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Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. Electroacupuncture (EA) has been shown to exert a neuroprotective effect in IS. However, its specific anti-IS mechanisms remain to be fully elucidated. By constructing a rat IS (middle cerebral artery occlusion, or MCAO) model and performing EA treatment, neurological deficit score, brain water content, and cerebral infarction were evaluated. ELISA was used to measure the levels of oxidative stress-related molecules (MDA, SOD, GSH, and CAT). Ferroptosis-related proteins (GPX4, SLC7A11, TfR1, L-ferritin, and hepcidin), neurological damage-related proteins (GFAP, Iba-1, and Nestin), α7nAChR, and mTOR pathway-related proteins (mTOR, p-mTOR, and SREBP1) in the rat brain penumbra were assessed by western blotting. Following EA treatment, neurological deficit scores, brain water content, cerebral infarction area, and GFAP, Iba-1, and Nestin expression were reduced. Additionally, EA treatment decreased MDA and increased SOD, GSH, and CAT. Moreover, the rats showed elevated GPX4 and SLC7A11 and lowered TfR1, L-ferritin, and hepcidin. In contrast, a7nAChR, mTOR, p-mTOR, and SREBP1 expression were upregulated. EA treatment inhibited OS and ferroptosis to exert a neuroprotective effect in IS, which might be realized via the activation of mTOR/SREBP1 signaling.
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Electroacupuntura , Ferroptosis , Accidente Cerebrovascular Isquémico , Estrés Oxidativo , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Ratas , Serina-Treonina Quinasas TOR/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/terapia , Modelos Animales de Enfermedad , Masculino , Humanos , Ratas Sprague-DawleyRESUMEN
SignificanceAdjusting the floating states when objects float on water shows great potential for assembly, mineral flotation, nanostructured construction, and floating robot design, but the real-time regulation of floating states is challenging. Inspired by the different floating states of a falling fruit, we propose a facile strategy to transform the object between different floating states based on a three-segment three-phase contact line evolution. In addition, the potential of floating state transformation in solar-powered water evaporation, interface catalysis, and drug delivery is demonstrated. These findings provide insights into floating regulation and show great potential for floating-related applications.
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Sistemas de Liberación de Medicamentos , Nanoestructuras , AguaRESUMEN
Traditional hydrogel-based wearable sensors with flexibility, biocompatibility, and mechanical compliance exhibit potential applications in flexible wearable electronics. However, the low sensitivity and poor environmental resistance of traditional hydrogels severely limit their practical application. Herein, high-ion-conducting poly(vinyl alcohol) (PVA) nanocomposite hydrogels were fabricated and applied for harsh environments. MXene ion-conducting microchannels and poly(sodium 4-styrenesulfonate) ion sources contributed to the directional transport of abundant free ions in the hydrogel, which significantly improved the sensitivity and mechanical-electric conversion of the nanocomposite hydrogel-based piezoelectric and triboelectric sensors. More importantly, the glycerol as an antifreezing agent enabled the hydrogel-based sensors to function in harsh environments. Therefore, the nanocomposite hydrogel exhibited high gauge factor (GF) at -20 °C (GF = 3.37) and 60 °C (GF = 3.62), enabling the hydrogel-based sensor to distinguish different writing letters and sounding words. Meanwhile, the hydrogel-based piezoelectric and triboelectric generators showed excellent mechanical-electric conversion performance regardless of low- (-20 °C) or high- (60 °C) temperature environments, which can be applied as a visual feedback system for information transmission without external power sources. This work provides self-powered nanocomposite hydrogel-based sensors that exhibit potential applications in flexible wearable electronics under harsh environmental conditions.
