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1.
Proc Natl Acad Sci U S A ; 121(14): e2318391121, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38527207

RESUMEN

The exploitation of novel wound healing methods with real-time infection sensing and high spatiotemporal precision is highly important for human health. Pt-based metal-organic cycles/cages (MOCs) have been employed as multifunctional antibacterial agents due to their superior Pt-related therapeutic efficiency, various functional subunits and specific geometries. However, how to rationally apply these nanoscale MOCs on the macroscale with controllable therapeutic output is still challenging. Here, a centimeter-scale Pt MOC film was constructed via multistage assembly and subsequently coated on a N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole (MPT)-stained silk fabric to form a smart wound dressing for bacterial sensing and wound healing. The MPT on silk fabric could be used to monitor wound infection in real-time through the bacteria-mediated reduction of MPT to its radical form via a color change. The MPT radical also exhibited an excellent photothermal effect under 660 nm light irradiation, which could not only be applied for photothermal therapy but also induce the disassembly of the Pt MOC film suprastructure. The highly ordered Pt MOC film suprastructure exhibited high biosafety, while it also showed improved antibacterial efficiency after thermally induced disassembly. In vitro and in vivo studies revealed that the combination of the Pt MOC film and MPT-stained silk can provide real-time information on wound infection for timely treatment through noninvasive techniques. This study paves the way for bacterial sensing and wound healing with centimeter-scale metal-organic materials.


Asunto(s)
Platino (Metal) , Infección de Heridas , Humanos , Platino (Metal)/farmacología , Cicatrización de Heridas , Vendajes , Antibacterianos/farmacología , Antibacterianos/química , Seda/química , Bacterias , Hidrogeles/farmacología
2.
J Biol Chem ; 300(4): 106791, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38403247

RESUMEN

DNA modifications add another layer of complexity to the eukaryotic genome to regulate gene expression, playing critical roles as epigenetic marks. In eukaryotes, the study of DNA epigenetic modifications has been confined to 5mC and its derivatives for decades. However, rapid developing approaches have witnessed the expansion of DNA modification reservoirs during the past several years, including the identification of 6mA, 5gmC, 4mC, and 4acC in diverse organisms. However, whether these DNA modifications function as epigenetic marks requires careful consideration. In this review, we try to present a panorama of all the DNA epigenetic modifications in eukaryotes, emphasizing recent breakthroughs in the identification of novel DNA modifications. The characterization of their roles in transcriptional regulation as potential epigenetic marks is summarized. More importantly, the pathways for generating or eliminating these DNA modifications, as well as the proteins involved are comprehensively dissected. Furthermore, we briefly discuss the potential challenges and perspectives, which should be taken into account while investigating novel DNA modifications.


Asunto(s)
Metilación de ADN , Epigénesis Genética , Eucariontes , Humanos , Eucariontes/genética , Eucariontes/metabolismo , Animales , ADN/metabolismo , ADN/genética , ADN/química
3.
Proc Natl Acad Sci U S A ; 119(32): e2201899119, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35914155

RESUMEN

The cellular and molecular components required for the formation of premetastatic niche (PMN) to promote lung metastasis need to be further investigated. Lung epithelial cells have been reported to exhibit immunomodulatory roles in lung homeostasis and also to mediate immunosuppressive PMN formation in lung metastasis. Here, by single-cell sequencing, we identified a tumor-polarized subpopulation of alveolar type 2 (AT2) epithelial cells with increased expression of glutathione peroxidase 3 (GPX3) and high production of interleukin (IL)-10 in the PMN. IL-10-producing GPX3+ AT2 cells inhibited CD4+ T cell proliferation but enhanced regulatory T cell generation. Mechanistically, tumor exosome-inducing GPX3 expression is required for GPX3+ AT2 cells to preferentially produce IL-10 by stabilizing hypoxia-inducible factor 1 (HIF-1α) and promoting HIF-1α-induced IL-10 production. Accordingly, conditional knockout of GPX3 in AT2 cells suppressed lung metastasis in spontaneous metastatic models. Together, our findings reveal a role of tumor-polarized GPX3+ AT2 cells in promoting lung PMN formation, adding insights into immune evasion in lung metastasis and providing potential targets for the intervention of tumor metastasis.


