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1.
EBioMedicine ; 105: 105203, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38896919

RESUMEN

BACKGROUND: Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing rates of breakthrough infections among vaccinated children. METHODS: We conducted a prospective longitudinal study to investigate the magnitude, specificity, and cytokine profile of antigen-specific T cell responses elicited by breakthrough SARS-CoV-2 infection in a cohort of mRNA-vaccinated children (n = 29) aged 5-11. This longitudinal analysis involved six distinct time points spanning a 16-month period post-vaccination, during which we analysed a total of 159 blood samples. All children who were followed for at least 12 months (n = 26) experienced a breakthrough infection. We conducted cytokine release assays using minimal blood samples, and we verified the cellular origin of these responses through intracellular cytokine staining. FINDINGS: After breakthrough infection, children who had received mRNA vaccines showed enhanced Th1 responses specific to Spike peptides. Additionally, their Spike-specific T cells exhibited a distinctive enrichment of CD4+ IFN-γ+IL10+ cells, a characteristic akin to adults with hybrid immunity. Importantly, vaccination did not impede the development of multi-specific T cell responses targeting Membrane, Nucleoprotein, and ORF3a/7/8 antigens. INTERPRETATION: Children, previously primed with a Spike-based mRNA vaccine and experiencing either symptomatic or asymptomatic breakthrough infection, retained the ability to enhance and diversify Th1/IL-10 antigen-specific T cell responses against multiple SARS-CoV-2 proteins. These findings mirror characteristics associated with hybrid cellular immunity in adults, known to confer resistance against severe COVID-19. FUNDING: This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002).


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/virología , SARS-CoV-2/inmunología , Niño , Estudios Longitudinales , Masculino , Femenino , Preescolar , Citocinas/metabolismo , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Estudios Prospectivos , Vacunación , Vacunas de ARNm/inmunología , Linfocitos T/inmunología , Células TH1/inmunología
2.
Adv Mater ; : e2404010, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935245

RESUMEN

The imperfect charge behavior at the interfaces of perovskite/electron-transport layer (ETL)/transparent conducting oxide (TCO) limits the further performance improvement of perovskite/silicon tandem solar cells. Herein, an indium tin oxide interlayer is deposited between ETL and TCO to address this issue. Specifically, the interlayer is prepared using an all-physical and H2O-free method, electron-beam evaporation, which can avoid any potential damage to the underlying perovskite and ETL layers. Moreover, the interlayer's composition can be readily tuned by changing the evaporator component, enabling authors to regulate the contact resistance and energy-level alignment of the ETL/TCO interface. Consequently, the resultant perovskite/silicon tandem solar cells exhibit an impressive power conversion efficiency (PCE) of 30.8% (certified 30.3%). Moreover, the device retains 98% of its initial PCE after continuous operation under ambient conditions for 1078 h, representing one of the most stable and efficient perovskite/silicon tandem solar cells.

3.
Mycopathologia ; 189(4): 59, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890181

RESUMEN

Dermatophyte biofilms frequently count for inadequate responses and resistance to standard antifungal treatments, resulting in refractory chronic onychomycosis infection. Although antimicrobial photodynamic therapy (aPDT) has clinically proven to exert significant antifungal effects or even capable of eradicating dermatophyte biofilms, considerably less is known about the molecular mechanisms underlying aPDT and the potential dysregulation of signaling networks that could antagonize its action. The aim of this study is to elucidate the molecular mechanisms underlining aPDT combat against dermatophyte biofilm in recalcitrant onychomycosis and to decipher the potential detoxification processes elicited by aPDT, facilitating the development of more effective photodynamic interventions. We applied genome-wide comparative transcriptome analysis to investigate how aPDT disrupting onychomycosis biofilm formed by three distinct dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, the most frequently occurring pathogenic species. In total, 352.13 Gb of clean data were obtained for the transcriptomes of dermatophyte biofilms with or without aPDT treatment, resulting in 2,422.42 million reads with GC content of 51.84%, covering 99.9%, 98.5% and 99.4% of annotated genes of T. rubrum, T. mentagrophytes, and M. gypseum, respectively. The genome-wide orthologous analysis identified 6624 transcribed single-copy orthologous genes in all three species, and 36.5%, 6.8% and 17.9% of which were differentially expressed following aPDT treatment. Integrative orthology analysis demonstrated the upregulation of oxidoreductase activities is a highly conserved detoxification signaling alteration in response to aPDT across all investigated dermatophyte biofilms. This study provided new insights into the molecular mechanisms underneath anti-dermatophyte biofilm effects of aPDT and successfully identified a conserved detoxification regulation upon the aPDT application.