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Hidrogeles , Nanocompuestos , Alcohol Polivinílico , Dispositivos Electrónicos Vestibles , Nanocompuestos/química , Alcohol Polivinílico/química , Hidrogeles/química , Conductividad Eléctrica , HumanosRESUMEN
SET domain bifurcated methyltransferase 1 (SETDB1) serves as a histone lysine methyltransferase, catalyzing the di- and tri-methylation of histone H3K9. Mounting evidence indicates that the abnormal expression or activity of SETDB1, either through amplification or mutation, plays a crucial role in tumorigenesis and progression. This is particularly evident in the context of tumor immune evasion and resistance to immune checkpoint blockade therapy. Furthermore, there is a robust association between SETDB1 dysregulation and an unfavorable prognosis across various types of tumors. The oncogenic role of SETDB1 primarily arises from its methyltransferase function, which contributes to the establishment of a condensed and transcriptionally inactive heterochromatin state. This results in the inactivation of genes that typically hinder cancer development and silencing of retrotransposons that could potentially trigger an immune response. These findings underscore the substantial potential for SETDB1 as an anti-tumor therapeutic target. Nevertheless, despite significant strides in recent years in tumor biology research, challenges persist in SETDB1-targeted therapy. To better facilitate the development of anti-tumor therapy targeting SETDB1, we have conducted a comprehensive review of SETDB1 in this account. We present the structure and function of SETDB1, its role in various tumors and immune regulation, as well as the advancements made in SETDB1 antagonists. Furthermore, we discuss the challenges encountered and provide perspectives for the development of SETDB1-targeted anti-tumor therapy.
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Histonas , Neoplasias , Humanos , Histonas/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Neoplasias/tratamiento farmacológico , MetilaciónRESUMEN
Metabolic acidosis-induced kidney injury (MAKI) is asymptomatic and lack of clinical biomarkers in early stage, but rapidly progresses to severe renal fibrosis and ultimately results in end-stage kidney failure. Therefore, developing rapid and noninvasive strategies direct responsive to renal tubular acidic microenvironment rather than delayed biomarkers are essential for timely renoprotective interventions. Herein, we develop pH-responsive luminescent gold nanoparticles (p-AuNPs) in the second near-infrared emission co-coated with 2,3-dimethylaleic anhydride conjugated ß-mercaptoethylamine and cationic 2-diethylaminoethanethiol hydrochloride, which showed sensitive pH-induced charge reversal and intrarenal self-assembly for highly sensitive and long-time (~24â h) imaging of different stages of MAKI. By integrating advantages of pH-induced intrarenal self-assembly and enhanced interactions between pH-triggered positively charged p-AuNPs and renal tubular cells, the early- and late-stage MAKI could be differentiated rapidly within 10â min post-injection (p.i.) with contrast index (CI) of 3.5 and 4.3, respectively. The corresponding maximum CI could reach 5.1 and 9.2 at 12â h p.i., respectively. Furthermore, p-AuNPs were demonstrated to effectively real-time monitor progressive recovery of kidney injury in MAKI mice after therapy, and also exhibit outstanding capabilities for drug screening. This pH-responsive strategy showed great promise for feedback on kidney dysfunction progression, opening new possibilities for early-stage diagnosis of pH-related diseases.
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Oro , Nanopartículas del Metal , Oro/química , Nanopartículas del Metal/química , Concentración de Iones de Hidrógeno , Animales , Ratones , Riñón/diagnóstico por imagen , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/inducido químicamente , HumanosRESUMEN
