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1.
Artículo en Inglés | MEDLINE | ID: mdl-38995708

RESUMEN

Random feature (RF) has been widely used for node consistency in decentralized kernel ridge regression (KRR). Currently, the consistency is guaranteed by imposing constraints on coefficients of features, necessitating that the RFs on different nodes are identical. However, in many applications, data on different nodes vary significantly on the number or distribution, which calls for adaptive and data-dependent methods that generate different RFs. To tackle the essential difficulty, we propose a new decentralized KRR algorithm that pursues consensus on decision functions, which allows great flexibility and well adapts data on nodes. The convergence is rigorously given, and the effectiveness is numerically verified: by capturing the characteristics of the data on each node, while maintaining the same communication costs as other methods, we achieved an average regression accuracy improvement of 25.5% across six real-world datasets.

2.
Biosens Bioelectron ; 261: 116458, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38852321

RESUMEN

Herein, a colorimetric-fluorescent hybrid bifunctional nanobead with Janus structure (J-cf-HBN) was synthesized via one-pot microemulsification. Oleylamine-coated AuNPs and aggregation-induced emission luminogens (AIEgens) were suggested as building blocks to obtain high-performance colorimetric-fluorescent signals. The as-prepared J-cf-HBNs were used as a signal amplification probe to construct an immunochromatographic assay (J-cf-HBNs-ICA) platform for the ultrasensitive detection of staphylococcal enterotoxin B (SEB) in milk samples. Owing to the rational spatial distribution of AuNPs and AIEgens, the J-cf-HBNs present a highly retained photoluminescence and enhanced colorimetric signals. Combined with a pair of highly affinitive anti-SEB antibodies, the J-cf-HBN-ICA platform enabled the fast naked-eye visualization and fluorescent quantitative detection of SEB in various milk matrices. Given the advantages of the dual-mode high-performance J-cf-HBNs, the proposed strip achieved a high sensitivity for SEB qualitative determination with a visual limit of detection (LOD) of 1.56 ng mL-1 and exhibited ultrasensitivity for SEB quantitative detection with a LOD of 0.09 ng mL-1, which is 139-fold lower than that of ELISA using same antibodies. In conclusion, this work provides new insights into the construction of multimode immunochromatographic methods for food safety detection in the field.


Asunto(s)
Técnicas Biosensibles , Colorimetría , Enterotoxinas , Oro , Límite de Detección , Nanopartículas del Metal , Leche , Leche/química , Enterotoxinas/análisis , Enterotoxinas/inmunología , Enterotoxinas/aislamiento & purificación , Animales , Técnicas Biosensibles/métodos , Colorimetría/métodos , Oro/química , Nanopartículas del Metal/química , Colorantes Fluorescentes/química , Contaminación de Alimentos/análisis , Cromatografía de Afinidad/métodos , Inmunoensayo/métodos
3.
Cell ; 187(13): 3233-3235, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38906100

RESUMEN

Somatic and sympathetic tones fluctuate together seamlessly across daily behaviors. In this issue of Cell, Zhang et al. describe populations of spinal projecting neurons in the rostral ventromedial medulla (rVMM) that harmonize somatic motor function and sympathetic activation. The coordinated regulation plays a vital role in supporting behaviors associated with various arousal states.


Asunto(s)
Tronco Encefálico , Bulbo Raquídeo , Publicaciones Periódicas como Asunto , Animales , Nivel de Alerta/fisiología , Sistema Nervioso Autónomo/fisiología , Tronco Encefálico/fisiología , Bulbo Raquídeo/fisiología , Neuronas/fisiología , Sistema Nervioso Simpático/fisiología , Nervios Espinales/fisiología
4.
Mikrochim Acta ; 191(7): 387, 2024 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-38869719

