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1.
Microb Pathog ; 190: 106638, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38574829

RESUMEN

Autophagy plays an important role in the lifecycle of viruses. However, there is currently a lack of systematic research on the relationship between Infectious Bronchitis Virus (IBV) and autophagy. This study aims to investigate the impact of IBV on autophagy and the role of autophagy in viral replication. We observed that IBV infection increased the expression of microtubule-associated protein 1 light chain 3, a marker of autophagy, decreased the expression of sequestosome 1, and led to elevated intracellular LC3 puncta levels. These findings suggest that IBV infection activates the autophagic process in cells. To investigate the impact of autophagy on the replication of IBV, we utilized rapamycin as an autophagy activator and 3-methyladenine as an autophagy inhibitor. Our results indicate that IBV promotes viral replication by inducing autophagy. Further investigation revealed that IBV induces autophagosome formation by inhibiting the mTOR-ULK1 pathway and activating the activity of vacuolar protein sorting 34 (VPS34), autophagy-related gene 14, and the Beclin-1 complex. VPS34 plays a crucial role in this process, as inhibiting VPS34 protein activity enhances cell proliferation after IBV infection. Additionally, inhibiting VPS34 significantly improves the survival rate of IBV-infected chicks, suppresses IBV replication in the kidney, and alleviates tracheal, lung, and kidney damage caused by IBV infection. In summary, IBV infection can induce autophagy by modulating the mTOR/ULK1 signaling pathway and activating the VPS34 complex, while autophagy serves to promote virus replication.


Asunto(s)
Autofagia , Pollos , Fosfatidilinositol 3-Quinasas Clase III , Virus de la Bronquitis Infecciosa , Replicación Viral , Virus de la Bronquitis Infecciosa/fisiología , Animales , Fosfatidilinositol 3-Quinasas Clase III/metabolismo , Pollos/virología , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/metabolismo , Sirolimus/farmacología , Beclina-1/metabolismo , Beclina-1/genética , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal , Línea Celular , Enfermedades de las Aves de Corral/virología , Autofagosomas/metabolismo , Autofagosomas/virología , Chlorocebus aethiops , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genética
2.
Immunity ; 57(2): 364-378.e9, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38301651

RESUMEN

Mutations of the CBP/p300 histone acetyltransferase (HAT) domain can be linked to leukemic transformation in humans, suggestive of a checkpoint of leukocyte compartment sizes. Here, we examined the impact of reversible inhibition of this domain by the small-molecule A485. We found that A485 triggered acute and transient mobilization of leukocytes from the bone marrow into the blood. Leukocyte mobilization by A485 was equally potent as, but mechanistically distinct from, granulocyte colony-stimulating factor (G-CSF), which allowed for additive neutrophil mobilization when both compounds were combined. These effects were maintained in models of leukopenia and conferred augmented host defenses. Mechanistically, activation of the hypothalamus-pituitary-adrenal gland (HPA) axis by A485 relayed shifts in leukocyte distribution through corticotropin-releasing hormone receptor 1 (CRHR1) and adrenocorticotropic hormone (ACTH), but independently of glucocorticoids. Our findings identify a strategy for rapid expansion of the blood leukocyte compartment via a neuroendocrine loop, with implications for the treatment of human pathologies.


Asunto(s)
Médula Ósea , Histona Acetiltransferasas , Humanos , Histona Acetiltransferasas/metabolismo , Médula Ósea/metabolismo , Histonas/metabolismo , Neutrófilos/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo
4.
Anal Chem ; 96(3): 1328-1335, 2024 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-38190500

