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1.
Nucleic Acids Res ; 52(5): 2724-2739, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38300794

RESUMEN

Transposons, as non-viral integration vectors, provide a secure and efficient method for stable gene delivery. In this study, we have discovered Mage (MG), a novel member of the piggyBac(PB) family, which exhibits strong transposability in a variety of mammalian cells and primary T cells. The wild-type MG showed a weaker insertion preference for near genes, transcription start sites (TSS), CpG islands, and DNaseI hypersensitive sites in comparison to PB, approaching the random insertion pattern. Utilizing in silico virtual screening and feasible combinatorial mutagenesis in vitro, we effectively produced the hyperactive MG transposase (hyMagease). This variant boasts a transposition rate 60% greater than its native counterpart without significantly altering its insertion pattern. Furthermore, we applied the hyMagease to efficiently deliver chimeric antigen receptor (CAR) into T cells, leading to stable high-level expression and inducing significant anti-tumor effects both in vitro and in xenograft mice models. These findings provide a compelling tool for gene transfer research, emphasizing its potential and prospects in the domains of genetic engineering and gene therapy.


Asunto(s)
Elementos Transponibles de ADN , Técnicas de Transferencia de Gen , Humanos , Ratones , Animales , Elementos Transponibles de ADN/genética , Terapia Genética , Linfocitos T/metabolismo , Transposasas/genética , Transposasas/metabolismo , Vectores Genéticos , Mamíferos/genética
2.
Proc Natl Acad Sci U S A ; 120(17): e2300376120, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37068258

RESUMEN

The high transmissibility of SARS-CoV-2 Omicron subvariants was generally ascribed to immune escape. It remained unclear whether the emerging variants have gradually acquired replicative fitness in human respiratory epithelial cells. We sought to evaluate the replicative fitness of BA.5 and earlier variants in physiologically active respiratory organoids. BA.5 exhibited a dramatically increased replicative capacity and infectivity than B.1.1.529 and an ancestral strain wildtype (WT) in human nasal and airway organoids. BA.5 spike pseudovirus showed a significantly higher entry efficiency than that carrying WT or B.1.1.529 spike. Notably, we observed prominent syncytium formation in BA.5-infected nasal and airway organoids, albeit elusive in WT- and B.1.1.529-infected organoids. BA.5 spike-triggered syncytium formation was verified by lentiviral overexpression of spike in nasal organoids. Moreover, BA.5 replicated modestly in alveolar organoids, with a significantly lower titer than B.1.1.529 and WT. Collectively, the higher entry efficiency and fusogenic activity of BA.5 spike potentiated viral spread through syncytium formation in the human airway epithelium, leading to enhanced replicative fitness and immune evasion, whereas the attenuated replicative capacity of BA.5 in the alveolar organoids may account for its benign clinical manifestation.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/genética , Nariz , Organoides , Glicoproteína de la Espiga del Coronavirus/genética , Anticuerpos Neutralizantes , Anticuerpos Antivirales
3.
Small ; : e2311299, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38366314

RESUMEN

Silicon (Si) anode has attracted broad attention because of its high theoretical specific capacity and low working potential. However, the severe volumetric changes of Si particles during the lithiation process cause expansion and contraction of the electrodes, which induces a repeatedly repair of solid electrolyte interphase, resulting in an excessive consuming of electrolyte and rapid capacity decay. Clearly known the deformation and stress changing at µÎµ resolution in the Si-based electrode during battery operation provides invaluable information for the battery research and development. Here, an in operando approach is developed to monitor the stress evolution of Si anode electrodes via optical fiber Bragg grating (FBG) sensors. By implanting FBG sensor at specific locations in the pouch cells with different Si anodes, the stress evolution of Si electrodes has been systematically investigated, and Δσ/areal capacity is proposed for stress assessment. The results indicate that the differences in stress evolution are nested in the morphological changes of Si particles and the evolution characteristics of electrode structures. The proposed technique provides a brand-new view for understanding the electrochemical mechanics of Si electrodes during battery operation.