While most missense mutations of the IKBKG gene typically result in Ectodermal Dysplasia with Immunodeficiency, there have been rare reported instances of missense mutations of the IKBKG gene causing both Incontinentia Pigmenti (IP) and immunodeficiency in female patients. In this study, we described an atypical IP case in a 19-year-old girl, characterized by hyperpigmented and verrucous skin areas over the entire body. Remarkably, she experienced recurrent red papules whenever she had a feverish upper respiratory tract infection. Immunohistochemical staining unveiled a substantial accumulation of CD68+ macrophages alongside the TNF-α positive cells in the dermis tissue of new pustules, with increased apoptotic basal keratinocytes in the epidermis tissue of these lesions. Starting from the age of 8 years old, the patient suffered from severe and sustained chronic respiratory mucous membrane scar hyperplasia and occluded subglottic lumen. In addition to elevated erythrocyte sedimentation rate values, inflammatory cells were observed in the pathologic lesions of endobronchial biopsies and Bronchoalveolar Lavage Fluid (BALF) smear. Further histological analysis revealed a destructive bronchus epithelium integrity with extensive necrosis. Simultaneously, the patient experienced recurrent incomplete intestinal obstructions and lips contracture. The patient's BALF sample displayed an augmented profile of proinflammatory cytokines and chemokines, suggesting a potential link to systemic hyperinflammation, possibly underlying the pathogenic injuries affecting the subglottic, respiratory, and digestive systems. Furthermore, the patient presented with recurrent pneumonias and multiple warts accompanied by a T+BlowNKlow immunophenotype. Next generation sequencing showed that the patient carried a novel de novo germline heterozygous missense mutation in the IKBKG gene (c. 821T>C, p. L274P), located in the highly conserved CC2 domain. TA-cloning sequencing of patient's cDNA yielded 30 mutant transcripts out of 44 clones. In silico analysis indicated that the hydrogen bond present between Ala270 and Leu274 in the wild-type NEMO was disrupted by the Leu274Pro mutation. However, this mutation did not affect NEMO expression in peripheral blood mononuclear cells (PBMCs). Moreover, patient PBMCs exhibited significantly impaired TNF-α production following Lipopolysaccharide (LPS) stimulation. X-chromosome inactivation in T cells and neutrophils were not severely skewed. Reduced levels of IκBα phosphorylation and degradation in patient's PBMCs were observed. The NF-κB luciferase reporter assay conducted using IKBKG-deficient HEK293T cells revealed a significant reduction in NF-kB activity upon LPS stimulation. These findings adds to the ever-growing knowledge on female IP that might contribute to the better understanding of this challenging disorder.
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Síndromes de Inmunodeficiencia , Incontinencia Pigmentaria , Niño , Femenino , Humanos , Adulto Joven , Células HEK293 , Quinasa I-kappa B/genética , Incontinencia Pigmentaria/diagnóstico , Incontinencia Pigmentaria/genética , Leucocitos Mononucleares , Lipopolisacáridos , Mutación Missense , Factor de Necrosis Tumoral alfaRESUMEN
Biomarker-activatable luminescent probes with high sensitivity and specificity show great promise in advanced bioimaging applications. However, the lack of stable biomarkers at an early stage is currently a major obstacle for sensitive early disease imaging. Herein, we develop a facile in vivo ligand exchange strategy to achieve renal-clearable activatable luminescent gold nanoparticles (AuNPs), which are independent of biomarkers for sensitive and long-time imaging of early kidney injury. Significantly activated emission in the second near-infrared region (â¼1026 nm) is realized from the ligand exchange of triphenylphosphine-3,3',3â³-trisulfonic acid (TPPTS)-coated AuNPs (â¼1.4 nm, TPPTS-AuNPs) with quantitative amounts of glutathione (GSH). The abundant GSH in cells, particularly in liver sinusoids, is then demonstrated successfully to activate the emission of TPPTS-AuNPs with an extremely low background for both cell imaging and in vivo visualization of visceral organs (e.g., liver and kidneys). In addition, the in vivo GSH-exchanged TPPTS-AuNPs show enhanced interactions with acidic renal tubular epithelial cells, resulting in sensitive (contrast index, â¼3.9) and long-time (>6.5 h) noninvasive monitoring of acidosis-induced early kidney injury. This facile ligand exchange strategy opens new possibilities for designing activatable luminescent probes independent of biomarkers for earlier disease diagnosis and treatment.