RESUMEN

Tumor-derived small extracellular vesicles (tEVs) as potential biomarkers possess abundant surface proteins closely related to parent cells, which are crucial for noninvasive cancer diagnosis. However, tEVs exhibit phenotype heterogeneity and low abundance, posing a significant challenge for multiplex detection with a high sensitivity. Herein, we developed a DNA gate-based exponential amplification CRISPR-Cas (DGEAC) system for accurate and ultrasensitive detection of tEVs, which can greatly improve the accuracy of breast cancer (BC) diagnosis. Based on the coexpression of CD63 and vascular endothelial growth factor (VEGF) on BC-derived tEVs, we developed a dual-aptamer-based AND gate fluorescent probe by proximity hybridization. By integrating the target recognition and trans-cleavage activity of Cas12a, an autocatalysis-driven exponential amplification circuit was developed for ultrasensitive detection of CD63 and VEGF proteins on tEVs, which could avoid false negative signals from single protein or other interfering proteins. We achieved highly sensitive detection of tEVs over a linear range from 1.75 × 103 to 3.5 × 108 particles/mL with a detection limit as low as 1.02 × 103 particles/mL. Furthermore, the DGEAC system can distinguish tEVs from tEVs derived from different BC cell lines, including MDA-MB-231, MCF-7, SKBR3, and MCF-10A. Compared to linear amplification (AUC 90.0%), the DGEAC system effectively differentiates BC in different stages (AUC 98.3%).


Asunto(s)
Técnicas Biosensibles , Vesículas Extracelulares , Neoplasias Mamarias Animales , Animales , Sistemas CRISPR-Cas/genética , Factor A de Crecimiento Endotelial Vascular/genética , ADN
5.
Adv Mater ; 36(8): e2309310, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38011899

RESUMEN

The intrinsically weak bonding structure in halide perovskite materials makes components in the thin films volatile, leading to the decomposition of halide perovskite materials. The reactions within the perovskite film are reversible provided that components do not escape the thin films. Here, a holistic approach is reported to improve the efficiency and stability of PSMs by preventing the effusion of volatile components. Specifically, a method for in situ generation of channel barrier layers for perovskite photovoltaic modules is developed. The resulting PSMs attain a certified aperture PCE of 21.37%, and possess remarkable continuous operation stability for maximum power point tracking (MPPT) of T90 > 1100 h in ambient air, and damp heat (DH) tracking of T93 > 1400 h.

6.
J Multidiscip Healthc ; 16: 4027-4038, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38111828

RESUMEN

Purpose: Elucidation of the cardio-oncologic knowledge among the oncology nurses of tertiary hospitals in Shanxi Province to provide better insights and directions for management by nursing managers. Background: China's National Health and Wellness Commission issued the Action Plan for Further Improving Nursing Services in June 2023, which requires nurses to provide patients with physical and mental holistic nursing services, such as medical care, condition observation, assistance with treatment, and health guidance. Most oncology patients are treated with chemotherapy, but the modality can cause greater harm to patients, especially cardiotoxicity. How to provide precise care for chemotherapy patients is a problem for nursing managers. Methods: In order to investigate the level of cardio-oncologic knowledge among the oncology nurses of tertiary care hospitals in Shanxi Province, China, a questionnaire was created based on the relevant literature and the provided instructions on cardio-oncology. The chi-squared test was performed for multiple comparisons of the level of knowledge of disease observation, health guidance, and implementation of treatment. Spearman correlation analysis was performed to analyze the correlation between the levels of cardio-oncologic knowledge and general information of hospitals and nurses. Results: Cardio-oncology awareness among the oncology nurses was 0.1%-44.7%, the awareness rate of single dimension was 0 to 3.9%, and overall awareness rate was 0. A partially significant difference was revealed in the two-by-two comparisons of the awareness rates of the three dimensions of disease observation, health guidance, and implementation of treatment (P < 0.05). A correlation was observed between the cardio-oncologic knowledge and some of the hospital and the nurses' general information data (P < 0.05). Conclusion: Oncology nurses exhibited a low rate of awareness related to cardio-oncology. Hospitals could establish oncology nursing teams to train the oncology nurses to promote their cardio-oncologic knowledge and ensure the quality of daily care provided by these nurses.

