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Base editors, developed from the CRISPR/Cas system, consist of components such as deaminase and Cas variants. Since their emergence in 2016, the precision, efficiency, and safety of base editors have been gradually optimized. The feasibility of using base editors in gene therapy has been demonstrated in several disease models. Compared with the CRISPR/Cas system, base editors have shown great potential in hematopoietic stem cells (HSCs) and HSC-based gene therapy, because they do not generate double-stranded breaks (DSBs) while achieving the precise realization of single-base substitutions. This precise editing mechanism allows for the permanent correction of genetic defects directly at their source within HSCs, thus promising a lasting therapeutic effect. Recent advances in base editors are expected to significantly increase the number of clinical trials for HSC-based gene therapies. In this review, we summarize the development and recent progress of DNA base editors, discuss their applications in HSC gene therapy, and highlight the prospects and challenges of future clinical stem cell therapies.
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Sistemas CRISPR-Cas , Edição de Genes , Terapia Genética , Doenças Hematológicas , Células-Tronco Hematopoéticas , Humanos , Terapia Genética/métodos , Edição de Genes/métodos , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Doenças Hematológicas/terapia , Doenças Hematológicas/genética , Sistemas CRISPR-Cas/genética , Animais , Transplante de Células-Tronco HematopoéticasRESUMO
Mn-based mullite oxides AMn2O5 (A = lanthanide, Y, Bi) is a novel type of ternary catalyst in terms of their electronic and geometric structures. The coexistence of pyramid Mn3+-O and octahedral Mn4+-O makes the d-orbital selectively active toward various catalytic reactions. The alternative edge- and corner-sharing stacking configuration constructs the confined active sites and abundant active oxygen species. As a result, they tend to show superior catalytic behaviors and thus gain great attention in environmental treatment and energy conversion and storage. In environmental applications, Mn-based mullites have been demonstrated to be highly active toward low-temperature oxidization of CO, NO, volatile organic compounds (VOCs), etc. Recent research further shows that mullites decompose O3 and ozonize VOCs from -20 °C to room temperature. Moreover, mullites enhance oxygen reduction reactions (ORR) and sulfur reduction reactions (SRR), critical kinetic steps in air-battery and Li-S batteries, respectively. Their distinctive structures also facilitate applications in gas-sensitive sensing, ionic conduction, high mobility dielectrics, oxygen storage, piezoelectricity, dehydration, H2O2 decomposition, and beyond. A comprehensive review from basic physicochemical properties to application certainly not only gains a full picture of mullite oxides but also provides new insights into designing heterogeneous catalysts.
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Reconstruction universally occurs over non-layered transition metal sulfides (TMSs) during oxygen evolution reaction (OER), leading to the formation of active species metal (oxy)hydroxide and thus significantly influences the OER performance. However, the reconstruction process and underlying mechanism quantitatively remain largely unexplored. Herein, we proposed an electrochemical reaction mechanism, namely sulfide oxidation reaction (SOR), to elucidate the reconstruction process of pyrite-type TMSs. Based on this mechanism, we evaluated the reconstruction capability of NiS2 doped with transition metals V, Cr, Mn, Fe, Co, Cu, Mo, Ru, Rh, and Ir within different doped systems. Two key descriptors were thus proposed to describe the reconstruction abilities of TMSs: USOR (the theoretical electric potential of SOR) and ΔU (the difference between the theoretical electric potential of SOR and OER), representing the initiation electric potential of reconstruction and the intrinsic reconstruction abilities of TMSs, respectively. Our finding shows that a lower USOR readily initiate reconstruction at a lower potential and a larger ΔU indicating a poorer reconstruction ability of the catalyst during OER. Furthermore, Fe-doped CoS2 was used to validate the rationality of our proposed descriptors, being consistent with the experiment findings. Our work provides a new perspective on understanding the reconstruction mechanism and quantifying the reconstruction of TMSs.
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We propose a constrained linear data-feature-mapping model as an interpretable mathematical model for image classification using a convolutional neural network (CNN). From this viewpoint, we establish detailed connections between the traditional iterative schemes for linear systems and the architectures of the basic blocks of ResNet- and MgNet-type models. Using these connections, we present some modified ResNet models that, compared with the original models, have fewer parameters but can produce more accurate results, thereby demonstrating the validity of this constrained learning data-feature-mapping assumption. Based on this assumption, we further propose a general data-feature iterative scheme to demonstrate the rationality of MgNet. We also provide a systematic numerical study on MgNet to show its success and advantages in image classification problems, particularly in comparison with established networks.
