RESUMO
The Wnt receptor Frizzled3 (FZD3) is important for brain axonal development and cancer progression. We report structures of FZD3 in complex with extracellular and intracellular binding nanobodies (Nb). The crystal structure of Nb8 in complex with the FZD3 cysteine-rich domain (CRD) reveals that the nanobody binds at the base of the lipid-binding groove and can compete with Wnt5a. Nb8 fused with the Dickkopf-1 C-terminal domain behaves as a FZD3-specific Wnt surrogate, activating ß-catenin signalling. The cryo-EM structure of FZD3 in complex with Nb9 reveals partially resolved density for the CRD, which exhibits positional flexibility, and a transmembrane conformation that resembles active GPCRs. Nb9 binds to the cytoplasmic region of FZD3 at the putative Dishevelled (DVL) or G protein-binding site, competes with DVL binding, and inhibits GαS coupling. In combination, our FZD3 structures with nanobody modulators map extracellular and intracellular interaction surfaces of functional, and potentially therapeutic, relevance.
Assuntos
Receptores Frizzled , Anticorpos de Domínio Único , Receptores Frizzled/metabolismo , Receptores Frizzled/química , Humanos , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/metabolismo , Ligação Proteica , Cristalografia por Raios X , Células HEK293 , Sítios de Ligação , Microscopia Crioeletrônica , Animais , Modelos Moleculares , Domínios Proteicos , Proteínas Desgrenhadas/metabolismo , Proteínas Desgrenhadas/química , Proteínas Desgrenhadas/genética , Via de Sinalização Wnt , beta Catenina/metabolismo , beta Catenina/químicaRESUMO
BACKGROUND: Evidence has revealed a connection between cuproptosis and the inhibition of tumor angiogenesis. While the efficacy of a model based on cuproptosis-related genes (CRGs) in predicting the prognosis of peripheral organ tumors has been demonstrated, the impact of CRGs on the prognosis and the immunological landscape of gliomas remains unexplored. METHODS: We screened CRGs to construct a novel scoring tool and developed a prognostic model for gliomas within the various cohorts. Afterward, a comprehensive exploration of the relationship between the CRG risk signature and the immunological landscape of gliomas was undertaken from multiple perspectives. RESULTS: Five genes (NLRP3, ATP7B, SLC31A1, FDX1, and GCSH) were identified to build a CRG scoring system. The nomogram, based on CRG risk and other signatures, demonstrated a superior predictive performance (AUC of 0.89, 0.92, and 0.93 at 1, 2, and 3 years, respectively) in the training cohort. Furthermore, the CRG score was closely associated with various aspects of the immune landscape in gliomas, including immune cell infiltration, tumor mutations, tumor immune dysfunction and exclusion, immune checkpoints, cytotoxic T lymphocyte and immune exhaustion-related markers, as well as cancer signaling pathway biomarkers and cytokines. CONCLUSION: The CRG risk signature may serve as a robust biomarker for predicting the prognosis and the potential viability of immunotherapy responses. Moreover, the key candidate CRGs might be promising targets to explore the underlying biological background and novel therapeutic interventions in gliomas.
Assuntos
Biomarcadores Tumorais , Glioma , Microambiente Tumoral , Humanos , Glioma/genética , Glioma/imunologia , Glioma/patologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Prognóstico , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica/genética , Nomogramas , Feminino , Masculino , Perfilação da Expressão Gênica , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The clinical features of cerebellar high-grade gliomas (cHGGs) in adults have not been thoroughly explored. This large-scale, population-based study aimed to comprehensively outline these traits and construct a predictive model. METHODS: Patient records diagnosed with gliomas were collected from various cohorts and analyzed to compare the features of cHGGs and supratentorial HGGs (sHGGs). Cox regression analyses were employed to identify prognostic factors for overall survival and to develop a nomogram for predicting survival probabilities in patients with cHGGs. Multiple machine learning methods were applied to evaluate the efficacy of the predictive model. RESULTS: There were significant differences in prognosis, with SEER-cHGGs showing a median survival of 7.5 months and sHGGs 14.9 months (p < 0.001). Multivariate Cox regression analyses revealed that race, WHO grade, surgical procedures, radiotherapy, and chemotherapy were independent prognostic factors for cHGGs. Based on these factors, a nomogram was developed to predict 1-, 3-, and 5-year survival probabilities, with AUC of 0.860, 0.837, and 0.810, respectively. The model's accuracy was validated by machine learning approaches, demonstrating consistent predictive effectiveness. CONCLUSIONS: Adult cHGGs are distinguished by distinctive clinical features different from those of sHGGs and are associated with an inferior prognosis. Based on these risk factors affecting cHGGs prognosis, the nomogram prediction model serves as a crucial tool for clinical decision-making in patient care.
