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INTRODUCTION: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and confers a high risk of stroke recurrence, despite aggressive medical therapy. Asymptomatic ICAS (aICAS) is a frequent finding on neuroimaging, and it's an independent risk factor for future stroke. Alirocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and effectively lower low-density lipoprotein cholesterol levels. We hypothesize that extra alirocumab in addition to statin therapy (EAST) could stabilize intracranial plaques in patients with aICAS. METHODS AND ANALYSIS: In this prospective, randomized, open-label, blinded end-point study, we will use high-resolution vessel-wall magnetic resonance imaging (HR-vwMRI) to evaluate the efficacy and safety of alirocumab in patients with asymptomatic ICAS. Eighty patients with aICAS (50â¯%-99â¯%) caused by unstable plaques will be assigned to the arm of alirocumab plus statin therapy, or the arm of statin therapy in a 1:1 ratio. Patients will undergo HR-vwMRI at recruitment and after 6 months. The primary outcome is changes in plaque features evaluated by HR-vwMRI after 6 months' treatment. This trial is being conducted at the first affiliated hospital of Nanjing medical university, China. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University. Written informed consents will be obtained from all participants. Study results will be published as peer-reviewed articles. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, Identifier: NCT06080256.
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BACKGROUNDS: Diabetic foot (DF) is a globally significant concern, with complications like diabetic foot ulcers (DFUs) posing major challenges despite medical advancements. Effective nursing strategies are crucial to preventing DF progression and reducing disability risk. However, nursing research in DF care is fragmented, necessitating a comprehensive bibliometric analysis to identify key trends, influential contributors, and critical research areas. PURPOSE: This study explored current trends in nursing methods for DF care and their impact on patient outcomes, utilizing CiteSpace, VOSviewer, and Bibliometrix to identify key contributors, influential countries, and noteworthy topics, aiming to provide valuable insights for healthcare professionals and researchers in the field. METHODS: Relevant publications from the Web of Science (WOS) Core Collection Science Citation Index Expanded were retrieved for the period between 2003 and 2023. We included peer-reviewed original articles or reviews related to diabetic foot (DF) and nursing. The following criteria were used for exclusion: â conference abstracts or corrigendum documents, â¡ unpublished articles, ⢠repeated publications, ⣠unrelated articles, ⤠case reports, and ⥠qualitative studies. CiteSpace was employed to identify top authors, institutions, countries, keywords, co-cited authors, journals, references, and research trends. VOSviewer was used to generate a network of authors, journals, and references. Bibliometrix was utilized to create maps of cooperating countries and keyword frequency charts, as well as a Sankey diagram illustrating the relationship between authors, keywords, and countries. RESULTS: A total of 305 relevant articles were included in this study. The research pertaining to nursing aspects of diabetic foot care exhibited a noticeable upward trend. The analysis in this study revealed that "amputation" held the highest centrality, indicating a critical area of focus in nursing interventions to prevent severe outcomes. "Diabetic foot ulcer" ranked first in terms of citation rate, emphasizing the ongoing challenges in managing DFUs through nursing care. In recent years, there was a shift in focus towards keywords such as "pressure ulcers", "burden", and "chronic wound" highlighting the evolving priorities in nursing research to address complex wound care, patient burden, and long-term management strategies. CONCLUSIONS: The current primary research focuses in nursing care for diabetic foot (DF) include wound management, offloading techniques, sensory protection, anti-infective treatment, education and self-management, and multidisciplinary teamwork. Future research should prioritize developing innovative nursing interventions tailored to individual patient needs, integrating advanced technologies like telemedicine and wearable devices for continuous monitoring, and exploring the psychological aspects of DFU management to improve patient adherence and outcomes. Additionally, more longitudinal studies are needed to assess the long-term effectiveness of various nursing strategies on patient quality of life.