7.
Chem Sci ; 14(48): 14290-14301, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38098706

RESUMEN

Ischemia-reperfusion-induced cardiomyocyte mortality constitutes a prominent contributor to global morbidity and mortality. However, early diagnosis and preventive treatment of cardiac I/R injury remains a challenge. Given the close relationship between ferroptosis and I/R injury, monitoring their pathological processes holds promise for advancing early diagnosis and treatment of the disease. Herein, we report a near-infrared (NIR) light-activated dual-responsive nanoprobe (UCNP@mSiO2@SP-NP-NAP) for controllable detection of hydrogen polysulfide (H2Sn) and sulfur dioxide (SO2) during ferroptosis-related myocardial I/R injury. The nanoprobe's responsive sites could be activated by NIR and Vis light modulation, reversibly alternating for at least 5 cycles. We employed the nanoprobe to monitor the fluctuation levels of H2Sn and SO2 in H9C2 cardiomyocytes and mice, revealing that H2Sn and SO2 levels were up-regulated during I/R. The NIR light-activated dual-responsive nanoprobe could be a powerful tool for myocardial I/R injury diagnosis. Moreover, we also found that inhibiting the initiation of the ferroptosis process contributed to attenuating cardiac I/R injury, which indicated great potential for treating I/R injury.

8.
Chem Sci ; 14(48): 14182-14192, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38098713

RESUMEN

It is a great challenge to effectively treat triple-negative breast cancer (TNBC) due to lack of therapeutic targets and drug resistance of systemic chemotherapy. Rational design of nanomedicine with good hemocompatibility is urgently desirable for combination therapy of TNBC. Herein, an erythrocyte membrane-camouflaged fluorescent covalent organic framework (COF) loaded with an NO donor (hydroxyurea, Hu), glucose oxidase (GOx) and cytosine-phosphate-guanine oligonucleotides (CPG) (COF@HGC) was developed for imaging-guided starving/nitric oxide (NO)/immunization synergistic treatment of TNBC. The substances of HGC are easily co-loaded onto the COF due to the ordered pore structure and large surface area. And a folic acid-modified erythrocyte membrane (FEM) is coated on the surface of COF@HGC to improve targeted therapy and haemocompatibility. When COF@HGC@FEM is internalized into tumor cells, hemoglobin (Hb) on FEM and GOx loaded on the COF can trigger cascade reactions to kill tumor cells due to the simultaneous production of NO and exhaustion of glucose. Meanwhile, the COF with excellent fluorescence properties can be used as a self-reporter for bioimaging. Furthermore, the CPG can reprogram tumor-associated macrophages from tumor-supportive phenotype to anti-tumor phenotype and enhance immunotherapy. Through the "three-in-one" strategy, the biomimetic nanoplatform can effectively inhibit tumor growth and reprogram the tumor immunosuppression microenvironment in the TNBC mouse model.

9.
Acta Biomater ; 170: 532-542, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37669712

RESUMEN

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for causing life-threatening infections that result in high morbidity and mortality rates. The development of advanced imaging and therapeutic methods for in vivo diagnosis and treatment of MRSA infections remains challenging. Here, we develop a hybrid nanoplatform based on rare-earth-doped nanoparticles (RENPs) sensitized by a moiety-engineered near-infrared (NIR) TPEO-820 dye and with a ZIF-8 layer that incorporates CysNO, a photochemically triggered nitric oxide donor. We then use the hybrid for both NIR-II bioimaging and photoactivatable treatment of MRSA-infected wounds. We show that the NIR dye sensitization leads to an 8.5-fold enhancement of the downshifting emission and facilitates deep-tissue NIR-II imaging of bacterial infections. Moreover, the sensitization strategy enhances the UV emission of RENPs by two orders of magnitude, leading to the efficiently controllable release of nitric oxide for effective disinfection of MRSA in vitro and in vivo. The hybrid nanoplatform thus offers promising opportunities for simultaneous localization and controllable treatment of MRSA. STATEMENT OF SIGNIFICANCE: Early detection and treatment of MRSA infections are crucial for reducing public health risks. It is a significant challenge that develops sensitive in vivo diagnosis and complete elimination of drug-resistant bacterial infections. Herein, a nanoplatform has been developed for photoactivatable therapy of MRSA infections and deep tissue NIR-II imaging. This platform utilizes lanthanide-doped rare earth nanoparticles (RENPs) that are sensitized by a moiety-engineered near-infrared (NIR) dye TPEO-820. The TPEO-820 sensitized RENPs exhibit 5 times increase in the release of NO concentration for MRSA treatment compared to unsensitized RENPs, enabling precise therapy of MRSA infection both in vitro and in vivo. Moreover, the platform demonstrates NIR-II luminescence in vivo, allowing for sensitive imaging in deep tissue for MRSA infection.

