plays a role in the prevention and treatment of IBD include improvement of oxidative damage, enhancement of immunity, maintenance of intestinal barrier integrity, and suppression of inflammatory cytokines, modulating the gut microbiota and other relevant factors. The review will improve our understanding of the complex mechanism by which vitamin E inhibits IBD, and it also provides references for doctors in clinical practice and researchers in this field.
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Huangqi Liuyi Decoction, a famous classical Chinese prescription, shows significant curative effect on diabetes and its complications, in which calycosin-7-glucoside, liquiritin and glycyrrhizic acid are the main components that playing these mentioned pharmacological activity, under the synergistic action of various other ingredients in the decoction. However, there are significant differences in the content of active compounds in Chinese medicinal materials, which mainly due to origin, picking seasons, and processing methods. Hence, the accurate content of the glycosides is the prerequisite for ensuring the pharmacological efficacy. Aiming at establishing an efficient extraction and determination method for accurate quantitative analysis of calycosin-7-glucoside, liquiritin and glycyrrhizic acid in Huangqi Liuyi Decoction, an on line solid-phase extraction-high-performance liquid chromatography method was developed, using a homemade bio-based monolithic adsorbent. The bio-based adsorbent was prepared in a stainless steel tube, using bio-monomers of methyleugenol and S-allyl-L-cysteine, which effectively reduced the dependence of the polymer field on non-renewable fossil resources and reduced carbon emissions. Furthermore, the prepared adsorbent owned abundant chemical groups, which can produce interactions of hydrogen bond, dipole-dipole, π-π and hydrophobic force with the target glycosides, thus improving the specific recognition ability of the adsorbent. The experiments were carried out on an LC-3000 HPLC instrument with a six-way valve. Methodology validation indicates that the recovery is in the range of 97.0%-103.4% with the RSD in the range of 1.6%-4.0%, due to the specific selectivity of the bio-based monolithic adsorbent for these three glycosides, and good matrix-removal ability for Huangqi Liuyi decoction. The limit of detection is 0.17, 0.50 and 0.33 µg/mL for calycosin-7-glucoside, liquiritin and glycyrrhizic acid, respectively, and the limit of quantitation is 0.50, 1.50 and 1.00 µg/mL, respectively, with the linear range of 2-200 µg/mL for calycosin-7-glucoside, and 5-500 µg/mL for liquiritin and glycyrrhizic acid. The present work provided a simple and efficient method for the extraction and determination of glycosides in complex medicinal plants.
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Astragalus propinquus , Medicamentos de Ervas Chinesas , Glicosídeos , Polímeros/análise , Ácido Glicirrízico , Medicamentos de Ervas Chinesas/química , Glucosídeos/análise , Cromatografia Líquida de Alta Pressão/métodosRESUMO
A monolithic adsorbent was designed aiming to the structure of osthole and columbianadin, and fabricated using diallyl phthalate as the monomer and ethylene dimethacrylate as the crosslinker with the addition of bamboo biochar, via polymerization reaction in a stainless-steel tube. The prepared composite adsorbent packed in the tube was used as a solid-phase extraction column for the extraction and determination of two coumarins (osthole and columbianadin) in Angelicae Pubescentis Radix, combing with a C18 analytical column through an HPLC instrument, which show excellent matrix-removal ability and good selectivity to osthole and columbianadin. Furthermore, the present adsorbent shows good applicability, which was used for the extraction of osthole from Duhuo Jisheng Pill. Compared to the commercial C18 and phenyl adsorbent, the present adsorbent own better selectivity and higher resolution. These results attributed to the enhanced specific surface area (141 m2/g) and enriched interaction sites of the resulting composite adsorbent, due to the doping of bamboo biochar, which can produce hydrogen bond, dipole-dipole, π-π and hydrophobic force interactions with the osthole and columbianadin. The methodology validation indicated that the present method showed good precision and good accuracy, and the composite adsorbent showed good preparative repeatability, which can be reused for no less than 100 times with the relative standard deviation ≤4.6 % (n = 100). The present work provided a simple and efficient method for the extraction and determination osthole and columbianadin from Angelicae Pubescentis Radix.