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Transcatheter edge-to-edge repair (TEER) has been established as a safe and effective option for treating patients with severe symptomatic degenerative mitral regurgitation (MR) who are at prohibitive surgical risk. However, the significant cost presents a considerable disease burden in low-income countries. This case details the treatment of a high-surgical-risk patient with severe degenerative MR by using the GeminiOne (Peijia Medical) system-a novel Chinese TEER device.
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OBJECTIVES: This study aimed to use all permanent teeth as the target and establish an automated dental age estimation method across all developmental stages of permanent teeth, accomplishing all the essential steps of tooth determination, tooth development staging, and dental age assessment. METHODS: A three-step framework for automatically estimating dental age was developed for children aged 3 to 15. First, a YOLOv3 network was employed to complete the tasks of tooth localization and numbering on a digital orthopantomogram. Second, a novel network named SOS-Net was established for accurate tooth development staging based on a modified Demirjian method. Finally, the dental age assessment procedure was carried out through a single-group meta-analysis utilizing the statistical data derived from our reference dataset. RESULTS: The performance tests showed that the one-stage YOLOv3 detection network attained an overall mean average precision 50 of 97.50 for tooth determination. The proposed SOS-Net method achieved an average tooth development staging accuracy of 82.97% for a full dentition. The dental age assessment validation test yielded an MAE of 0.72 years with a full dentition (excluding the third molars) as its input. CONCLUSIONS: The proposed automated framework enhances the dental age estimation process in a fast and standard manner, enabling the reference of any accessible population. CLINICAL RELEVANCE: The tooth development staging network can facilitate the precise identification of permanent teeth with abnormal growth, improving the effectiveness and comprehensiveness of dental diagnoses using pediatric orthopantomograms.
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Aprendizaje Profundo , Humanos , Niño , Tercer Molar , Odontogénesis , Radiografía PanorámicaRESUMEN
The phylogenetic status of the family Nitidulidae and its sister group relationship remain controversial. Also, the status of the subfamily Meligethinae is not fully understood, and previous studies have been mainly based on morphology, molecular fragments, and biological habits, rather than the analysis of the complete mitochondrial genome. Up to now, there has been no complete mitochondrial genome report of Meligethinae. In this study, the complete mitochondrial genomes of Meligethinus tschungseni and Brassicogethes affinis (both from China) were provided, and they were compared with the existing complete mitochondrial genomes of Nitidulidae. The phylogenetic analysis among 20 species of Coleoptera was reconstructed via PhyloBayes analysis and Maximum likelihood (ML) analysis, respectively. The results showed that the full lengths of Meligethinus tschungseni and Brassicogethes affinis were 15,783 bp and 16,622 bp, and the AT contents were 77% and 76.7%, respectively. Each complete mitochondrial genome contains 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and a control region (A + T-rich region). All the PCGs begin with the standard start codon ATN (ATA, ATT, ATG, ATC). All the PCGs terminate with a complete terminal codon, TAA or TAG, except cox1, cox2, nad4, and nad5, which terminate with a single T. Furthermore, all the tRNAs have a typical clover-leaf secondary structure except trnS1, whose DHU arm is missing in both species. The two newly sequenced species have different numbers and lengths of tandem repeat regions in their control regions. Based on the genetic distance and Ka/Ks analysis, nad6 showed a higher variability and faster evolutionary rate. Based on the available complete mitochondrial genomes, the results showed that the four subfamilies (Nitidulinae, Meligethinae, Carpophilinae, Epuraeinae) of Nitidulidae formed a monophyletic group and further supported the sister group relationship of Nitidulidae + Kateretidae. In addition, the taxonomic status of Meligethinae and the sister group relationship between Meligethinae and Nitidulinae (the latter as currently circumscribed) were also preliminarily explored.