4.
J Transl Med ; 22(1): 494, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38790051

RESUMEN

BACKGROUND: Diabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities of the heart and ultimately evolves to heart failure. IL-37 exerts a substantial influence on the regulation of inflammation and metabolism. Whether IL-37 is involved in DCM is unknown. METHODS: The plasma samples were collected from healthy controls, diabetic patients and DCM patients, and the level of IL-37 and its relationship with heart function were observed. The changes in cardiac function, myocardial fibrosis and mitochondrial injury in DCM mice with or without IL-37 intervention were investigated in vivo. By an in vitro co-culture approach involving HG challenge of cardiomyocytes and fibroblasts, the interaction carried out by cardiomyocytes on fibroblast profibrotic activation was studied. Finally, the possible interactive mediator between cardiomyocytes and fibroblasts was explored, and the intervention role of IL-37 and its relevant molecular mechanisms. RESULTS: We showed that the level of plasma IL-37 in DCM patients was upregulated compared to that in healthy controls and diabetic patients. Both recombinant IL-37 administration or inducing IL-37 expression alleviated cardiac dysfunction and myocardial fibrosis in DCM mice. Mechanically, hyperglycemia impaired mitochondria through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA. Fibroblasts then engulfed these mtDNA-enriched vesicles, thereby activating TLR9 signaling and the cGAS-STING pathway to initiate pro-fibrotic process and adverse remodeling. However, the presence of IL-37 ameliorated mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, resulting in a reduction in release of mtDNA-enriched vesicle and ultimately attenuating the progression of DCM. CONCLUSIONS: Collectively, our study demonstrates a protective role of IL-37 in DCM, offering a promising therapeutic agent for this disease.


Asunto(s)
ADN Mitocondrial , Cardiomiopatías Diabéticas , Fibrosis , Interleucina-1 , Miocitos Cardíacos , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Apoptosis/efectos de los fármacos , Cardiomiopatías Diabéticas/patología , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/tratamiento farmacológico , ADN Mitocondrial/metabolismo , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Interleucina-1/metabolismo , Ratones Endogámicos C57BL , Miocardio/patología , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismo
5.
Mol Pharm ; 21(5): 2272-2283, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38607681

RESUMEN

Over the years, there has been significant interest in PEGylated lipid-based nanocarriers within the drug delivery field. The inevitable interplay between the nanocarriers and plasma protein plays a pivotal role in their in vivo biological fate. Understanding the factors influencing lipid-based nanocarrier and protein corona interactions is of paramount importance in the design and clinical translation of these nanocarriers. Herein, discoid-shaped lipid nanodiscs (sNDs) composed of different phospholipids with varied lipid tails and head groups were fabricated. We investigated the impact of phospholipid components on the interaction between sNDs and serum proteins, particle stability, and biodistribution. The results showed that all of these lipid nanodiscs remained stable over a 15 day storage period, while their stability in the blood serum demonstrated significant differences. The sND composed of POPG exhibited the least stability due to its potent complement activation capability, resulting in rapid blood clearance. Furthermore, a negative correlation between the complement activation capability and serum stability was identified. Pharmacokinetic and biodistribution experiments indicated that phospholipid composition did not influence the capability of sNDs to evade the accelerated blood clearance phenomenon. Complement deposition on the sND was inversely associated with the area under the curve. Additionally, all lipid nanodiscs exhibited dominant adsorption of apolipoprotein. Remarkably, the POPC-based lipid nanodisc displayed a significantly higher deposition of apolipoprotein E, contributing to an obvious brain distribution, which provides a promising tool for brain-targeted drug delivery.


Asunto(s)
Nanopartículas , Fosfolípidos , Corona de Proteínas , Corona de Proteínas/química , Animales , Fosfolípidos/química , Distribución Tisular , Ratones , Nanopartículas/química , Portadores de Fármacos/química , Nanoestructuras/química , Masculino , Activación de Complemento/efectos de los fármacos , Lípidos/química , Sistemas de Liberación de Medicamentos/métodos , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/química
6.
Environ Sci Technol ; 58(14): 6083-6092, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38547129