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Carvão Vegetal , Sasa , Cumarínicos , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Excessive swelling is one important factor that leads to high fuel permeability and limited operating concentration of methanol for proton exchange membranes. Herein, a collaborative strategy of main-chain and molecular-network engineering is applied to lower swelling ratio and improve methanol resistance for highly sulfonated polyimide. Two m-phenylenediamine monomers (4-(2,3,5,6-tetrafluoro-4-vinylphenoxy)benzene-1,3-diamine and 4,6-bis(2,3,5,6-tetrafluoro-4-vinylphenoxy)benzene-1,3-diamine) with tetrafluorostyrol groups are designed and synthesized. Two series of cross-linked sulfonated polyimides (CSPI-Ts, CSPI-Bs) are prepared from the two diamines, 4,4'-diaminostilbene-2,2'-disulfonic acid and 1,4,5,8-naphthalenetetracarboxylicdianhydride. The rigid main-chain structure is cornerstone for wet CSPI-Ts and CSPI-Bs remaining stable at elevated temperatures. The introduction of hydrophobic cross-linked network further improves their dimensional stability and methanol resistance. CSPI-Ts and CSPI-Bs show obviously improved performances containing high proton conductivity (121 ± 0.27-158 ± 0.35 S cm-1 ), low swelling ratio (9.6 ± 0.40%-16.1 ± 0.01%) and methanol permeability (4.14-7.69 × 10-7 cm2 s-1 ) at 80 °C. The direct methanol fuel cell (DMFC) is assembled from CSPI-T-10 with balanced properties, and it exhibits high maximum power density (PDmax ) of 82.3 and 72.6 mW cm-2 in 2 and 10 m methanol solution, respectively. The ratio of PDmax in 10 m methanol solution to the value in 2 m methanol solution is as high as 88%. The CSPI-T-10 is promising proton exchange membrane candidate for DMFC application.
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Benzeno , Metanol , Prótons , Alcanossulfonatos , DiaminasRESUMO
CONTEXT.: Thalassemia is the most widely distributed monogenic autosomal recessive disorder in the world. Accurate genetic analysis of thalassemia is crucial for thalassemia prevention. OBJECTIVE.: To compare the clinical utility of a third-generation sequencing-based approach termed comprehensive analysis of thalassemia alleles with routine polymerase chain reaction (PCR) in genetic analysis of thalassemia and explore the molecular spectrum of thalassemia in Hunan Province. DESIGN.: Subjects in Hunan Province were recruited, and hematologic testing was performed. Five hundred four subjects positive on hemoglobin testing were then used as the cohort, and third-generation sequencing and routine PCR were used for genetic analysis. RESULTS.: Of the 504 subjects, 462 (91.67%) had the same results, whereas 42 (8.33%) exhibited discordant results between the 2 methods. Sanger sequencing and PCR testing confirmed the results of third-generation sequencing. In total, third-generation sequencing correctly detected 247 subjects with variants, whereas PCR identified 205, which showed an increase in detection of 20.49%. Moreover, α triplications were identified in 1.98% (10 of 504) hemoglobin testing-positive subjects in Hunan Province. Seven hemoglobin variants with potential pathogenicity were detected in 9 hemoglobin testing-positive subjects. CONCLUSIONS.: Third-generation sequencing is a more comprehensive, reliable, and efficient approach for genetic analysis of thalassemia than PCR, and allowed for a characterization of the thalassemia spectrum in Hunan Province.