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Oro , Nanopartículas del Metal , Ligandos , Riñón/diagnóstico por imagen , GlutatiónRESUMEN
Tumor suppressor genes (TSGs) play a crucial role in tumorigenesis and drug resistance. We analyzed the subtypes of clear cell renal cell carcinoma (ccRCC) mediated by 8 genes contained in the 3p21.3 tumor suppressor gene cluster and their effects on TME cell infiltration based on the TCGA database. The risk score model was established by principal component analysis. The hub gene NPRL2 was selected by protein-protein interactions (PPI) analysis. The effect of NPRL2 on sunitinib sensitivity of ccRCC was verified by using CCK-8, colony formation assay, wound healing assay, transwell assay and xenograft tumor model. Changes in protein expression were detected by Western blotting. We found that 8 TSGs were all differentially expressed in ccRCC samples, which could divide ccRCC into two subtypes. The constructed risk score model could predict the prognosis and drug sensitivity of ccRCC patients, and was an independent prognostic factor for ccRCC. Over-expression of NPRL2 promoted apoptosis, inhibited EMT, decreased the phosphorylation of the PI3K/AKT/mTOR signaling pathway to inhibit its activity, and promoted the sensitivity of sunitinib to ccRCC cells. Collectively, our findings increased the understanding of TSGs in ccRCC, suggesting that NPRL2 as a TSG could enhance sunitinib sensitivity to ccRCC cells.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Fosfatidilinositol 3-Quinasas , Sunitinib , Proteínas Supresoras de Tumor/genéticaRESUMEN
PURPOSE: To investigate the dose-effect relationship between the dose-volume parameters of residual gross tumor volume (GTVres) and clinical prognosis in MRI image-guided adaptive brachytherapy (IGABT) of patients with locally advanced cervical cancer in our center. MATERIALS AND METHOD: The clinical data of 93 patients with locally advanced cervical squamous cell cancer who received external beam radiotherapy (EBRT) combined with IGABT⯱ chemotherapy in our center were retrospectively analyzed. The disease stage, overall treatment time (OTT), chemotherapy, and the dose-volume parameters D90, D98, and D100 of GTVres, the intermediate-risk clinical target volume (CTVIR), and the high-risk clinical target volume (CTVHR) of the patients were statistically analyzed. Kaplan-Meier and uni- and multivariable Cox regression analyses were used to analyze 2year overall survival (OS), progression-free survival (PFS), and local control rate (LC). A probit model was employed to assess the dose-effect relationship between the volume and dose-volume parameters of GTVres and 2year OS, PFS, and LC. RESULTS: The median follow-up time was 19.6 months and 2year OS, PFS, and LC were 79.6%, 68.8%, and 94.6%, respectively. CTVHR D90 was an independent influencing factor for 2year PFS (Pâ¯= 0.041); GTVresBT1 volume was an independent factor for 2year OS, PFS, and LC (Pâ¯< 0.001). The probit model showed that at GTVresBT1 volumeâ¯< 32.86â¯cm3, the expected 2year LC wasâ¯> 90%; at GTVres D98â¯> 129.12 GyEQD2, the expected 2year OS wasâ¯> 90%. CONCLUSION: Both the volume and dose-volume parameters of GTVres are promising predictors in assessment of IGABT prognosis of cervical cancer.
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Braquiterapia , Radioterapia Guiada por Imagen , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/patología , Estudios Retrospectivos , Dosificación Radioterapéutica , Resultado del Tratamiento , Braquiterapia/efectos adversos , Carga Tumoral , Estadificación de Neoplasias , Pronóstico , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: We herein described the coexistence of hemophagocytic lymphohistiocytosis (HLH) and histiocytic necrotizing lymphadenitis, alternatively known as the Kikuchi disease (KD), secondary to hemodialysis catheter-related bloodstream infection (BSI) caused by Corynebacterium striatum. CASE PRESENTATION: A patient on maintenance hemodialysis had developed persistent fever and Corynebacterium striatum was subsequently identified from the culture of both catheter tip and peripheral blood. During mitigation of the BSI, however, his fever was unabated and ensuing workup further found thrombocytopenia, hyperferritinemia, hypertriglyceridemia, low NK cell activity and a surge in serum CD25 levels. Moreover, biopsy of the bone marrow and lymph node detected histopathological evidence of hemophagocytosis and KD, respectively. Upon these abnormalities, the title-bound diagnosis was considered and the patient was eventually recovered from the treatment of dexamethasone instead of antibiotics. Consistently, aberrations in his serum CD25 levels and NK cell activity had subsided two months after discharge. CONCLUSIONS: Arguably, this encounter offered a unique chance to unravel the principal pathogenic cascade in immunobiology that made the three entities one disease continuum. As such, our work may add new understandings of HLH and/or KD secondary to severe infections in general and excessive release of cytokines in particular among patients with kidney diseases. The resultant early diagnosis is crucial to initiate appropriate treatment and improve the survival of patients with these challenging and potentially life-threatening disorders.