RESUMEN

Despite significant advances in understanding the general health impacts of air pollution, the toxic effects of air pollution on cells in the human respiratory tract are still elusive. A robust, biologically relevant in vitro model for recapitulating the physiological response of the human airway is needed to obtain a thorough understanding of the molecular mechanisms of air pollutants. In this study, by using 1-nitropyrene (1-NP) as a proof-of-concept, we demonstrate the effectiveness and reliability of evaluating environmental pollutants in physiologically active human airway organoids. Multimodal imaging tools, including live cell imaging, fluorescence microscopy, and MALDI-mass spectrometry imaging (MSI), were implemented to evaluate the cytotoxicity of 1-NP for airway organoids. In addition, lipidomic alterations upon 1-NP treatment were quantitatively analyzed by nontargeted lipidomics. 1-NP exposure was found to be associated with the overproduction of reactive oxygen species (ROS), and dysregulation of lipid pathways, including the SM-Cer conversion, as well as cardiolipin in our organoids. Compared with that of cell lines, a higher tolerance of 1-NP toxicity was observed in the human airway organoids, which might reflect a more physiologically relevant response in the native airway epithelium. Collectively, we have established a novel system for evaluating and investigating molecular mechanisms of environmental pollutants in the human airways via the combinatory use of human airway organoids, multimodal imaging analysis, and MS-based analyses.


Asunto(s)
Contaminantes Atmosféricos , Pirenos , Sistema Respiratorio , Humanos , Reproducibilidad de los Resultados , Organoides , Imagen Multimodal
7.
Acta Pharmacol Sin ; 45(3): 646-659, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37845342

RESUMEN

Higher drug loading employed in nanoscale delivery platforms is a goal that researchers have long sought after. But such viewpoint remains controversial because the impacts that nanocarriers bring about on bodies have been seriously overlooked. In the present study we investigated the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin (PLD). We prepared PLDs with two different drug loading rates: high drug loading rate, H-Dox, 12.9% w/w Dox/HSPC; low drug loading rate, L-Dox, 2.4% w/w Dox/HSPC (L-Dox had about 5 folds drug carriers of H-Dox at the same Dox dose). The pharmaceutical properties and biological effects of H-Dox and L-Dox were compared in mice, rats or 4T1 subcutaneous tumor-bearing mice. We showed that the lowering of doxorubicin loading did not cause substantial shifts to the pharmaceutical properties of PLDs such as in vitro and in vivo stability (stable), anti-tumor effect (equivalent effective), as well as tissue and cellular distribution. Moreover, it was even more beneficial for mitigating the undesired biological effects caused by PLDs, through prolonging blood circulation and alleviating cutaneous accumulation in the presence of pre-existing anti-PEG Abs due to less opsonins (e.g. IgM and C3) deposition on per particle. Our results warn that the effects of drug loading would be much more convoluted than expected due to the complex intermediation between nanocarriers and bodies, urging independent investigation for each individual delivery platform to facilitate clinical translation and application.


Asunto(s)
Doxorrubicina , Polietilenglicoles , Ratones , Ratas , Animales , Línea Celular Tumoral , Doxorrubicina/farmacología , Polietilenglicoles/farmacología , Portadores de Fármacos
8.
Proc Biol Sci ; 290(2009): 20231563, 2023 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-37876192

RESUMEN

Members of the phylum Cnidaria include sea anemones, corals and jellyfish, and have successfully colonized both marine and freshwater habitats throughout the world. The understanding of how cnidarians adapt to extreme environments such as the dark, high-pressure deep-sea habitat has been hindered by the lack of genomic information. Here, we report the first chromosome-level deep-sea cnidarian genome, of the anemone Actinernus sp., which was 1.39 Gbp in length and contained 44 970 gene models including 14 806 tRNA genes and 30 164 protein-coding genes. Analyses of homeobox genes revealed the longest chromosome hosts a mega-array of Hox cluster, HoxL, NK cluster and NKL homeobox genes; until now, such an array has only been hypothesized to have existed in ancient ancestral genomes. In addition to this striking arrangement of homeobox genes, analyses of microRNAs revealed cnidarian-specific complements that are distinctive for nested clades of these animals, presumably reflecting the progressive evolution of the gene regulatory networks in which they are embedded. Also, compared with other sea anemones, circadian rhythm genes were lost in Actinernus sp., which likely reflects adaptation to living in the dark. This high-quality genome of a deep-sea cnidarian thus reveals some of the likely molecular adaptations of this ecologically important group of metazoans to the extreme deep-sea environment. It also deepens our understanding of the evolution of genome content and organization of animals in general and cnidarians in particular, specifically from the viewpoint of key developmental control genes like the homeobox-encoding genes, where we find an array of genes that until now has only been hypothesized to have existed in the ancient ancestor that pre-dated both the cnidarians and bilaterians.