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Talassemia , Talassemia beta , Humanos , Talassemia/diagnóstico , Talassemia/genética , Testes Hematológicos , Testes de Coagulação Sanguínea , Reação em Cadeia da Polimerase/métodos , Hemoglobinas , Mutação , Genótipo , Talassemia beta/diagnóstico , Talassemia beta/genéticaRESUMO
BACKGROUND: Thalassemia, a common autosomal hereditary blood disorder worldwide, mainly contains α- and ß-thalassemia. The α-globin gene triplicates allele is harmless for carriers, but aggravates the phenotype of ß-thalassemia. Therefore, it is particularly crucial to accurately detect the structural variants of α-globin gene clusters. CASE REPORT: We reported a 28-year-old man, the proband, with microcytic hypochromic anemia. From pedigree analysis, his mother and sister had hypochromic microcytosis, and his father was normal. Genetic testing of thalassemia identified a novel α-globin gene triplicate named αααanti4.2del726bp (NC_000016.10:g.170769_174300dupinsAAAAAA) by third-generation sequencing (TGS) in the proband and his father, which was further validated by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. The genotypes of the proband's mother and sister were both -α3.7/αα compounded with heterozygous HBB:c.126_129delCTTT. They were categorized as silent α-thalassemia with co-inheritance of ß-thalassemia trait. The proband's genotype additionally had the α-globin gene triplicates compared with his mother and sister, which increased the imbalance between α/ß-globin, so the proband had more severe hematological parameters. The proband's wife was diagnosed as HBA2:c.427T > C heterozygosis, and his daughter had the novel α-globin gene triplicates compounded with HBA2:c.427T > C, therefore the girl might be asymptomatic. CONCLUSION: The identification of the novel α-globin gene triplicates provides more insight for the research of thalassemia variants and indicates that TGS has signiï¬cant advantages on genetic testing of thalassemia for the reliability, accuracy and comprehensiveness.
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Talassemia alfa , Talassemia beta , Masculino , Feminino , Humanos , Adulto , Talassemia beta/genética , Linhagem , alfa-Globinas/genética , Reprodutibilidade dos Testes , Genótipo , Talassemia alfa/diagnóstico , Talassemia alfa/genética , MutaçãoRESUMO
Peptides are important components of human nutrition and health, and considered as safe, nontoxic, and easily absorbed potential drugs. Anti-hypoxia peptides are a kind of peptides that can prevent hypoxia or hypoxia damage. In this paper, the sources, preparations, and molecular mechanisms of anti-hypoxia peptides were systemically reviewed. The combination of bioinformatics, chemical synthesis, enzymatic hydrolysis, and microbial fermentation are recommended for efficient productions of anti-hypoxic peptides. The mechanisms of anti-hypoxic peptides include interference with glycolytic process and HIF-1α pathway, mitochondrial apoptosis, and inflammatory response. In addition, bioinformatics analysis, including virtual screening and molecular docking, provides an alternative or auxiliary method for exploring the potential anti-hypoxic activities and mechanisms of peptides. The potential challenges and prospects of anti-hypoxic peptides are also discussed. This paper can provide references for researchers in this field and promote further research and clinical applications of anti-hypoxic peptides in the future.
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Licorice is a frequently applied herb with potential edible and medicinal value based on various flavonoids and triterpenes. However, studies on detailed flavonoid and triterpene metabolism and the molecular basis of their biosynthesis in licorice are very limited, especially under drought conditions. In the present study, we carried out transcriptome, proteome, and metabolome experiments. To ultimately combine three omics for analysis, we performed a bioinformatics comparison, integrating transcriptome data and proteome data through a Cloud platform, along with a simplified biosynthesis of primary flavonoids and triterpenoids in the KEGG pathway based on metabolomic results. The biosynthesis pathways of triterpenes and flavonoids are enriched at both gene and protein levels. Key flavonoid-related genes (PAL, 4CL, CHS, CHI, CYP93C, HIDH, HI4OMT, and CYP81E1_7) and representative proteins (HIDH, CYP81E1_7, CYP93C, and VR) were obtained, which all showed high levels after drought treatment. Notably, one R2R3-MYB transcription factor (Glyur000237s00014382.1), a critical regulator of flavonoid biosynthesis, achieved a significant upregulated expression as well. In the biosynthesis of glycyrrhizin, both gene and protein levels of bAS and CYP88D6 have been found with upregulated expression under drought conditions. Most of the differentially expressed genes (DEGs) and proteins (DEPs) showed similar expression patterns and positively related to metabolic profiles of flavonoid and saponin. We believe that suitable drought stress may contribute to the accumulation of bioactive constituents in licorice, and our research provides an insight into the genetic study and quality breeding in this plant.