10.
J Multidiscip Healthc ; 16: 1905-1914, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37465015

RESUMEN

Purpose: To clarify the implementation of the admission process under the public crisis of COVID-19 pandemic. Methods: A real-world study was conducted to collect data on the normal and public crisis situations at a tertiary hospital in China and understand the views of 18 head nurses on the necessity of the admission process in public crisis situations. Independent t-test and chi-square test were used to analyze the work data in two situations; Spearman correlation analysis was performed to determine the correlation of work data with two situations of process implementation, and differences between the head nurses' views of necessity of the admission process and actual implementation under public crisis situations were analyzed. Results: Significant differences were observed in the working data between the normal and public crisis situations (P < 0.05), and the implementation of the admission process was not in place. The number of nurses on duty was positively correlated with each item of admission process (P < 0.05), the rest of work data were negatively correlated with each item in the admission process (P < 0.05), and there was a significant difference between the necessity of each item in the admission process and the actual implementation results (P < 0.05). Conclusion: Public crisis leads to the lack of implementation of admission process, and the original admission process and quality control standards are not applicable during the public crisis situation.

11.
Nature ; 620(7974): 643-650, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37437602

RESUMEN

In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour1,2. The scope and mechanisms of behavioural modifications by the immune system are not yet well understood. Here, using mouse models of food allergy, we show that allergic sensitization drives antigen-specific avoidance behaviour. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus and central amygdala. Allergen avoidance requires immunoglobulin E (IgE) antibodies and mast cells but precedes the development of gut allergic inflammation. The ability of allergen-specific IgE and mast cells to promote avoidance requires cysteinyl leukotrienes and growth and differentiation factor 15. Finally, a comparison of C57BL/6 and BALB/c mouse strains revealed a strong effect of the genetic background on the avoidance behaviour. These findings thus point to antigen-specific behavioural modifications that probably evolved to promote niche selection to avoid unfavourable environments.


Asunto(s)
Alérgenos , Reacción de Prevención , Hipersensibilidad a los Alimentos , Animales , Ratones , Alérgenos/inmunología , Reacción de Prevención/fisiología , Núcleo Amigdalino Central/fisiología , Modelos Animales de Enfermedad , Hipersensibilidad a los Alimentos/genética , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina E/inmunología , Intestinos/inmunología , Mastocitos/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Núcleos Parabraquiales/fisiología , Núcleo Solitario/fisiología
12.
Anal Chem ; 95(27): 10330-10336, 2023 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-37366594

RESUMEN

Small extracellular vesicles (sEVs) derived from tumors contain a vast amount of cellular information and are regarded as a potential diagnostic biomarker for noninvasive cancer diagnosis. Nevertheless, it remains challenging to accurately measure sEVs from clinical samples due to the low abundance of these vesicles as well as their phenotypic heterogeneity. Herein, a polymerase-driven logic signal amplification system (PLSAS) was developed for the high-sensitivity detection of sEV surface proteins and breast cancer (BC) identification. Aptamers were introduced to serve as sensing modules to specifically recognize target proteins. By changing the input DNA sequences, two polymerase-driven primer exchange reaction systems were rationally designed for DNA logic computing. This allows for autonomous targeting of a limited number of targets using "OR" and "AND" logic, leading to a significant increase in fluorescence signals and enabling the specific and ultrasensitive detection of sEV surface proteins. In this work, we investigated surface proteins of mucin 1 (MUC1) and the epithelial cell adhesion molecule (EpCAM) as model proteins. When MUC1 or EpCAM proteins were used as single signal input in the "OR" DNA logic system, the detection limit of sEVs was 24 or 58 particles/µL, respectively. And MUC1 and EpCAM proteins of sEVs can be simultaneously detected in the AND logic method, which can significantly reduce the effect of phenotypic heterogeneity of sEVs to distinguish the source of sEVs derived from various mammary cell lines, such as MCF-7, MDA MB 231, SKBR3, and MCF-10A. The approach has achieved high discrimination in serologically tested positive BC samples (AUC 98.1%) and holds significant potential in advancing the early diagnosis and prognostic assessments of BC.


