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1.
J Mater Chem B ; 12(13): 3249-3261, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38466580

RESUMO

Over the past few decades, the critical role played by cellular contractility associated mechanotransduction in the regulation of cell functions has been revealed. In this case, numerous biomaterials have been chemically or structurally designed to manipulate cell behaviors through the regulation of cellular contractility. In particular, adhesive proteins including fibronectin, poly-L-lysine and collagen type I have been widely applied in various biomaterials to improve cell adhesion. Therefore, clarifying the effects of adhesive proteins on cellular contractility has been valuable for the development of biomaterial design. In this study, reference-free traction force microscopy with a well-organized microdot array was designed and prepared to investigate the relationship between adhesive proteins, cellular contractility, and mechanotransduction. The results showed that fibronectin and collagen type I were able to promote the assembly of focal adhesions and further enhance cellular contraction and YAP activity. In contrast, although poly-L-lysine supported cell spreading and elongation, it was inefficient at inducing cell contractility and activating YAP. Additionally, compared with cellular morphogenesis, cellular contraction was essential for YAP activation.


Assuntos
Fibronectinas , Mecanotransdução Celular , Fibronectinas/metabolismo , Mecanotransdução Celular/fisiologia , Microscopia de Força Atômica , Colágeno Tipo I , Polilisina , Tração , Adesão Celular , Materiais Biocompatíveis
2.
Altern Ther Health Med ; 29(8): 798-802, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37708555

RESUMO

Objective: Circulating biomarkers can be used as effective prediction tools for AMI diagnosis and prognosis, but their prediction efficiency is limited and still needs to be explored. The study aimed to investigate the changes of myocardial troponin I (cTn I), myoglobin (Mb), and butyryl cholinesterase (BChE) levels in patients with acute myocardial infarction (AMI) and its clinical predictive efficacy. Methods: In this prospective cohort study, fifty patients with AMI who received PCI (AMI group) and 50 healthy subjects who underwent physical examination (reference group) during the same period were included. According to the occurrence of short-term major adverse cardiovascular events (MACE) during 6-month follow-up, they were divided into MACE group and non-MACE group . The difference of Mb, BChE, and cTnI levels was compared, and the ROC curve was drawn to analyze the prediction efficiency. Results: Compared with the reference group or non-MACE group, Mb and cTnI significantly increased and BChE significantly decreased inAMI group and MACE group, respectively (P < .05). The AUC of Mb, cTnI and BChE in diagnosing AMI occurrence and prognosis were all > 0.75, and the sensitivity and specificity were all > 85.00%. cTnI, Mb and BChE have good diagnostic efficacy in disease occurrence and prognosis evaluation of AMI patients. Conclusions: High expression of Mb and cTnI and low expression of BChE can increase the risk of AMI incidence and MACE occurrence and have high diagnostic efficacy, which can be used as sensitive factors in clinical AMI diagnosis and evaluation. Thess provided a theoretical foundation for AMI diagnosis and MACE preventing in AMI patients.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Troponina I , Mioglobina , Estudos Prospectivos , Infarto do Miocárdio/diagnóstico , Prognóstico , Biomarcadores , Colinesterases
3.
Small ; 19(20): e2207628, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36808872

RESUMO

Radiofrequency (RF) diodes used for fifth and sixth-generation (5G and 6G) mobile and wireless communication networks generally require ultrahigh cut-off frequencies and high integration densities of devices with different functions on a single chip and at low cost. Carbon nanotube diodes are promising devices for radiofrequency applications, but the cut-off frequencies are still far below the theoretical estimates. Here, a carbon nanotube diode that operates in the millimeter-wave frequency bands and is based on solution-processed, high-purity carbon nanotube network films is reported. The carbon nanotube diodes exhibit an intrinsic cut-off frequency over 100 GHz and the as-measured bandwidth can exceed 50 GHz at least. Furthermore, The rectification ratio of the carbon nanotube diode by approximately three times by using yttrium oxide for local p-type doping in the diode channel is improved.