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Perovskite (PVSK) photovoltaic (PV) devices are undergoing rapid development and have reached a certified power conversion efficiency (PCE) of 26.1% at the cell level. Tremendous efforts in material and device engineering have also increased moisture, heat, and light-related stability. Moreover, the solution-process nature makes the fabrication process of perovskite photovoltaic devices feasible and compatible with some mature high-volume manufacturing techniques. All these features render perovskite solar modules (PSMs) suitable for terawatt-scale energy production with a low levelized cost of electricity (LCOE). In this review, the current status of perovskite solar cells (PSCs) and modules and their potential applications are first introduced. Then critical challenges are identified in their commercialization and propose the corresponding solutions, including developing strategies to realize high-quality films over a large area to further improve power conversion efficiency and stability to meet the commercial demands. Finally, some potential development directions and issues requiring attention in the future, mainly focusing on further dealing with toxicity and recycling of the whole device, and the attainment of highly efficient perovskite-based tandem modules, which can reduce the environmental impact and accelerate the LCOE reduction are put forwarded.
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Polymorphic structures of transition metal dichalcogenides (TMDs) host exotic electronic states, like charge density wave and superconductivity. However, the number of these structures is limited by crystal symmetries, which poses a challenge to achieving tailored lattices and properties both theoretically and experimentally. Here, we report a coloring-triangle (CT) latticed MoTe2 monolayer, termed CT-MoTe2, constructed by controllably introducing uniform and ordered mirror-twin-boundaries into a pristine monolayer via molecular beam epitaxy. Low-temperature scanning tunneling microscopy and spectroscopy (STM/STS) together with theoretical calculations reveal that the monolayer has an electronic Janus lattice, i.e., an energy-dependent atomic-lattice and a Te pseudo-sublattice, and shares the identical geometry with the Mo5Te8 layer. Dirac-like and flat electronic bands inherently existing in the CT lattice are identified by two broad and two prominent peaks in STS spectra, respectively, and verified with density-functional-theory calculations. Two types of intrinsic domain boundaries were observed, one of which maintains the electronic-Janus-lattice feature, implying potential applications as an energy-tunable electron-tunneling barrier in future functional devices.
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Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.
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Layered charge-density-wave (CDW) materials have gained increasing interest due to their CDW stacking-dependent electronic properties for practical applications. Among the large family of CDW materials, those with star of David (SOD) patterns are very important due to the potentials for quantum spin liquid and related device applications. However, the spatial extension and the spin coupling information down to the nanoscale remain elusive. Here, we report the study of heterochiral CDW stackings in bilayer (BL) NbSe2 with high spatial resolution. We reveal that there exist well-defined heterochiral stackings, which have inhomogeneous electronic states among neighboring CDW units (star of David, SOD), significantly different from the homogeneous electronic states in the homochiral stackings. Intriguingly, the different electronic behaviors are spatially localized within each SOD with a unit size of 1.25 nm, and the gap sizes are determined by the different types of SOD stackings. Density functional theory (DFT) calculations match the experimental measurements well and reveal the SOD-stacking-dependent correlated electronic states and antiferromagnetic/ferromagnetic couplings. Our findings give a deep understanding of the spatial distribution of interlayer stacking and the delicate modulation of the spintronic states, which is very helpful for CDW-based nanoelectronic devices.