Asunto(s)
Cnidarios , Anémonas de Mar , Animales , Anémonas de Mar/genética , Genes Homeobox , Filogenia , Evolución Molecular , Familia de Multigenes
9.
Mediators Inflamm ; 2023: 7807302, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37954637

RESUMEN

Background: Alleviating mild cognitive impairment (MCI) is crucial to delay the progression of Alzheimer's disease (AD). Jia-Wei-Kai-Xin-San (JWKXS) is applied for treating AD with MCI. However, the mechanism of JWKXS in the treatment of MCI is unclear. Thus, this study aimed to investigate the effect and mechanism of JWKXS in SAMP8 mice models of MCI. Methods: MCI models were established to examine learning and memory ability and explore the pathomechanisms in brain of SAMP8 mice at 4, 6, and 8 months. The mice were treated for 8 weeks and the effects of JWKXS on MCI were characterized through Morris water maze and HE/Nissl's/immunohistochemical staining. Its mechanism was predicted by the combination of UPLC-Q-TOF/MS and system pharmacology analysis, further verified with SAMP8 mice, BV2 microglial cells, and PC12 cells. Results: It was found that 4-month-old SAMP8 mice exhibited MCI. Two months of JWKXS treatment improved the learning and memory ability, alleviated the hippocampal tissue and neuron damage. Through network pharmacology, four key signaling pathways were found to be involved in treatment of MCI by JWKXS, including TLR4/NF-κB pathway, NLRP3 inflammasome activation, and intrinsic and extrinsic apoptosis. In vitro and in vivo experiments demonstrated that JWKXS attenuated neuroinflammation by inhibiting microglia activation, suppressing TLR4/NF-κB and NLRP3 inflammasome pathways, and blocking the extrinsic and intrinsic apoptotic pathways leading to neuronal apoptosis suppression in the hippocampus. Conclusion: JWKXS treatment improved the learning and memory ability and conferred neuroprotective effects against MCI by inducing anti-inflammation and antiapoptosis. Limitations. The small sample size and short duration of the intervention limit in-depth investigation of the mechanisms. Future Prospects. This provides a direction for further clarification of the anti-AD mechanism, and provides certain data support for the formulation to move toward clinical practice.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Ratas , Ratones , Animales , Inflamasomas/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Receptor Toll-Like 4/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Enfermedad de Alzheimer/tratamiento farmacológico , Antiinflamatorios/uso terapéutico
10.
Horm Metab Res ; 54(1): 25-32, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34986497

RESUMEN

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.


Asunto(s)
Acromegalia/tratamiento farmacológico , Acromegalia/metabolismo , Metabolismo de los Lípidos , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Acromegalia/sangre , Acromegalia/diagnóstico , Adulto , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Femenino , Glucosa/metabolismo , Hormona de Crecimiento Humana/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Lípidos/sangre , Masculino , Estudios Retrospectivos , Carga Tumoral/efectos de los fármacos
11.
Mol Cell Biochem ; 476(5): 2111-2124, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33528706

RESUMEN

MicroRNAs (miRNA), endogenous non-coding RNAs approximately 22 nucleotides long, regulate gene expression by mediating translational inhibition or mRNA degradation. Exosomes are a tool for intercellular transmission of information in which miRNA exchange plays an important role. Under pathophysiological conditions in the central nervous system (CNS), cellular transmission of exosomal miRNAs can regulate signaling pathways. Exosomal miRNAs are involved in the occurrence and development of diverse CNS diseases, such as traumatic brain injury, spinal cord injury, stroke, neurodegenerative diseases, epilepsy, and glioma. The use of exosomes as transport vehicles for certain miRNAs provides a novel therapeutic strategy for CNS diseases. Furthermore, the exosomes in body fluids change with the occurrence of diseases, indicating that subtle changes in physiological and pathological processes in vivo could be recognized by analyzing exosomes. Exosomal analysis is expected to act as a novel tool for diagnosis and prediction of neurological diseases. In this review, we present the current understanding of the implications of miRNAs in CNS diseases and summarize the role and mechanism of action of exosomal miRNA in nervous system disease models.