4.
Front Med (Lausanne) ; 10: 1327191, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38293300

RESUMO

Objective: The study aimed to evaluate the pregnancy outcomes of dichorionic diamniotic twin pregnancies that were reduced to singletons at different gestational ages. Study design: This was a retrospective cohort study of twin pregnancies that underwent fetal reduction to singletons in a single tertiary referral center between 2011 and 2020. A total of 433 cases were included. The cohort was divided into five groups according to gestational age at surgery: Group A: <16 weeks (125 cases); Group B: 16-19+6 weeks (80 cases); Group C: 20-23+6 weeks (74 cases); Group D: 24-26+6 weeks (48 cases); and Group E: ≥27 weeks (106 cases). Outcome data were obtained by reviewing the electronic medical records or interviews. Results: Selective reduction was technically successful. The clinical characteristics of the population were not different. The overall live birth rate and the survival rate were 96.5 and 95.4%, respectively. Although the rate of spontaneous miscarriage was comparable, gestational age at delivery significantly differed among groups (p < 0.001). Additionally, there was a trend that gestational age at delivery decreased with the increasing gestational age at surgery in Groups A, B, C, and D, whereas gestational age at delivery in Group E was later than that in Group D. In Groups A, B, C, and D, the rates of preterm birth at <32 weeks and <34 weeks increased with the increasing gestational age at surgery, while the rates in Group E were significantly lower than that in Group D. Regression analysis showed that timing of reduction may be an independent factor after adjusting for maternal age, parity, pre-pregnancy BMI, ART, and cervical length. Conclusion: Selective reduction performed by experienced hands for a dizygotic abnormal twin is safe and effective. Gestational age at surgery (<26+6 weeks) was inversely correlated with gestational age at delivery and positively with the rate of preterm birth. Reduction after 27 weeks, where legal, can be performed with a good outcome for the retained fetus.

5.
J Mater Chem B ; 11(1): 99-108, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36477803

RESUMO

Breast cancer is considered as a worldwide disease due to its high incidence and malignant metastasis. Although numerous techniques have been developed well to conduct breast cancer therapy, the influence of micropattern-induced interfacial heterogeneity on the molecular mechanism and nuclear signalling transduction of carcinogenesis is rarely announced. In this study, PDMS stencil-assisted micropatterns were fabricated on tissue culture plates to manage cell clustering colony by adjusting initial cell seeding density and the size of microholes. The curvature of each microholes was controlled to construct the interfacial heterogeneity of MDA-MB231 cancer cells at the periphery of micropatterned colony. The distinguished focal adhesion (FA) and cytoskeleton distribution at the central and peripheral regions of the cell colony were regulated by heterogeneous properties. The interfacial heterogeneity of FA and cytoskeleton would induce the biased tension force to encourage more ezrin expression at the periphery and further promote DNA synthesis, therefore disclosing a stem-like phenotype in heterogeneous cells. This study will provide a value source of information for the development of micropattern-induced heterogeneity and the interpretation of metastatic mechanism in malignant breast cancer cells.


Assuntos
Adesões Focais , Neoplasias , Adesões Focais/metabolismo , Citoesqueleto/metabolismo , Núcleo Celular , Transdução de Sinais , DNA/metabolismo , Neoplasias/metabolismo
6.
Genes (Basel) ; 13(12)2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-36553497