Asunto(s)
Vesículas Extracelulares , Neoplasias , Proteínas de la Membrana , Molécula de Adhesión Celular Epitelial , Nucleotidiltransferasas , Línea Celular
13.
ACS Appl Mater Interfaces ; 15(21): 25550-25557, 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37197996

RESUMEN

The wide-band-gap inorganic CsPbI2Br perovskite material provides a highly matched absorption range with the indoor light spectrum and is expected to be used in the fabrication of highly efficient indoor photovoltaic cells (IPVs) and self-powered low-power Internet of Things (IoT) sensors. However, the defects that cause nonradiative recombination and ion migration are assumed to form leakage loss channels, resulting in a severe impact on the open-circuit voltage (VOC) and the fill factor (FF) of IPVs. Herein, we introduce poly(amidoamine) (PAMAM) dendrimers with multiple passivation sites to fully repair the leakage channels in the devices, taking into account the characteristics of IPVs that are extremely sensitive to nonradiative recombination and shunt resistance. The as-optimized IPVs demonstrate a promising PCE of 35.71% under a fluorescent light source (1000 lux), with VOC increased from 0.99 to 1.06 V and FF improved from 75.21 to 84.39%. The present work provides insight into the photovoltaic mechanism of perovskites under full sun and indoor light, which provides guidance for perovskite photovoltaic technology with industrialization prospects.

14.
BMJ Open ; 13(5): e070553, 2023 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-37236662

RESUMEN

INTRODUCTION: In recent decades, there has been a significant increase in childlessness. This paper analysed childlessness in China, specifically examining its socio and regional disparities. METHODS: With data from China's 2020 population census, supplemented with data from China's 2010 population census and 2015 inter-censual 1% population sample survey, we used a basic indicator of age-specific childlessness proportion, a decomposition method, and probability distribution models to analyse, fit and project childlessness. RESULTS: We presented age-specific childlessness proportions for women as a whole and by socioeconomic features, decomposition and projection results. The childlessness proportion increased markedly from 2010 to 2020, reaching 5.16% for women aged 49. The proportion is highest for city women, followed by township women, and is lowest among village women, at 6.29%, 5.50% and 3.72 % for women aged 49, respectively. The proportion for women aged 49 with high college education or above was 7.98%, and only 4.42% for women with junior high school education. The proportion also exhibits marked provincial discrepancies, and the total fertility rate is negatively correlated with childlessness at the province level. The decomposition results distinguished the different contribution of change in educational structure and change in childlessness proportion for subgroups to the total childlessness proportion change. It is projected that city women, women with high education will have higher childlessness proportion, and the proportion will further increase with the rapid increase in education level and urbanisation. CONCLUSIONS: Childlessness has risen to a relatively high level, and varies among women with different characteristics. This should be taken into consideration in China's countermeasures to reduce childlessness and curtail further fertility decline accordingly.


Asunto(s)
Censos , Fertilidad , Femenino , Humanos , Dinámica Poblacional , Demografía , China/epidemiología , Tasa de Natalidad , Países en Desarrollo , Economía
15.
bioRxiv ; 2023 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-37090652