Asunto(s)
Comunicación Celular , Enfermedades del Sistema Nervioso Central/metabolismo , MicroARN Circulante/metabolismo , Exosomas/metabolismo , Transducción de Señal , Animales , Enfermedades del Sistema Nervioso Central/patología , Exosomas/patología , Humanos
12.
Sensors (Basel) ; 21(14)2021 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-34300374

RESUMEN

A method based on equal frequency resampling is proposed to suppress laser nonlinear frequency sweeping for the ultimate spatial resolution in optical frequency domain reflectometry. Estimation inaccuracy of the sweeping frequency distribution caused by the finite sampling rate in the auxiliary interferometer can be efficiently compensated by the equal frequency resampling method. With the sweeping range of 130 nm, a 12.1 µm spatial resolution is experimentally obtained. In addition, the sampling limitation of the auxiliary interferometer-based correction is discussed. With a 200 m optical path delay in the auxiliary interferometer, a 21.3 µm spatial resolution is realised at the 191 m fibre end. By employing the proposed resampling and a drawing tower FBG array to enhance the Rayleigh backscattering, a distributed temperature sensing over a 105 m fibre with a sensing resolution of 1 cm is achieved. The measured temperature uncertainty is limited to ±0.15 °C.

13.
BMC Genomics ; 21(1): 726, 2020 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-33076831

RESUMEN

BACKGROUND: Teleost fish play important roles in aquatic ecosystems and aquaculture. Threadfins (Perciformes: Polynemidae) show a range of interesting biology, and are of considerable importance for both wild fisheries and aquaculture. Additionally, the four-finger threadfin Eleutheronema tetradactylum is of conservation relevance since its populations are considered to be in rapid decline and it is classified as endangered. However, no genomic resources are currently available for the threadfin family Polynemidae. RESULTS: We sequenced and assembled the first threadfin fish genome, the four-finger threadfin E. tetradactylum. We provide a genome assembly for E. tetradactylum with high contiguity (scaffold N50 = 56.3 kb) and high BUSCO completeness at 96.5%. The assembled genome size of E. tetradactylum is just 610.5 Mb, making it the second smallest perciform genome assembled to date. Just 9.07-10.91% of the genome sequence was found to consist of repetitive elements (standard RepeatMasker analysis vs custom analysis), making this the lowest repeat content identified to date for any perciform fish. A total of 37,683 protein-coding genes were annotated, and we include analyses of developmental transcription factors, including the Hox, ParaHox, and Sox families. MicroRNA genes were also annotated and compared with other chordate lineages, elucidating the gains and losses of chordate microRNAs. CONCLUSIONS: The four-finger threadfin E. tetradactylum genome presented here represents the first available genome sequence for the ecologically, biologically, and commercially important clade of threadfin fish. Our findings provide a useful genomic resource for future research into the interesting biology and evolution of this valuable group of food fish.


Asunto(s)
Genoma , Perciformes , Animales , Perciformes/genética
14.
BMC Endocr Disord ; 20(1): 103, 2020 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-32660469

RESUMEN

BACKGROUND: To evaluate the association between high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR), and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted in 1210 patients with T2DM, among whom 265 had DKD. The severity of DKD was assessed by estimated-glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (ACR). The relationship between ESR, hsCRP and DKD was analyzed by multivariate logistic analysis. The relationship between ESR and eGFR, ESR or ACR was analyzed by multivariate linear regression. RESULTS: ESR (23.0 [12.0 ~ 41.5] mm/h versus 12.0 [7.0 ~ 22.0] mm/h, P <  0.001) and hsCRP (3.60 [2.20 ~ 7.65] versus 2.90 [1.80 ~ 5.60] mg/L mg/L, P <  0.01) values were significantly higher in patients with DKD than those without. Patients with higher ESR or hsCRP had lower eGFR and higher ACR. After adjusted for gender, age, hemoglobin, plasma proteins, HbA1c, lipid profiles, and the usage of renin-angiotensin system inhibitors, ESR but not hsCRP was independently associated with the rate and severity of DKD in patients with T2DM. CONCLUSION: ESR was independently associated with the rate and severity of DKD in patients with T2DM.