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Glycyrrhiza uralensis , Glycyrrhiza , Glycyrrhiza uralensis/genética , Secas , Multiômica , Proteoma/metabolismo , Melhoramento Vegetal , Flavonoides/metabolismo , Ácido Glicirrízico/metabolismo , Regulação da Expressão Gênica de Plantas , TranscriptomaRESUMO
With the change in people's lifestyle, diabetes has emerged as a chronic disease that poses a serious threat to human health, alongside tumor, cardiovascular, and cerebrovascular diseases. α-glucosidase inhibitors, which are oral drugs, have proven effective in preventing and managing this disease. Studies have suggested that bioactive peptides could serve as a potential source of α-glucosidase inhibitors. These peptides possess certain hypoglycemic activity and can effectively regulate postprandial blood glucose levels by inhibiting α-glucosidase activity, thus intervening and regulating diabetes. This paper provides a systematic summary of the sources, isolation, purification, bioavailability, and possible mechanisms of α-glucosidase inhibitory peptides. The sources of the α-glucosidase inhibitory peptides were introduced with emphasis on animals, plants, and microorganisms. This paper also points out the problems in the research process of α-glucosidase inhibitory peptide, with a view to providing certain theoretical support for the further study of this peptide.
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Diabetes Mellitus , Inibidores de Glicosídeo Hidrolases , Animais , Humanos , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , alfa-Glucosidases , Peptídeos/farmacologia , Peptídeos/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/químicaRESUMO
Background: An association between the healthy eating index (HEI)-2015 and risk of abdominal aortic calcification (AAC) is unclear in the general population of the United States (U.S.). Therefore, we examined the relationship between HEI-2015 and AAC risk in our research. Methods: A cross-sectional study of National Health and Nutrition Examination Surveys (NHANES) participants between 2013 and 2014 was conducted. For the analysis of the association between HEI-2015 and AAC, the restricted cubic spline (RCS) plot and multivariable logistic regression models were used. In addition, we also conducted subgroup analysis for the relationship between HEI-2015 and AAC. Results: There was a total of 1162 individuals. As shown by the RCS plot, HEI-2015 was linked with AAC risk in a U-shaped pattern (P for nonlinearity < 0.05). Taking into account known confounding variables, compared with the lowest quartiles, the odds ratios with 95% confidence intervals for AAC across the quartiles were 0.637 (0.425,0.956), 0.763 (0.499, 1.167), and 0.842 (0.561, 1.265). Based on the results of subgroup analysis, the HEI-2015 and AAC risk were U-curve correlated among all age groups, sex, with or without hypertension or DM, and BMI of <30 kg/m2. The greens and beans, and whole fruits are independent protective factor for AAC. Conclusions: The U-shaped relationships exist between HEI-2015 and prevalence of AAC in the general U.S. population. Consequently, prevalence of AAC may be mitigated with reasonable and balanced diet.