RESUMEN

Metabolic homeostasis is one of the most exquisitely tuned systems in mammalian physiology. Metabolic homeostasis requires multiple redundant systems to cooperate to maintain blood glucose concentrations in a narrow range, despite a multitude of physiological and pathophysiological pressures. Cancer is one of the canonical pathophysiological settings in which metabolism plays a key role. In this study, we utilized REnal Gluconeogenesis Analytical Leads (REGAL), a liquid chromatography-mass spectrometry/mass spectrometry-based stable isotope tracer method that we developed to show that in conditions of metabolic stress, the fasting hepatokine fibroblast growth factor-21 (FGF-21)1,2 coordinates a liver-brain-kidney axis to promote renal gluconeogenesis. FGF-21 promotes renal gluconeogenesis by enhancing ß2 adrenergic receptor (Adrb2)-driven, adipose triglyceride lipase (ATGL)-mediated intrarenal lipolysis. Further, we show that this liver-brain-kidney axis promotes gluconeogenesis in the renal parenchyma in mice and humans with renal cell carcinoma (RCC). This increased gluconeogenesis is, in turn, associated with accelerated RCC progression. We identify Adrb2 blockade as a new class of therapy for RCC in mice, with confirmatory data in human patients. In summary, these data reveal a new metabolic function of FGF-21 in driving renal gluconeogenesis, and demonstrate that inhibition of renal gluconeogenesis by FGF-21 antagonism deserves attention as a new therapeutic approach to RCC.

16.
BMC Nurs ; 22(1): 136, 2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37098520

RESUMEN

AIM: This study developed a set of competency evaluation indicators for billing nurses in China. BACKGROUND: In clinical practice, nurses often take up billing responsibilities that are accompanied by certain risks. However, the competency evaluation index system for billing nurses has not been established in China. METHODS: This study consisted of two main phases of research design: the first phase included a literature review and semi-structured interviews. Individual semi-structured interviews were conducted with 12 nurses in billing departments and 15 nurse managers in related departments. Concepts distilled from the literature review were linked to the results of the semi-structured interviews; this phase produced the first draft of indicators for assessing the professional competence of nurses in billing departments. In the second phase, two rounds of correspondence were conducted with 20 Chinese nursing experts using the Delphi method to test and evaluate the content of the index. The consensus was defined in advance as a mean score of 4.0 or above, with at least 75% agreement among participants. In this way, the final indicator framework was determined. RESULTS: Using the iceberg model as a theoretical foundation, the literature review identified four main dimensions and associated themes. The semi-structured interviews confirmed all of the themes from the literature review while generating new themes, both of which were incorporated into the first draft of the index. Then two rounds of the Delphi survey were conducted. The positive coefficients of experts in the two rounds were 100% and 95%, respectively, while the authority coefficients were 0.963 and 0.961, respectively. The coefficients of variation were 0.00-0.33 and 0.05-0.24, respectively. The competency evaluation index system for billing nurses consisted of 4 first-level indicators, 16 s-level indicators, and 53 third-level indicators. CONCLUSION: The competency evaluation index system for billing nurses, which was developed on the basis of the iceberg model, was scientific and applicable. IMPLICATIONS FOR NURSING MANAGEMENT: The competency assessment index system for billing nurses may provide an effective practical framework for nursing administration to evaluate, train, and assess the competency of billing nurses.

17.
Chem Commun (Camb) ; 59(34): 5122-5125, 2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37039428

RESUMEN

ATP stimulus-responsive tetrahedral DNA-gated fluorescent covalent organic frameworks (COFs) were developed for estradiol (E2) delivery and controllable release. The fluorescent COFs with an efficient E2 loading showed great potential against myocardial ischemia and reperfusion injury.


Asunto(s)
Estructuras Metalorgánicas , Daño por Reperfusión Miocárdica , Humanos , Estradiol , Estructuras Metalorgánicas/farmacología , Colorantes
18.
Int J Biol Macromol ; 241: 124536, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37085065

RESUMEN

Hydrogel-based strain sensors have garnered significant attention for their potential for human health monitoring. However, its practical application has been hindered by water loss, freezing, and structural impairment during long-term motion monitoring. Here, a strain sensor based on double-network (DN) hydrogel of polyacrylamide (PAAm)/carboxymethylcellulose (CMC) was developed in a ternary solvent system of lithium chloride (LiCl)/ethylene glycol (EG)/H2O through a facile one-pot radical polymerization strategy. The incorporation of EG effectively mitigated the hydration of lithium salts by generating stable ion clusters with Li+ and stronger hydrogen bonds within the polymer matrix. The sensor demonstrated excellent mechanical properties, including a stretchability of 1858 %, toughness of 1.80 MJ/m3, and recoverability of 102 %. Furthermore, the LiCl/EG/H2O ternary system resulted in high conductivity, excellent anti-freezing performance, and superior sensing stability. In addition, the sensor exhibited remarkable sensitivity, enabling the monitoring of human movements ranging from subtle to significant deformations, including throat motion and bending of the elbow, wrist, finger, and lower limb. This study presents a viable approach for constructing hydrogel-based strain sensors with exceptional sensing stability for long-term tracking of human motions.