RESUMEN

A novel construction strategy is introduced for an ultrasensitive dynamic light scattering (DLS) immunosensor targeting alpha fetoprotein (AFP). This approach relies on a self-assembled heptamer fusion protein (A1-C4bpα), incorporating the dual functions of multivalent recognition and crosslinking aggregation amplification due to the presence of seven AFP-specific A1 nanobodies on the A1-C4bpα heptamer. Leveraging antibody-functionalized magnetic nanoparticles for target AFP capture and DLS signal output, the proposed heptamer-assisted DLS immunosensor offers high sensitivity, strong specificity, and ease of operation. Under the optimized conditions, the designed DLS immunosensor demonstrates excellent linear detection of AFP in the concentration range 0.06 ng mL-1 to 512 ng mL-1, with a detection limit of 15 pg mL-1. The selectivity, accuracy, precision, practicability, and reliability of this newly developed method were further validated through an assay of AFP levels in spiked and actual human serum samples. This work introduces a novel approach for constructing ultrasensitive DLS immunosensors, easily extendable to the sensitive determination of other targets via simply replacing the nanobody sequence, holding great promise in various applications, particularly in disease diagnosis.


Asunto(s)
Dispersión Dinámica de Luz , Límite de Detección , alfa-Fetoproteínas , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/inmunología , Humanos , Inmunoensayo/métodos , Anticuerpos Inmovilizados/inmunología , Técnicas Biosensibles/métodos , Anticuerpos de Dominio Único/química , Anticuerpos de Dominio Único/inmunología , Nanopartículas de Magnetita/química
5.
Neural Comput ; 36(7): 1380-1409, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38776967

RESUMEN

Sparse canonical correlation analysis (CCA) is a useful statistical tool to detect latent information with sparse structures. However, sparse CCA, where the sparsity could be considered as a Laplace prior on the canonical variates, works only for two data sets, that is, there are only two views or two distinct objects. To overcome this limitation, we propose a sparse generalized canonical correlation analysis (GCCA), which could detect the latent relations of multiview data with sparse structures. Specifically, we convert the GCCA into a linear system of equations and impose ℓ1 minimization penalty to pursue sparsity. This results in a nonconvex problem on the Stiefel manifold. Based on consensus optimization, a distributed alternating iteration approach is developed, and consistency is investigated elaborately under mild conditions. Experiments on several synthetic and real-world data sets demonstrate the effectiveness of the proposed algorithm.

6.
Animals (Basel) ; 14(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38731350

RESUMEN

The rabbitfish, Siganus oramin, is a commercially important table fish in southeastern China. However, there have been few studies on its gonad development and reproduction regulation. Comparative transcriptome analysis was first performed on adult male and female gonads of S. oramin. In total, 47,070 unigenes were successfully assembled and 22,737 unigenes were successfully annotated. Through comparative transcriptome analysis of male and female gonads, a total of 6722 differentially expressed genes were successfully identified, with 3528 upregulated genes and 3154 downregulated genes in the testes. In addition, 39 differentially expressed reproduction-related genes were identified. Finally, quantitative real-time PCR was used to validate the expression levels of several differentially expressed genes. These results provide important data for further studying the function of reproduction-related genes and the molecular mechanism regulating gonad development and reproduction in S. oramin.

7.
Invest Ophthalmol Vis Sci ; 65(5): 7, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38700875

RESUMEN

Purpose: This study aimed to explore the underlying mechanisms of the observed visuomotor deficit in amblyopia. Methods: Twenty-four amblyopic (25.8 ± 3.8 years; 15 males) and 22 normal participants (25.8 ± 2.1 years; 8 males) took part in the study. The participants were instructed to continuously track a randomly moving Gaussian target on a computer screen using a mouse. In experiment 1, the participants performed the tracking task at six different target sizes. In experiments 2 and 3, they were asked to track a target with the contrast adjusted to individual's threshold. The tracking performance was represented by the kernel function calculated as the cross-correlation between the target and mouse displacements. The peak, latency, and width of the kernel were extracted and compared between the two groups. Results: In experiment 1, target size had a significant effect on the kernel peak (F(1.649, 46.170) = 200.958, P = 4.420 × 10-22). At the smallest target size, the peak in the amblyopic group was significantly lower than that in the normal group (0.089 ± 0.023 vs. 0.107 ± 0.020, t(28) = -2.390, P = 0.024) and correlated with the contrast sensitivity function (r = 0.739, P = 0.002) in the amblyopic eyes. In experiments 2 and 3, with equally visible stimuli, there were still differences in the kernel between the two groups (all Ps < 0.05). Conclusions: When stimulus visibility was compensated, amblyopic participants still showed significantly poorer tracking performance.