Asunto(s)
Arthrodermataceae , Biopelículas , Perfilación de la Expresión Génica , Fotoquimioterapia , Biopelículas/efectos de los fármacos , Arthrodermataceae/efectos de los fármacos , Arthrodermataceae/genética , Microsporum/efectos de los fármacos , Microsporum/genética , Humanos , Antifúngicos/farmacología , Onicomicosis/microbiología , Onicomicosis/tratamiento farmacológico , Transcriptoma
4.
Small ; : e2401447, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693087

RESUMEN

Topological defects are widely recognized as effective active sites toward a variety of electrochemical reactions. However, the role of defect curvature is still not fully understood. Herein, carbon nanomaterials with rich topological defect sites of tunable curvature is reported. The curved defective surface is realized by controlling the high-temperature pyrolytic shrinkage process of precursors. Theoretical calculations demonstrate bending the defect sites can change the local electronic structure, promote the charge transfer to key intermediates, and lower the energy barrier for oxygen reduction reaction (ORR). Experimental results convince structural superiority of highly-curved defective sites, with a high kinetic current density of 22.5 mA cm-2 at 0.8 V versus RHE for high-curvature defective carbon (HCDC), ≈18 times that of low-curvature defective carbon (LCDC). Further raising the defect densities in HCDC leads to the dual-regulated products (HCHDC), which exhibit exceptionally outstanding ORR activity in both alkaline and acidic media (half-wave potentials: 0.88 and 0.74 V), outperforming most of the reported metal-free carbon catalysts. This work uncovers the curvature-activity relationship in carbon defect for ORR and provides new guidance to design advanced catalysts via curvature-engineering.

5.
Biosens Bioelectron ; 255: 116271, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38583355

RESUMEN

The metal-organic frameworks (MOFs) nanozyme-mediated paper-based analytical devices (PADs) have shown great potential in portable visual determination of phenolic compounds in the environment. However, most MOF nanozymes suffer from poor dispersibility and block-like structure, which often prompts deposition and results in diminished enzymatic activity, severely hindering their environmental applications. Here, we proposed colorimetric PADs for the visual detection of dichlorophen (Dcp) based on its significant inhibitory effect on the two-dimensional (2D) MOF nanozyme activity. Specifically, we synthesized a 2D Cu TCPP (Fe) (defined as 2D-CTF) MOF nanozyme exhibiting excellent dispersibility and remarkable peroxidase-like (POD-like) activity, which could catalyze the oxidation and subsequent color change of 3,3',5,5'-tetramethylbenzidine even under neutral conditions. Notably, the POD-like activity of 2D-CTF demonstrated a unique response to Dcp because of the occupation of Fe-N4 active sites on the 2D-CTF. This property enables the use of 2D-CTF as a highly efficient catalyst to develop colorimetric PADs for naked-eye and portable detection of Dcp. We believe that the proposed colorimetric PADs offer an efficient method for Dcp assay and open fresh avenues for the advancement of colorimetric sensors for analyzing of phenolic toxic substances in real samples.


Asunto(s)
Técnicas Biosensibles , Diclorofeno , Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , Técnicas Biosensibles/métodos , Peroxidasas/química , Peroxidasa , Colorimetría/métodos , Fenoles , Peróxido de Hidrógeno/química
6.
Vaccine ; 42(12): 2951-2954, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38584057

RESUMEN

Heterologous Sinovac-CoronaVac booster(s) in 12-17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination.


