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Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time. All conjugate vaccines induced cytokine secretion in murine and human macrophages in vitro, and promoted specific antibody production in vivo. Notably, a conjugate containing imidazoquinoline TLR7/8 agonist (TLR7/8a1) showed the greatest enhancement in Th1/2 balanced antibody response. To minimize the interference with the protein antigenic integrity, we further developed a systematic glycoconjugation strategy to conjugate this TLR7/8a1 onto the glycan chains of SARS-CoV-2 S1 glycoprotein via oxime ligation, in which S1 containing different numbers of aldehyde groups were obtained by differential periodate oxidation. The resulting TLR7/8a1-S1 conjugate triggered a potent humoral and cellular immunity in vivo. Together these data demonstrate the promise of these TLR7 and TLR7/8 agonists as effective built-in adjuvants, and the versatile oxime ligation strategy might broaden potential applications in designing different conjugate vaccines.
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Fragile X syndrome is the leading genetic cause of intellectual disability and autism spectrum disorders. Female premutation carriers exhibit no obvious symptoms during reproductive age, but the premutation allele can expand to full mutation when transmitted to the fetus. Given the relatively low prevalence but large population, the distinct health care system, the middle-income economic status, and low awareness among public and medical professionals, the optimal genetic screening strategy remains unknown. We conducted a pilot study of Fragile X carrier screening in China, involving 22,245 pregnant women and women with childbearing intentions, divided into control and pilot groups. The prevalence of Fragile X carriers in the control group was 1 of 850, similar to East Asian populations. Strikingly, the prevalence of Fragile X carriers in the pilot group was 1 of 356, which can be attributed to extensive medical training, participant education, and rigorous genetic counseling and testing protocols. Cost-effectiveness analyses of four strategies-no screening, population-based screening, targeted screening, and our pilot screening-indicated that our pilot screening was the most cost-effective option. A follow-up survey revealed that 55% of respondents reported undergoing screening because of their family history. We have successfully established a standardized system, addressing the challenges of low prevalence, limited awareness, and genetic testing complexities. Our study provides practical recommendations for implementing Fragile X carrier screening in China.
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Background: Non-invasive prenatal tests (NIPT) are used to screen for trisomy 21, 18, and 13. This study investigated NIPT performance and the clinical significance of its results. Methods: Pregnant women (n = 282,911) participating in a free NIPT (April 2018-December 2021) were screened for common trisomies, and the results were retrospectively analyzed. NIPT performance was evaluated by its positive predictive value (PPV), sensitivity, and specificity. Results were analyzed using number, percentage, and chi-squared/t-test analyses. Results: After NIPT screening, patients with common trisomies (n = 746) included 457 with T21, 160 with T18, and 129 with T13. Seven false negative cases were identified. High PPV (86.81 %, 56.81 %, 18.18 %), sensitivity (99.25 %, 98.33 %, 100.00 %), and specificity (99.98 %, 99.98 %, 99.97 %) values were detected for trisomy 21, 18, and 13, respectively. The PPVs of common trisomies were significantly different between pregnant women older than 35 (85.53 %, 136/159) and those aged 35 or younger (58.90 %, 311/528) (χ2 = 125.02, P = 2.20e-16). As the NIPT uptake increased from 2018 to 2021, live-born birth defect incidence decreased. Conclusion: NIPT performed well in screening for T21, T18, and T13. Our discoveries offer an important and useful guideline in laboratory and clinical genetic counseling.
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Zeugodacus cucurbitae (Coquillett) is a significant pest affecting fruit and vegetables in tropical and subtropical regions, and its development and reproduction are enhanced after exposure to short-term high-temperature stress at 45 °C. Vitellogenin (Vg) is an essential precursor of yolk protein formation in eggs and plays a vital role in the ovarian development of insects. Interfering with the Z. cucurbitae vitellogenin receptor (ZcVgR) gene in short-term high-temperature conditions decreases the fecundity of female adults, while the transcription level of the ZcVg3 gene increases. To elucidate the reproductive function of the ZcVg3 gene and the synergistic relationship among the ZcVgs genes under short-term high temperatures, this study injected siRNA to interfere with the ZcVg3 gene after subjecting Z. cucurbitae to a 1 h treatment at 45 °C and 25 °C. The expression of the ZcVg3 gene was suppressed, leading to the upregulation of the ZcVg1 and ZcVg2 genes, and the expression of the ZcVgR gene was initially decreased and then increased. Silencing the ZcVg3 gene after a 1 h treatment at 45 °C resulted in a reduction of approximately 84.7% and 75.9% in the fecundity and spawning days of female adults compared to the control. The development rate of their ovaries and the ovarian diameter significantly decreased, and their lifespan was reduced by 71%. The ZcVg3 gene plays a crucial role in the reproduction of Z. cucurbitae in short-term high-temperature conditions. The results of this study provide potential targets for the development of RNAi-based techniques for the control of Z. cucurbitae.