Asunto(s)
Biomarcadores/análisis , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/diagnóstico , Anciano , Estudios Transversales , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
15.
Nano Lett ; 19(8): 5077-5085, 2019 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-31283241

RESUMEN

Atomically thin two-dimensional (2D) materials are promising candidates for sub-10 nm transistor channels due to their ultrathin body thickness, which results in strong electrostatic gate control. Properly scaling a transistor technology requires reducing both the channel length (distance from source to drain) and the contact length (distance that source and drain interface with semiconducting channel). Contact length scaling remains an unresolved epidemic for transistor scaling, affecting devices from all semiconductors-silicon to 2D materials. Here, we show that clean edge contacts to 2D MoS2 can provide immunity to the contact-scaling problem, with performance that is independent of contact length down to the 20 nm regime. Using a directional ion beam, in situ edge contacts of various metal-MoS2 interfaces are studied. Characterization of the intricate edge interface using cross-sectional electron microscopy reveals distinct morphological effects on the MoS2 depending on its thickness-from monolayer to few-layer films. The in situ edge contacts also exhibit an order of magnitude higher performance compared to the best-reported ex situ metal edge contacts. Our work provides experimental evidence for a solution to contact scaling in transistors, using 2D materials with clean edge contact interfaces, opening a new way of designing devices with 2D materials.

16.
Opt Lett ; 44(22): 5493-5496, 2019 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-31730091

RESUMEN

In this work, we studied surface-enhanced Raman scattering (SERS) of MS2 (M=Mo, W) monolayers that were transferred onto Ag nanorod arrays. Compared to the suspended monolayers, the Raman intensity of monolayers on an Ag nanorod substrate was strongly enhanced for both in-plane and out-of-plane vibration modes: up to 8 (5) for E2g and 20 (23) for A1g in MoS2 (WS2). This finding reveals a promising SERS substrate for achieving uniform and strong enhancement for two-dimensional materials in the applications of optical detecting and sensing.

17.
Endocr Pract ; 25(6): 562-571, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30865541

RESUMEN

Objective: To investigate in vivo correlates of erectile dysfunction (ED) in male patients with acromegaly. Methods: Fifty-one male patients with acromegaly were assessed by the International Index of Erectile Function-5 and Acromegaly Quality of Life (Acro-QoL) questionnaires. The measurement of serum nitric oxide (NO) were performed in patients and age-matched nonacromegalic controls. Results: Among 51 patients analyzed, 32 (62.7%) had ED. Patients with ED showed lower Acro-QoL scores regarding global (69.8 ± 17.7 versus 79.4 ± 11.2; P = .035) and personal relationship dimensions (59.6 ± 22.1 versus 76.8 ± 17.6; P = .012) than non-ED patients. ED patients were older (44.5 ± 11.2 years versus 33.2 ± 8.5 years; P = .04) and showed higher growth hormone (GH) levels (15.5 µg/L [interquartile range of 9.5 to 34.5 µg/L] versus 5.9 µg/L [interquartile range of 3.4 to 13.9 µg/L]; P = .001) compared to non-ED patients. The cutoff values for identifying ED were 7.9 µg/L for random GH and 5.3 µg/L for GH nadir after oral administration of 75 g of glucose. There was no significant difference in total testosterone levels between the two groups (6.36 ± 4.24 nmol/L versus 9.54 ± 5.50 nmol/L; P = .299). The NO levels in patients with acromegaly were significantly lower than those in nonacromegalic controls (8.77 ± 1.78 µmol/L versus 19.19 ± 5.02 µmol/L, respectively; P = .049). Furthermore, the NO levels were even lower in ED patients than those in non-ED patients (5.14 ± 0.98 µmol/L versus 12.09 ± 3.44 µmol/L; P = .027). Conclusion: Our study showed that ED is prevalent in male acromegalic patients and may be associated with systemic endothelial dysfunction induced by excessive GH. Further studies investigating the mechanism of GH and ED are required. Abbreviations: Acro-QoL = Acromegaly Quality of Life; ED = erectile dysfunction; FSH = follicle-stimulating hormone; GH = growth hormone; IGF-1 = insulin-like growth factor 1; IIEF-5 = international index of erection function-5; LH = luteinizing hormone; MRI = magnetic resonance imaging; NO = nitric oxide; OGTT = oral glucose tolerance test; QoL = quality of life; ROC = receiver operating characteristic.