Asunto(s)
Ambliopía , Agudeza Visual , Humanos , Ambliopía/fisiopatología , Masculino , Femenino , Adulto , Adulto Joven , Agudeza Visual/fisiología , Psicofísica/métodos , Percepción de Movimiento/fisiología , Sensibilidad de Contraste/fisiología , Movimientos Oculares/fisiología
8.
Adv Mater ; 36(27): e2313381, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38647215

RESUMEN

Aggregation-induced emission luminogen (AIEgen)-functionalized organic-inorganic hybrid nanoparticles (OINPs) are an emerging category of multifunctional nanomaterials with vast potential applications. The spatial arrangement and positioning of AIEgens and inorganic compounds in AIEgen-functionalized OINPs determine the structures, properties, and functionalities of the self-assembled nanomaterials. In this work, a facile and general emulsion self-assembly tactic for synthesizing well-defined AIEgen-functionalized OINPs is proposed by coassembling alkane chain-functionalized inorganic nanoparticles with hydrophobic organic AIEgens. As a proof of concept, the self-assembly and structural evolution of plasmonic-fluorescent hybrid nanoparticles (PFNPs) from concentric circle to core shell and then to Janus structures is demonstrated by using alkane chain-modified AuNPs and AIEgens as building blocks. The spatial position of AuNPs in the signal nanocomposite is controlled by varying the alkane ligand length and density on the AuNP surface. The mechanism behind the formation of various PFNP nanostructures is also elucidated through experiments and theoretical simulation. The obtained PFNPs with diverse structures exhibit spatially tunable optical and photothermal properties for advanced applications in multicolor and multimode immunolabeling and photothermal sterilization. This work presents an innovative synthetic approach of constructing AIEgen-functionalized OINPs with diverse structures, compositions, and functionalities, thereby championing the progressive development of these OINPs.

9.
Front Endocrinol (Lausanne) ; 15: 1287795, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38455656

RESUMEN

Background: Inflammation is a predictor of severe complications in patients with COVID-19 infection under a variety of clinical settings. A few studies suggested that COVID-19 infection was a trigger of hyperglycemic crises including diabetic ketoacidosis (DKA) and/or hyperglycemic hyperosmolar state (HHS). However, the association between inflammation and hyperglycemic crises in diabetic patients with COVID-19 infection is unclear. Methods: One hundred and twenty-four patients with type 2 diabetes mellitus (T2DM) and COVID-19 infection from January 2023 to March 2023 were retrospectively analyzed. Demographic, clinical, and laboratory data, especially inflammatory markers including white blood cell (WBC), neutrophils, neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP) and procalcitonin (PCT) were collected and compared between patients with or without DKA and/or HHS. Multivariable logistic regression analysis was conducted to explore the association between inflammatory biomarkers and the prevalence of hyperglycemic crises. Patients were followed up 6 months for outcomes. Results: Among 124 diabetic patients with COVID-19, 9 were diagnosed with DKA or HHS. Comparing COVID-19 without acute diabetic complications (ADC), patients with DKA or HHS showed elevated levels of c-reactive protein (CRP, P=0.0312) and procalcitonin (PCT, P=0.0270). The power of CRP and PCT to discriminate DKA or HHS with the area under the receiver operating characteristics curve (AUROC) were 0.723 and 0.794, respectively. Multivariate logistic regression indicated 1.95-fold and 1.97-fold increased risk of DKA or HHS with 1-unit increment of CRP and PCT, respectively. However, neither CRP nor PCT could predict poor outcomes in diabetic patients with COVID-19. Conclusion: In this small sample size study, we firstly found that elevated serum CRP and PCT levels increased the risk of hyperglycemic crises in T2DM patients with COVID-19 infection. More study is needed to confirm our findings.