RESUMO

(1) Background: Numerous etiologies may lead to non-immune hydrops fetalis (NIHF). However, the causes remain unclear in half of NIHF cases following current standard assessment. The application of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) can improve the identification of the etiologies. This study aimed to investigate the etiologies of NIHF in the era of next-generation sequence (NGS) following a unified prenatal work-up flow for diagnosis. (2) Methods: A retrospective analysis was conducted on NIHF cases that were collected prospectively to explore the underlying etiologies according to a unified prenatal diagnosis work-up flow at Shanghai First Maternity and Infant Hospital between Jan 2016 and Dec 2019. The medical records for all NIHF cases were reviewed, and the causes of NIHF were classified as confirmed (diagnostic), suspected, or unknown. (3) Results: Prenatal and postnatal medical records for a total of 145 NIHF cases were reviewed, 48.3% (70/145) of the cases were identified to be with confirmed etiologies, and 10.3% (15/145) with suspected etiologies. Among 85 cases with confirmed or suspected etiologies, 44.7% were diagnosed with genetic disorders, 20% with chylothorax/chyloascites diagnosed postnatally, 12.9% with fetal structural anomalies, 12.9% with fetal anemia, 7% (6 cases) with fetal arrhythmia, and 2.3% (2 cases) with placenta chorioangioma. In cases with genetic disorders, 8 aneuploidies were detected by CMA, and 30 cases had single-gene disorders identified by ES (29/30) or targeted gene panel (1/30). There were still 41.4% cases (60/145) with unknown causes after this unified prenatal diagnostic work-up flow. (4) Conclusions: In the era of NGS, the causes of NIHF were identified in 58.6% of cases, with genetic disorders being the most common ones. NGS is helpful in determining the genetic etiology of NIHF when CMA results cannot explain NIHF, but 41.4% of cases were still with unknown causes under the unified prenatal diagnostic work-up flow in this single-center study.


Assuntos
Hidropisia Fetal , Ultrassonografia Pré-Natal , Lactente , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Hidropisia Fetal/diagnóstico , Hidropisia Fetal/genética , Primeiro Trimestre da Gravidez , China
7.
J Nanobiotechnology ; 20(1): 499, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36424661

RESUMO

Gene transfection was supposed to be the most promising technology to overcome the vast majority of diseases and it has been popularly reported in clinical applications of gene therapy. In spite of the rapid development of novel transfection materials and methods, the influence of morphology-dependent nanomechanics of malignant osteosarcoma on gene transfection is still unsettled. In this study, cell spreading and adhesion area was adjusted by the prepared micropatterns to regulate focal adhesion (FA) formation and cytoskeletal organization in osteosarcoma cells. The micropattern-dependent FA and cytoskeleton could induce different cellular nanomechanics to affect cell functions. Our results indicated that transfection efficiency was improved with enlarging FA area and cell nanomechanics in micropatterned osteosarcoma. The difference of gene transfection in micropatterned cells was vigorously supported by cellular internalization capacity, Ki67 proliferation ability and YAP mechanotranduction through the regulation of focal adhesion and cytoskeletal mechanics. This study is an attempt to disclose the relationship of cell nanomechanics and gene transfection for efficient gene delivery and develop multifunctional nanomedicine biomaterials for accurate gene therapy in osteosarcoma cells.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Adesões Focais , Citoesqueleto/metabolismo , Osteossarcoma/genética , Osteossarcoma/terapia , Osteossarcoma/metabolismo , Transfecção , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia , Neoplasias Ósseas/metabolismo
8.
ACS Nano ; 16(12): 21482-21490, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36416375

RESUMO

High-density semiconducting aligned carbon nanotube (A-CNT) arrays have been demonstrated with wafer-scale preparation of materials and have shown high performance in P-type field-effect transistors (FETs) and great potential for applications in future digital integrated circuits (ICs). However, high-performance N-type FETs (N-FETs) have not yet been implemented with A-CNTs, making development of complementary metal-oxide-semiconductor (CMOS) technology, a necessary component for modern digital ICs, impossible. In this work, we reveal the mechanism hindering the realization of A-CNT N-FETs contacted by low-work-function metals and develop corresponding solutions to promote the performance of N-FETs to that of P-type FETs (P-FETs). The fabricated scandium (Sc)-contacted A-CNT N-FET with a 100 nm gate length exhibits an on-state current (Ion) of 800 µA/µm and a peak transconductance (gm) of 250 µS/µm, representing the highest performance of CNT-based N-FETs to date. Moreover, CMOS technology has been developed to realize N- and P-FETs with symmetric high performance based on A-CNTs. The fabricated A-CNT CMOS FETs show electron and hole mobilities of 325 and 241 cm2 V-1 s-1, respectively, which are slightly higher than the corresponding values of Si CMOS transistors. Our scalable fabrication of A-CNT CMOS FETs with comparable electronic performance to Si CMOS will promote the application of CNT-based electronics in digital ICs.