Asunto(s)
Carboximetilcelulosa de Sodio , Hidrogeles , Humanos , Conductividad Eléctrica , Enlace de Hidrógeno , Litio , Cloruro de Litio
19.
Virol J ; 20(1): 18, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36721152

RESUMEN

Coronavirus disease 2019 is a global pandemic caused by SARS-CoV-2. The emergence of its variant strains has posed a considerable challenge to clinical treatment. Therefore, drugs capable of inhibiting SARS-CoV-2 infection, regardless of virus variations, are in urgently need. Our results showed that the endosomal acidification inhibitor, Bafilomycin A1 (Baf-A1), had an inhibitory effect on the viral RNA synthesis of SARS-CoV-2, and its Beta and Delta variants at the concentration of 500 nM. Moreover, the human lung xenograft mouse model was used to investigate the anti-SARS-CoV-2 effect of Baf-A1. It was found that Baf-A1 significantly inhibited SARS-CoV-2 replication in the human lung xenografts by in situ hybridization and RT-PCR assays. Histopathological examination showed that Baf-A1 alleviated SARS-CoV-2-induced diffuse inflammatory infiltration of granulocytes and macrophages and alveolar endothelial cell death in human lung xenografts. In addition, immunohistochemistry analysis indicated that Baf-A1 decreased inflammatory exudation and infiltration in SARS-CoV-2-infected human lung xenografts. Therefore, Baf-A1 may be a candidate drug for SARS-CoV-2 treatment.


Asunto(s)
COVID-19 , Humanos , Animales , Ratones , Xenoinjertos , SARS-CoV-2 , Células Epiteliales Alveolares , Modelos Animales de Enfermedad
20.
BMC Med Genomics ; 16(1): 32, 2023 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-36823654

RESUMEN

BACKGROUND: Multiple myeloma (MM) is an incurable and relapse-prone disease with apparently prognostic heterogeneity. At present, the risk stratification of myeloma is still incomplete. Pyroptosis, a type of programmed cell death, has been shown to regulate tumor growth and may have potential prognostic value. However, the role of pyroptosis-related genes (PRGs) in MM remains undetermined. The aims of this study were to identify potential prognostic biomarkers and to construct a predictive model related to PRGs. METHODS: Sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Non-negative matrix factorization (NMF) was performed to identify molecular subtype screening. LASSO regression was used to screen for prognostic markers, and then a risk score model was constructed. The Maxstat package was utilized to calculate the optimal cutoff value, according to which patients were divided into a high-risk group and a low-risk group, and the survival curves were plotted using the Kaplan-Meier (K-M) method. Nomograms and calibration curves were established using the rms package. RESULTS: A total of 33 PRGs were extracted from the TCGA database underlying which 4 MM molecular subtypes were defined. Patients in cluster 1 had poorer survival than those in cluster 2 (p = 0.035). A total of 9 PRGs were screened out as prognostic markers, and the predictive ability of the 9-gene risk score for 3-year survival was best (AUC = 0.658). Patients in the high-risk group had worse survival than those in the low-risk group (p < 0.001), which was consistent with the results verified by the GSE2658 dataset. The nomogram constructed by gender, age, International Staging System (ISS) stage, and risk score had the best prognostic predictive performance with a c-index of 0.721. CONCLUSION: Our model could enhance the predictive ability of ISS staging and give a reference for clinical decision-making. The new, prognostic, and pyroptosis-related markers screened out by us may facilitate the development of novel risk stratification for MM. CLINICAL TRIAL REGISTRATION: Not applicable.


Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/genética , Pronóstico , Piroptosis/genética , Apoptosis , Factores de Riesgo
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