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BACKGROUND: Mobile health (mHealth) apps are rapidly emerging technologies in China due to strictly controlled medical needs during the COVID-19 pandemic while continuing essential services for chronic diseases. However, there have been no large-scale, systematic efforts to evaluate relevant apps. OBJECTIVE: We aim to provide a landscape of mHealth apps in China by describing and comparing digital health concerns before and after the COVID-19 outbreak, including mHealth app data flow and user experience, and analyze the impact of COVID-19 on mHealth apps. METHODS: We conducted a semilongitudinal survey of 1593 mHealth apps to study the app data flow and clarify usage changes and influencing factors. We selected mHealth apps in app markets, web pages from the Baidu search engine, the 2018 top 100 hospitals with internet hospitals, and online shopping sites with apps that connect to smart devices. For user experience, we recruited residents from a community in southeastern China from October 2019 to November 2019 (before the outbreak) and from June 2020 to August 2020 (after the outbreak) comparing the attention of the population to apps. We also examined associations between app characteristics, functions, and outcomes at specific quantiles of distribution in download changes using quantile regression models. RESULTS: Rehabilitation medical support was the top-ranked functionality, with a median 1.44 million downloads per app prepandemic and a median 2.74 million downloads per app postpandemic. Among the top 10 functions postpandemic, 4 were related to maternal and child health: pregnancy preparation (ranked second; fold change 4.13), women's health (ranked fifth; fold change 5.16), pregnancy (ranked sixth; fold change 5.78), and parenting (ranked tenth; fold change 4.03). Quantile regression models showed that rehabilitation (P75, P90), pregnancy preparation (P90), bodybuilding (P50, P90), and vaccination (P75) were positively associated with an increase in downloads after the outbreak. In the user experience survey, the attention given to health information (prepandemic: 249/375, 66.4%; postpandemic: 146/178, 82.0%; P=.006) steadily increased after the outbreak. CONCLUSIONS: mHealth apps are an effective health care approach gaining in popularity among the Chinese population following the COVID-19 outbreak. This research provides direction for subsequent mHealth app development and promotion in the postepidemic era, supporting medical model reformation in China as a reference, which may provide new avenues for designing and evaluating indirect public health interventions such as health education and health promotion.
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COVID-19 , Aplicaciones Móviles , Telemedicina , Niño , Humanos , Femenino , Pandemias , ChinaRESUMEN
Advanced exfoliation techniques are crucial for exploring the intrinsic properties and applications of 2D materials. Though the recently discovered Au-enhanced exfoliation technique provides an effective strategy for the preparation of large-scale 2D crystals, the high cost of gold hinders this method from being widely adopted in industrial applications. In addition, direct Au contact could significantly quench photoluminescence (PL) emission in 2D semiconductors. It is therefore crucial to find alternative metals that can replace gold to achieve efficient exfoliation of 2D materials. Here, the authors present a one-step Ag-assisted method that can efficiently exfoliate many large-area 2D monolayers, where the yield ratio is comparable to Au-enhanced exfoliation method. Differing from Au film, however, the surface roughness of as-prepared Ag films on SiO2 /Si substrate is much higher, which facilitates the generation of surface plasmons resulting from the nanostructures formed on the rough Ag surface. More interestingly, the strong coupling between 2D semiconductor crystals (e.g., MoS2 , MoSe2 ) and Ag film leads to a unique PL enhancement that has not been observed in other mechanical exfoliation techniques, which can be mainly attributed to enhanced light-matter interaction as a result of extended propagation of surface plasmonic polariton (SPP). This work provides a lower-cost and universal Ag-assisted exfoliation method, while at the same time offering enhanced SPP-matter interactions.
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A critical challenge in genetic diagnostics is the assessment of genetic variants associated with diseases, specifically variants that fall out with canonical splice sites, by altering alternative splicing. Several computational methods have been developed to prioritize variants effect on splicing; however, performance evaluation of these methods is hampered by the lack of large-scale benchmark datasets. In this study, we employed a splicing-region-specific strategy to evaluate the performance of prediction methods based on eight independent datasets. Under most conditions, we found that dbscSNV-ADA performed better in the exonic region, S-CAP performed better in the core donor and acceptor regions, S-CAP and SpliceAI performed better in the extended acceptor region and MMSplice performed better in identifying variants that caused exon skipping. However, it should be noted that the performances of prediction methods varied widely under different datasets and splicing regions, and none of these methods showed the best overall performance with all datasets. To address this, we developed a new method, machine learning-based classification of splice sites variants (MLCsplice), to predict variants effect on splicing based on individual methods. We demonstrated that MLCsplice achieved stable and superior prediction performance compared with any individual method. To facilitate the identification of the splicing effect of variants, we provided precomputed MLCsplice scores for all possible splice sites variants across human protein-coding genes (http://39.105.51.3:8090/MLCsplice/). We believe that the performance of different individual methods under eight benchmark datasets will provide tentative guidance for appropriate method selection to prioritize candidate splice-disrupting variants, thereby increasing the genetic diagnostic yield.