Asunto(s)
Vacuna BNT162 , Vacunación , Vacunas de Productos Inactivados , Adolescente , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162/efectos adversos , Vacunación/efectos adversos , Vacunas de Productos Inactivados/efectos adversos , Niño
7.
Biosens Bioelectron ; 257: 116295, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38653013

RESUMEN

Hyperbolic metamaterial (HMM) biosensors based on metals have superior performance in comparison with conventional plasmonic biosensors in the detection of low concentrations of molecules. In this study, a nanorod HMM (NHMM) biosensor based on refractive index changes for carcinoembryonic antigen (CEA) detection is developed using secondary antibody modified gold nanoparticle (AuNP-Ab2) nanocomposites as signal amplification element for the first time. Numerical analysis based on finite element method is conducted to simulate the perturbation of the electric field of bulk plasmon polariton (BPP) supported by a NHMM in the presence of a AuNP. The simulation reveals an enhancement of the localized electric field, which arises from the resonant coupling of BPP to the localized surface plasmon resonance supported by AuNPs and is beneficial for the detection of changes of the refractive index. Furthermore, the AuNP-Ab2 nanocomposites-based NHMM (AuNP/Ab2-NHMM) biosensor enables CEA detection in the visible and near-infrared regions simultaneously. The highly sensitive detection of CEA with a wide linear range of 1-500 ng/mL is achieved in the near-infrared region. The detectable concentration of the AuNP/Ab2-NHMM biosensor has a 50-fold decrease in comparison with a NHMM biosensor. A low detection limit of 0.25 ng/mL (1.25 pM) is estimated when considering a noise level of 0.05 nm as the minimum detectable wavelength shift. The proposed method achieves high sensitivity and good reproducibility for CEA detection, which makes it a novel and viable approach for biomedical research and early clinical diagnostics.


Asunto(s)
Técnicas Biosensibles , Antígeno Carcinoembrionario , Oro , Límite de Detección , Nanopartículas del Metal , Nanotubos , Resonancia por Plasmón de Superficie , Oro/química , Antígeno Carcinoembrionario/sangre , Antígeno Carcinoembrionario/análisis , Nanopartículas del Metal/química , Nanotubos/química , Humanos , Resonancia por Plasmón de Superficie/métodos , Técnicas Biosensibles/métodos , Anticuerpos Inmovilizados/química
8.
Dig Dis Sci ; 69(6): 2184-2192, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38653945

RESUMEN

BACKGROUND: The role of endoscopic resection (ER) in gastric gastrointestinal stromal tumors (GISTs) has not been fully elucidated. AIMS: The purpose of this work was to evaluate the clinical effectiveness and safety of ER in patients with GISTs originating from the muscularis propria (MP). METHODS: A total of 233 consecutive patients with gastric GISTs originating from the MP layer, who underwent ER between February 2012 and May 2023, were included in this study. Clinical characteristics, tumor features, and outcomes were recorded and compared between patients who underwent en bloc resection and piecemeal resection. RESULTS: Among the 233 patients, the median size of GISTs was 12 mm (range 5-60 mm). Risk assessment categorized 190 patients as very low risk, 26 as low risk, 10 as moderate risk, and 7 as high risk. The procedures performed included endoscopic submucosal excavation (127 cases), endoscopic full-thickness resection (103 cases), and submucosal tunneling endoscopic resection (3 cases). The complete and R0 resection rate was 93.1%. Complications occurred in 4.7% of cases (perioperative perforations 1.7%, perioperative bleeding 1.3%, both 0.9%), resulting in conversion to surgery in 1.3% of cases. Risk factors associated with piecemeal resection were tumor size [odds ratio (OR) 0.402, 95% confidence interval (CI) 0.207-0.783; P = 0.007] and shape (OR 0.045, 95% CI 0.009-0.235; P < 0.001). CONCLUSIONS: ER is proven to be an effective and reasonably safe approach for gastric GISTs originating from the MP. Notably, larger tumor size and irregular shape are identified as risk factors for piecemeal resection during ER procedures.