Asunto(s)
Acromegalia , Disfunción Eréctil , Hormona de Crecimiento Humana , Humanos , Factor I del Crecimiento Similar a la Insulina , Masculino , Calidad de Vida
18.
J Ultrasound Med ; 38(9): 2249-2257, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29194699

RESUMEN

OBJECTIVES: To evaluate the features of adrenal masses on ultrasonography and correlate the findings with the pathologic diagnoses to help distinguish benign from malignant adrenal lesions. METHODS: Ultrasonography was performed in 1363 patients with adrenal lesions. The following ultrasonographic parameters were recorded: size, shape, margin, echogenicity, echo texture, cystic necrosis, calcifications, and blood supply. The sensitivity and specificity of aggressive features for predicting malignancy were calculated. RESULTS: Of 1385 adrenal lesions, 66 (4.8%) were malignant: 33 malignant pheochromocytomas, 20 adrenal cortical carcinomas, 10 metastases, 2 leiomyosarcomas, and 1 primitive neuroectodermal tumor. The remaining 1319 (95.2%) lesions were benign: 832 adenomas, 182 pheochromocytomas, 153 nodular adrenal hyperplasia, 54 myelolipomas, 42 cysts, 23 ganglioneuromas, 10 schwannomas, 8 cortical tumor eosinophils, 4 teratomas, 4 tuberculosis, 4 primary pigmented nodular adrenocortical disease, and 3 Castleman disease. Most of the tumors were regular and hypoechoic. The malignant lesions were significantly larger than the benign lesions (mean ± SD, 6.3 ± 2.4 versus 4.6 ± 1.7 cm; P < .01). Significant differences between malignant and benign tumors were observed when comparing the shape, margins, echo texture and vascularization of the analyzed lesions (P < .01). An irregular shape, poor definition of margins, heterogeneous echo texture, and vascularization indicated malignancy, with sensitivity and specificity of 45.5% and 97.0%, 34.8% and 99.2%, 92.4% and 97.3%, and 15.2% and 97.5%, respectively. CONCLUSIONS: Ultrasonography could be an effective diagnostic supplementary tool for adrenal tumors. A large size, irregular shape, poorly defined margins, heterogeneous echo texture, and vascularization of adrenal lesions could be effective indicators of malignancy.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Ultrasonografía/métodos , Adolescente , Glándulas Suprarrenales/diagnóstico por imagen , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto Joven
19.
Opt Express ; 26(4): 3870-3881, 2018 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-29475244

RESUMEN

The sensitivity of a sensor to strain or the temperature variations due to distributed Brillouin scattering are partially related to the type of fibers used and the Brillouin scattering induced effective index. In this paper, a highly nonlinear fiber that can generate a higher Brillouin scattering signal is compared to a standard single mode fiber in a short-time-Fourier-transform Brillouin optical time domain reflectometer (STFT-BOTDR). The results show that much higher signal to noise ratios of the Brillouin scattering spectrum and smaller frequency uncertainties in the sensing measurement can be achieved in the highly nonlinear fiber for comparable launched powers. With a measurement speed of 4 Hz, the frequency uncertainty can be 0.43 MHz, corresponding to 10 µÎµ in strain or 0.43°C in temperature uncertainty for the highly nonlinear fiber. In contrast, for the standard single mode fiber case, the value would increase to about 1.02 MHz (25 µÎµ or 1.02°C), demonstrating the advantage of the highly nonlinear fiber for distributed strain/temperature sensing.

20.
Nano Lett ; 17(6): 3613-3618, 2017 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-28505462

RESUMEN

We report that the refractive index of transition metal dichacolgenide (TMDC) monolayers, such as MoS2, WS2, and WSe2, can be substantially tuned by >60% in the imaginary part and >20% in the real part around exciton resonances using complementary metal-oxide-semiconductor (CMOS) compatible electrical gating. This giant tunablility is rooted in the dominance of excitonic effects in the refractive index of the monolayers and the strong susceptibility of the excitons to the influence of injected charge carriers. The tunability mainly results from the effects of injected charge carriers to broaden the spectral width of excitonic interband transitions and to facilitate the interconversion of neutral and charged excitons. The other effects of the injected charge carriers, such as renormalizing bandgap and changing exciton binding energy, only play negligible roles. We also demonstrate that the atomically thin monolayers, when combined with photonic structures, can enable the efficiencies of optical absorption (reflection) tuned from 40% (60%) to 80% (20%) due to the giant tunability of the refractive index. This work may pave the way toward the development of field-effect photonics in which the optical functionality can be controlled with CMOS circuits.

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