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Leek (Allium fistulosum L.), a common and widely used food ingredient, is a traditional medicine used in Asia to treat a variety of diseases. Leeks contain a variety of bioactive substances, including sulfur compounds, dietary fiber, steroid compounds and flavonoid compounds. Many studies have shown that these active ingredients produce the following effects: promotion of blood circulation, lowering of cholesterol, relief of fatigue, anti-inflammation, anti-bacteria, regulation of cell metabolism, anti-cancer, anti-oxidation, and the lowering of fat and blood sugar levels. In this paper, the main bioactive components and biological functions of leeks were systemically reviewed, and the action mechanisms of bioactive components were discussed. As a common food, the health benefits of leeks are not well known, and there is no systematic summary of leek investigations. In light of this, it is valuable to review the recent progress and provide reference to investigators in the field, which will promote future applications and investigations of leeks.
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OBJECTIVE: The 4.2â kb deletion (-α4.2/) is a common a+-thalassemia with a carrier rate, followed by the South-East Asian deletion (-SEA) and the 3.7â kb deletion (-α3.7/). There are few reports about 4.2â kb deletion sub-types. Herein, we present a patient with double heterozygous -α4.2â /-α4.2â ¡who was identified using third-generation sequencing (TGS). METHODS: Hematology and hemoglobin fraction analysis were carried out by complete blood count (CBC) and capillary electrophoresis (CE). Gap-PCR was used to detect the common deletional α-thalassemia, and multiple ligation-dependent probe amplification (MLPA) was performed to screen the large deletion. Sanger sequencing identified the variant. The different deletions were confirmed by TGS. RESULTS: CBC showed the patient with microcytic hypochromic anemia, and CE indicated the presence of a Hb variant. Gap-PCR and MLPA detected 4.2â kb deletion homozygotes (-α4.2/-α4.2). The Hb variant was confirmed as Hb Q-Thailand by Sanger sequencing. The patient was identified as compound heterozygous of 4.2â kb deletion and Hb Q-Thailand (-α4.2/-α4.2-Q-Thailand, -α4.2â /-α4.2â ¡) using TGS. CONCLUSIONS: Hb Q-Thailand (-α4.2-Q-Thailand/) complex 4.2â kb deletion heterozygote (-α4.2/) is easily misdiagnosed as 4.2â kb homozygous using Gap-PCR and MLPA. The TGS enables the identification of the two different 4.2â kb deletion sub-types.
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Anemia Hipocrômica , Humanos , Anemia Hipocrômica/genética , Povo Asiático , Eletroforese Capilar , Heterozigoto , Homozigoto , Análise de Sequência de DNARESUMO
BACKGROUND: Hemophilia A (HA) is the most frequently occurring X-linked bleeding disorder caused by heterogeneous variants in the F8 gene, one of the largest genes known. Conventional molecular analysis of F8 requires a combination of assays, usually including long-range polymerase chain reaction (LR-PCR) or inverse-PCR for inversions, Sanger sequencing or next-generation sequencing for single-nucleotide variants (SNVs) and indels, and multiplex ligation-dependent probe amplification for large deletions or duplications. MATERIALS AND METHODS: This study aimed to develop a LR-PCR and long-read sequencing-based assay termed comprehensive analysis of hemophilia A (CAHEA) for full characterization of F8 variants. The performance of CAHEA was evaluated in 272 samples from 131 HA pedigrees with a wide spectrum of F8 variants by comparing to conventional molecular assays. RESULTS: CAHEA identified F8 variants in all the 131 pedigrees, including 35 intron 22-related gene rearrangements, 3 intron 1 inversion (Inv1), 85 SNVs and indels, 1 large insertion, and 7 large deletions. The accuracy of CAHEA was also confirmed in another set of 14 HA pedigrees. Compared with the conventional methods combined altogether, CAHEA assay demonstrated 100% sensitivity and specificity for identifying various types of F8 variants and had the advantages of directly determining the break regions/points of large inversions, insertions, and deletions, which enabled analyzing the mechanisms of recombination at the junction sites and pathogenicity of the variants. CONCLUSION: CAHEA represents a comprehensive assay toward full characterization of F8 variants including intron 22 and intron 1 inversions, SNVs/indels, and large insertions and deletions, greatly improving the genetic screening and diagnosis for HA.