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Linfadenitis Necrotizante Histiocítica , Linfohistiocitosis Hemofagocítica , Sepsis , Humanos , Linfadenitis Necrotizante Histiocítica/complicaciones , Linfadenitis Necrotizante Histiocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/complicaciones , Diálisis Renal/efectos adversos , Sepsis/complicacionesRESUMEN
Ultrasmall luminescent gold nanoparticles (AuNPs) with excellent capabilities to cross biological barriers offer great promise in designing intelligent model nanomedicines for investigating structure-property relationships at the subcellular level. However, the strict surface controllability of ultrasmall AuNPs is challenging because of their small size. Herein, we report a facile in situ method for precisely controlling DNA aptamer valences on the surface of luminescent AuNPs with emission in the second near-infrared window using a phosphorothioate-modified DNA aptamer, AS1411, as a template. The discrete DNA aptamer number of AS1411-functionalized AuNPs (AS1411-AuNPs, ≈1.8â nm) with emission at 1030â nm was controlled in one aptamer (V1), two aptamers (V2), and four aptamers (V4). It was then discovered that not only the tumor-targeting efficiencies but also the subcellular transport of AS1411-AuNPs were precisely dependent on valences. A slight increase in valence from V1 to V2 increased tumor-targeting efficiencies and resulted in higher nucleus accumulation, whereas a further increase in valence (e.g., V4) significantly increased tumor-targeting efficiencies and led to higher cytomembrane accumulation. These results provide a basis for the strict surface control of nanomedicines in the precise regulation of in vivo transport at the subcellular level and their translation into clinical practice in the future.
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Aptámeros de Nucleótidos , Nanopartículas del Metal , Neoplasias , Humanos , Oro , ADNRESUMEN
Heterogeneous structures are used as energy storage devices because of their ability to accelerate charge transfer, which greatly contributes to the rate capability of devices. However, the construction of heterostructures with conspicuous electrochemical properties remains a huge challenge. In this study, a design of heterostructured Ni3 Se4 /CoSe2 nanospheres encapsulated by a carbon shell (Ni3 Se4 /CoSe2 @C) synthesized through facile hydrothermal and annealing methods is presented. The Ni3 Se4 /CoSe2 @C exhibits excellent cyclic performance with a capacity of 420 mA h g-1 at 0.5 A g-1 after 100 cycles for Na-storage and 330.1 mA h g-1 at 0.1 A g-1 after 200 cycles for K-storage. The excellent cyclic performance can be attributed to the carbon coating that maintains the structural stability and enhances electrical conductivity, and significantly, the heterostructures that promote ion/electron transport. The sodium storage mechanism of the Ni3 Se4 /CoSe2 @C is revealed by ex situ X-ray powder diffraction, ex situ high-resolution transmission electron microscopy, and in situ electrochemical impedance spectra analyses. The first principles density functional theory calculation is performed to prove that the heterostructure on the Ni3 Se4 /CoSe2 interface can induce an electric field and thus improve the electrochemical reaction kinetics. This study provides an effective approach for constructing heterostructured composites for high-performance alkaline batteries.
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Nonlinear elastic materials are significant for engineering and micromechanics. Droplets with the merits of easy-accessibility, diversity, and energy-absorption capability exhibit a variety of non-Hookean elastic behaviors. Herein, benefiting from the confinement of heterogeneous-wettable parallel plates, the non-Hookean mechanics of the droplet-based spring are systematically investigated. Experimental results and theoretical analysis reveal that the force generated by the spring varies nonlinearly with its deformation, and a force model is accordingly built to depict the mechanics of springs with different sized/numbered droplets and confined by different wettability patterns. Importantly, for the droplet-based spring, the droplet-plate contact area expands nonlinearly with the pressing force, which is employed to optimize the output performance of the droplet-based triboelectric nanogenerator to 226% compared with the control test. This finding deepens the understanding of the non-Hookean behavior of droplet-based springs, and sheds light on applications in energy harvesting, micromechanics, and miniature optic/electric devices.