Asunto(s)
Células Epiteliales Alveolares , Interleucina-10 , Neoplasias Pulmonares , Células Epiteliales Alveolares/citología , Linfocitos T CD4-Positivos/citología , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Pulmón/citología , Pulmón/patología , Neoplasias Pulmonares/patología , Metástasis de la Neoplasia , Escape del Tumor
4.
Nano Lett ; 24(8): 2661-2670, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38345313

RESUMEN

Nanomaterial-assisted chemodynamic therapy (CDT) has received considerable attention in recent years. It outperforms other modalities by its distinctive reactive oxygen species (ROS) generation through a nonexogenous stimulant. However, CDT is limited by the insufficient content of endogenous hydrogen peroxide (H2O2). Herein, a biodegradable MnS@HA-DOX nanocluster (MnS@HA-DOX NC) was constructed by in situ biomineralization from hyaluronic acid, to enlarge the ROS cascade and boost Mn2+-based CDT. The acid-responsive NCs could quickly degrade after internalization into endo/lysosomes, releasing Mn2+, H2S gas, and anticancer drug doxorubicin (DOX). The Fenton-like reaction catalyzed by Mn2+ was amplified by both H2S and DOX, producing a mass of cytotoxic ·OH radicals. Through the combined action of gas therapy (GT), CDT, and chemotherapy, oxidative stress would be synergistically enhanced, inducing irreversible DNA damage and cell cycle arrest, eventually resulting in cancer cell apoptosis.


Asunto(s)
Peróxido de Hidrógeno , Neoplasias , Humanos , Especies Reactivas de Oxígeno , Peróxido de Hidrógeno/farmacología , Doxorrubicina/farmacología , Apoptosis , Biomineralización , Gases , Línea Celular Tumoral , Microambiente Tumoral
5.
Nano Lett ; 24(15): 4649-4657, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38572971

RESUMEN

Deep-seated bacterial infections (DBIs) are stubborn and deeply penetrate tissues. Eliminating deep-seated bacteria and promoting tissue regeneration remain great challenges. Here, a novel radical-containing hydrogel (SFT-B Gel) cross-linked by a chaotropic effect was designed for the sensing of DBIs and near-infrared photothermal therapy (NIR-II PTT). A silk fibroin solution stained with 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-methylpyridin-1-ium) (TPT3+) was employed as the backbone, which could be cross-linked by a closo-dodecaborate cluster (B12H122-) through a chaotropic effect to form the SFT-B Gel. More interestingly, the SFT-B Gel exhibited the ability to sense DBIs, which could generate a TPT2+• radical with obvious color changes in the presence of bacteria. The radical-containing SFT-B Gel (SFT-B★ Gel) possessed strong NIR-II absorption and a remarkable photothermal effect, thus demonstrating excellent NIR-II PTT antibacterial activity for the treatment of DBIs. This work provides a new approach for the construction of intelligent hydrogels with unique properties using a chaotropic effect.


Asunto(s)
Fototerapia , Terapia Fototérmica , Hidrogeles/farmacología
6.
Apoptosis ; 29(7-8): 967-980, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38886312

RESUMEN

With global warming, extreme environmental heat is becoming a social issue of concern, which can cause adverse health results including heatstroke (HS). Severe heat stress is characterized by cell death of direct heat damage, excessive inflammatory responses, and coagulation disorders that can lead to multiple organ dysfunction (MODS) and even death. However, the significant pathophysiological mechanism and treatment of HS are still not fully clear. Various modes of cell death, including apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis are involved in MODS induced by heatstroke. In this review, we summarized molecular mechanism, key transcriptional regulation as for HSF1, NRF2, NF-κB and PARP-1, and potential therapies of cell death resulting in CNS, liver, intestine, reproductive system and kidney injury induced by heat stress. Understanding the mechanism of cell death provides new targets to protect multi-organ function in HS.