9.
Int J Mol Sci ; 23(19)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36233186

RESUMO

The genotype and phenotype of acral melanoma are obviously different from UV-radiation-induced melanoma. Based on the clinical data, mechanical stimulation is believed to be a potential cause of acral melanoma. In this case, it is desirable to clarify the role of mechanical stimulation in the progression of acral melanoma. However, the pathological process of cyclic straining that stimulates acral melanoma is still unclear. In this study, the influence of cyclic straining on melanoma cell proliferation was analyzed by using a specifically designed cell culture system. In the results, cyclic straining could promote melanoma cell proliferation but was inefficient after the disruption of cytoskeleton organization. Therefore, the mechanotransduction mechanism of promoted proliferation was explored. Both myosin and actin polymerization were demonstrated to be related to cyclic straining and further influenced the morphogenesis of melanoma cells. Additionally, the activation of mechanosensing transcription factor YAP was related to regulatory morphogenesis. Furthermore, expression levels of melanoma-involved genes were regulated by cyclic straining and, finally, accelerated DNA synthesis. The results of this study will provide supplementary information for the understanding of acral melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Actinas/genética , Actinas/metabolismo , Proliferação de Células/genética , DNA , Humanos , Mecanotransdução Celular/fisiologia , Melanoma/genética , Morfogênese , Fatores de Transcrição/metabolismo
10.
Transgenic Res ; 31(6): 647-660, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36053433

RESUMO

Insulators in vertebrates play a role in genome architecture and orchestrate temporo-spatial enhancer-promoter interactions. In plants, insulators and their associated binding factors have not been documented as of yet, largely as a result of a lack of characterized insulators. In this study, we took a comprehensive strategy to identify and validate the enhancer-blocking insulator CW198. We show that a 1.08-kb CW198 fragment from Arabidopsis can, when interposed between an enhancer and a promoter, efficiently abrogate the activation function of both constitutive and floral organ-specific enhancers in transgenic Arabidopsis and tobacco plants. In plants, both transcriptional crosstalk and spreading of histone modifications were rarely detectable across CW198, which resembles the insulation property observed across the CTCF insulator in the mammalian genome. Taken together, our findings support that CW198 acts as an enhancer-blocking insulator in both Arabidopsis and tobacco. The significance of the present findings and their relevance to the mitigation of mutual interference between enhancers and promoters, as well as multiple promoters in transgenes, is discussed.


Assuntos
Arabidopsis , Elementos Isolantes , Animais , Elementos Isolantes/genética , Elementos Facilitadores Genéticos/genética , Arabidopsis/genética , Regiões Promotoras Genéticas/genética , Transgenes/genética , Mamíferos/genética
11.
Front Bioeng Biotechnol ; 10: 922159, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711638

RESUMO

High transmembrane delivery efficiency of nanoparticles has attracted substantial interest for biomedical applications. It has been proved that the desired physicochemical properties of nanoparticles were efficient for obtaining a high cellular uptake capacity. On the other hand, biophysical stimuli from in situ microenvironment were also indicated as another essential factor in the regulation of cellular uptake capacity. Unfortunately, the influence of colony morphology on cellular uptake capacity was rarely analyzed. In this study, micropatterned PDMS stencils containing circular holes of 800/1,200 µm in diameter were applied to control colonies' size. The amino-modified nanoparticles were cocultured with micropatterned colonies to analyze the influence of colonies' morphology on the cellular uptake capacity of nanoparticles. Consequently, more endocytosed nanoparticles in larger colonies were related with a bigger dose of nanoparticles within a larger area. Additionally, the high cell density decreased the membrane-nanoparticles' contacting probability but enhanced clathrin-mediated endocytosis. With these contrary effects, the cells with medium cell density or located in the peripheral region of the micropatterned colonies showed a higher cellular uptake capacity of nanoparticles.