Assuntos
Neoplasias Cerebelares , Glioma , Nomogramas , Humanos , Feminino , Masculino , Glioma/mortalidade , Glioma/patologia , Glioma/terapia , Pessoa de Meia-Idade , Adulto , Prognóstico , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/terapia , Gradação de Tumores , Idoso , Aprendizado de Máquina , Programa de SEER , Adulto JovemRESUMO
Background: Exploring potential biomarkers for predicting clinical outcomes and developing targeted therapies for acute myeloid leukemia (AML) is of utmost importance. This study aimed to investigate the expression pattern of the thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway and its role in the prognosis of AML patients. Methods: In this study, we examined the prognostic value of TXNIP/NLRP3 pathway in AML patients using microarray data from Gene Expression Omnibus (GEO) and transcriptome data from the Cancer Genome Atlas (TCGA) to develop a prognostic model and validated the results by quantitative real-time PCR (qRT-PCR) in a validation cohort of 26 AML patients and 18 healthy individuals from Jinan University (JNU) database. Results: Analysis of the GSE13159 database revealed that TXNIP, interleukin 1 beta (IL1B) within the TXNIP/NLRP3 pathway were significantly upregulated and caspase1 (CASP1) was downregulated in AML patients (TXNIP, P = 0.031; IL1B, P = 0.042; CASP1, P = 0.038). Compared to high NLRP3 expression, AML patients with low NLRP3 expression had a longer overall survival (OS) in the GSE12417 dataset (P = 0.004). Moreover, both the training and validation results indicated that lower TXNIP, NLRP3, and IL1B expression were associated with favorable prognosis (GSE12417, P = 0.009; TCGA, P = 0.050; JNU, P = 0.026). According to the receiver operating characteristic curve analysis, this model demonstrated a sensitivity of 84% for predicting three-year survival. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using TXNIP/NLRP3/IL1B genes in novel targeted therapies for AML.
Assuntos
Biomarcadores Tumorais , Proteínas de Transporte , Inflamassomos , Interleucina-1beta , Leucemia Mieloide Aguda , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Feminino , Masculino , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Inflamassomos/metabolismo , Inflamassomos/genética , Transdução de Sinais/genética , Adulto , Idoso , Regulação Leucêmica da Expressão Gênica , Tiorredoxinas/genética , Tiorredoxinas/metabolismoRESUMO
The benefits of rapidly up-titrating evidence-based treatments following heart failure (HF) hospitalizations were demonstrated in the The Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies (STRONG-HF) trial and emphasized in contemporary HF guidelines. We aimed to assess up-titration patterns of guideline-directed medical treatments in the Taiwanese HF population. Combining data from the Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry and the Treatment with Angiotensin Receptor neprilysin inhibitor for Taiwan Acute Heart Failure (TAROT-AHF) study cohort, we formed the "Taiwan real-world cohort". We compared these data with subgroups of patients with left ventricular ejection fraction ≤40% in the STRONG-HF trial. Patients in the Taiwan cohort exhibited similar blood pressure, heart rate and N-terminal pro B-type natriuretic peptide levels at discharge compared with those in the STRONG-HF trial. A higher proportion of patients in the STRONG-HF high-intensity care group received up-titrations compared with those in the usual care group and the Taiwan cohort. Composite all-cause mortality or HF hospitalization at 180 days for patients in the high-intensity care group, usual care group, and Taiwan cohort were 17.4%, 23.7%, and 31.9%, respectively, with differences largely contributed by HF hospitalization (10.1%, 17.9%, and 27.6%, respectively), whereas all-cause mortality rates were similar (11.0%, 9.6%, and 9.3%, respectively). Gender did not affect this trend. In conclusion, our data highlights a treatment gap between the STRONG-HF trial and real-world practices in Taiwan, urging prompt optimization of HF therapy.