Asunto(s)
Muerte Celular , Golpe de Calor , Golpe de Calor/genética , Golpe de Calor/patología , Golpe de Calor/terapia , Golpe de Calor/metabolismo , Golpe de Calor/fisiopatología , Humanos , Animales , Apoptosis , FN-kappa B/metabolismo , FN-kappa B/genética , Respuesta al Choque Térmico , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/genética , Insuficiencia Multiorgánica/patología , Insuficiencia Multiorgánica/metabolismo , Insuficiencia Multiorgánica/genética , Factores de Transcripción del Choque Térmico/metabolismo , Factores de Transcripción del Choque Térmico/genética
7.
BMC Med ; 22(1): 328, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39135035

RESUMEN

BACKGROUND: Mothers play a crucial role in influencing their daughters' HPV vaccination decisions. Addressing barriers to receiving HPV vaccination among mothers of girls may achieve two goals in one strike: increasing vaccination coverage among both mothers and their daughters. This study aims to examine the HPV vaccination uptake and its determinants among mothers of girls in China at both the individual and interpersonal levels. METHODS: From July to October 2023, a cross-sectional online study was conducted to investigate HPV vaccine refusal for daughters aged 9-17 years among 11,678 mothers in Shenzhen, China. A randomized selection method was employed, targeting 11 primary schools and 13 secondary schools in Shenzhen. The research team invited mothers of girls to participate in an anonymous online survey. Multilevel logistic regression models (level 1: schools; level 2: individual participants) were employed to analyze the data. RESULTS: Among 11,678 mothers, 41.1% self-reported receiving at least one dose of HPV vaccination. Through multilevel logistic regression analysis, eight items measuring illness representations of HPV, which refers to how people think about HPV, were associated with higher HPV vaccination uptake (AOR: 1.02-1.14). These items included identity (identifying symptoms of HPV), timeline (whether HPV is acute/chronic), negative consequences, personal and treatment control (whether HPV is under volitional control), concern, negative emotions, and coherence (overall understanding of HPV). In addition, participants refusing HPV vaccines for the index daughters (AOR: 0.82, 95%CI: 0.76, 0.89) had lower vaccine uptake. Perceived more difficulties in accessing the 9-valent vaccines (AOR: 1.06, 95%CI: 1.04, 1.08) and more satisfaction with vaccine-related promotional materials (AOR: 1.50, 95%CI: 1.46, 1.54) at the individual level were associated with higher vaccine uptake. At the interpersonal factors, higher frequency of exposure to testimonials given by others about HPV vaccination on social media (AOR: 1.19, 95%CI: 1.14, 1.25) and thoughtful consideration of the veracity of the information (AOR: 1.11, 95%CI: 1.07, 1.16) were correlated with higher HPV vaccination uptake. CONCLUSIONS: These findings offer essential implications for modifying HPV disease perceptions, addressing difficulties in accessing the 9-valent HPV vaccines, and enhancing health communication needs to improve HPV vaccine uptake among mothers of girls.


Asunto(s)
Madres , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Medios de Comunicación Sociales , Humanos , Estudios Transversales , Femenino , Adolescente , China , Vacunas contra Papillomavirus/administración & dosificación , Infecciones por Papillomavirus/prevención & control , Niño , Madres/psicología , Adulto , Vacunación/psicología , Conocimientos, Actitudes y Práctica en Salud , Núcleo Familiar , Aceptación de la Atención de Salud , Persona de Mediana Edad , Encuestas y Cuestionarios
8.
Small ; 20(8): e2304082, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37767608

RESUMEN

Bioenergetic deficits are known to be significant contributors to neurodegenerative diseases. Nevertheless, identifying safe and effective means to address intracellular bioenergetic deficits remains a significant challenge. This work provides mechanistic insights into the energy metabolism-regulating function of colloidal Au nanocrystals, referred to as CNM-Au8, that are synthesized electrochemically in the absence of surface-capping organic ligands. When neurons are subjected to excitotoxic stressors or toxic peptides, treatment of neurons with CNM-Au8 results in dose-dependent neuronal survival and neurite network preservation across multiple neuronal subtypes. CNM-Au8 efficiently catalyzes the conversion of an energetic cofactor, nicotinamide adenine dinucleotide hydride (NADH), into its oxidized counterpart (NAD+ ), which promotes bioenergy production by regulating the intracellular level of adenosine triphosphate. Detailed kinetic measurements reveal that CNM-Au8-catalyzed NADH oxidation obeys Michaelis-Menten kinetics and exhibits pH-dependent kinetic profiles. Photoexcited charge carriers and photothermal effect, which result from optical excitations and decay of the plasmonic electron oscillations or the interband electronic transitions in CNM-Au8, are further harnessed as unique leverages to modulate reaction kinetics. As exemplified by this work, Au nanocrystals with deliberately tailored structures and surfactant-free clean surfaces hold great promise for developing next-generation therapeutic agents for neurodegenerative diseases.