Asunto(s)
COVID-19 , Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Coma Hiperglucémico Hiperosmolar no Cetósico , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Coma Hiperglucémico Hiperosmolar no Cetósico/diagnóstico , Coma Hiperglucémico Hiperosmolar no Cetósico/epidemiología , Coma Hiperglucémico Hiperosmolar no Cetósico/etiología , Estudios Retrospectivos , Proteína C-Reactiva , Polipéptido alfa Relacionado con Calcitonina , COVID-19/complicaciones , Cetoacidosis Diabética/complicaciones , Biomarcadores , Inflamación/complicaciones
10.
Int Wound J ; 21(3): e14783, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38472107

RESUMEN

Endoscopic submucosa dissection (ESD) has been applied extensively in the treatment of large intestine tumours due to its high total excision ratio. Nevertheless, there is a high incidence of adverse reactions in colon ESD, and the efficacy of prophylactic ESD following ESD in prevention of postoperative haemorrhage is still disputed. The purpose of this meta-analysis is to evaluate the effectiveness of prophylaxis of wound closure in large intestine ESD after operation. For eligibility, we looked through three databases: PubMed, Embase and Cochrane Library. Heterogenity was measured by means of a chi-square method of Q-statistic and an I2 test. Fixed or random effects models were used for data processing. Based on the retrieval policy, we found a total of 1286 papers, and then we collected nine papers to extract the data. Regarding postoperative haemorrhage, there was a significant reduction in the risk of wound haemorrhage in the wound closure group than in the control group (OR, 0.29; 95% CI, 0.19-0.44 p < 0.0001). No statistical significance was found in the incidence of perforation in the wound closure and the control group (OR, 0.45; 95% CI, 0.19-1.03 p = 0.06). There was a significant reduction in the incidence of postoperation fever among those in the wound closure group than in the control group (OR, 0.37; 95% CI, 0.15-0.93 p = 0.04). Preventive endoscopic closure decreased the rate of ESD in colon disease, but did not significantly decrease the rate of postoperation perforation and postoperative fever. Future research will be required to clarify the risk factors and classify high-risk individuals in order to formulate a cost-effective prevention strategy.


Asunto(s)
Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Complicaciones Posoperatorias , Humanos , Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa/métodos , Endoscopía , Complicaciones Posoperatorias/epidemiología , Hemorragia Posoperatoria , Resultado del Tratamiento
11.
J Agric Food Chem ; 72(11): 5966-5974, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38446589

RESUMEN

Mycotoxin contamination is an important issue for food safety and the environment. Removing mycotoxins from food without losing nutrients and flavor components remains a challenge. In this study, a novel strategy was proposed for the targeted removal of aflatoxin B1 (AFB1) from peanut oil using an amphipathic enzyme-metal hybrid nanoreactor (PL-GOx-Fe3O4@COF) constructed with covalent organic frameworks (COFs) which can selectively adsorb AFB1. Due to the confined space provided by COFs and the proximity effect between GOx and Fe3O4, the detoxification of AFB1 is limited in the nanoreactor without affecting the composition and properties of the oil. The detoxification efficiency of AFB1 in the chemoenzymatic cascade reaction catalyzed by PL-GOx-Fe3O4@COF is six times higher than that of the combination of free GOx and Fe3O4. The AFB1 transformation product has nontoxicity to kidney and liver cells. This study provides a powerful tool for the targeted removal of mycotoxins from edible oils.


Asunto(s)
Aflatoxina B1 , Inocuidad de los Alimentos , Aflatoxina B1/toxicidad , Hepatocitos , Aceite de Cacahuete , Nanotecnología
12.
Food Chem ; 447: 138997, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38513493

RESUMEN

Herein we developed a multicolor lateral flow immunoassay (LFIA) test strip for rapid and simultaneous quantitative detection of aflatoxin B1 (AFB1) and zearalenone (ZEN). Three differently colored aggregation-induced emission nanoparticles (AIENPs) were designed as LFIA signal tags, with red and green AIENPs for targeting AFB1 and ZEN at the test line, and yellow AIENPs for indicating the validity of the test strip at the control (C) line. After surface functionalization with antibodies, the developed AIENP-based multicolor LFIA allows simultaneous and accurate quantification of AFB1 and ZEN using an independent C-line assisted ratiometric signal output strategy. The detection limits of AFB1 and ZEN were 6.12 and 26 pg/mL, respectively. The potential of this method for real-world applications was well demonstrated in corn and wheat. Overall, this multicolor LFIA shows great potential for field screening of multiple mycotoxins and can be extended to rapid and simultaneous monitoring of other small molecule targets.