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Modelos Teóricos , Redes Neurais de Computação , Modelos LinearesRESUMO
Objective: The purpose of this study was to compare the clinical and radiological outcomes of unilateral biportal endoscopic (UBE) and percutaneous posterior endoscopic cervical discectomy (PE) keyhole surgeries. Methods: Patients diagnosed with cervical spondylotic radiculopathy (CSR) treated by UBE or PE keyhole surgery from May 2017 to April 2020 were retrospectively analyzed. The length of incision, fluoroscopic time, postoperative hospital stay, and total cost were compared. The clinical efficacy was assessed using a visual analog scale (VAS), neck disability index (NDI), and modified MacNab criteria. Moreover, the C2-7 Cobb's angle, range of motion (ROM), intervertebral height, vertebral horizontal displacement, and angular displacement of the surgical segment were measured. Results: A total of 154 patients were enrolled, including 89 patients in the UBE group and 65 patients in the PE group, with a follow-up period of 24-32 months. Compared with PE surgery, UBE surgery required shorter fluoroscopic times (6.76 ± 1.09 vs. 8.31 ± 1.10 s) and operation times (77.48 ± 17.37 vs. 84.92 ± 21.97 min) but led to higher total hospitalization costs and longer incisions. No significant differences were observed in the postoperative hospital stay, bleeding volume, VAS score, NDI score, effective rate, or complication rate between the UBE and PE groups. Both the C2-7 Cobb's angle and ROM increased significantly after surgery, with no significant differences between groups. There were no significant differences between intervertebral height, vertebral horizontal displacement, and angular displacement of the surgical segment at different times. Conclusions: Both UBE and PE surgeries in the treatment of CSR were effective and similar after 24 months. The fluoroscopic and operation times of UBE were shorter than those of PE.
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Endoscopia , Espondilose , Humanos , Estudos Retrospectivos , Pescoço , Espondilose/complicações , Espondilose/cirurgia , Vértebras Cervicais/cirurgia , Resultado do TratamentoRESUMO
Background: Vascular dementia (VD), associated with cerebrovascular injury, is characterized by severe cognitive impairment. Jianpi Tianjing Decoction (JTD) has been widely used to treat VD. However, its molecular targets and mechanisms of action in this treatment remain unclear. This study integrated network pharmacology and proteomics to identify targets and mechanisms of JTD in the treatment of VD and to provide new insights and goals for clinical treatments. Methods: Systematic network pharmacology was used to identify active chemical compositions, potential targets, and mechanisms of JTD in VD treatment. Then, a mouse model of VD was induced via transient bilateral common carotid artery occlusion to verify the identified targets and mechanisms of JTD against VD using 4D label-free quantitative proteomics. Results: By screening active chemical compositions and potential targets in relevant databases, 187 active chemical compositions and 416 disease-related compound targets were identified. In vivo experiments showed that JTD improved learning and memory in mice. Proteomics also identified 112 differentially expressed proteins in the model and sham groups and the JTD and model groups. Integrating the network pharmacology and proteomics results revealed that JTD may regulate expressions of cytochrome c oxidase subunit 7C, metabotropic glutamate receptor 2, Slc30a1 zinc transporter 1, and apolipoprotein A-IV in VD mice and that their mechanisms involve biological processes like oxidative phosphorylation, regulation of neuron death, glutamate secretion, cellular ion homeostasis, and lipoprotein metabolism. Conclusions: JTD may suppress VD development via multiple components, targets, and pathways. It may thus serve as a complementary treatment option for patients with VD.
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The quality of Tibetan matsutake drops during cold chain transportation. To extend the shelf life and improve the market value, this study analyzed the matsutake logistics process, and optimized the dynamic monitoring and quality management systems for post-harvest matsutake with different preservation packaging in the cold chain. This system monitored the micro-environmental parameters of the cold chain in real time, and it identified the best preservation method by analyzing the quality change characteristics of the matsutake with different preservation packaging. It was concluded that the matsutake were best preserved under the conditions of modified atmosphere packaging. The data analysis on the collected data verified the performance of the system. Relevant personnel were invited to participate in the system performance analysis and offer optimization suggestions to improve the applicability of the established monitoring system. The optimized model could provide a more effective theoretical reference for the dynamic monitoring and quality management of the system.