Asunto(s)
Tumores del Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Anciano , Adulto , Anciano de 80 o más Años , Resección Endoscópica de la Mucosa/métodos , Resección Endoscópica de la Mucosa/efectos adversos , Mucosa Gástrica/cirugía , Mucosa Gástrica/patología , Resultado del Tratamiento , Estudios Retrospectivos , Gastroscopía/métodos , Gastroscopía/efectos adversos , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
9.
Acta Biomater ; 180: 407-422, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38614414

RESUMEN

Facile construction of a fully biodegradable spherical nucleic acid (SNA) nanoplatform is highly desirable for clinical translations but remains rarely explored. We developed herein the first polycarbonate-based biodegradable SNA nanoplatform for self-codelivery of a chemotherapeutic drug, doxorubicin (DOX), and a human liver-specific miR122 for synergistic chemo-gene therapy of hepatocellular carcinoma (HCC). Ring-opening polymerization (ROP) of a carbonate monomer leads to a well-defined polycarbonate backbone for subsequent DOX conjugation to the pendant side chains via acidic pH-cleavage Schiff base links and miR122 incorporation to the chain termini via click coupling, affording an amphiphilic polycarbonate-DOX-miR122 conjugate, PBis-Mpa30-DOX-miR122 that can self-assemble into stabilized SNA. Besides the desired biodegradability, another notable merit of this nanoplatform is the use of miR122 not only for gene therapy but also for enhanced innate immune response. Together with the ICD-triggering effect of DOX, PBis-Mpa30-DOX-miR122 SNA-mediated DOX and miR122 codelivery leads to synergistic immunogenicity enhancement, resulting in tumor growth inhibition value (TGI) of 98.1 % significantly higher than those of the groups treated with only drug or gene in a Hepa1-6-tumor-bearing mice model. Overall, this study develops a useful strategy toward biodegradable SNA construction, and presents a drug and gene-based self-codelivery SNA with synergistic immunogenicity enhancement for efficient HCC therapy. STATEMENT OF SIGNIFICANCE: Facile construction of a fully biodegradable SNA nanoplatform is useful for in vivo applications but remains relatively unexplored likely due to the synthetic challenge. We report herein construction of a polycarbonate-based SNA nanoplatform for co-delivering a chemotherapeutic drug, DOX, and a human liver-specific miR-122 for synergistic HCC treatment. In addition to the desired biodegradability properties, this SNA nanoplatform integrates DOX-triggered ICD and miR-122-enhanced innate immunity for simultaneously activating adaptive and innate immunities, which leads to potent antitumor efficiency with a TGI value of 98.1 % in a Hepa1-6-tumor-bearing mice model.


Asunto(s)
Inmunidad Adaptativa , Doxorrubicina , Inmunidad Innata , MicroARNs , Doxorrubicina/farmacología , Doxorrubicina/química , MicroARNs/genética , Animales , Inmunidad Innata/efectos de los fármacos , Humanos , Inmunidad Adaptativa/efectos de los fármacos , Ratones , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Nanopartículas/química , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Ratones Desnudos , Ratones Endogámicos BALB C
10.
Asian Nurs Res (Korean Soc Nurs Sci) ; 18(2): 89-96, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38583799

RESUMEN

PURPOSE: This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China. METHOD: Between February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the general information questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap methods to examine the mediating effects of coping styles between mindfulness and affiliate stigma. RESULTS: (1) The total affiliate stigma score of parents of children with autism was 48.53 (standard deviation:: 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = 0.33, p < .01) and negatively correlated with negative coping style, affiliate stigma (r = -0.38, -0.39, p < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = -0.34, p < .01) and positively correlated with negative coping style (r = 0.41, p < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. CONCLUSIONS: Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.