Asunto(s)
Nanopartículas del Metal , Micotoxinas , Zearalenona , Zearalenona/análisis , Aflatoxina B1/análisis , Anticuerpos Monoclonales , Micotoxinas/análisis , Inmunoensayo/métodos , Límite de Detección , Contaminación de Alimentos/análisis
13.
Risk Manag Healthc Policy ; 17: 573-586, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38501130

RESUMEN

Aim: To investigate the current status of experience and support of nurses as second victims and explore its related factors in nurses. Design: A sequential, explanatory, mixed-method study was applied. Methods: A total of 406 nurses from seven tertiary hospitals in China were chosen as participants between September to October 2023. The Chinese version of the Second Victim Experience and Support Questionnaire (SVEST), Somatic Complaints of Sub-health Status Questionnaire (SCSSQ) and Generalized Anxiety Disorder (GAD-7) were applied to collect quantitative data. Eight nurses were selected for a qualitative study through in-depth interviews. Through interpretive phenomenological analysis, the interview data were analysed to explore the experience and support of nurses as second victims. Results: Practice distress (15.74 ± 4.97) and psychological distress (15.48 ± 3.74) were the highest dimensions, indicating Chinese nurses experienced second victim-related practice and psychological distress. Nurses with different gender, age, education, marital status, income, working hours, professional titles, and unit types have different levels of second victim-related experience and support (p < 0.05). In addition, the score of SVEST was positively associated with SCSSQ (r = 0.444) and GAD-7 (r = 0.490) (p < 0.05). This qualitative study found that the experience and support of nurses as second victims included nurses' perceptions and needs for patient safety events; psychological, physical and practice distress of nurses; and nurses and hospitals coping style after patient safety events. Discussion: Our findings suggest that nurses who are second victims of patient safety events experience severe practice and psychological distress, indicating that nursing managers should pay attention to psychological and practice distress of nurses after patient safety events and provide effective preventive measures.

14.
Nat Commun ; 15(1): 1819, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418467

RESUMEN

Dendritic mechanisms driving input-output transformation in starburst amacrine cells (SACs) are not fully understood. Here, we combine two-photon subcellular voltage and calcium imaging and electrophysiological recording to determine the computational architecture of mouse SAC dendrites. We found that the perisomatic region integrates motion signals over the entire dendritic field, providing a low-pass-filtered global depolarization to dendrites. Dendrites integrate local synaptic inputs with this global signal in a direction-selective manner. Coincidental local synaptic inputs and the global motion signal in the outward motion direction generate local suprathreshold calcium transients. Moreover, metabotropic glutamate receptor 2 (mGluR2) signaling in SACs modulates the initiation of calcium transients in dendrites but not at the soma. In contrast, voltage-gated potassium channel 3 (Kv3) dampens fast voltage transients at the soma. Together, complementary mGluR2 and Kv3 signaling in different subcellular regions leads to dendritic compartmentalization and direction selectivity, highlighting the importance of these mechanisms in dendritic computation.


Asunto(s)
Células Amacrinas , Receptores de Glutamato Metabotrópico , Animales , Ratones , Células Amacrinas/fisiología , Calcio , Transducción de Señal , Dendritas/fisiología
15.
Adv Mater ; 36(21): e2313953, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38400833

RESUMEN

Engineered bacteria are widely used in cancer treatment because live facultative/obligate anaerobes can selectively proliferate at tumor sites and reach hypoxic regions, thereby causing nutritional competition, enhancing immune responses, and producing anticancer microbial agents in situ to suppress tumor growth. Despite the unique advantages of bacteria-based cancer biotherapy, the insufficient treatment efficiency limits its application in the complete ablation of malignant tumors. The combination of nanomedicine and engineered bacteria has attracted increasing attention owing to their striking synergistic effects in cancer treatment. Engineered bacteria that function as natural vehicles can effectively deliver nanomedicines to tumor sites. Moreover, bacteria provide an opportunity to enhance nanomedicines by modulating the TME and producing substrates to support nanomedicine-mediated anticancer reactions. Nanomedicine exhibits excellent optical, magnetic, acoustic, and catalytic properties, and plays an important role in promoting bacteria-mediated biotherapies. The synergistic anticancer effects of engineered bacteria and nanomedicines in cancer therapy are comprehensively summarized in this review. Attention is paid not only to the fabrication of nanobiohybrid composites, but also to the interpromotion mechanism between engineered bacteria and nanomedicine in cancer therapy. Additionally, recent advances in engineered bacteria-synergized multimodal cancer therapies are highlighted.