12.
Chem Biodivers ; 19(6): e202200255, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35560978

RESUMO

To discover novel molecules with unique mechanism against plant pathogenic oomycetes, sixteen new sulfonate derivatives of ethyl maltol (3a-p) were synthesized by structural modification of 2-ethyl-3-hydroxy-4H-pyran-4-one, and their anti-oomycete activity against a serious agricultural disease, Phytophthora capsici Leonian was determined in this study. Among all tested compounds, derivatives 3e, 3m and 3p exhibited the most potent anti-oomycete activity against P. capsici with EC50 values of 19.40, 21.04 and 31.10 mg/L, respectively; especially 3e and 3m showed the best promising and pronounced anti-oomycete activity than zoxamide (EC50 =26.87 mg/L). The results further proved that 4-tert-butylphenylsulfonyl group, 3-nitro-4-chlorophenylsulfonyl group and 8-quinolinesulfonyl group introduced at the hydroxy position of ethyl maltol or maltol were necessary for obtaining the most potent compounds. Further mechanism studies of P. capsici treated with 3e demonstrated that this compound can affect the growth of mycelia by disrupting the integrity of the membrane, and the higher the concentration of the compound is, the greater the degree of membrane integrity damage. These important results will pave the way for further modification of ethyl maltol to develop potential new fungicides.


Assuntos
Fungicidas Industriais , Phytophthora , Fungicidas Industriais/farmacologia , Doenças das Plantas , Plantas , Pironas
13.
Prenat Diagn ; 42(7): 873-880, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35584285

RESUMO

OBJECTIVE: To investigate the use of chromosomal microarray (CMA) and Exome sequencing (ES) in fetuses with congenital heart disease (CHD). METHODS: The Fetal Medicine Unit of Shanghai First Maternity and Infant Hospital records were reviewed to ascertain all cases diagnosed with CHD by level 2 ultrasound examination between 2016 and 2019. Cases were categorized as isolated or associated with other abnormalities or fetal growth restriction. CMA was offered to all cases as a first-line genetic test followed by ES when CMA was non-diagnostic. RESULTS: Of the 586 ascertained, 84 (14.3%) had causative CMA abnormality, of which 8.8% (35/400) were in fetuses with isolated CHD and 26.3% (49/186) in those with other abnormalities. ES was performed in 47 cases with a negative CMA. Causative variants were identified in two (10.5%, 2/19) isolated cases and four(14.3%, 4/28) with other abnormalities. CONCLUSION: Invasive procedures with CMA should be offered in pregnancies complicated by both non-isolated and isolated cardiac abnormalities. When CMA is not diagnostic, ES can add diagnostic value in both groups and should be considered even for fetuses with an isolated CHD.


Assuntos
Exoma , Cardiopatias Congênitas , China/epidemiologia , Aberrações Cromossômicas , Feminino , Feto , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/genética , Humanos , Análise em Microsséries/métodos , Gravidez , Diagnóstico Pré-Natal/métodos , Ultrassonografia Pré-Natal
14.
Chem Biodivers ; 19(4): e202101039, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35261147

