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The 2024 moment magnitude 7.5 Noto Peninsula (Japan) earthquake caused devastation to communities and was generated by a complex rupture process. Using space geodetic and seismic observations, we have shown that the event deformed the peninsula with a peak uplift reaching 5 meters at the west coast. Shallow slip exceeded 10 meters on an offshore fault. Peak stress drop was greater than 10 megapascals. This devastating event began with a slow rupture propagation lasting 15 to 20 seconds near its hypocenter, where seismic swarms had surged since 2020 because of lower-crust fluid supply. The slow start was accompanied by intense high-frequency seismic radiation. These observations suggest a distinct coseismic slip mode reflecting high heterogeneity in fault properties within a fluid-rich fault zone.
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BACKGROUND: MicroRNAs (miRNAs) are important non-coding RNA entities that affect gene expression and function by binding to target mRNAs, leading to degradation of the mRNAs or inhibiting their translation. MiRNAs are widely involved in a variety of biological processes, such as cell differentiation, development, metabolism, and apoptosis. In addition, miRNAs are associated with many diseases, including cancer. However, conventional detection techniques often suffer from shortcomings such as low sensitivity, so we need to develop a rapid and efficient detection strategy for accurate detection of miRNAs. RESULTS: We have developed an innovative homogeneous electrochemiluminescence (ECL) biosensor. This biosensor employs CRISPR/Cas12a gene editing technology for accurate and efficient detection of microRNA (miRNA). Compared to conventional technologies, this biosensor employs a unique homogeneous detection format that eliminates laborious probe fixation steps and greatly simplifies the detection process. By using two amplification techniques - isothermal amplification and T7 RNA polymerase amplification - the biosensor improves the sensitivity and specificity of the assay, providing excellent detection performance in the assay. This makes it possible to evaluate miRNA directly from a variety of biological samples such as cell lysates and diluted human serum. Experimental results convincingly demonstrate the extraordinary performance of this biosensor, including its extremely low detection limit of 1.27 aM, high sensitivity, reproducibility and stability. SIGNIFICANCE: The application of our constructed sensor in distinguishing between cancerous and non-cancerous cell lines highlights its potential for early cancer detection and monitoring. This innovative approach represents a major advancement in the field of miRNA detection, providing a user-friendly, cost-effective, and sensitive solution with broad implications for clinical diagnosis and patient care, especially in point-of-care settings.
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Técnicas Biosensibles , Sistemas CRISPR-Cas , Técnicas Electroquímicas , Mediciones Luminiscentes , MicroARNs , Humanos , Técnicas Biosensibles/métodos , MicroARNs/análisis , MicroARNs/sangre , MicroARNs/genética , Sistemas CRISPR-Cas/genética , Técnicas Electroquímicas/métodos , Límite de Detección , Proteínas Asociadas a CRISPR/genética , Proteínas Bacterianas , EndodesoxirribonucleasasRESUMEN
Introduction: With the rapid development of artificial intelligence and Internet-of-Things technology, internal support systems among families are gradually weakening, which can no longer satisfy the current demands of older adults. In this context, smart senior care has become a new development direction. However, existing studies on the demand for smart senior care are primarily concentrated in economically developed provinces and mega-cities in eastern China; their research results or conclusions may not apply to underdeveloped areas in the Western region. Therefore, our study selects Lanzhou as a representative city in an underdeveloped western region to investigate the demand of older adults for smart senior care and analyze the influencing factors. Methods: This cross-sectional study included 4,815 older adults from Lanzhou, China. A structured questionnaire was designed to investigate the demands of the older adults for smart senior care and analyze thie influencing factors. The Chi-square test was used for single factor analysis of each variable. The logistic regression model included the statistically significant variables to analyze factors influencing older adults' demand for smart senior care. A significance level of p < 0.05 was considered statistically significant. Results: Among the surveyed older adults, 1,625 (33.75%) expressed a demand for smart senior care. The finding indicated that participants' age, level of education, marital status, monthly income, number of children, type of endowment insurance, and knowledge of smart senior care were significantly associated with their demands for smart senior care (p < 0.05). Notably, medical care emerged as the smart senior care service with the highest demand rate (79.45%). Conclusion: In Lanzhou, older adults show a low level of knowledge but a high demand for smart senior care. Their demand is influenced by personal, family, health conditions, senior care security, and other factors. To advance smart senior care, government departments should accelerate the improvement of the laws and regulations on smart senior care while vigorously enhancing the service's publicity to raise knowledge about it. Additionally, the service contents for smart senior care should be expanded to meet the diversified demands of older adults.