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Synthetic α-galactosylceramide (αGalCer) and its analogues as powerful agonists for natural killer T (NKT) cell manipulation have received significant attention in immunotherapy and adjuvant development. However, identifying new potent NKT cell agonists, especially those with Th1 selectivity that promote anticancer effects, remains a challenging task. In this work, we introduced a sulfonamide group into the acyl chain of αGalCer to form additional hydrogen bonds to intensify the glycolipid/CD1d interaction. Two compounds GCS-11 and GCS-12 demonstrated remarkable potency while exhibiting different cytokine induction patterns. Compared to αGalCer, the Th1-biased GCS-11 exhibited a 6-fold increase in IFN-γ but not IL-4, while the Th1/2-balanced GCS-12 elicited 7- and 5-fold increase in IFN-γ and IL-4, respectively, in vivo. These findings place them among the most potent NKT cell agonists, with superior antitumor effects. Therefore, hydrogen-bond-involved derivatization could be a powerful strategy to develop potent and polarized NKT cell agonists for various immunotherapies.
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Antígenos CD1d , Citocinas , Desenho de Fármacos , Galactosilceramidas , Ligação de Hidrogênio , Células T Matadoras Naturais , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/efeitos dos fármacos , Células T Matadoras Naturais/metabolismo , Animais , Galactosilceramidas/química , Galactosilceramidas/farmacologia , Galactosilceramidas/síntese química , Camundongos , Citocinas/metabolismo , Antígenos CD1d/metabolismo , Antígenos CD1d/química , Humanos , Interleucina-4/metabolismo , Relação Estrutura-Atividade , Camundongos Endogâmicos C57BL , Interferon gama/metabolismo , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular TumoralRESUMO
BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.
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Testes Genéticos , Atrofia Muscular Espinal , Triagem Neonatal , Humanos , Recém-Nascido , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Projetos Piloto , Testes Genéticos/normas , Testes Genéticos/métodos , Triagem Neonatal/normas , Triagem Neonatal/métodos , China , Teste em Amostras de Sangue Seco/normas , Teste em Amostras de Sangue Seco/métodos , Garantia da Qualidade dos Cuidados de Saúde , Laboratórios Clínicos/normas , Proteína 1 de Sobrevivência do Neurônio Motor/genéticaRESUMO
In recombinant protein-producing yeast strains, cells experience high production-related stresses similar to high temperatures. It is possible to increase recombinant protein production by enhancing thermotolerance, but few studies have focused on this topic. Here we aim to identify cellular regulators that can simultaneously activate thermotolerance and high yield of recombinant protein. Through screening at 46 °C, a heat-resistant Kluyveromyces marxianus (K. marxianus) strain FDHY23 is isolated. It also exhibits enhanced recombinant protein productivity at both 30 °C and high temperatures. The CYR1N1546K mutation is identified as responsible for FDHY23's improved phenotype, characterized by weakened adenylate cyclase activity and reduced cAMP production. Introducing this mutation into the wild-type strain greatly enhances both thermotolerance and recombinant protein yields. RNA-seq analysis reveals that under high temperature and recombinant protein production conditions, CYR1 mutation-induced reduction in cAMP levels can stimulate cells to improve its energy supply system and optimize material synthesis, meanwhile enhance stress resistance, based on the altered cAMP signaling cascades. Our study provides CYR1 mutation as a novel target to overcome the bottleneck in achieving high production of recombinant proteins under high temperature conditions, and also offers a convenient approach for high-throughput screening of recombinant proteins with high yields.