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Empalme Alternativo , Empalme del ARN , Biología Computacional/métodos , Exones , Humanos , Aprendizaje Automático , MutaciónRESUMEN
BACKGROUND: As aortic aneurysms (AAs) enlarge, they can become life-threatening if left undiagnosed or neglected. At present, there is a lack of radical treatments for preventing disease progression. Therefore, we aimed to identify effective drug targets that slow the progression of AAs. METHODS: A Mendelian randomization (MR) analysis was conducted to identify therapeutic targets which are associated with AAs. Summary statistics for AAs were obtained from two datasets: the UK Biobank (2228 cases and 408,565 controls) and the FinnGen study (3658 cases and 244,907 controls). Cis-expression quantitative trait loci (cis-eQTL) for druggable genes were retrieved from the eQTLGen Consortium and used as genetic instrumental variables. Colocalization analysis was performed to determine the probability that single nucleotide polymorphisms (SNPs) associated with AAs and eQTL shared causal genetic variants. FINDINGS: Four drug targets (BTN3A1, FASN, PLAU, and PSMA4) showed significant MR results in two independent datasets. Proteasome 20S subunit alpha 4 (PSMA4) and plasminogen activator, urokinase (PLAU) in particular, were found to have strong evidence for colocalization with AAs, and abdominal aortic aneurysm in particular. Additionally, except for the association between PSMA4 and intracranial aneurysms, no association between genetically proxied inhibition of PLAU and PSMA4 was detected in increasing the risk of other cardiometabolic risks and diseases. INTERPRETATION: This study supports that drug-targeting PLAU and PSMA4 inhibition may reduce the risk of AAs. FUNDING: This work was supported by National Key R&D Program of China (NO. 2017YFC0909400), Nature Science Foundation of China (No. 91839302, 81790624), Project supported by Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01), and Tongji Hospital Clinical Research Flagship Program (no. 2019CR207).
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Aneurisma de la Aorta , Análisis de la Aleatorización Mendeliana , Antígenos CD , Butirofilinas , China , Humanos , Complejo de la Endopetidasa Proteasomal , Activador de Plasminógeno de Tipo UroquinasaRESUMEN
Objective: ALPK3 is associated with a recessive form of pediatric cardiomyopathy accompanied by musculoskeletal and craniofacial abnormalities. Heterozygous truncating variants in this gene (ALPK3tv) have recently been confirmed as a cause of autosomal dominant hypertrophic cardiomyopathy (HCM). Whether ALPK3 is also implicated in HCM in East Asia and the effect of missense variants in ALPK3 on HCM remains unresolved. Methods: We compared the frequency of rare deleterious variants in ALPK3 in a study cohort comprised of 793 HCM cases of East Asian descent to that in the controls subset of Genome Aggregation Database (gnomAD). Gene burden test was used to assess this association. The involvement of these variants in HCM was further validated by independent cohort. The clinical characteristics and prognoses of these carriers were compared with sarcomere-positive and negative patients. Results: Rare deleterious variants in ALPK3 were significantly enriched in HCM compared with gnomAD controls (truncating: 4/793 vs. 4/4523, P = 0.02; missense: 25/793 vs. 46/4523, P = 2.56e-5). Replication in an independent cohort provided more supporting evidence. Further comparisons revealed that ALPK3 carriers displayed more severe hypertrophy in interventricular septum (IVS) and apex, as well as greater maximal left ventricular wall thickness, relative to sarcomere negatives. Conclusion: Heterozygous rare variants in ALPK3, both missense and truncating variants, are associated with HCM in East Asians.