RESUMO

In order to discover highly active fungicides, sixteen novel sulfonate derivatives of Fenjuntong were synthesized by structural modification of 2'-hydroxybutyrophenone, and their anti-oomycete activity against Phytophthora capsici Leonian was determined in this study. Among all tested compounds, compound 3b displayed more significant anti-oomycete activity than the precursor Fenjuntong against P. capsici, and the EC50 values of 3b and Fenjuntong were 84.50 and 517.25 mg/L, respectively. By comparing the anti-oomycete activity of compounds 3a-p, I-a-p, and II-a-p, the following conclusions were drawn: (1) Hydroxy group is well tolerated, and sulfonylation of hydroxy group enhances its anti-oomycete activity. (2) The proper length of the ketone carbonyl chain is very important for their anti-oomycete activity. (3) The presence of a site methoxy group in the structural skeleton is closely related to the anti-oomycete activity. These important results will pave the way for further modification of Fenjuntong to develop potential new fungicides.


Assuntos
Fungicidas Industriais , Phytophthora , Fungicidas Industriais/química , Doenças das Plantas
15.
Twin Res Hum Genet ; 25(1): 50-55, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35249587

RESUMO

The aim of this study was to determine the pregnancy loss rate of amniocentesis with double-needle insertions in twin pregnancies. This was a retrospective study of twin pregnancies who underwent amniocentesis with double-needle insertion between 2010 and 2019 at a single center. The pregnancy loss rates were recorded as single or double fetal loss before 24 weeks' gestation and within 4 weeks after the procedure. Risk factors for pregnancy loss after amniocentesis were also assessed. A total of 678 twin pregnancies with amniocentesis were finally included. The pregnancy loss rates before 24 weeks' gestation and within 4 weeks after the procedure were 0.9% and 1.9%, respectively. Only one fetal loss was presumed to be a direct result of the procedure. All other cases were complicated by structural or chromosomal anomalies. Twin pregnancies with abnormal ultrasound findings had a significantly higher rate of pregnancy loss with a relative risk of 4.81 (95% CI [1.03, 22.2]). Our study showed a low pregnancy loss rate after amniocentesis in twin pregnancies with double-needle insertions technique of sampling, which can help decision making in prenatal screening and diagnosis for twin pregnancies.


Assuntos
Aborto Espontâneo , Amniocentese , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/genética , Amniocentese/efeitos adversos , Amniocentese/métodos , Feminino , Idade Gestacional , Humanos , Gravidez , Gravidez de Gêmeos , Estudos Retrospectivos
16.
Fetal Diagn Ther ; 49(3): 138-144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35139508

RESUMO

OBJECTIVE: We aimed to study the value of exome sequencing (ES) in severe pleural effusion with nonimmune hydrops fetalis (NIHF) that underwent thoracoamniotic shunt (TAS). METHODS: It was a retrospective study of NIHF that underwent TAS between 2012 and 2020 at Shanghai First Maternity and Infant Hospital. After a detailed assessment, NIHF cases with aneuploidies, infections, and structural anomalies were excluded, and TAS was offered to cases with severe pleural effusion. Quantitative fluorescence polymerase chain reaction (QF-PCR) was conducted to exclude Trisomy 21, 18, and 13 before fetal therapy, and chromosomal microarray analysis (CMA) was offered to all the cases. Before 2019, ES was retrospectively performed using stored fetal DNA extracted from prenatal samples; from 2019 onward, ES was discussed and offered before intrauterine therapies. RESULTS: A total of 18 NIHF cases underwent TAS with negative CMA and continuing pregnancy were included. Fetal hydrops was relieved in 16 cases (88.9%). The median gestational ages at intervention and at delivery were 31.2 (22.0-33.1) weeks and 34.3 (29.7-38.6) weeks, respectively. The neonatal survival rate was 72.2% (13/18), and no causative gene variants were identified from ES in any survivors. Pathogenic or likely pathogenic variants were detected in 3 out of 5 neonatal deaths. If rapid ES could have been available to guide fetal therapy, the neonatal survival rate after TAS would have increased from 72.2% to 86.7%. CONCLUSIONS: Single-gene disorders were one of the major causes of perinatal death in NIHF cases that underwent fetal therapy. Prenatal rapid ES may be of good promise in NIHF to explore precise etiology and guide fetal therapy.