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OBJECTIVE: The purpose of this study was to investigate the learning curve and complications of unilateral biportal endoscopy (UBE) in the treatment of lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS). METHODS: This was a retrospective cohort analysis of 197 consecutive patients who received UBE unilateral laminotomy bilateral decompression (UBE-ULBD) or lumbar discectomy (UBE-LD) surgery, including 107 males and 90 females with an average age of 64.83 ± 14.29 years. Cumulative sum (CUSUM) and risk-adjusted cumulative sum analysis (RA-CUSUM) were used to evaluate the learning curve, with the occurrence of complications defined as surgical failure, and variables of different phase of the learning curve were compared. RESULTS: The cutoff point of learning curve of UBE surgery was 54 cases according to CUSUM analysis. The learning curve of UBE-ULBD and UBE-LD were divided into 3 phases. The first cutoff points were 31 and 12 cases, and the second cutoff point were 67 and 32 cases respectively. With the progress of the learning curve, the operation time and postoperative hospital stays decreased. The visual analogue scale and Oswestry Disability Index at the last follow-up were significantly lower than that before surgery. The incidence of surgical failure was 6.11% and began to decrease after the 89th case based on RA-CUSUM analysis. The surgical failure rate decreased from 10.11% to 2.78 after the 89th case with significant different. CONCLUSION: UBE surgery is effective in the treatment of LDH and LSS with low incidence of complications. But a learning curve of at least 54 cases still required for mastering UBE surgery.
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With the enhancement of consumers' food safety awareness, consumers have become more stringent on meat quality. This study constructs an intelligent dynamic prediction model based on knowledge rules and integrates flexible humidity sensors into the non-destructive monitoring of the Internet of Things to provide real-time feedback and dynamic adjustments for the chilled chicken cold chain. The optimized sensing equipment can be attached to the inside of the packaging to deal with various abnormal situations during the cold chain, effectively improving the packaging effect. Through correlation analysis of collected data and knowledge rule extraction of critical factors in the cold chain, the established quality evaluation and prediction model achieved detailed chilled chicken quality level classification and intelligent quality prediction. The obtained results show that the accuracy of the prediction model is higher than 90.5%, and all the regression coefficients are close to 1.00. The relevant personnel (workers and cold chain managers) were invited to participate in the performance analysis and optimization suggestion to improve the applicability of the established prediction model. The optimized model can provide a more efficient theoretical reference for timely decision-making and further e-commerce management.
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The hydrogen evolution reaction (HER) is significantly influenced by the evolved H2 bubble diffusion rate on the surface of the electrode, which involves the blocking and release of the active site at the catalytic interface. Rational design of nanostructured catalysts could not only sharply enhance the specific surface area but also provide large amounts of channels for gas release. Herein, NiCo-nanowire-derived multimetal chalcogenides grown in situ on carbon cloth [denoted as (NiCo)S2@MoS2/CC] are presented by serial hydrothermal methods. The obtained hierarchical nanowire array architecture affords abundant surface-active sites and is conducive to permeate electrolytes. The surface adsorption/desorption behavior of the heterostructure catalyst was optimized through regulating MoS2 concentration. Owing to the synergistic effect of metal Ni and Co and the interaction of the (NiCo)S2@MoS2 heterostructure, (NiCo)S2@MoS2/CC-2 delivers a relatively low overpotential of 74 mV at a current density of 10 mA cm-2 and displays a small Tafel slope of 54 mV dec-1 for HER catalysis, surpassing that of the recently reported MoS2-based electrocatalysts. Such a strategy through nanostructure optimization and electron interaction of the heterostructure could improve the electrocatalytic HER performance for multimetal chalcogenides in an alkaline medium.