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Humectabilidad , Fenómenos FísicosRESUMEN
In this Letter, we demonstrate a third-order cascaded Raman shift in an all-solid fluorotellurite fiber pumped by a 1550â nm nanosecond laser. The fluorotellurite glass with a composition of TeO2-BaF2-Y2O3 (TBY) has a usable Raman shift of â¼785â cm-1 and a Raman gain coefficient of â¼1.65 × 10-12 m/W at 1550â nm, which is approximately 25.4 times larger than that of silica glass. By using a 5.38 m fluorotellurite fiber as the Raman gain medium and a 1550â nm nanosecond laser as the pump light, a third-order cascaded Raman shift is obtained via spontaneous cascaded Raman amplification in the fluorotellurite fiber, causing the generation of the first-, second-, and third-order Stokes emissions that peak at 1765, 2049, and 2438â nm, respectively. For an average pump power of â¼491.5â mW, the output power of the generated first-, second-, and third-order Stokes light is approximately 14.1, 67.4, and 31.6â mW, respectively. The corresponding conversion efficiency is approximately 2.87%, 13.70%, and 6.43%, respectively. Our results show that fluorotellurite fibers are promising Raman gain media for constructing cascaded Raman fiber lasers with a wide range of wavelengths.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) has had a devastating impact on public health services worldwide. Currently, there are no standard remedies or therapies for COVID-19. it is important to identify and diagnose COVID-19 to control the spread. But clinical symptoms of COVID-19 are very similar to those of other respiratory viruses. RESULTS: As a result, the diagnosis of COVID-19 relies heavily on detecting pathogens. We established a bunch of triplex new TaqMan real-time PCR assays. Three sets of primers and probes (targeting the ORF1ab, N, and E genes, respectively) are poorly consistent with other human coronaviruses and the human influenza virus. The sensitivity of established PCR assays notices as few as 100 copies per PCR of the ORF1ab, N, and E genes. Meanwhile, standard curves concluded from constant PCR reaction all showed glorious linear correlations between Ct values and the polymer loading copy variety (correlation coefficient (R2 ) of ORF1ab, N, and E genes is 0.996, 0.991, and 0.998, respectively). Surveillance of RNA-based pseudovirus demonstrated that they were identified to be positive with respect to SARS-CoV-2 and that established PCR assays are achievable. CONCLUSION: The assays established provide a smaller reaction volume for diagnosing COVID-19.
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Prueba de Ácido Nucleico para COVID-19/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , SARS-CoV-2/genética , Cartilla de ADN , Humanos , ARN Viral , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Sensibilidad y EspecificidadRESUMEN
Assembly-induced emission enhancement has been widely observed for luminophors but it causes emission decrease after disassembly. The construction of unique nanoassemblies with disassembly-induced emission enhancement (DIEE) is demanded. Herein, by taking advantages of alterable siloxane bridge crosslinking states, we report a facile strategy to fabricate water-soluble nanoassemblies of luminescent gold nanoparticles (AuNPs) with abnormal DIEE. The fabricated AuNP nanoassemblies with dominant interparticle crosslinking showed a redshifted emission at ≈1070â nm with quantum yields (QYs) of 1.8 %. After disassembly, the nanoassemblies with increased intraparticle crosslinking exhibited a unique DIEE (>6 folds, QYs, 12 %) due to the enhanced ligand-to-metal charge transition. Besides, the disassembly facilitated renal clearance of AuNPs to reduce nonspecific retention in the body, opening new possibilities for designing highly emissive renal-clearable nanostructures toward more bioapplications.