Asunto(s)
NAD , Enfermedades Neurodegenerativas , Humanos , NAD/química , Oro/química , Oxidación-Reducción
9.
Opt Lett ; 49(2): 210-213, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38194530

RESUMEN

The kinetics of optical switching due to the insulator-metal phase transition in a VO2 thin film is studied experimentally at different laser pulse repetition frequencies (PRFs) in the NIR range and compared with temperature kinetics obtained through the thermal conductance calculations. Two switching processes have been found with characteristic times <2 ms and <15 ms depending on the PRF; the former is explained by the accumulation of metallic domains remaining after a single-pulse phase transition, and the latter is referred to the heat accumulation in the film. Consequently, the dynamics of the microscopic domains is leading in the initiation of phase transition under pulse-periodic conditions compared to the macroscopic heat transfer. The reverse transition at the radiation turn-off depends on the PRF with a time coefficient of 17.5 µs/kHz and is determined by the metallic domains' decay in the film. The results are important for understanding the nature of the insulator-metal transition in thin films of VO2 as well as using them in all-optical switches of pulse-periodic laser radiation.

10.
Opt Lett ; 49(2): 298-301, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38194552

RESUMEN

The distinctive properties and facile integration of 2D materials hold the potential to offer promising avenues for the on-chip photonic devices, and the expeditious and nondestructive identification and localization of diverse fundamental building blocks become key prerequisites. Here, we present a methodology grounded in digital image processing and deep learning, which effectively achieves the detection and precise localization of four monolayer-thick triangular single crystals of transition metal dichalcogenides with the mean average precision above 90%, and the approach demonstrates robust recognition capabilities across varied imaging conditions encompassing both white light and monochromatic light. This stands poised to serve as a potent data-driven tool enhancing the characterizing efficiency and holds the potential to expedite research initiatives and applications founded on the utilization of 2D materials.

11.
Reprod Biol Endocrinol ; 22(1): 74, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918809

RESUMEN

BACKGROUND: Erectile dysfunction (ED) is a common male sexual dysfunction, with an increasing incidence, and the current treatment is often ineffective. METHODS: Vascular endothelial growth factor (VEGFA) was used to treat bone marrow-derived mesenchymal stem cells (BM-MSCs), and their cell migration rates were determined by Transwell assays. The expression of the von Willebrand Factor (vWF)VE-cadherin, and endothelial nitric oxide synthase(eNOS) endothelial markers was determined by qRT‒PCR and Western blot analyses. The MALAT1-induced differentiation of BM-MCs to ECs via the CDC42/PAK1/paxillin pathway was explored by transfecting VEGFA-induced BM-MSC with si-MALAT1 and overexpressing CDC42 and PAK1. The binding capacity between CDC42, PAK1, and paxillin in VEGFA-treated and non-VEGFA-treated BM-MSCs was examined by protein immunoprecipitation. MiR-206 was overexpressed in VEGFA-induced BM-MSC, and the binding sites of MALAT1, miR-206, and CDC42 were identified using a luciferase assay. Sixty male Sprague‒Dawley rats were divided into six groups (n = 10/group). DMED modelling was demonstrated by APO experiments and was assessed by measuring blood glucose levels. Erectile function was assessed by measuring the intracavernosa pressure (ICP) and mean arterial pressure (MAP). Penile erectile tissue was analysed by qRT‒PCR, Western blot analysis, and immunohistochemical staining. RESULTS: MALAT1 under VEGFA treatment conditions regulates the differentiation of BM-MSCs into ECs by modulating the CDC42/PAK1/paxillin axis. In vitro experiments demonstrated that interference with CDC42 and MALAT1 expression inhibited the differentiation of BM-MSCs to ECs. CDC42 binds to PAK1, and PAK1 binds to paxillin. In addition, CDC42 in the VEGFA group had a greater ability to bind to PAK1, whereas PAK1 in the VEGFA group had a greater ability to bind to paxillin. Overexpression of miR-206 in VEGFA-induced BM-MSCs demonstrated that MALAT1 competes with the CDC42 3'-UTR for binding to miR-206, which in turn is involved in the differentiation of BM-MSCs to ECs. Compared to the DMED model group, the ICP/MAP ratio was significantly greater in the three BM-MSCs treatment groups. CONCLUSIONS: MALAT1 facilitates BM-MSC differentiation into ECs by regulating the miR-206/CDC42/PAK1/paxillin axis to improve ED. The present findings revealed the vital role of MALAT1 in the repair of BM-MSCs for erectile function and provided new mechanistic insights into the BM-MSC-mediated repair of DMED.