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Hemofilia A , Humanos , Hemofilia A/diagnóstico , Hemofilia A/genética , Fator VIII/genética , Testes Genéticos , Íntrons , Reação em Cadeia da Polimerase Multiplex , MutaçãoRESUMO
DNA aptamers are single-stranded DNA oligonucleotide sequences that bind to specific targets with high affinity. Currently, DNA aptamers can be produced only by in vitro synthesis. It is difficult for DNA aptamers to have a sustained impact on intracellular protein activity, which limits their clinical application. In this study, we developed a DNA aptamer expression system to generate DNA aptamers with functional activity in mammalian cells by mimicking retroviruses. Using this system, DNA aptamers targeting intracellular Ras (Ra1) and membrane-bound CD71 (XQ2) were successfully generated in cells. In particular, the expressed Ra1 not only specifically bound to the intracellular Ras protein but also inhibited the phosphorylation of downstream ERK1/2 and AKT. Furthermore, by inserting the DNA aptamer expression system for Ra1 into a lentivirus vector, the system can be delivered into cells and stably produce Ra1 over time, resulting in the inhibition of lung cancer cell proliferation. Therefore, our study provides a novel strategy for the intracellular generation of DNA aptamers with functional activity and opens a new avenue for the clinical application of intracellular DNA aptamers in disease treatment.
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Aptâmeros de Nucleotídeos , Animais , Aptâmeros de Nucleotídeos/genética , Retroviridae/genética , DNA de Cadeia Simples , Lentivirus/genética , Técnica de Seleção de Aptâmeros/métodos , MamíferosRESUMO
The decentralized manycore architecture is broadly adopted by neuromorphic chips for its high computing parallelism and memory locality. However, the fragmented memories and decentralized execution make it hard to deploy neural network models onto neuromorphic hardware with high resource utilization and processing efficiency. There are usually two stages during the model deployment: one is the logical mapping that partitions parameters and computations into small slices and allocate each slice into a single core with limited resources; the other is the physical mapping that places each logical core to a physical location in the chip. In this work, we propose the mapping limit concept for the first time that points out the resource saving upper limit in logical and physical mapping. Furthermore, we propose a closed-loop mapping strategy with an asynchronous 4D model partition for logical mapping and a Hamilton loop algorithm (HLA) for physical mapping. We implement the mapping methods on our state-of-the-art neuromorphic chip, TianjicX. Extensive experiments demonstrate the superior performance of our mapping methods, which can not only outperform existing methods but also approach the mapping limit. We believe the mapping limit concept and the closed-loop mapping strategy can help build a general and efficient mapping framework for neuromorphic hardware.
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Isolation of circulating fetal nucleated red blood cells (cfNRBCs) from maternal peripheral blood provides a superior strategy for noninvasive prenatal genetic diagnosis. Recent technical advances in single-cell isolation and genetic analyses have promoted the clinical application of circulating fetal cell-based noninvasive prenatal diagnosis. However, the lack of highly specific ligands for rare circulating fetal cell enrichment from massive maternal cells significantly impedes the clinical transformation progress. In this work, aptamers specific to NRBCs were developed through clinical sample-based cell-SELEX. Herein, the complex clinical system provides natural selection stringency through binding competition between target and background cells, and it empowers aptamers with high specificity. An aptamer-based strategy was also established to isolate cfNRBCs from maternal peripheral blood. Results show the remarkable selectivity and affinity of developed aptamers, enabling efficient enrichment of cfNRBCs from abundant maternal cells. Moreover, screening for fetal sex and trisomy syndrome achieved high accuracy through chromosome analysis of enriched cfNRBCs. To the best of our knowledge, this is the first report to develop aptamer ligands for cfNRBC enrichment, providing an efficient strategy to screen cfNRBC-specific ligands and demonstrating broad application potential for cfNRBC-based noninvasive prenatal diagnosis.