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Nanopartículas del Metal , Nanoestructuras , Oro/química , Nanopartículas del Metal/química , LuminiscenciaRESUMEN
The high clinical and genetic heterogeneity makes it difficult to reach a confirmative diagnosis of suspected pediatric respiratory inherited diseases. Many patients with monogenic respiratory disorders could be missed without genetic testing. We performed a single-center study in Beijing Children's Hospital to demonstrate the clinical utility of exome sequencing (ES) as a first-tier test by evaluating the diagnostic yields of ES for inherited diseases with respiratory symptoms. A total of 107 patients were recruited in this study. We identified 51 pathogenic or likely pathogenic variants in 37 patients by ES (with or without copy number variants sequencing). The overall diagnostic yield was 34.6% (37/107). The most frequent disorders in our cohort were primary immunodeficiency disease (PIDs) (18/37, 48.6%) and primary ciliary dyskinesia (PCD) (9/37, 24.3%). We further reviewed the directive outcomes of genetic testing on the 37 positive cases. Our study demonstrated the effectiveness of ES as a first-tier test in China for diagnosing monogenic diseases of the respiratory system. In the era of precision medicine, ES as a first-tier test can rapidly make a molecular diagnosis and direct the intervention of the positive cases in pediatric respiratory medicine.
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Exoma , Pruebas Genéticas , Niño , Estudios de Cohortes , Variaciones en el Número de Copia de ADN , Exoma/genética , Humanos , Secuenciación del ExomaRESUMEN
Surface functionalization of gold nanoparticles (AuNPs) with thiolate ligands is a successful strategy for controlling their stability, nanotoxicity, circulation, and interaction with biological environments as leading nanomedicines. However, the effects of the weak anchoring groups of NH2 and COOH have been long-term ignored because of the well-recognized strong anchoring site of S-Au. Herein, the authors achieve controllable weak anchoring sites of the luminescent AuNPs using a typical thiolate peptide such as glutathione with anchoring groups of SH, COOH, and NH2 . Additionally, they establish that not only the strong anchoring site of S-Au, but also the weak anchoring sites from N-Au and COO-Au are critical to the behavior of AuNPs at both in vitro and in vivo levels. These results open up new possibilities for the fundamental understanding of the significance of the weak anchoring sites in the future surface functionalization of nanomedicines toward advanced theranostics.
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Oro , Nanopartículas del Metal , Ligandos , Luminiscencia , NanomedicinaRESUMEN
A multicenter study was performed to evaluate the value of testing gastric aspirate (GA) with Xpert MTB/RIF Ultra assay (Ultra) for childhood tuberculosis (TB) detection in China. In total, 129 children with active TB and 173 children without TB were enrolled. The sensitivity of Ultra in bacteriologically confirmed TB and probable TB cases was 87.5% (42/48) and 44.4% (36/81), respectively. The specificity of Ultra was high (99.4%, 172/173). When Ultra, culture, and acid-fast bacilli outcomes were integrated as a composite reference standard, the percentage of children with definite TB increased from 37.2% (48/129) to 67.4% (87/129). The sensitivity of Ultra is 80.0% (40/50) in children aged <4 years, which is significantly higher than that in older children (48.1%, 38/79) (P < 0.001). Ultra conducted using GA samples can provide faster results, allowing an early and accurate TB diagnosis, especially in younger children with difficulty producing sputum.
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Mycobacterium tuberculosis , Tuberculosis , Niño , Preescolar , China , Humanos , Mycobacterium tuberculosis/genética , Sensibilidad y Especificidad , Esputo , Tuberculosis/diagnósticoRESUMEN
In this Letter, we demonstrate 22.7 W mid-infrared (MIR) supercontinuum (SC) generation in all-solid fluorotellurite fibers. All-solid fluorotellurite fibers based on ${{\rm TeO}_2} {\text -} {{\rm BaF}_2}{\text -}{{\rm Y}_2}{{\rm O}_3}$TeO2-BaF2-Y2O3 and ${{\rm TeO}_2}$TeO2 modified fluoroaluminate glasses are fabricated by using a rod-in-tube method. By using a 0.6 m long fluorotellurite fiber with a core diameter of 11 µm as the nonlinear medium and a high-power 1.93-2.5 µm SC fiber laser as the pump source, we obtain 22.7 W SC generation from 0.93 to 3.95 µm in the fiber for a pump power of 39.7 W. The 10 dB bandwidth is about 1633 nm, and the corresponding spectral range is from 1890 to 3523 nm. The optical-to-optical conversion efficiency is about 57.2%. Our results show that all-solid fluorotellurite fibers are promising nonlinear media for constructing high-power MIR SC light sources.