Asunto(s)
Nanomedicina , Neoplasias , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Humanos , Nanomedicina/métodos , Animales , Bacterias , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico
16.
Immun Inflamm Dis ; 12(1): e1145, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38270300

RESUMEN

BACKGROUND: Inflammatory bone resorption is a prominent risk factor for implantation failure. Simvastatin (SIM) has anti-inflammatory effects independent of cholesterol lowering and reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts. However, the specific mechanism of inflammatory bone loss alleviation by SIM remains to be elucidated. We hypothesized that SIM relieves inflammatory bone loss by modulating autophagy and suppressing the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) signaling pathway. METHODS AND RESULTS: RAW264.7 cells were stimulated by lipopolysaccharide (LPS) after being pretreated with various concentrations of SIM. Osteoclast (OC) differentiation, formation and activity were evaluated by tartrate-resistant acid phosphatase staining, F-actin ring staining and bone resorption pit assays, respectively. We observed autophagosomes by transmission electron microscopy. Then NLRP3 inhibitor MCC950 was used to further explore the corresponding molecular mechanism underlying anti-inflammatory bone resorption, the expression of autophagy-related proteins and NLRP3 signaling pathway factors in pre-OCs were evaluated by western blot analysis, and the expression of OC-specific molecules was analyzed using reverse transcription-quantitative polymerase chain reaction. The results showed that SIM decreased the expression of tumor necrosis factor-α, whereas increased Interleukin-10. In addition, SIM inhibited LPS-induced OC differentiation, formation, bone resorption activity, the level of autophagosomes, and OC-specific markers. Furthermore, SIM significantly suppressed autophagy by downregulating LC3II, Beclin1, ATG7, and NLRP3-related proteins expression while upregulating P62 under inflammatory conditions. CONCLUSIONS: SIM may reduce autophagy secretion to attenuate LPS-induced osteoclastogenesis and the NLRP3 signaling pathway participates in this process, thus providing theoretical basis for the application of this drug in peri-implantitis.


Asunto(s)
Resorción Ósea , Osteogénesis , Humanos , Autofagia , Lipopolisacáridos/toxicidad , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de Señal
18.
Adv Healthc Mater ; 13(11): e2303643, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38115727

RESUMEN

Photodynamic therapy (PDT) with aggregation-induced emission (AIE) photosensitizers (PSs) is a promising therapeutic strategy to achieve better anticancer results. However, eradicating solid tumors completely by PDT alone can be difficult owing to the inherent drawbacks of this treatment, and the combination of PDT with other therapeutic modalities provides opportunities to achieve cooperative enhancement interactions among various treatments. Herein, this work presents the construction of a biocompatible nanocomposite, namely CaO2@DOX@ZIF@ASQ, featuring light-responsive reactive oxygen species (ROS) generation and tumor-targeting oxygen and hydrogen peroxide discharge, as well as controlled doxorubicin (DOX) and copper ion release, thus allowing the combined PDT/CT/CDT effect by AIE PS-enhanced PDT, DOX-based chemotherapy (CT), and copper-involved Fenton-like reaction-driven chemodynamic therapy (CDT). In vitro and in vivo studies verify that the generation of both ROS and O2 by this nanomedicine, stimulated by light, exhibits superior anticancer efficacy, alleviating tumor hypoxia and achieving synergistic PDT/CT/CDT therapeutic effect. This multifunctional nanomedicine remarkably suppresses the tumor growth with minimized systemic toxicity, providing a new strategy for constructing multimodal PDT/CT/CDT therapeutic systems to overcome hypoxia limitations, and potentially increase the antitumor efficacy at lower doses of PSs and chemotherapeutic drugs, thus minimizing potential toxicity to non-malignant tissues.