Assuntos
Insuficiência Cardíaca , Hospitalização , Volume Sistólico , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/terapia , Taiwan/epidemiologia , Feminino , Masculino , Hospitalização/estatística & dados numéricos , Idoso , Volume Sistólico/fisiologia , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Sistema de Registros , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêuticoRESUMO
Over the past 3 decades, a diverse collection of small protein domains have been used as scaffolds to generate general purpose protein-binding reagents using a variety of protein display and enrichment technologies. To expand the repertoire of scaffolds and protein surfaces that might serve this purpose, we have explored the utility of (i) a pair of anti-parallel alpha-helices in a small highly disulfide-bonded 4-helix bundle, the CC4 domain from reversion-inducing Cysteine-rich Protein with Kazal Motifs and (ii) a concave beta-sheet surface and two adjacent loops in the human FN3 domain, the scaffold for the widely used monobody platform. Using M13 phage display and next generation sequencing, we observe that, in both systems, libraries of â¼30 million variants contain binding proteins with affinities in the low µM range for baits corresponding to the extracellular domains of multiple mammalian proteins. CC4- and FN3-based binding proteins were fused to the N- and/or C-termini of Fc domains and used for immunostaining of transfected cells. Additionally, FN3-based binding proteins were inserted into VP1 of AAV to direct AAV infection to cells expressing a defined surface receptor. Finally, FN3-based binding proteins were inserted into the Pvc13 tail fiber protein of an extracellular contractile injection system particle to direct protein cargo delivery to cells expressing a defined surface receptor. These experiments support the utility of CC4 helices B and C and of FN3 beta-strands C, D, and F together with adjacent loops CD and FG as surfaces for engineering general purpose protein-binding reagents.
Assuntos
Biblioteca de Peptídeos , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Animais , Humanos , Bacteriófago M13 , Técnicas de Visualização da Superfície Celular , Células HEK293 , Ligação ProteicaRESUMO
CD38 is the main NADase in mammalian cells. It regulates the homeostasis of nicotinamide adenine dinucleotide (NAD+) and extracellular nucleotides. Its function plays an important role in infection and aging. However, its potential functions in tumor cells have not been fully elucidated. In the present study, we demonstrated that lactate, which is derived from tumor metabolism remodeling, upregulates the expression of CD38 through OXPHOS-driven Hippo-TAZ pathway. The highly expressed CD38 converts NAD + to adenosine through the CD203a/CD73 complex and adenosine binds and activates its receptor A2AR, inducing the expression of Snail and promoting the invasion and metastasis of lung cancer cells. This finding elucidates a new perspective on the interplay between NAD + metabolism and glycolysis in tumor development.
RESUMO
The rapid loss of global biodiversity can greatly affect the normal functioning of ecosystems. However, how biodiversity losses affect plant community structure and soil nutrients is unclear. We conducted a field experiment to examine the short- and long-term effects of removing plant functional groups (Gramineae, Cyperaceae, legumes, and forbs) on the interrelationships among the species diversity, productivity, community structure, and soil nutrients in an alpine meadow ecosystem at Menyuan County, Qinghai Province. The variations in the species richness, above- and belowground biomass of the community gradually decreased over time. Species richness and productivity were positively correlated, and this correlation tended to be increasingly significant over time. Removal of the Cyperaceae, legumes, and other forbs resulted in fewer Gramineae species in the community. Soil total nitrogen, phosphorus, organic matter, and moisture contents increased significantly in the legume removal treatment. The removal of other forbs led to the lowest negative cohesion values, suggesting that this community may have difficulty recovering its previous equilibrium state within a short time. The effects of species removal on the ecosystem were likely influenced by the species structure and composition within the community. Changes in the number of Gramineae species indicated that they were more sensitive and less resistant to plant functional group removal. Legume removal may also indirectly cause distinct community responses through starvation and compensation effects. In summary, species loss at the community level led to extensive species niche shifts, which caused community resource redistribution and significant changes in community structure.