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Necesidades y Demandas de Servicios de Salud , Humanos , China , Anciano , Estudios Transversales , Masculino , Femenino , Encuestas y Cuestionarios , Anciano de 80 o más Años , Persona de Mediana Edad , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Servicios de Salud para Ancianos/estadística & datos numéricosRESUMEN
BACKGROUND: Reirradiation with stereotactic body radiotherapy (SBRT) for patients with primary or secondary lung malignancies represents an appealing definitive approach, but its feasibility and safety are not well defined. The purpose of this study was to investigate the tumor control probability (TCP) and toxicity for patients receiving reirradiation with SBRT. PATIENTS AND METHODS: Eligible patients with recurrence of primary or secondary lung malignancies from our hospital were subjected to reirradiation with SBRT, and PubMed- and Embase-indexed articles were reviewed. The patient characteristics, pertinent SBRT dosimetric details, local tumor control, and toxicities were extracted. The logistic dose-response models were compared for TCP and overall survival (OS) in terms of the physical dose and three-, four-, and five-fraction equivalent doses. RESULTS: The data of 17 patients from our hospital and 195 patients extracted from 12 articles were summarized. Reirradiation with SBRT yielded 2-year estimates of 80% TCP for doses of 50.10 Gy, 55.85 Gy, and 60.54 Gy in three, four, and five fractions, respectively. The estimated TCP with common fractionation schemes were 50%, 60%, and 70% for 42.04 Gy, 47.44 Gy, and 53.32 Gy in five fractions, respectively. Similarly, the 2-year estimated OS was 50%, 60%, and 70% for 41.62 Gy, 46.88 Gy, and 52.55 Gy in five fractions, respectively. Central tumor localization may be associated with severe toxicity. CONCLUSIONS: Reirradiation with SBRT doses of 50-60 Gy in 3-5 fractions is feasible for appropriately selected patients with recurrence of peripheral primary or secondary lung malignancies, but should be carefully considered for centrally-located tumors due to potentially severe toxicity. Further studies are warranted for optimal dose/fractionation schedules and more accurate selection of patients suitable for reirradiation with SBRT.
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Neoplasias Pulmonares , Radiocirugia , Reirradiación , Humanos , Radiocirugia/efectos adversos , Reirradiación/efectos adversos , Neoplasias Pulmonares/patología , Fraccionamiento de la Dosis de Radiación , Probabilidad , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patologíaRESUMEN
Spinal muscular atrophy (SMA) is a recessive, neurodegenerative disorder. It is one of the most common genetic causes of infant mortality and is characterized by muscle weakness, loss of ambulation, and respiratory failure. SMA is primarily caused by a homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene. Humans possess a second, nearly identical copy of SMN, known as the SMN2 gene. Although the disease severity correlates inversely with the number of SMN2 copies present, it can never completely compensate for the loss of SMN1 in patients with SMA; SMN2 expresses only a fraction of the functional SMN transcript. The SMN protein is ubiquitous in human cells and plays several roles, ranging from assembling the spliceosome machinery to autophagy, RNA metabolism, signal transduction, cellular homeostasis, DNA repair, and recombination. Although the underlying mechanism remains unclear, anterior horn cells of the spinal cord gray matter are highly vulnerable to decreased SMN protein levels. To harness SMN2's ability to provide SMN function, two treatment strategies have been approved by the Food and Drug Administration (FDA), including an antisense oligonucleotide, nusinersen (Spinraza), and a small molecule, risdiplam (Evrysdi). Onasemnogene abeparvovec (Zolgensma) is an FDA-approved adeno-associated virus 9-mediated gene replacement therapy that creates a copy of the human SMN1 gene. In this review, we summarize the SMA etiology and FDA-approved therapies, and discuss the development of SMA therapeutic strategies and the challenges we faced.
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Atrofia Muscular Espinal , Humanos , Lactante , Homocigoto , Neuronas Motoras/metabolismo , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/terapia , Oligonucleótidos Antisentido/genética , Oligonucleótidos Antisentido/uso terapéutico , Eliminación de Secuencia , Proteína 1 para la Supervivencia de la Neurona Motora/genéticaRESUMEN
A novel dual-template magnetic molecularly imprinted polymer (MMIP) was synthesized to extract normetanephrine (NMN), metanephrine (MN) and 3-methoxytyramine (3-MT) from spot urine samples. As the adsorbent of dispersive solid-phase extraction (d-SPE), the MMIP was prepared using dopamine and MN as dual templates, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the crosslinking reagent and magnetic nanoparticles as the magnetic core. NMN, MN, 3-MT and creatinine (Cr) in spot urine samples were selectively enriched by d-SPE and detected by HPLC-fluorescence detection/ultraviolet detection. The peak area (A) ratios of NMN, MN and 3-MT to Cr were used for the diagnosis of pheochromocytomas and paragangliomas (PPGLs). The results showed that the adsorption efficiencies of MMIP for target analytes were all higher than 89.0%, and the coefficient variation precisions of intra-assay and inter-assay for the analytes were within 4.9% and 6.3%, respectively. The recoveries of the analytes were from 93.2% to 112.8%. The MMIP was still functional within 14 days and could be reused at least seven times. The d-SPE and recommended solid-phase extraction (SPE) were both used to pretreat spot urine samples from 18 PPGLs patients and 22 healthy controls. The correlation coefficients of ANMN/ACr and AMN/ACr between d-SPE and SPE were both higher than 0.95. In addition, the areas under the receiver operator curves for spot urine ANMN/ACr, AMN/ACr and plasma free NMN and MN were 0.975, 0.773 and 0.990, 0.821, respectively, indicating the two methods had the similar performances. The d-SPE method took only 20 min, which was effective in clinical application.