Asunto(s)
Doxorrubicina , Nanomedicina , Fotoquimioterapia , Fármacos Fotosensibilizantes , Especies Reactivas de Oxígeno , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Animales , Doxorrubicina/farmacología , Doxorrubicina/química , Humanos , Especies Reactivas de Oxígeno/metabolismo , Nanomedicina/métodos , Ratones , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacología , Ratones Endogámicos BALB C , Femenino , Cobre/química , Cobre/farmacología , Ratones Desnudos
19.
J Agric Food Chem ; 72(1): 857-864, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38134022

RESUMEN

Salmonellosis continues to impose a significant economic burden globally. Rapid and sensitive detection of Salmonella is crucial to preventing the outbreaks of foodborne illnesses, yet it remains a formidable challenge. Herein, a dual-functional tetrahedron multivalent aptamer assisted amplification-free CRISPR/Cas12a assay was developed for Salmonella detection. In the system, the aptamer was programmatically assembled on the tetrahedral DNA nanostructure to fabricate a multivalent aptamer (TDN-multiApt), which displayed a 3.5-fold enhanced avidity over the monovalent aptamer and possessed four CRISPR/Cas12a targeting fragments to amplify signal. Therefore, TDN-multiApt could directly activate Cas12a to achieve the second signal amplification without any nucleic acid amplification. By virtue of the synergism of high avidity and cascaded signal amplifications, the proposed method allowed the ultrasensitive detection of Salmonella as low as 7 cfu mL-1. Meanwhile, this novel platform also exhibited excellent specificity against target bacteria and performed well in the detection of various samples, indicating its potential application in real samples.


Asunto(s)
Técnicas Biosensibles , Sistemas CRISPR-Cas , Humanos , Salmonella/genética , Oligonucleótidos , Bioensayo , Brotes de Enfermedades , Técnicas de Amplificación de Ácido Nucleico
20.
Shanghai Kou Qiang Yi Xue ; 32(4): 375-379, 2023 Aug.
Artículo en Chino | MEDLINE | ID: mdl-38044730

RESUMEN

PURPOSE: To explore the effects of allicin on insulin resistance and free fatty acids (FFAs) levels in obese rats with periodontitis. METHODS: Forty rats were randomly divided into healthy group, periodontitis group, and low, medium and high dose groups, with 8 rats in each group. The healthy group was healthy rats, and the other groups were induced by sodium glutamate(MSG). After successfully establishing an obesity model, the maxillary molars were ligated and smeared to establish a periodontitis model. Both the periodontitis group and the healthy group were given normal saline, and the allicin low, medium and high dose groups were given allicin 20,40 and 60 mg·kg-1·d-1, mixed with feed for oral administration. After 21 days of treatment, the fasting blood glucose(FPG), fasting insulin (FINS), insulin resistance index (HOMA-IR) scores and FFAs levels of the homeostatic model in rats were detected. The protein expression of TLR4/MyD88 signaling pathway were compared. Statistical analysis was performed with SPSS 22.0 software package. RESULTS: Compared with the healthy group, FPG, FINS levels, HOMA-IR, IL-6 and TNF-α levels of the periodontitis group were significantly increased, and the expression of TLR4 and MyD88 proteins was significantly increased(P<0.05). Compared with the periodontitis group, FPG, FINS levels, HOMA-IR, IL-6 and TNF-α levels of low, medium and high-doses groups were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (P<0.05). Compared with the low-dose group, the levels of FPG and FINS, HOMA-IR, IL-6 and TNF-α levels of the middle and high-dose groups were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (P<0.05). Compared with the middle-dose group, the levels of FPG and FINS, HOMA-IR, IL-6 and TNF-α levels of the high-dose group were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (P<0.05). After treatment, FFAs of the low, medium and high-dose groups were significantly lower than those before treatment(P<0.05). Compared with the healthy group, FFAs levels of the periodontitis group, low-dose and medium-dose groups were significantly increased. Compared with the periodontitis group, FFAs levels of the low, medium and high-dose groups were significantly increased. Compared with the low-dose group, FFAs levels of the high-dose group were significantly increased. Compared with the middle-dose group, FFAs levels of the high-dose group were significantly increased (P<0.05). CONCLUSIONS: Allicin can improve insulin resistance and obesity in obese rats with periodontitis, and its mechanism of action is related to the TLR4/MyD88 signaling pathway.


Asunto(s)
Resistencia a la Insulina , Periodontitis , Ratas , Animales , Ácidos Grasos no Esterificados , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Receptor Toll-Like 4/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Obesidad/metabolismo , Insulina/metabolismo
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