RESUMO
Polyethylene terephthalate (PET) is a widely used packaging material and has high value in recycling. However, under China's dominant informal recycling system, most PET bottles are downcycled into fibers. The deposit-refund system (DRS) is considered a feasible mechanism to facilitate the high-value recycling of PET bottles. To comparatively evaluate the environmental performance [reduction of greenhouse gas (GHG) and pollutant emissions] under different scenarios using life cycle assessments, including the current system based on informal recycling, an improved system with a larger contribution from the source separation of municipal solid waste, and evolving systems with DRS application, five scenarios were set up. The DRS can reduce GHG emissions and the comprehensive environmental impact by 0.538 kg CO2 /kg PET bottles and 1.73 × 10-3 PE/kg PET bottles, respectively, compared to informal recycling. It can be concluded that the DRS-based recycling approach and the bottle-to-bottle recycling provide the substantial emission reduction potential of GHGs and pollutants.
Assuntos
Gases de Efeito Estufa , Gerenciamento de Resíduos , Polietilenotereftalatos , Meio Ambiente , Resíduos Sólidos , Reciclagem , ChinaRESUMO
Recently, many password guessing algorithms have been proposed, seriously threatening cyber security. In this paper, we systematically review over thirty methods for password guessing published between 2016 and 2023. First, we introduce a taxonomy for classifying the existing methods into trawling guessing and targeted guessing. Second, we present an extensive benchmark dataset that can assist researchers and practitioners in successive works. Third, we conduct a bibliometric analysis to present trends in this field and cross-citation between reviewed papers. Further, we discuss the open challenges of password guessing in terms of diverse application scenarios, guessing efficiency, and the combination of traditional and deep learning methods. Finally, this review presents future research directions to guide successive research and development of password guessing.
RESUMO
PURPOSE: To investigate the prognostic factors of survival and develop a predictive nomogram model for elderly GBM patients. METHODS: Elderly patients (> = 65 years) with histologically diagnosed GBM were extracted from the SEER database. Survival analysis of overall survival (OS) was performed by Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were used to determine independent prognostic factors and these factors were used to further construct the nomogram model. RESULTS: A total of 9068 elderly GBM patients (5122 males and 3946 females) were included, with a median age of 72 years (65-96 years). All patients were divided randomly into the training group (n = 6044) and the validation group (n = 3024) by a ratio of 2:1. Cox regression analyses on OS showed eight independent prognostic factors (race, age, tumor side, tumor size, metastasis, surgery, radiotherapy, and chemotherapy) in the training cohort. Also, seven variables (except for race) were identified on CSS in the training group. By comprising these variables, the nomogram models on OS and CSS for predicting the 6-month, 1-year, and 2-year survival probability were constructed and exhibited moderate consistency, respectively. Then, they could be validated well in the validation cohort and by C-index, time-dependent ROC curve, calibration plot, and DCA curve. CONCLUSIONS: Nomogram models on OS and CSS could provide an applicable tool to predict the survival probability and provide clinical references regarding treatment strategies and prognosis.
RESUMO
This study aims to develop a 30 kHz/12 kW silicon carbide (SiC)/Si integrated hybrid power module (iHPM) for variable frequency drive applications, particularly industrial servo motor control, and, additionally, to theoretically and experimentally assess its dynamic characteristics and efficiency during operation. This iHPM integrates a brake circuit, a three-phase Si rectifier, and a three-phase SiC inverter within a single package to achieve a minimal current path. A space-vector pulse width modulation (SVPWM) scheme is used to control the inverter power switches. In order to reduce parasitic inductance and power loss, an inductance cancellation design is implemented in the Si rectifier and SiC inverter. The switching transients and their parasitic effects during a three-phase operation are assessed through an electromagnetic-circuit co-simulation model, by which the power loss and efficiency of the iHPM are estimated. The modeled parasitic inductance of the inverter is validated through inductance measurement, and the effectiveness of the simulated results in terms of switching transients and efficiency is verified using the experimental results of the double pulse test and open-loop inverter operation, respectively. In addition, the power loss and efficiency of the SiC MOSFET inverter are experimentally compared against those of a commercial Si IGBT inverter.