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Neoplasias de las Glándulas Suprarrenales , Impresión Molecular , Paraganglioma , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Creatinina , Dopamina/análogos & derivados , Humanos , Fenómenos Magnéticos , Metanefrina/orina , Impresión Molecular/métodos , Polímeros Impresos Molecularmente , Normetanefrina/orina , Paraganglioma/diagnóstico , Paraganglioma/orina , Feocromocitoma/diagnósticoRESUMEN
A pulse chemisorption system combining a Tian-Calvet microcalorimeter (Setaram Sensys EVO 600) and an automated chemisorption apparatus (Micromeritics Autochem II 2920) was established to accurately measure differential adsorption heats of gas molecules' chemisorption on solid surfaces in a flow-pulse mode. Owing to high sensitivity and high degree of automation in a wide range of temperatures from -100 to 600 °C, this coupled system can present adsorption heats as a function of adsorption temperature and adsorbate coverage. The functions of this system were demonstrated by successful measurements of CO adsorption heats on Pd surfaces at various temperatures and also at different CO coverages by varying the CO concentration in the pulse dose. Key parameters, including adsorption amounts, integral adsorption heats, and differential adsorption heats of CO adsorption on a Pd/CeO2 catalyst, were acquired. Our adsorption-microcalorimetry system provides a powerful technique for the investigation of adsorption processes on powder catalysts.
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OBJECTIVE: To make the previously developed biosynthesis of L-2-aminobutyric acid (L-ABA) more suitable for the industrial-scale production. RESULTS: A recyclable biotransformation system was developed based on immobilized enzyme technology. The conversion yield of L-threonine (at 90 g l(-1)) reached 99.9 % and the theoretical yield of L-ABA reached more than 90 % using the optimized biotransformation system by the individual immobilization of threonine deaminase and the co-immobilization of L leucine dehydrogenase and formate dehydrogenase. 90 g L-threonine l(-1) was converted to 73.9 g L-ABA l(-1) >95 % theoretical yield, within 120-145 min in 30 batch transformation experiments. CONCLUSION: The recyclable biotransformation system is promising to fulfill industrial requirements for L-ABA production.
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Aminobutiratos/metabolismo , Leucina-Deshidrogenasa/metabolismo , Treonina Deshidratasa/metabolismo , Biotransformación , Enzimas Inmovilizadas , Equipo Reutilizado/economía , Escherichia coli/metabolismo , Leucina-Deshidrogenasa/aislamiento & purificación , Treonina Deshidratasa/aislamiento & purificaciónRESUMEN
Composite scaffolds of mesoporous bioactive glass (MBG)/polycaprolactone (PCL) and conventional bioactive glass (BG)/PCL were fabricated by a solvent casting-particulate leaching method, and the structure and properties of the composite scaffolds were characterized. The measurements of the water contact angles suggest that the incorporation of either MBG or BG into PCL can improve the hydrophilicity of the composites, and the former is more effective than the later. The bioactivity of the composite scaffold is evaluated by soaking the scaffolds in a simulated body fluid (SBF) and the results show that the MBG/PCL composite scaffolds can induce a dense and continuous layer of apatite after soaking in SBF for 3 weeks, as compared with the scattered and discrete apatite particles on the BG/PCL composite scaffolds. Such improvements (improvements of the hydrophilicity and apatite forming ability) should be helpful for the extensive applications of PCL scaffold in tissue engineering.
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Vidrio/química , Poliésteres/química , Calcio/química , Iones/química , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Nitrógeno/química , Fósforo/química , Silicio/química , Soluciones , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
We report the design and synthesis of a covalently bonded AlQ3/SiO2 hybrid material with strong blue light emission by a sol-gel approach, which make AlQ3 solution-processable and chemically stable.