Asunto(s)
Adaptación Psicológica , Trastorno del Espectro Autista , Atención Plena , Padres , Estigma Social , Humanos , Masculino , Femenino , Trastorno del Espectro Autista/psicología , Trastorno del Espectro Autista/enfermería , China , Padres/psicología , Adulto , Niño , Persona de Mediana Edad , Encuestas y Cuestionarios , Preescolar
11.
Heliyon ; 10(5): e27181, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38449603

RESUMEN

Nowadays, the ongoing electrical vehicles and energy storage devices give a great demand of high-energy-density lithium battery. The commercial graphite anode has been reached the limit of the theoretical capacity. Herein, we introduce lithium metal anode to demonstrate the promising anode which can replace graphite. Lithium metal has a high theoretical capacity and the lowest electrochemical potential. Hence, using lithium metal as the anode material of lithium batteries can reach the limit of energy and power density of lithium batteries. However, lithium metal has huge flaw such as unstable SEI layer, volume change and dendrites formation. Therefore, we give a review of the lithium metal anode on its issues and introduce the existing research to overcome these. Besides, we give the perspective that the engineering problems also restrict the commercial use of lithium metal. This review provides the reasonable method to enhance the lithium metal performance and give the development direction for the subsequent research.

12.
Biomark Med ; 18(2): 69-77, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38440878

RESUMEN

Background: This study aimed to investigate the clinical value of the red blood cell distribution width (RDW) in severe Mycoplasma pneumoniae pneumonia (MPP). Methods: A total of 185 children with diagnosed severe MPP were included. The patients' case records and laboratory examination data were analyzed retrospectively. The children were grouped into quartiles based on RDW. Results: Univariate analysis revealed that RDW was significantly correlated with the Pediatric Risk of Mortality (PRISM) III score, Sepsis-Related Organ Failure Assessment score, incidence of invasive intubation and 30-day in-hospital mortality. After adjustment for the severity of illness, multivariate analysis revealed that the PRISM III score and RDW were factors independently associated with 30-day in-hospital mortality. Conclusion: This study revealed that RDW could be correlated with the long-term prognosis and severity of severe MPP.


Asunto(s)
Mycoplasma pneumoniae , Neumonía , Niño , Humanos , Estudios Retrospectivos , Factores de Riesgo , Índices de Eritrocitos , Pronóstico , Eritrocitos , Neumonía/diagnóstico
13.
Innovation (Camb) ; 5(3): 100599, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38510071

RESUMEN

Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation (LT) is critical for precise clinical management strategies. Here, we performed a single-cell multi-omics analysis of peripheral blood mononuclear cells (PBMCs) collected from LT patients (with and without acute cellular rejection [ACR]) at 13 time points. Validation was performed in two independent cohorts with additional LT patients and healthy controls. Our study revealed a four-phase recovery process after LT and delineated changes in immune cell composition, expression programs, and interactions along this process. The intensity of the immune response differs between the ACR and non-ACR patients. Notably, the newly identified inflamed NK cells, CD14+RNASE2+ monocytes, and FOS-expressing monocytes emerged as predictive indicators of ACR. This study illuminates the longitudinal evolution of the immune cell landscape under tacrolimus-based immunosuppressive treatment during LT recovery, providing a four-phase framework that aids the clinical management of LT patients.