Assuntos
Anormalidades Cardiovasculares , Derrame Pleural , Anormalidades Cardiovasculares/complicações , China , Exoma , Feminino , Humanos , Hidropisia Fetal/genética , Hidropisia Fetal/cirurgia , Lactente , Recém-Nascido , Derrame Pleural/genética , Derrame Pleural/cirurgia , Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-Natal
17.
Clin Chim Acta ; 528: 16-28, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35065907

RESUMO

BACKGROUND: Fetalhyperechogenickidneys (HEK)are associated with a wide range of etiologies and prognoses. Prenatal counselling and management can be extremely challenging, especially for isolated HEK. METHODS: A total of 28 pregnancies were screened by ultrasonography with HEK from March 1, 2016 to December 31, 2020. Genetic testings for aneuploidy and copy number variations (CNVs) are routine during the investigation for etiologies of fetal HEK in our unit. Trio-whole exome sequencing(WES) was offered to the family when karyotyping and microarray were not diagnostic.A systematic review (SR) was conducted to use the authoritative literature retrieval databases describing genetic testings' results in prenatal HEK cases. RESULTS: In the 28 HEK fetuses, 2 (7.14%) cases were identified with chromosome abnormalities and 6 (21.43%) cases were detected with pathogenic CNVs. Through trio-WES analysis, pathogenic or likely pathogenic variations were detected in the following genes: PKD1, BBS2, BBS9, HNF1B, PKHD1 and ETFA in another 10 (35.71%) fetuses. And the remaining 10 (35.71%) cases were undiagnosed. The pooled data from all reviewed studies indicate that HNF1B gene heterozygous deletion or mutation are the most common genetic causes associated with HEK. CONCLUSION: This is the first study to accurately describe the genotype ratio at different levels of genetic testing associated with fetal HEK. Our study has suggested that trio-WES could improve the detection rate and efficiency ofidentification genetic pathologies in fetuseswith isolated HEK. The WES results provide new evidences to guide prenatal counseling and management.


Assuntos
Variações do Número de Cópias de DNA , Nefropatias , Variações do Número de Cópias de DNA/genética , Feminino , Feto/diagnóstico por imagem , Humanos , Rim , Gravidez , Diagnóstico Pré-Natal
18.
Plant J ; 109(3): 541-554, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34773305

RESUMO

Insulators characterized in Drosophila and mammals have been shown to play a key role in the restriction of promiscuous enhancer-promoter interactions, as well as reshaping the topological landscape of chromosomes. Yet the role of insulators in plants remains poorly understood, in large part because of a lack of well-characterized insulators and binding factor(s). In this study, we isolated a 1.2-kb RS2-9 insulator from the Oryza sativa (rice) genome that can, when interposed between an enhancer and promoter, efficiently block the activation function of both constitutive and floral organ-specific enhancers in transgenic Arabidopsis and Nicotiana tabacum (tobacco). In the rice genome, the genes flanking RS2-9 exhibit an absence of mutual transcriptional interactions, as well as a lack of histone modification spread. We further determined that O. sativa Homeobox 1 (OSH1) bound two regions of RS2-9, as well as over 50 000 additional sites in the rice genome, the majority of which resided in intergenic regions. Mutation of one of the two OSH1-binding sites in RS2-9 impaired insulation activity by up to 60%, whereas the mutation of both binding sites virtually abolished insulator function. We also demonstrated that OSH1 binding sites were associated with 72% of the boundaries of topologically associated domains (TADs) identified in the rice genome, which is comparable to the 77% of TAD boundaries bound by the insulator CCCTC-binding factor (CTCF) in mammals. Taken together, our findings indicate that OSH1-RS2-9 acts as a true insulator in plants, and highlight a potential role for OSH1 in gene insulation and topological organization in plant genomes.