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OBJECTIVE: To investigate the clinical effect of percutaneous endoscopic lumbar discectomy (PELD) through bone tunnel in the treatment of migrated lumbar intervertebral disc herniation. METHODS: The clinical data of 42 patients with migrated lumbar intervertebral disc herniation treated through PELD techniques were retrospectively analyzed from October 2015 to December 2018. There were 26 males and 16 females, aged from 39 to 71 years old with a mean of(58.55±7.16) years. There were 7 cases where the affected segment was L3,4, 24 cases of L4,5, and 11 cases of L5S1. According to modified free nucleus pulposus classification, 3 cases of type A1, 6 cases of type A2, 8 cases of type B1, 8 cases of type B2, 6 cases of type C1, and 11 cases of C2. Among these 42 cases, 22 patients were treated with transpedicular approach (transpedicular approach group), 6 cases were type A2, 6 cases were type B2 and 10 cases were type C2, and 20 cases with translaminar approach(translaminar approach group), 3 cases were type A1, 8 cases were type B1, 6 cases were type C1, 2 cases were type B2 and 1 case was type C2. The operation time, intraoperative and postoperative complications of the two groups were recorded, and the pain visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to assess the improvement of the clinical symptoms before surgery, immediately after surgery, and 12 months after surgery, and the modified Macnab evaluation system was used to evaluate the clinical efficacy. RESULTS: The operative time was from 69 to 105 min with a mean of (88.29±9.85) min;and no intraoperative complications such as neurovascular injury or dural tear were occurredin all patients. One case in the transpedicular approach group was changed to general anesthesia and translaminar approach due to local anesthesia intolerance. All the patients were followed up from 13 to 34 months, with a mean of (13.71±3.56) months. VAS and ODI were significantly improved in two groups immediately after surgery and 12 months after surgery (P<0.05). According to modified Macnab criteria, 27 cases obtained excellent results, 11 good, 3 fair, and 1 poor. There were no postoperative complications such as lumbar fractures and postoperative infections in the follow-up patients. CONCLUSION: For migrated intervertebral disc herniation, the modified nucleus pulposus classification can be used to estimate the precise target before operation, and the reasonable bone tunnel approach can be selected to obtain good results.
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Discotomia Percutânea , Deslocamento do Disco Intervertebral , Núcleo Pulposo , Adulto , Idoso , Endoscopia , Feminino , Humanos , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To reduce losses from the various disasters, regional water security evaluation and risk control model is studied. The model is built upon different kinds of indices in water security system, proceeding from the whole structure and its parts of evaluation, forewarning and decision making analysis. Based on China's national conditions, this study firstly advances an evaluation index system of regional water security, which includes three subsystems of water resource security, water environment security, and water disaster control security. Secondly, fuzzy analytic hierarchy process based on accelerating genetic algorithm (AGA-FAHP) combines with entropy weight method (EW) to determine the objective weights of evaluation indexes. The subjective and objective weights can be integrated by the principle of minimum relative information entropy. The subsystem weights are obtained by using AGA-FAHP. Then regional water security evaluation model is established. Thirdly, the comparison judging method is adopted to divide warning degree of water security with the comprehensive evaluation index and forewarning standards, and then the local conditions for proposing planning schemes. Finally, decision making analysis is employed to find the effective indices based on projection pursuit technique with the ideal point method in multi-index decision. This study takes Jiangsu province, China as an example. The evaluation results from 2000 to 2015 show that the development trend of water security is increasing on the whole except in several individual years. Risk forewarning doesn't take place in recent years. But risk is always there. So, project and non-project measures are proposed for the corresponding forewarning levels. From light warnings for three times and moderate warning for once in 2000, 2001, 2002, and 2004, index 1, 3, 4, 11, 13, 17, and 18 are selected as the effective indices to decision making analysis in common. Then, the solution schemes are given as the processing method accordingly. This conclusion is reasonable and its method is practical that match the reality. It suggests that the presented model is feasible with theory and application, which can offer advice in regional water security management to some extent.
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Abastecimento de Água , Água , ChinaRESUMO
Apremilast (APST) is an effective inhibitor of phosphodieasterase 4 (PDE4) which is the first oral drug for the treatment of adult patients with active psoriatic arthritis. However, Apremilast's low solubility restricts its dissolution and bioavailability. In this study, APST solid dispersion with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA) was developed to improve the dissolution and bioavailability of APST by spray drying. A series of TPGS were synthesized to elucidate the effect of the ratio of monoester to diester on solubilizing capacity. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR) were used to characterize the solid dispersion, and the results showed that APST was amorphous in solid dispersion. In vitro dissolution study showed that the dissolution rate of solid dispersion in phosphate buffered saline (pH 6.8) was remarkably increased, reaching a release of 90% within 10 min. Moreover, in vivo pharmacokinetics study revealed that the bioavailability of solid dispersion in rats had significant improvement. In particular, its Cmax and AUClast were nearly 22- and 12.9-fold greater as compared to APST form B, respectively. In conclusion, APST solid dispersion with TPGS and PVPVA is an alternative drug delivery system to improve the solubility and oral bioavailability of APST.