14.
J Adv Nurs ; 80(7): 2813-2821, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38482900

RESUMEN

AIM: To measure the association of leader-member exchange and team-member exchange with nurses' innovative behaviours through social exchange theory. BACKGROUND: The field of nursing is actively advocating innovation. Other fields have proven that leader-member exchange and team-member exchange can promote innovative behaviour, but such an association is not clear in nursing. DESIGN: A cross-sectional study. METHODS: A total of 560 nurses were selected from five tertiary hospitals in Henan Province (China) by multistage sampling. Data were collected from a self-report questionnaire. Thirty nurses in the pre-survey were used to verify the validity of the questionnaire. SPSS PROCESS macro was used to verify the association of leader-member exchange and team-member exchange with nurses' innovative behaviours. RESULTS: Leader-member exchange and team-member exchange were significantly associated with nurses' innovative behaviours, and team-member exchange had a mediating effect on the relationship between leader-member exchange and innovative behaviour. CONCLUSIONS: Leader-member exchange and team-member exchange positively affect nurses' innovative behaviours. Leader-member exchange can promote nurses' innovative behaviours through the mediating role of team-member exchange. IMPACT: This study indicated that leader-member exchange and team-member exchange should be given more attention in promoting nurses' innovative behaviours. This finding has implications for the promotion of innovative behaviours in nurses. Leaders need to focus on the innovative needs of nurses and offer support. Meanwhile, leadership training programs are necessary for managers to create positive team relationships. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.


Asunto(s)
Liderazgo , Personal de Enfermería en Hospital , Humanos , Estudios Transversales , Adulto , Femenino , Masculino , China , Encuestas y Cuestionarios , Personal de Enfermería en Hospital/psicología , Relaciones Interprofesionales , Persona de Mediana Edad , Actitud del Personal de Salud
15.
Adv Sci (Weinh) ; 11(24): e2306388, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38477522

RESUMEN

CD47-SIRPα axis is an immunotherapeutic target in tumor therapy. However, current monoclonal antibody targeting CD47-SIRPα axis is associated with on-target off-tumor and antigen sink effects, which significantly limit its potential clinical application. Herein, a biomimetic nano-degrader is developed to inhibit CD47-SIRPα axis in a site-specific manner through SIRPα degradation, and its efficacy in acute myocardial infarction (AMI) is evaluated. The nano-degrader is constructed by hybridizing liposome with red blood cell (RBC) membrane (RLP), which mimics the CD47 density of senescent RBCs and possesses a natural high-affinity binding capability to SIRPα on macrophages without signaling capacity. RLP would bind with SIRPα and induce its lysosomal degradation through receptor-mediated endocytosis. To enhance its tissue specificity, Ly6G antibody conjugation (aRLP) is applied, enabling its attachment to neutrophils and accumulation within inflammatory sites. In the myocardial infarction model, aRLP accumulated in the infarcted myocardium blocks CD47-SIRPα axis and subsequently promoted the efferocytosis of apoptotic cardiomyocytes by macrophage, improved heart repair. This nano-degrader efficiently degraded SIRPα in lysosomes, providing a new strategy for immunotherapy with great clinical transformation potential.


Asunto(s)
Antígeno CD47 , Macrófagos , Receptores Inmunológicos , Antígeno CD47/inmunología , Antígeno CD47/metabolismo , Animales , Receptores Inmunológicos/metabolismo , Ratones , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Modelos Animales de Enfermedad , Infarto del Miocardio/inmunología , Inhibidores de Puntos de Control Inmunológico/farmacología , Antígenos de Diferenciación/inmunología , Fagocitosis/efectos de los fármacos , Biomimética/métodos , Humanos , Eferocitosis
16.
BMC Plant Biol ; 24(1): 105, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38342903