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AMP Cíclico , Kluyveromyces , Proteínas Recombinantes , Transdução de Sinais , AMP Cíclico/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Kluyveromyces/genética , Kluyveromyces/metabolismo , Termotolerância/genética , Mutação , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Temperatura AltaRESUMO
OBJECTIVE: To determine the detection rate of chromosomal abnormalities and pregnancy outcomes in fetuses with intrauterine growth restriction. Study design A total of 151 fetal samples with intrauterine growth restriction were divided into the isolated fetal growth restriction (FGR) group, FGR group with structural malformation, and FGR group with non-structural malformation, according to ultrasound abnormalities. The enrolled patients were divided into an early onset FGR group (<32 weeks) and a late-onset FGR group (≥32 weeks). Chromosomal karyotype and microarray analyses were performed and pregnancy outcomes were monitored. Results The karyotypes of 122 patients were analyzed. Four patients exhibited abnormal chromosome numbers or structures. Variations in copy number were detected in 151 cases; 19 cases were found to have chromosomal abnormalities, with a positivity rate of 12.6 %. There was one trisomy in 18 cases, one trisomy in 21 cases, eight pathogenic copy number variations (CNVs), and nine CNVs of unknown clinical significance. The detection rate of FGR combined with structural malformation was significantly higher than that of isolated FGR group. The detection rate of FGR with structural malformations was significantly higher than that with non-structural malformations. The positive detection rate in the FGR group was similar to that in the FGR group with non-structural malformations, with no statistical significance. Chromosomal abnormalities were detected in 17 patients with early onset FGR, with a positivity rate of 13.8 %. Two cases of chromosomal abnormalities were detected in the late-onset FGR group, with a positive rate of 7.1 %, with no statistical significance. A total of 151 fetuses with FGR were followed up for pregnancy outcomes, resulting in 36 cases of pregnancy termination and 13 cases of loss to follow-up. Among the 102 delivered fetuses, six exhibited delayed growth and development, one presented with hypospadias, and another failed the hearing screening. The remaining 94 fetuses demonstrated normal growth and development. Conclusions This study confirms the value of CNV detection in fetuses and dynamic ultrasound monitoring for fetuses with intrauterine growth restriction.
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Aberrações Cromossômicas , Retardo do Crescimento Fetal , Resultado da Gravidez , Humanos , Retardo do Crescimento Fetal/genética , Feminino , Gravidez , Adulto , China/epidemiologia , Ultrassonografia Pré-Natal , Cariotipagem , Variações do Número de Cópias de DNA , Adulto Jovem , População do Leste AsiáticoRESUMO
Zeugodacus cucurbitae (Coquillett) is an important fruit and vegetable pest, especially in high-temperature seasons. In our previous research, we developed a temperature-sensitive sustained-release attractant for Z. cucurbitae, that not only can control the release rate of cuelure according to the temperature change, but also shows an excellent trapping effect on Z. cucurbitae. To further enhance the killing effect of the temperature-sensitive attractant on Z. cucurbitae, this study proposed using it in combination with an insecticide to prepare a temperature-sensitive insecticide for Z. cucurbitae. Based on the controlled release technology of pesticides, a temperature-sensitive Z. cucurbitae insecticide was developed by using PNIPAM gel as a temperature-sensitive switch to carry both cuelure and insecticide at the same time. In addition, the lethal effect of different pesticides on Z. cucurbitae were tested by indoor toxicity test, and the best pesticide combination was screened out. The temperature-sensitive insecticide prepared in this study not only had excellent thermal response and controlled release ability, but also enhanced its toxicological effects on Z. cucurbitae because it contained insecticides. Among them, combining thiamethoxam and clothianidin with the temperature-sensitive attractants was the most effective, and their lethality reached more than 97% against Z. cucurbitae. This study is not only of great practical significance for the monitoring and controlling Z. cucurbitae, but also provides theoretical basis and reference value for the combination of temperature-sensitive attractant and insecticide.
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Inseticidas , Neonicotinoides , Temperatura , Inseticidas/farmacologia , Animais , Neonicotinoides/farmacologia , Nitrocompostos/farmacologia , Controle de Insetos/métodos , Gorgulhos/efeitos dos fármacos , Tiazóis/farmacologiaRESUMO
In this study, alumina ceramics with hierarchical pores were successfully fabricated using freeze casting. Experimental studies show that both the solid loading of the slurry and the thermal insulation layer at the interface of the slurry and cooling plate can influence the pore characteristics of cast samples. In order to examine the pore characteristics and evaluate the permeability of the freeze-cast samples fabricated under different conditions, a generative adversarial network (GAN) method was employed to reconstruct the three-dimensional (3D) microstructure from two-dimensional (2D) scanning electron microscopy (SEM) images of the samples. Furthermore, GAN 3D reconstruction was validated against X-ray tomography 3D reconstruction results. Based on the GAN reconstructed microstructures, the permeability and pore distribution of the various samples were analyzed. The sample cast with 35 wt.% solid loading shows an optimal permeability.
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Background: Preeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors. Methods: We retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24-45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher's exact test and Mann-Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors. Results: By using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively. Conclusion: Incorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.