Asunto(s)
Diferenciación Celular , Disfunción Eréctil , Células Madre Mesenquimatosas , MicroARNs , Paxillin , ARN Largo no Codificante , Ratas Sprague-Dawley , Transducción de Señal , Proteína de Unión al GTP cdc42 , Quinasas p21 Activadas , Masculino , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Diferenciación Celular/genética , Proteína de Unión al GTP cdc42/metabolismo , Proteína de Unión al GTP cdc42/genética , Ratas , Quinasas p21 Activadas/genética , Quinasas p21 Activadas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Disfunción Eréctil/terapia , Disfunción Eréctil/genética , Disfunción Eréctil/metabolismo , Paxillin/metabolismo , Paxillin/genética , Células Endoteliales/metabolismo , Células Cultivadas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética
12.
Inorg Chem ; 63(5): 2418-2430, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38264973

RESUMEN

Uranyl cation, as an emerging photocatalyst, has been successfully applied to synthetic chemistry in recent years and displayed remarkable catalytic ability under visible light. However, the molecular-level reaction mechanisms of uranyl photocatalysis are unclear. Here, we explore the mechanism of the stepwise benzylic C-H oxygenation of typical alkyl-substituted aromatics (i.e., toluene, ethylbenzene, and cumene) via uranyl photocatalysis using theoretical and experimental methods. Theoretical calculation results show that the most favorable reaction path for uranyl photocatalytic oxidation is as follows: first, hydrogen atom transfer (HAT) from the benzyl position to form a carbon radical ([R•]), then oxygen addition ([R•] + O2 → [ROO•]), then radical-radical combination ([ROO•] + [R•] → [ROOR] → 2[RO•]), and eventually [RO•] reduction to produce alcohols, of which 2° alcohol would further be oxidized to ketones and 1° would be stepwise-oxygenated to acids. The results of the designed verification experiments and the capture of reactive intermediates were consistent with those of theoretical calculations and the previously reported research that the active benzylic C-H would be stepwise-oxygenated in the presence of uranyl. This work deepens our understanding of the HAT mechanism of uranyl photocatalysis and provides important theoretical support for the relevant application of uranyl photocatalysts in organic transformation.

13.
J Sex Marital Ther ; 50(3): 303-314, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37981896

RESUMEN

This study investigated patterns of sexual agreement for extra-dyadic sex and their associations with sexual risk behaviors among men who have sex with men (MSM) having a regular male sex partner (RP) in China. A cross-sectional telephone survey was conducted among 530 MSM recruited through multiple sources in Hong Kong, China, between April and December 2020. This study was based on a subsample of 368 participants who had an RP in the past 6 months. Logistic regression models were fitted. Among the participants, 27.2%, 13.0%, and 3.0% had a closed agreement, an in-between agreement, and an open agreement, respectively. Compared to no agreement, a closed agreement was associated with fewer extra-dyadic partners and fewer instances of condomless sex with extra-dyadic partners. Those who had more positive attitudes toward a closed agreement, perceived more support from significant others to create a closed agreement, and perceived higher behavioral control of refraining from sex with extra-dyadic partners were more likely to have a closed agreement with RP. Those who were concerned that a closed agreement would impair freedom and sexual desire were less likely to have such an agreement. A closed agreement is a potentially useful risk reduction strategy for Chinese MSM with an RP.