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To reveal genetic risks of early-onset sporadic dilated cardiomyopathy (DCM) patients in the Chinese Han population, we enlisted 363 DCM cases and 414 healthy controls. Whole-exome sequencing and phenotypic characterization were conducted. In total, we identified 26 loss-of-function (LOF) candidates and 66 pathogenic variants from 33 genes, most of which were novel. The deleterious variants can account for 25.07% (91/363) of all patients. Furthermore, rare missense variants in 21 genes were found to be significantly associated with DCM in burden tests. Other than rare variants, twelve common SNPs were significantly associated with an increased risk of DCM in allele-based genetic model association analysis. Of note, in the cumulative risk model, high-risk subjects had a 3.113-fold higher risk of developing DCM than low-risk subjects. Also, DCM in the high-risk group had a younger age of onset than that in the low-risk group. In terms of cardiac function, the mean left ventricular ejection fraction of patients with the deleterious variants was lower than those without (27.73%±10.02% vs. 30.61%±10.85%, P=0.026). To conclude, we mapped a comprehensive atlas of genetic risks in Chinese patients with DCM that might lead to new insights into the mechanisms and risk stratification for DCM.
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Cardiomiopatía Dilatada , Cardiomiopatía Dilatada/genética , China , Humanos , Volumen Sistólico , Función Ventricular Izquierda , Secuenciación del ExomaRESUMEN
Sequential encoding of motor programs is essential for behavior generation. However, whether it is critical for instinctive behavior is still largely unknown. Mouse hunting behavior typically contains a sequential motor program, including the prey search, chase, attack, and consumption. Here, we reveal that the neuronal activity in the lateral periaqueductal gray (LPAG) follows a sequential pattern and is time-locked to different hunting actions. Optrode recordings and photoinhibition demonstrate that LPAGVgat neurons are required for the prey detection, chase and attack, while LPAGVglut2 neurons are selectively required for the attack. Ablation of inputs that could trigger hunting, including the central amygdala, the lateral hypothalamus, and the zona incerta, interrupts the activity sequence pattern and substantially impairs hunting actions. Therefore, our findings reveal that periaqueductal gray neuronal ensembles encode the sequential hunting motor program, which might provide a framework for decoding complex instinctive behaviors.
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Conducta Animal/fisiología , Neuronas/metabolismo , Sustancia Gris Periacueductal/metabolismo , Animales , Electromiografía , Área Hipotalámica Lateral/metabolismo , Área Hipotalámica Lateral/fisiología , Inmunohistoquímica , Masculino , Ratones , Neuronas/fisiología , Prueba de Campo Abierto , Sustancia Gris Periacueductal/fisiología , Zona Incerta/metabolismo , Zona Incerta/fisiologíaRESUMEN
BACKGROUND: The genetic basis of a considerable fraction of hypertrophic cardiomyopathy (HCM) cases remains unknown. Whether the gene encoding RNA binding motif protein 20 (RBM20) is implicated in HCM and the correlation of clinical characteristics of RBM20 heterozygotes with HCM remain unresolved. We aimed to investigate the association between RBM20 variants and HCM. METHODS: We compared rare variants in the RBM20 gene by exome sequencing in 793 patients with HCM and 414 healthy controls. Based on a case-control approach, we used optimal sequence kernel association test (SKAT-O) to explore whether RBM20 is associated with HCM. The genetic distribution of RBM20 rare variants was then compared between HCM heterozygotes and dilated cardiomyopathy (DCM) heterozygotes. Clinical features and prognosis of RBM20 heterozygotes were compared with nonheterozygotes. RESULTS: Gene-based association analysis implicated RBM20 as a susceptibility gene for developing HCM. Patients with RBM20 variants displayed a higher prevalence of sudden cardiac arrest (SCA) (6.7% vs 0.9%, P = 0.001), increased sudden cardiac death (SCD) risk factor counts and impaired left ventricle systolic function. Further survival analysis revealed that RBM20 heterozygotes had higher incidences of resuscitated cardiac arrest, recurrent nonsustained ventricular tachycardia, and malignant arrhythmias. Mendelian randomization suggested that RBM20 expression in the left ventricle was causally associated with HCM and DCM with opposite effects. CONCLUSIONS: This study identified RBM20 as a potential causal gene of HCM. RBM20 variants are associated with increased risk for SCA in HCM.