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Formas de Dosagem , Inibidores da Fosfodiesterase 4/química , Povidona/análogos & derivados , Talidomida/análogos & derivados , Vitamina E/química , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Inibidores da Fosfodiesterase 4/farmacocinética , Povidona/química , Difração de Pó , Ratos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Talidomida/química , Talidomida/farmacocinéticaRESUMO
We prove some new results concerning the approximation rate of neural networks with general activation functions. Our first result concerns the rate of approximation of a two layer neural network with a polynomially-decaying non-sigmoidal activation function. We extend the dimension independent approximation rates previously obtained to this new class of activation functions. Our second result gives a weaker, but still dimension independent, approximation rate for a larger class of activation functions, removing the polynomial decay assumption. This result applies to any bounded, integrable activation function. Finally, we show that a stratified sampling approach can be used to improve the approximation rate for polynomially decaying activation functions under mild additional assumptions.
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Redes Neurais de ComputaçãoRESUMO
Pulse feeling , representing the tactile arterial palpation of the heartbeat, has been widely used in traditional Chinese medicine (TCM) to diagnose various diseases. The quantitative relationship between the pulse wave and health conditions however has not been investigated in modern medicine. In this paper, we explored the correlation between pulse pressure wave (PPW), rather than the pulse key features in TCM, and pregnancy by using deep learning technology. This computational approach shows that the accuracy of pregnancy detection by the PPW is 84% with an area under the curve (AUC) of 91%. Our study is a proof of concept of pulse diagnosis and will also motivate further sophisticated investigations on pulse waves.
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Pressão Sanguínea/fisiologia , Aprendizado de Máquina , Pulso Arterial , Área Sob a Curva , Simulação por Computador , Feminino , Humanos , Modelos Logísticos , Gravidez , Curva ROC , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Sudden cardiac death due to malignant arrhythmias is a common cause of death in dilated cardiomyopathy (DCM). Whether genetic variants increase the risk of arrhythmias in DCM is unknown. OBJECTIVE: The purpose of this study was to investigate the genetic causes of arrhythmias in DCM patients. METHODS: Whole-exome sequencing and high-depth targeted next-generation sequencing (142-gene panel) were used. Eight specific DCM pedigrees with arrhythmias and 2 separate cohorts of 1232 consecutive unrelated sporadic DCM patients from 3 medical centers (550 in the discovery cohort, 682 in the replication cohort) were analyzed; 470 (250 in the discovery cohort, 220 in the replication cohort) suffered from arrhythmias (DCM-A group) and 762 (300 in the discovery cohort, 462 in the replication cohort) did not (DCM-NA group). All identified causative variants were Sanger sequenced to eliminate false-positive results and then screened in 700 unrelated matched arrhythmia- and DCM-free healthy controls. RESULTS: We identified long QT syndrome (LQTS)-causative variants that independently cosegregated in 2 unrelated DCM-LQTS pedigrees. Pathogenic variants in arrhythmia-related genes (ion channelopathies) were identified in 4.9% (23/470) of sporadic DCM-A patients (4.0% in the discovery cohort, 5.9% in the replication cohort) but only 0.1% (1/762) of sporadic DCM-NA patients (P = 2.16 × 10-9). These arrhythmia-related pathogenic variants included long QT syndrome, atrial fibrillation, sick sinus syndrome, cardiac conduction disease, and Brugada syndrome. CONCLUSION: Some arrhythmias in DCM patients are caused by arrhythmia-related pathogenic variants. For DCM patients with explicit arrhythmias, arrhythmia-causative genetic screening may help to explain the etiology and decision-making.