RESUMEN

BACKGROUND: Nitrogen (N) metabolism-related key genes and conserved amino acid sites in key enzymes play a crucial role in improving N use efficiency (NUE) under N stress. However, it is not clearly known about the molecular mechanism of N deficiency-induced improvement of NUE in the N-sensitive rhizomatous medicinal plant Panax notoginseng (Burk.) F. H. Chen. To explore the potential regulatory mechanism, the transcriptome and proteome were analyzed and the three-dimensional (3D) information and molecular docking models of key genes were compared in the roots of P. notoginseng grown under N regimes. RESULTS: Total N uptake and the proportion of N distribution to roots were significantly reduced, but the NUE, N use efficiency in biomass production (NUEb), the recovery of N fertilizer (RNF) and the proportion of N distribution to shoot were increased in the N0-treated (without N addition) plants. The expression of N uptake- and transport-related genes NPF1.2, NRT2.4, NPF8.1, NPF4.6, AVP, proteins AMT and NRT2 were obviously up-regulated in the N0-grown plants. Meanwhile, the expression of CIPK23, PLC2, NLP6, TCP20, and BT1 related to the nitrate signal-sensing and transduction were up-regulated under the N0 condition. Glutamine synthetase (GS) activity was decreased in the N-deficient plants, while the activity of glutamate dehydrogenase (GDH) increased. The expression of genes GS1-1 and GDH1, and proteins GDH1 and GDH2 were up-regulated in the N0-grown plants, there was a significantly positive correlation between the expression of protein GDH1 and of gene GDH1. Glu192, Glu199 and Glu400 in PnGS1 and PnGDH1were the key amino acid residues that affect the NUE and lead to the differences in GDH enzyme activity. The 3D structure, docking model, and residues of Solanum tuberosum and P. notoginseng was similar. CONCLUSIONS: N deficiency might promote the expression of key genes for N uptake (genes NPF8.1, NPF4.6, AMT, AVP and NRT2), transport (NPF1.2 and NRT2.4), assimilation (proteins GS1 and GDH1), signaling and transduction (genes CIPK23, PLC2, NLP6, TCP20, and BT1) to enhance NUE in the rhizomatous species. N deficiency might induce Glu192, Glu199 and Glu400 to improve the biological activity of GS1 and GDH, this has been hypothesized to be the main reason for the enhanced ability of N assimilation in N-deficient rhizomatous species. The key genes and residues involved in improving NUE provide excellent candidates for the breeding of medicinal plants.


Asunto(s)
Panax notoginseng , Plantas Medicinales , Nitrógeno/metabolismo , Plantas Medicinales/genética , Plantas Medicinales/metabolismo , Panax notoginseng/genética , Panax notoginseng/metabolismo , Simulación del Acoplamiento Molecular , Fitomejoramiento , Aminoácidos/metabolismo , Regulación de la Expresión Génica de las Plantas
17.
Food Chem ; 445: 138668, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38367555

RESUMEN

Zilpaterol hydrochloride (zilpaterol) is used in animal feed as it can increase the lean meat mass. However, consuming zilpaterol-containing animal products may damage human health. Therefore, rapid detection of zilpaterol is attracting increasing research attention. This study aimed to developed a fast, accurate, and ultrasensitive fluorescence immunoassay based on CdTe quantum dots (QDs). A CdTe QD fluorescence sensor was synthesized from thioglycolic acid using a simple hydrothermal method. The morphology and structure of the CdTe QDs were characterized using transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy. The detection limits of our method in swine urine and pork samples were 0.5 µg/L and 1.2 µg/kg, respectively. A wide linear range of 0.1-10000 µg/L (R2 = 0.996) was achieved. Both within-run precision (CVw) and between-run precision (CVb) were ≤ 10 %. The method was then successfully applied for the analysis of zilpaterol contents in swine urine and pork samples.


Asunto(s)
Compuestos de Cadmio , Carne de Cerdo , Puntos Cuánticos , Carne Roja , Compuestos de Trimetilsililo , Animales , Humanos , Porcinos , Colorantes Fluorescentes/química , Puntos Cuánticos/química , Agua , Compuestos de Cadmio/química , Telurio/química , Espectrometría de Fluorescencia/métodos
18.
Food Chem X ; 21: 101140, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38322763

RESUMEN

The effect of adding bamboo shoots to stewing on the quality and flavor of chicken soup has never been reported. Therefore, this study investigated the effects of 4 kinds of bamboo shoots on the edible quality, volatile and water-soluble flavor components of Chahua chicken soup. The results showed that adding bamboo shoots changed the sensory and nutritional quality of chicken soup. A total of 62 volatile flavor components were identified by HS-SPME-GC-MS, of which 12 were identified as characteristic volatile flavor components, and 9 were the main reasons for the flavor differences between bamboo shoot chicken soup with blank chicken soup. LC-MS found that after adding bamboo shoots, the differential water-soluble components in chicken soup significantly increased, and most of the increased components have been proven to have physiological functional activity. In conclusion, adding bamboo shoots improved the nutritional and sensory quality, and changed the flavor components of chicken soup.