Assuntos
Elementos Facilitadores Genéticos/fisiologia , Oryza/genética , Oryza/metabolismo , Regiões Promotoras Genéticas/fisiologia , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Fatores de Transcrição/fisiologia
19.
Autoimmunity ; 55(1): 43-51, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34755577

RESUMO

MicroRNAs (miRs) are reported to regulate myocardial infarction (MI). This study was performed to investigate the function and mechanism of miR-17-5p in myocardial remodelling after MI. Initially, a mouse model of MI was established and MI mice were infected with lentivirus antago-miR-17-5p vector. High expression of miR-17-5p was found in myocardial tissues after MI. After inhibiting miR-17-5p expression, myocardial fibrosis, scarring, and cardiomyocyte apoptosis were improved, LC3-II/LC3-I ratio and Beclin-1 expression were decreased but p62 expression was increased. The dual-luciferase assay suggested that miR-17-5p targeted STAT3 and negatively regulated its expression. Then, after inhibiting STAT3 expression using STAT3 inhibitor S31-201, the fibrosis, scarring, and cardiomyocyte apoptosis were deteriorated, along with the rise of LC3-II/LC3-I and Beclin-1 expression, the reduction of p62 expression and the reversion of MI attenuation. In conclusion, inhibition of miR-17-5p can inhibit myocardial autophagy through targeting STAT3 and then inhibit myocardial remodelling, thereby protecting the myocardium after MI.


Assuntos
MicroRNAs , Infarto do Miocárdio , Fator de Transcrição STAT3 , Animais , Apoptose/genética , Autofagia/genética , Regulação para Baixo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Miocárdio , Miócitos Cardíacos/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
20.
BMC Pregnancy Childbirth ; 21(1): 436, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158005

RESUMO

BACKGROUND: The common use of singleton fetal growth standard to access twin growth might lead to over-monitoring and treatment. We aimed to develop fetal growth standards for Chinese twins based on ultrasound measurements, and compare it with Zhang's and other twin fetal growth charts. METHODS: A cohort of uncomplicated twin pregnancies were prospectively followed in 2014-2017. Smoothed estimates of fetal growth percentiles for both monochorionic (MC) and dichorionic (DC) twins were obtained using a linear mixed model. We also created growth charts for twins using a model-based approach proposed by Zhang et al. Our twin standards were compared with Hadlock's (singleton) in predicting adverse perinatal outcomes. RESULTS: A total of 398 twin pregnancies were included, with 214 MC and 582 DC live-born twins. The MC twins were slightly lighter than the DC twins, with small differences throughout the gestation. Our ultrasound-based fetal weight standards were comparable to that using Zhang's method. Compared with previous references/standards from the US, Brazil, Italy and UK, our twins had very similar 50th percentiles, but narrower ranges between the 5th and 95th or 10th and 90th percentiles. Compared with the Hadlock's standard, the risks of neonatal death and adverse perinatal outcomes for small for gestational age (SGA) versus non-SGA were substantially elevated using our standards. CONCLUSIONS: A normal fetal growth standard for Chinese twins was created. The differences between MC and DC twins were clinically insignificant. The 50th weight percentiles of the Chinese twins were identical to those in other races/ethnicities but the ranges were markedly narrower. Our standard performed much better than the Hadlock's in predicting low birth weight infants associated with adverse perinatal outcomes in twin pregnancies. The present study also indicated that Zhang's method is applicable to Chinese twins, and other areas may use Zhang's method to generate their own curves for twins if deemed necessary.


Assuntos
Desenvolvimento Fetal , Peso Fetal , Gráficos de Crescimento , Gravidez de Gêmeos/fisiologia , Povo Asiático , Biometria , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Prospectivos , Padrões de Referência , Ultrassonografia Pré-Natal
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