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Hong Kong , Estudios Transversales , Conducta Sexual , Parejas Sexuales , China
14.
BMC Cardiovasc Disord ; 24(1): 461, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198782

RESUMEN

BACKGROUND: This study aims to identify a morphological indicator of aortic dissection (AD) based on the geometrical characteristics of the thoracic aorta. METHODS: We evaluated computed tomographic angiograms of 63 samples with AD (22 with type A AD, 41 with type B AD) and 71 healthy samples. Via centerline extraction and spatial transformation, the spatial entanglement of the aorta was minimized, and the expanded 2D aortic morphology was obtained. The 2D morphology of the thoracic aorta was fit to a circle. The applicability of the fitting circle method for identifying aortic dissection was verified by multivariable logistic regression analysis. RESULTS: Via the 3D coordinate transformation algorithm, the optimal aortic view was obtained. On this view, the geometrical characteristics of the thoracic aortas of the healthy controls were similar to a portion of a circle (sum of residuals: 3502.45 ± 2566.71, variance: 86.23 ± 56.60), while that of AD samples had poorer similarity to the circle (sum of residuals: 5404.78 ± 3891.69, variance: 129.90 ± 90.09). This difference was significant (p < 0.001). A logistic regression model showed that increased deformation of the thoracic aorta was a significant indicator of aortic dissection (odds ratio: 1.35, p = 0.034). CONCLUSIONS: The morphology of the healthy thoracic aorta could be fit to a circle, while that of the dissected aorta had poorer similarity to the circle. The statistics of the circle are an effective indicator of aortic deformation in AD. TRIAL REGISTRATION: This study is registered in the Chinese Clinical Trial Registry (ChiCTR2000029219).


Asunto(s)
Aorta Torácica , Aneurisma de la Aorta Torácica , Disección Aórtica , Aortografía , Angiografía por Tomografía Computarizada , Valor Predictivo de las Pruebas , Interpretación de Imagen Radiográfica Asistida por Computador , Humanos , Disección Aórtica/diagnóstico por imagen , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/patología , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios de Casos y Controles , Adulto , Estudios Retrospectivos , Tomografía Computarizada Multidetector
15.
Proc Natl Acad Sci U S A ; 118(15)2021 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-33833056

RESUMEN

Embryonic stem cells (ESCs) and induced pluripotent stem cells have the potential to differentiate to all cell types of an adult individual and are useful for studying development and for translational research. However, extrapolation of mouse and human ESC knowledge to deriving stable ESC lines of domestic ungulates and large livestock species has been challenging. In contrast to ESCs that are usually established from the blastocyst, mouse expanded potential stem cells (EPSCs) are derived from four-cell and eight-cell embryos. We have recently used the EPSC approach and established stem cells from porcine and human preimplantation embryos. EPSCs are molecularly similar across species and have broader developmental potential to generate embryonic and extraembryonic cell lineages. We further explore the EPSC technology for mammalian species refractory to the standard ESC approaches and report here the successful establishment of bovine EPSCs (bEPSCs) from preimplantation embryos of both wild-type and somatic cell nuclear transfer. bEPSCs express high levels of pluripotency genes, propagate robustly in feeder-free culture, and are genetically stable in long-term culture. bEPSCs have enriched transcriptomic features of early preimplantation embryos and differentiate in vitro to cells of the three somatic germ layers and, in chimeras, contribute to both the embryonic (fetal) and extraembryonic cell lineages. Importantly, precise gene editing is efficiently achieved in bEPSCs, and genetically modified bEPSCs can be used as donors in somatic cell nuclear transfer. bEPSCs therefore hold the potential to substantially advance biotechnology and agriculture.


Asunto(s)
Bovinos/genética , Células Madre Embrionarias/citología , Técnicas de Transferencia Nuclear/veterinaria , Cultivo Primario de Células/métodos , Animales , Blastocisto/citología , Linaje de la Célula , Células Cultivadas , Células Madre Embrionarias/metabolismo , Cultivo Primario de Células/veterinaria , Transcriptoma
16.
J Med Internet Res ; 26: e49362, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250213