RESUMO
Antibodies are the major components of adaptive immunity for the recognition of diverse antigens. Six complementarity-determining regions (CDRs) from each heavy chain and light chain present the antigen-binding site, which determines the antigen-binding specificity. Here, we describe the detailed method of a novel display technology termed antibody display technology (ADbody) (Hsieh and Chang, bioRxiv, 2021), based on the novel structure of human antibodies from malaria-endemic regions of Africa (Hsieh and Higgins, eLife 6:e27311, 2017). The principle of ADbody is to insert proteins of interest (POI) into the heavy-chain CDR3 while still retaining the biological function of POI on the antibody. In this chapter, we described how to use the ADbody method to display challenging and unstable POI on the antibody in mammalian cells. Collectively, this method is designed to provide an alternative outside the current display systems and to generate novel synthetic antibodies.
Assuntos
Anticorpos , Cadeias Pesadas de Imunoglobulinas , Animais , Humanos , Anticorpos/química , Regiões Determinantes de Complementaridade , Antígenos , Tecnologia , MamíferosRESUMO
Diverse extracellular proteins negatively regulate WNT signaling. One such regulator is adenomatosis polyposis coli down-regulated 1 (APCDD1), a conserved single-span transmembrane protein. In response to WNT signaling in a variety of tissues, APCDD1 transcripts are highly up-regulated. We have determined the three-dimensional structure of the extracellular domain of APCDD1, and this structure reveals an unusual architecture consisting of two closely apposed ß-barrel domains (ABD1 and ABD2). ABD2, but not ABD1, has a large hydrophobic pocket that accommodates a bound lipid. The APCDD1 ECD can also bind to WNT7A, presumably via its covalently bound palmitoleate, a modification that is common to all WNTs and is essential for signaling. This work suggests that APCDD1 functions as a negative feedback regulator by titrating WNT ligands at the surface of responding cells.
Assuntos
Polipose Adenomatosa do Colo , Proteínas de Membrana , Humanos , Proteínas de Membrana/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Via de Sinalização Wnt , Lipídeos , beta Catenina/genética , beta Catenina/metabolismoRESUMO
A high oleic acid content is considered an essential characteristic in the breeding of high-quality rapeseed in China. Long-chain non-coding RNA (lncRNA) molecules play an important role in the plant's growth and its response to stress. To better understand the role of lncRNAs in regulating plant reproductive development, we analyzed whole-transcriptome and physiological data to characterize the dynamic changes in lncRNA expression during the four representative times of seed development of high- and low-oleic-acid rapeseed in three regions. We identified 21 and 14 lncRNA and mRNA modules, respectively. These modules were divided into three types related to region, development stages, and material. Next, we analyzed the key modules related to the oil content and the oleic acid, linoleic acid, and linolenic acid contents with physiological data and constructed the key functional network analysis on this basis. Genes related to lipid metabolism, such as 3-ketoacyl-CoA synthase 16 (KCS16) and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), were present in the co-expression network, suggesting that the effect of these genes on lipid metabolism might be embodied by the expression of these lncRNAs. Our results provide a fresh insight into region-, development-stage-, and material-biased changes in lncRNA expression in the seeds of Brassica napus. Some of these lncRNAs may participate in the regulatory network of lipid accumulation and metabolism, together with regulated genes. These results may help elucidate the regulatory system of lncRNAs in the lipid metabolism of high-oleic-acid rapeseed seeds.