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Arritmias Cardíacas/genética , Cardiomiopatia Dilatada/complicações , Testes Genéticos/métodos , Sistema de Condução Cardíaco/fisiopatologia , Adulto , Idoso , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/fisiopatologia , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Adulto JovemRESUMO
To solve the energy crisis problem, many efforts have been devoted to develop clean and sustainable alternatives to fossil fuels. Among varieties of pathways to obtain clean energy, electrochemical water splitting is a promising approach. Herein, we had successfully synthesized the NiCo2S4@porous nitrogen-doped carbon nanofibers (NiCo2S4@NCNF) nanocomposite via three successive steps consisted of in-situ oxidative polymerization, calcination, and solvothermal sulfuration reaction processes. The effect of controlled molar ratios to electrocatalytic performance was studied in detail. The optimized NiCo2S4@NCNF nanocomposite exhibits superior electrocatalytic activity for hydrogen evolution reaction with a small overpotential of 117â¯mV to drive a current density of 10â¯mAâ¯cm-2. More importantly, it exhibits similar electrocatalytic activity to the initial state even after successive cyclic voltammetry scan for 3000 cycles, indicating its excellent long-term stability. The superior electrochemical performance is attributed to the developed three-dimensional (3D) network nanostructure derived from bacterial cellulose nanofibers, the highly conductive porous nitrogen-doped carbon nanofibers, and the synergistic effect between metal Ni and Co of NiCo2S4. This study permits a new pathway to design efficient electrocatalysts based on eco-friendly materials for the production of clean hydrogen energy.
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BACKGROUND: Pathogenic variants in human phospholamban coding gene (PLN) are known to cause hereditary dilated cardiomyopathy with heart failure in an autosomal dominant mode. METHODS: We performed high-depth targeted next-generation sequencing using a cardiomyopathy-panel containing 80 disease-related genes in 650 unrelated patients with non-ischemic cardiomyopathy to identify potential pathogenic PLN variants. To comprehensively evaluate the genetic cause of the proband and his pedigree, whole-exome sequencing and Sanger sequencing were performed. RESULTS: A novel homozygous nonsense variant (p.Glu2Ter, c.4G>T) in PLN was identified in a 36-year-old male suffering from dilated cardiomyopathy with severe heart failure. No more cardiomyopathy-causing variant or likely pathogenic copy number variation was identified. This variant was not detected in 800 unrelated healthy controls. Furthermore, the variant is not in the Exome Aggregation Consortium or the Genome Aggregation databases. Western blots showed that this variant significantly reduced the expression of phospholamban. Furthermore, in pedigree analysis, we found that all five heterozygous PLN-p.Glu2Ter carriers (including four elder relatives) had normal heart size and cardiac function, which revealed a novel autosomal recessive inheritance mode. CONCLUSIONS: Our study identified a novel pathogenic variant of PLN, and revealed a novel pathogenic inheritance mode of PLN causing dilated cardiomyopathy with heart failure.
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Proteínas de Ligação ao Cálcio/genética , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , Códon sem Sentido/genética , Variação Genética/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adulto , Idoso , Sequência de Aminoácidos , Criança , Variações do Número de Cópias de DNA/genética , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/genética , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Differently expressed circular RNAs (circRNAs) have been reported to play a considerable role in tumor behavior; however, the expression profile and biological function of circRNAs in papillary thyroid carcinoma (PTC) remains unknown. Thus, the study was aimed to characterize the circRNA expression profile to comprehensively understand the biological behavior of PTC. METHODS: We investigated the expression profile of circRNAs using circRNA microarray in three pairs of PTC and adjacent normal tissues. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate eight candidate circRNAs in 40 paired PTC tumors and adjacent normal samples. Next, we employed a bioinformatics tool to identify putative miRNA and circRNA-associated downstream genes, followed by constructing a network map of circRNA-miRNA-mRNA interactions and exploring the potential role of the candidate circRNAs. RESULTS: In total, 206 up- and 177 downregulated circRNAs were identified in PTC tissues (fold change >1.5; P < 0.05). The expression levels of eight candidate circRNAs confirmed by qRT-PCR were significantly different between the PTC and normal samples. The downstream genes of candidate circRNAs participated in various biological processes and signaling pathways. The most up and downregulated circRNAs were hsa_circRNA_007148 and hsa_circRNA_047771. The lower expression level of hsa_circRNA_047771 was associated BRAFV600 mutation, lymph node metastasis (LNM), as well as with advanced TNM stage (all P < 0.05). The higher expression level of hsa_circRNA_007148 was significantly correlated with LNM (P < 0.05). The areas under receiver operating curve were 0.876 (95% CI [0.78-0.94]) for hsa_circRNA_047771 and 0.846 (95% CI [0.75-0.96]) for hsa_circRNA_007148. DISCUSSION: The study suggests that dysregulated circRNAs play a critical role in PTC pathogenesis. PTC-related hsa_circRNA_047771 and hsa_circRNA_007148 may serve as potential diagnostic biomarkers and prognostic predictors for PTC patients.