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Weak antigens represented by MUC1 are poorly immunogenic, which greatly constrains the development of relevant vaccines. Herein, we developed a multifunctional lipidated protein as a carrier, in which the TLR1/2 agonist Pam3CSK4 was conjugated to the N-terminus of MUC1-loaded carrier protein BSA through pyridoxal 5'-phosphate-mediated transamination reaction. The resulting Pam3CSK4-BSA-MUC1 conjugate was subsequently incorporated into liposomes, which biomimics the membrane structure of tumor cells. The results indicated that this lipidated protein carrier significantly enhanced antigen uptake by APCs and obviously augmented the retention of the vaccine at the injection site. Compared with the BSA-MUC1 and BSA-MUC1 + Pam3CSK4 groups, Pam3CSK4-BSA-MUC1 evoked 22- and 11-fold increases in MUC1-specific IgG titers. Importantly, Pam3CSK4-BSA-MUC1 elicited robust cellular immunity and significantly inhibited tumor growth. This is the first time that lipidated protein was constructed to enhance antigen immunogenicity, and this universal carrier platform exhibits promise for utilization in various vaccines, holding the potential for further clinical application.
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Lipossomos , Mucina-1 , Animais , Mucina-1/imunologia , Mucina-1/química , Camundongos , Humanos , Lipopeptídeos/química , Lipopeptídeos/imunologia , Lipopeptídeos/farmacologia , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/química , Soroalbumina Bovina/química , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Feminino , Camundongos Endogâmicos BALB C , Antígenos/imunologia , Linhagem Celular TumoralRESUMO
With the vigorous development of the Internet of Things, 5G technology, and artificial intelligence, flexible wearable sensors have received great attention. As a simple and low-cost power supply in wearable sensors, the triboelectric nanogenerator (TENG) has a wide range of applications in the field of flexible electronics. However, most polymers are thermally poor conductors (less than 0.1 W/(m·K)), resulting in insufficient heat dissipation performance and limiting the development of TENG. In this study, a high-performance non-woven fabric TENG with strong thermal conductivity (0.26 W/m·K) was achieved by introducing ZrB2 into the polyurethane (PU) matrix. The excellent output performance with an open circuit voltage (Voc) of 347.6 V, a short circuit current (Isc) of 3.61 µA, and an accumulated charge of 142.4 nC endows it with good sensitivity. The electrospun PU/ZrB2 composites exhibit excellent sensing performance to detect body movements in situ, such as pressing, clapping, running, and walking. Moreover, the generated power can light up 224 LED bulbs as a demonstration of self-powering ability.
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Shape memory hydrogels provide a worldwide scope for functional soft materials. However, most shape memory hydrogels exhibit poor mechanical properties, leading to low actuation strength, which severely limits their applications in smart biomimetic devices. Herein, a strategy for muscle-inspired shape memory-oriented polyvinyl alcohol (PVA)-natural rubber latex (NRL) hydrogel (OPNH) with multiscale oriented structure is demonstrated. The shape memory function comes from the stretch-induced crystallization of natural rubber (NR), while PVA forms strong hydrogen bonding interactions with proteins and phospholipids on the surface of NRL particles. Meanwhile, the reconfigurable interactions of PVA and NR produce a multiscale-oriented structure during stretch-drying, improving the mechanical and shape memory properties. The resultant OPNH shows excellent interfacial compatibility, exhibiting outstanding mechanical performance (3.2 MPa), high shape fixity (≈80%) and shape recovery ratio (≈92%), high actuation strength (206 kPa), working capacity (105 kJ m- 3), extremely short response time (≈2 s), low response temperature (28 °C) and smart thermal responsiveness. It can even maintain muscle-like working capacity when lifting a load equivalent to 372 times its weight, providing a new class shape memory material for the application in smart biomimetic muscles and multistimulus responsive devices.
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Nitric oxide (NO) gas molecules have demonstrated remarkable anti-tumor effects and minimal susceptibility to drug resistance, establishing as a promising modality for effective tumor treatment. However, how to realize its stable and efficient delivery in vivo is still a challenge. In this study, we have developed a heat-responsive biomimetic nano erythrocyte (M/B@R) by loading a NO donor (BNN6) onto mesoporous Prussian blue (M-PB) and subsequently enveloping them with red blood cell membranes. The preserved integrity of the red blood cell membrane (RBCm) structure could ensure its excellent biosafety, prolong its circulation time within the bloodstream and then enhance the accumulation of BNN6 at tumor sites. When M/B@R is stimulated by near-infrared light (NIR-II, 808 nm) irradiation, the nanoparticle could generate significant heat for photothermal therapy (PTT) by the characteristic NIR absorption of M-PB and then NO could also be efficiently released. The generated NO further facilitates the formation of ONOO-, a highly toxic species to tumors, while also alleviating tumor hypoxia. Remarkably, M/B@R, with NIR as the excitation source, induces combined lethality through hyperthermia, DNA damage, and tumor hypoxia relief. This novel combination strategy provides a new avenue for PTT/NO-induced cancer therapy.