19.
Transl Cancer Res ; 13(1): 249-267, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38410237

RESUMEN

Background: The prognosis of patients with kidney renal clear cell carcinoma (KIRC), a life-threatening condition, is poor. Immunogenic cell death (ICD) induces regulated cell death via immunogenic signal secretion and exposure. ICD induces regulated cell death through immunogenic signal secretion and exposure. ICD plays an essential role in tumorigenesis, however, the role of ICD in KIRC remains unclear. Methods: This study examined the expression levels of 34 ICD-related genes in The Cancer Genome Atlas (TCGA) data set. Signature genes linked to KIRC survival were identified using Cox regression. Next, a prognostic risk model (RM) was built. Subsequently, the KIRC patients were divided into low- and high-risk groups. Kaplan-Meier curves and receiver operating characteristic (ROC) curves were plotted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were carried out to investigate the possible role of differential gene expression between the two groups. The immune microenvironment (IME) was assessed using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression, CIBERSORT, and single-sample gene-set enrichment analysis algorithms. An enrichment analysis was used to determine the biological significance of these regulatory networks we conducted. The relationship between immune checkpoint gene expression and risk score, and the relationship between treatment outcome and gene expression were assessed using correlation analyses. Results: We developed a KIRC RM based on five ICD-related genes (i.e., FOXP3, IFNB1, IL6, LY96, and TLR4), which were identified as the prognostic signature genes. Using the TCGA data set, we conducted a survival analysis and found that the 3-year RM had an area under the curve (AUC) of 0.735, which validated the reliability of the signature. Similarly, using the International Cancer Genome Consortium (ICGC) data set, we found that the 3-year RM had an AUC of 0.732. Conclusions: A RM based on five ICD-related genes was built to predict the prognosis of KIRC patients. This RM predicted patient prognosis and reflected the tumor IME of KIRC patients. Thus, this RM could be used to promote individualized treatments and provide potential novel targets for immunotherapy.

20.
J Alzheimers Dis ; 97(3): 1211-1221, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38217603

RESUMEN

BACKGROUND: Accumulating evidence has demonstrated that hyperglycemia is a possible risk factor for mild cognitive impairment or Alzheimer's disease. Diabetic retinopathy (DR) has been identified as a risk factor for dementia in patients with diabetes. OBJECTIVE: This study aimed to investigate the causal relationships between DR and brain structure, cognitive function, and dementia. METHODS: We performed bidirectional two-sample Mendelian randomization for DR, brain structure, cognitive function, and dementia using the inverse-variance weighted method. RESULTS: Inverse-variance weighted analysis showed the association of DR with vascular dementia (OR = 1.68, 95% CI: 1.01-2.82), and dementia was significantly associated with the increased risk of non-proliferative DR (NPDR) (OR = 1.76, 95% CI: 1.04-2.98). Furthermore, better cognitive performance was significantly associated with a reduced risk of NPDR (OR = 0.85, 95% CI: 0.74-0.98). No association was observed between DR and brain structure. CONCLUSIONS: These findings suggest that the association of DR with vascular dementia. The reciprocal effect of cognitive performance and dementia on NPDR risk highlights the potential benefits of dementia prevention for reducing the burden of DR.


Asunto(s)
Demencia Vascular , Diabetes Mellitus , Retinopatía Diabética , Humanos , Retinopatía Diabética/epidemiología , Retinopatía Diabética/genética , Demencia Vascular/genética , Análisis de la Aleatorización Mendeliana , Encéfalo , Cognición , Estudio de Asociación del Genoma Completo
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