Assuntos
Brassica napus , Brassica rapa , RNA Longo não Codificante , Brassica napus/genética , Brassica napus/metabolismo , Ácido Oleico/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Óleos de Plantas/metabolismo , Metabolismo dos Lipídeos/genética , Melhoramento Vegetal , Brassica rapa/genética , Brassica rapa/metabolismo , Sementes/metabolismoRESUMO
The color of rapeseed (Brassica napus L.) petal is usually yellow but can be milky-white to orange or pink. Thus, the petal color is a popular target in rapeseed breeding programs. In his study, metabolites and RNA were extracted from the yellow (Y), yellow/purple (YP), light purple (LP), and purple (P) rapeseed petals. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), RNA-Seq, and quantitative real-time (qRT-PCR) analyses were performed to analyze the expression correlation of differential metabolites and differential genes. A total of 223 metabolites were identified in the petals of the three purple and yellow rapeseed varieties by UPLC-MS/MS. A total of 20511 differentially expressed genes (DEGs) between P, LP, YP, versus Y plant petals were detected. This study focused on the co-regulation of 4898 differential genes in the three comparison groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation and quantitative RT-PCR analysis showed that the expression of BnaA10g23330D (BnF3'H) affects the synthesis of downstream peonidin and delphinidin and is a key gene regulating the purple color of petals in B. napus. L. The gene may play a key role in regulating rapeseed flower color; however, further studies are needed to verify this. These results deepen our understanding of the molecular mechanisms underlying petal color and provide the theoretical and practical basis for flower breeding targeting petal color.
Assuntos
Brassica napus , Brassica napus/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Melhoramento Vegetal , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , CorRESUMO
In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. The structure was solved using single-wavelength anomalous diffraction from sulfur-containing residues (sulfur SAD) to generate phase information. Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. Overall, ~2/3 of the ~390 amino acids within the PLVAP ECD adopt a helical configuration, as determined by CD. We also determined the sequence and epitope of MECA-32, an anti-PLVAP antibody. Taken together, these data lend strong support to the model of capillary diaphragms formulated by Tse and Stan in which approximately ten PLVAP dimers are arranged within each 60- to 80-nm-diameter opening like the spokes of a bicycle wheel. Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP.
Assuntos
Diafragma , Células Endoteliais , Diafragma/metabolismo , Células Endoteliais/metabolismo , Proteínas de Transporte/metabolismo , Endotélio Vascular/metabolismo , Dissulfetos/metabolismo , Dicroísmo CircularRESUMO
Objective:To explore the characteristics of abnormal chromosome karyotype of common external genital malformations in male children.Methods:A retrospective analysis of the clinical data of 2 408 children was made in outpatient or inpatient from January 2012 to December 2017. The mean age was (38±7) months. There were 1115 cases of hypospadias, 189 cases of cryptorchidism, 304 cases of micropenis, 681 cases of concealed penis and 119 cases of disorders of sex development. All children were tested for chromosome 550 band in peripheral blood, and the results of chromosome karyotype were analyzed.Results:A total of 131 cases of abnormal chromosome karyotypes were detected, with a detection rate of 5.4%, including 46 cases of chromosome number abnormalities, 85 cases of structural abnormalities, 64 cases of sex chromosome abnormalities and 67 cases of autosomal abnormalities. The karyotype of chromosome was 46, XY, inv (9) (p12q13) in 28 cases accounting for 21.4%. It was followed by 47, XXY, with 16 cases, accounting for 12.2%. The detection rate of chromosomal abnormalities in children with disorders of sex development was 12.6%(15 cases), hypospadias was 5.5%(61 cases), cryptorchidism was 5.3%(10 cases), micropenis was 4.9%(15 cases), and concealed penis was 4.4%(30 cases).Conclusions:Chromosomal abnormalities are not uncommon in male children with external genital malformations. Chromosome structural abnormalities are more common than quantitative abnormalities, and sex chromosome abnormalities account for a comparable proportion to autosomal abnormalities.
RESUMO
In this paper, a special ultrasonic microforming method, Micro Ultrasonic thin Sheetmetal Forming using molten plastic as a flexible punch (short as Micro-USF), was used to conduct micro-punching experiments on stainless steel sheet with thickness of 10 µm and 20 µm. The influence of ultrasonic vibration on forming force and forming quality were investigated. The experimental results showed that the forming force required for punching thin sheet metal decreased gradually as the ultrasonic time or ultrasonic power increased. By applying the ultrasonic vibration effect, the forming force could be decreased dramatically and the maximum value of forming force drop could reach 86%. Moreover, with the application of ultrasonic vibration, the size accuracy and shape accuracy of micro-holes could be increased by 36.92% and 22.65%, but the cross-section quality of micro-holes were not significantly improved.