RESUMEN

BACKGROUND: Male factory workers in China are vulnerable to HIV transmission. Commercial and nonmarital noncommercial contacts are the driving forces of heterosexual HIV transmission among male factory workers in China. There is a lack of effective HIV interventions for male factory workers in China. OBJECTIVE: The primary objective of this randomized controlled trial was to compare the efficacy of an enhanced versus the standard version of a WeChat mini program in reducing sexual intercourse with nonregular female sex partners and female sex workers among male factory workers in Shenzhen, China. METHODS: A nonblinded 2-arm parallel randomized controlled trial was conducted between December 2021 and April 2023. Participants were adult male factory workers in Shenzhen who had access to a smartphone and WeChat. Those who had oral or anal sex with a man or self-reported as HIV positive were excluded. A total of 247 participants were randomly assigned to the intervention group (n=125, 50.6%) or the control group (n=122, 49.4%); 221 (89.5%) and 220 (89.1%) completed follow-up surveys at T1 (6 months after completion of the interventions) and T2 (6 months after T1). Participants in the control group had access to the standard WeChat mini program that provided basic HIV-related knowledge and information about local free HIV testing services. Participants in the intervention group had access to the enhanced WeChat mini program. The enhanced mini program covered all the information in the standard mini program. In addition, the enhanced mini program assessed users' behaviors and invited users to watch different web-based videos on reducing nonmarital sexual contacts and promoting HIV testing based on their behavioral characteristics at months 0 and 1. The videos were developed based on in-depth interviews with male factory workers. Intention-to-treat analysis was used for outcome analyses. Multiple imputation was used to replace missing outcome values at T1 and T2. RESULTS: At T1, fewer participants in the intervention group reported sexual intercourse with a nonregular female sex partner in the past 6 months compared with the control group (1/125, 0.8% vs 8/122, 6.6%; relative risk=0.12, 95% CI 0.02-0.96; P=.02). However, there were no between-group differences in sexual intercourse with a nonregular female sex partner at T2 (10/125, 8% vs 14/122, 11.5%; P=.36) or sexual intercourse with a female sex worker at T1 (2/125, 1.6% vs 2/122, 1.6%; P=.98) or T2 (8/125, 6.4% vs 8/122, 6.6%; P=.96). CONCLUSIONS: The enhanced WeChat mini program was more effective than the standard WeChat mini program in reducing sexual intercourse with nonregular female sex partners among male factory workers in the short term but not in the longer term. Improvements should be made to the WeChat mini program before implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05811611; https://clinicaltrials.gov/study/NCT05811611.


Asunto(s)
Infecciones por VIH , Heterosexualidad , Humanos , Masculino , Adulto , Infecciones por VIH/prevención & control , Heterosexualidad/estadística & datos numéricos , China , Femenino , Trabajadores Sexuales/estadística & datos numéricos , Conducta Sexual , Parejas Sexuales , Adulto Joven
17.
Nano Lett ; 23(14): 6610-6618, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37458704

RESUMEN

Diabetic ulcers have received much attention in recent years due to their high incidence and mortality, motivating the scientific community to develop various strategies for such chronic disease treatments. However, the therapeutic outcome of these approaches is highly compromised by invasive bacteria and a severe inflammatory microenvironment. To overcome these dilemmas, microenvironment-responsive self-delivery glucose oxidase@manganese sulfide (GOx@MnS) nanoparticles (NPs) are developed by one-step biomineralization. When they encounter the high glucose level in the ulcer site, GOx particles catalyze glucose to decrease the local pH and trigger the steady release of both manganese ions (Mn2+) and hydrogen sulfide (H2S). Mn2+ reacts with hydrogen peroxide to generate hydroxyl radicals for the elimination of bacterial infection; meanwhile, H2S is able to suppress the inflammatory response and accelerate diabetic wound healing through macrophage polarization. The excellent biocompatibility, strong bactericidal activity, and considerable immunomodulatory effect promise GOx@MnS NPs have great therapeutic potential for diabetic wound treatment.


Asunto(s)
Diabetes Mellitus , Sulfuro de Hidrógeno , Nanopartículas , Humanos , Glucosa Oxidasa/uso terapéutico , Glucosa , Peróxido de Hidrógeno
18.
Stroke ; 54(4): 1037-1045, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36916272