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Cardiomiopatía Hipertrófica/genética , ADN/genética , Estudios de Asociación Genética/métodos , Predisposición Genética a la Enfermedad , Mutación , Proteínas de Unión al ARN/genética , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/metabolismo , Análisis Mutacional de ADN , Femenino , Estudios de Seguimiento , Pruebas Genéticas , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Proteínas de Unión al ARN/metabolismo , Estudios RetrospectivosRESUMEN
Powder to bulk processes, such as additive manufacturing and metal injection molding (MIM), have enabled great potential for complex metal designing and manufacturing. However, additive manufacturing process normally introduces a high residue stress and textures due to the locally intense temperature. MIM is an excellent batch manufacturing process; nevertheless, it is not suitable for rapid screening and development of new metal compositions and structures due to the slow sintering process. Herein, an ultrafast high-temperature sintering (UHS) process is reported that enables the rapid synthesis and sintering of bulk metals/alloys and intermetallic compounds. In this process, elemental powders are mixed and pressed into pellets, followed by UHS sintering in just seconds at a temperature between 1000 and 3000 °C. Three representative compositions, including pure metals, intermetallics, and multielement alloys, are demonstrated with a broad range of melting points. The UHS process for metal sintering is nonmaterials specific, in addition to being extremely rapid, which make it suitable for materials discovery. Furthermore, the sintering method does not apply pressure to the samples, making it compatible with 3D printing and other additive manufacturing processes of complex structures. This rapid sintering technique will greatly facilitate the development and manufacturing of metals and alloys.
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Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10-6) after 10 000 times permutation test (P = 2.49 × 10-3). Moreover, another independent cohort, including 423 cases and 734 non-STAD subjects (N = 1157), replicated our results (P = 0.021). Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues, and its expression was related to the extracellular matrix (ECM) pathway. Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway. We wanted to expand the knowledge of the genetic basis and pathology of STAD, which may further help in providing better genetic counseling to the patients.
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Disección Aórtica , Disección Aórtica/genética , Estudios de Casos y Controles , Análisis por Conglomerados , Estudios de Cohortes , Colágeno Tipo III/genética , Biología Computacional , Predisposición Genética a la Enfermedad , HumanosRESUMEN
Li metal holds great promise to be the ultimate anode choice owing to its high specific capacity and low redox potential. However, processing Li metal into thin-film anode with high electrochemical performance and good safety to match commercial cathodes remains challenging. Herein, a new method is reported to prepare ultrathin, flexible, and high-performance Li-Sn alloy anodes with various shapes on a number of substrates by directly stamping a molten metal solution. The printed anode is as thin as 15 µm, corresponding to an areal capacity of ≈3 mAh cm-2 that matches most commercial cathode materials. The incorporation of Sn provides the nucleation center for Li, thereby mitigating Li dendrites as well as decreasing the overpotential during Li stripping/plating (e.g., <10 mV at 0.25 mA cm-2 ). As a proof-of-concept, a flexible Li-ion battery using the ultrathin Li-Sn alloy anode and a commercial NMC cathode demonstrates good electrochemical performance and reliable cell operation even after repetitive deformation. The approach can be extended to other metal/alloy anodes such as Na, K, and Mg. This study opens a new door toward the future development of high-performance ultrathin alloy-based anodes for next-generation batteries.