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Ferrocianetos , Hipertermia Induzida , Neoplasias Nasofaríngeas , Humanos , Fototerapia , Óxido Nítrico , Carcinoma Nasofaríngeo , Membrana CelularRESUMO
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
Adhesive hydrogels (AHs) are considered ideal materials for flexible sensors. However, the lack of effective energy dissipation networks and sparse surface polar groups in AHs lead to poor mechanical properties and interfacial adhesion, which limit their practical application. Herein, a tough, long-lasting adhesive and highly conductive nanocomposite hydrogel (PACPH) was fabricated via the synergy of interfacial entanglement and adhesion group densification. PACPH was obtained by the in situ polymerization of highly carboxylated cellulose nanocrystals (SCNCPA, surface pre-grafted polyacrylic acid chains, C-COOH = 11.5 mmol g-1) with the acrylic acid precursor. The unique tacticity of SCNCPA provides strong interface entanglement and multiple hydrogen bonds with the PACPH network, which further increases the energy dissipated during SCNCPA displacements, and enhances the mechanical properties of PACPH (tensile strength = 1.45 MPa, modulus = 332 kPa, and fracture toughness = 13.2 MJ m-3). Meanwhile, SCNCPA increases the density of surface polar groups in PAPCH and also acts as an anchor point to improve the adhesion strength (>2-3 times) of PACPH on various substrates. The combination of excellent mechanical, adhesive, and conductive properties of the PAPCH-integrated patches enables long-term monitoring of human daily activities and electrocardiogram (ECG) signals, verifying that PAPCH is a promising material platform for the further development of flexible sensors and other health management devices.
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Background: Paternal uniparental disomy (UPD) of chromosome 7 is extremely rare, and only a few postnatal cases have been reported. The effects on growth were discordant in these cases, and the relevance of paternal UPD(7) to growth caused by imprinting remains questionable. Case presentation: Here, we report a prenatal case that underwent invasive prenatal diagnosis due to the high risk of Down's syndrome and failed noninvasive prenatal screening. The fetus had a normal karyotype and no apparent copy number variation. Homozygous copy-neutral regions on chromosome 7 were identified using a single nucleotide polymorphism (SNP) array; the data for the parent-child trios showed that the fetus carried the whole paternal isodisomy of chromosome 7. Whole exome and Sanger sequencing revealed a homozygous frameshift mutation in SUGCT at 7p14.1, from the heterozygous carrier father, with no contribution from the mother. The parents decided to continue with the pregnancy after genetic counseling, and the neonate had normal physical findings at birth and showed overweight after birth during a long-term intensive follow-up. Conclusion: We report the first prenatal case who carried paternal UPD(7) and homozygous SUGCT mutation with an overweight phenotype after birth. The overweight may be caused by paternal UPD(7) or homozygous frameshift mutation of SUGCT, or both of them, but it is unclear which contributes more.
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Cytoglobin (Cygb) is a 21-kDa heme-protein that belongs to the globin superfamily and is expressed in vertebrate tissues. It can participate in the oxidative stress response in organisms through the porphyrin ring. Previous studies have shown that this protein, also known as YdCygb, has potential immune abilities in the infection of Vibrio harveyi in yellow drum (Nibea albiflora). In this study, we report the role of Cygb in the immune response of teleost fish for the first time. Quantitative RT-PCR analysis indicated that YdCygb was highly expressed in the liver and intestine of yellow drum, and its expression can be upregulated by pathogenic attack. The cellular distribution of YdCygb-EGFP proteins was observed in cell membrane, cytoplasm, and nucleus in the kidney cells of N. albiflora. Furthermore, a comparative transcriptome analysis between the YdCygb overexpression group and control vector group identified 28 differentially expressed genes (DEGs). The analysis showed that ANPEP, CLDN5, ORM1/2, SERPINC1 and HPN and ITGAM might play important regulatory roles to Cygb in fish. Notably, using GST-pull down technology, we identified 3-phosphoglyceraldehyde dehydrogenase and intermediate filament protein as direct interactors with YdCygb, playing a role against V. harveyi. The molecular and functional characterization of YdCygb provides better understanding of the genetic basis of disease resistance traits in yellow drum and sheds new light on the functioning of Cygb and its potential regulatory signaling pathway as well.