RESUMEN

BACKGROUND: Multidelay arterial spin labeling (ASL) is a novel perfusion method of ASL, with arterial transit time (ATT) calculated by multiple postlabeling delays to correct cerebral blood flow (CBF). We verify the accuracy of multidelay ASL in evaluating the ischemic penumbra and perfusion levels in patients with acute ischemic stroke, compared with computed tomography perfusion (CTP). METHODS: Patients with acute ischemic stroke with anterior circulation large vessel occlusion received baseline CTP, multidelay ASL, and diffusion-weighted imaging (DWI) in succession. Multidelay ASL image was processed to reconstruct ATT, CBF without ATT correction, and CBF corrected by ATT. The consistency of hypoperfusion and ischemic penumbra volume calculated by CTP and multidelay ASL were quantified by intraclass correlation coefficient (ICC) in 2-way mixed effects, absolute agreement, and single measure. Wilcoxon signed-rank test was used to compare the difference in penumbra volume between CTP, corrected ASL, and uncorrected ASL. RESULTS: Thirty patients were included. Hypoperfusion volume based on multidelay ASL with different thresholds were 117.95 (87.77-151.49) mL for corrected relative CBF<40%, 130.29 (85.99-249.37) mL for CBF corrected by ATT<20 mL·100g-1·min-1, no statistical difference (P>0.05) compared with the volume of CTP, and consistency was almost excellent (ICC, 0.91) and substantial consistent (ICC, 0.727). The volumes of ischemic penumbra were 91.00 (42.68-125.27) mL for corrected relative CBF<40%-DWI, 108.94 (62.03-150.86) mL for CBF corrected by ATT<20 mL·100 g-1·min-1-DWI, which showed no statistical difference compared with the penumbra volume of CTP (P>0.05). The consistency was excellent (ICC, 0.822) and moderate (ICC, 0.501), respectively. The volume of uncorrected relative CBF <40%-DWI was 209.57 (123.21-292.45) mL, statistically larger than corrected relative CBF <40%-DWI (P<0.001) and CTP (P<0.001). The volume of uncorrected CBF<20 mL·100g-1·min-1-DWI was 186.23 (86.56-298.22) mL, statistically larger than CBF corrected by ATT<20 mL·100g-1·min-1-DWI (P<0.001) and CTP(P<0.001). CONCLUSIONS: The volume of ischemic penumbra determined by CBF/DWI mismatch based on multidelay ASL is consistent with CTP. The penumbra volume calculated by CBF adjusted by ATT is more accurate.


Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Enfermedades Vasculares , Humanos , Imagen por Resonancia Magnética/métodos , Marcadores de Spin , Imagen de Difusión por Resonancia Magnética , Perfusión , Circulación Cerebrovascular/fisiología , Accidente Cerebrovascular/diagnóstico por imagen
19.
Biochem Biophys Res Commun ; 652: 31-34, 2023 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-36809702

RESUMEN

Vibrational strong coupling (VSC) has been reported as a polariton-based method for modulating the rate of biochemical reactions. Herein, we studied how VSC modulates the sucrose hydrolysis. By monitoring the refractive index-induced shift of Fabry-Pérot microcavity, in which the catalytic efficiency of sucrose hydrolysis can be increased at least two times, as VSC was tuned to resonate with the stretching vibration of O-H bonds. This research provides new evidence for applying VSC in life sciences, which holds great promise to improving enzymatic industries.


Asunto(s)
Disciplinas de las Ciencias Biológicas , Sacarasa , Vibración , Catálisis , Sacarosa
20.
Biol Reprod ; 108(6): 887-901, 2023 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-37040346

RESUMEN

The mule is the interspecific hybrid of horse and donkey and has hybrid vigor in muscular endurance, disease resistance, and longevity over its parents. Here, we examined adult fibroblasts of mule (MAFs) compared with the cells from their parents (donkey adult fibroblasts and horse adult fibroblasts) (each species has repeated three independent individuals) in proliferation, apoptosis, and glycolysis and found significant differences. We subsequently derived mule, donkey, and horse doxycycline (Dox)-independent induced pluripotent stem cells (miPSCs, diPSCs, and hiPSCs) from three independent individuals of each species and found that the reprogramming efficiency of MAFs was significantly higher than that of cells of donkey and horse. miPSCs, diPSCs, and hiPSCs all expressed the high levels of crucial endogenous pluripotency genes such as POU class 5 homeobox 1 (POU5F1, OCT4), SRY-box 2 (SOX2), and Nanog homeobox (NANOG) and propagated robustly in single-cell passaging. miPSCs exhibited faster proliferation and higher pluripotency and differentiation than diPSCs and hiPSCs, which were reflected in co-cultures and separate-cultures, teratoma formation, and chimera contribution. The establishment of miPSCs provides a unique research material for the investigation of "heterosis" and perhaps is more significant to study hybrid gamete formation.


Asunto(s)
Células Madre Pluripotentes Inducidas , Caballos , Animales , Reprogramación Celular , Equidae , Células Cultivadas , Diferenciación Celular/genética , Fibroblastos , Factor 3 de Transcripción de Unión a Octámeros/genética
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