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1.
J Am Chem Soc ; 146(39): 26983-26993, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39294849

RESUMEN

While polyphenolic substances stand as excellent antibacterial agents, their antimicrobial properties rely on the auxiliary support of micro-/nanostructures. Despite offering a novel avenue for enhancing polymer performance, controllable fabrication of mesoporous polymeric nanomaterials encounters significant challenges due to intricate intermolecular forces. In this article, mesoporous catechin nanoparticles have been successfully fabricated using a balanced multivariate interaction approach. The harmonization of the water-ethanol ratio and ionic strength effectively balances the forces of hydrogen bonding and π-π stacking, facilitating the controlled assembly of mesostructures. The mesoporous catechin nanoparticles exhibit a uniform spherical structure (∼100 nm), open mesopores with a diameter of ∼15 nm, and a high surface area of ∼106 m2 g-1. While exhibiting a good biocompatibility and negative surface charge, the mesoporous catechins possess outstanding antibacterial ability and function as an antibiotic mesoformulation without the necessity of loading any drugs. This mesoformulation inhibits 50% in vitro Staphylococcus aureus growth with a low concentration of ∼10 µg mL-1 and achieves complete inhibition at ∼25 µg mL-1. In a mouse wound model, accelerated wound healing and complete closure within 6-8 days are achieved. Proteomics of bacteria reveals that the excellent antibacterial property is attributed to the synergetic effect of mesoformulation's mesostructure and the catechin molecule intervening in bacterial metabolism. Overall, this work may pave a novel way for the future exploration of polymer nanomaterials and antibiotic formulations.


Asunto(s)
Antibacterianos , Catequina , Nanopartículas , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Staphylococcus aureus/efectos de los fármacos , Catequina/química , Catequina/farmacología , Nanopartículas/química , Animales , Ratones , Porosidad , Pruebas de Sensibilidad Microbiana , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Propiedades de Superficie , Tamaño de la Partícula , Cicatrización de Heridas/efectos de los fármacos
2.
Ann Surg Oncol ; 31(3): 1553-1561, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37996639

RESUMEN

BACKGROUND: Choosing the appropriate treatment for elderly patients with esophageal cancer remains a contentious issue. While surgery is still a valid option, we aimed to identify predictors and outcomes in elderly esophagectomy patients with esophageal cancer. PATIENTS AND METHODS: We analyzed characteristics, surgical outcomes, survival rates, cause-specific mortality, and recurrence in 120 patients with stage I-IV esophageal cancer. Univariate and multivariate analyses were used to identify risk factors for event-free survival (EFS) and overall survival (OS). RESULTS: The median follow-up period was 31 months, with 5-year overall survival (OS) and event-free survival (EFS) rates standing at 45.2% and 41.5%, respectively. Notably, lower body mass index (BMI ≤ 22 kg/m2) and reduced preoperative albumin levels (pre-ALB < 40 g/L) led to a significant decrease in OS rates. Postoperative pulmonary complications resulted in higher in-hospital and 90-day mortality rates. After about 31 months post-surgery, the rate of cancer-specific deaths stabilized. The most common sites for distant metastasis were the lungs, supraclavicular lymph nodes, liver, and bone. The study identified lower BMI, lower pre-ALB levels, and postoperative pulmonary complications as independent risk factors for poorer EFS and OS outcomes. CONCLUSIONS: Esophagectomy remains a safe and feasible treatment for elderly patients, though the prevention of postoperative pulmonary infection is crucial. Factors such as lower BMI, lower pre-ALB levels, advanced tumor stage, postoperative pulmonary complications, and certain treatment modalities significantly influence the outcomes in elderly esophagectomy patients. These findings provide critical insights into the characteristics and outcomes of this patient population.


Asunto(s)
Neoplasias Esofágicas , Esofagectomía , Humanos , Anciano , Pronóstico , Esofagectomía/métodos , Estadificación de Neoplasias , Neoplasias Esofágicas/patología , Ganglios Linfáticos/patología , Estudios Retrospectivos , Tasa de Supervivencia , Complicaciones Posoperatorias/patología
3.
Ann Surg Oncol ; 31(7): 4250-4260, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38334847

RESUMEN

BACKGROUND: The prognosis of limited-stage small cell lung cancer (LS-SCLC) after surgery usually is estimated at diagnosis, but how the prognosis actually evolves over time for patients who survived for a predefined time is unknown. METHODS: Data on patients with a diagnosis of LS-SCLC after surgery between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year conditional cancer-specific survival (CCSS) and conditional overall survival (COS) were calculated. RESULTS: This study analyzed 997 patients (555 women, 55.7%) with a median age, of 67 years (interquartile range [IQR], 60-73 years). The 5-year CCSS and COS increased from 44.7% and 38.3%, respectively, at diagnosis to 83.7% and 67.9% at 5 years after diagnosis. Although there were large differences with different stages (stages I, II, and III) at diagnosis (respectively 59.5%, 28.4%; 28.1% for CCSS and 50.6%, 24.8%, and 23.6% for COS), the gap decreased with time, and the rates were similar after 5 years (respectively 85.0%, 80.3%, and 79.4% for CCSS; 65.6%, 56.9%, and 61.3% for COS). The 5-year conditional survival for the patients who received lobectomy was better than for those who received sublobectomy or pneumonectomy. Multivariable analyses showed that only age and resection type were independent predictors for CCSS and COS, respectively, throughout the period. CONCLUSION: Conditional survival estimates for LS-SCLC generally increased over time, with the most significant improvement in patients with advanced stage of disease. Resection type and old age represented extremely important determinants of prognosis after a lengthy event-free follow-up period.


Asunto(s)
Neoplasias Pulmonares , Estadificación de Neoplasias , Programa de VERF , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Femenino , Carcinoma Pulmonar de Células Pequeñas/cirugía , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/patología , Persona de Mediana Edad , Masculino , Tasa de Supervivencia , Anciano , Pronóstico , Estudios de Seguimiento , Neumonectomía/mortalidad , Estudios de Cohortes
4.
Exp Eye Res ; 244: 109928, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38750781

RESUMEN

The corneal epithelium, located as the outermost layer of the cornea, is inherently susceptible to injuries that may lead to corneal opacities and compromise visual acuity. Rapid restoration of corneal epithelial injury is crucial for maintaining the transparency and integrity of the cornea. Cell spray treatment emerges as an innovative and effective approach in the field of regenerative medicine. In our study, a cell spray printing platform was established, and the optimal printing parameters were determined to be a printing air pressure of 5 PSI (34.47 kPa) and a liquid flow rate of 30 ml/h. Under these conditions, the viability and phenotype of spray-printed corneal epithelial cells were preserved. Moreover, Lycium barbarum glycopeptide (LBGP), a glycoprotein purified from wolfberry, enhanced proliferation while simultaneously inhibiting apoptosis of the spray-printed corneal epithelial cells. We found that the combination of cell spray printing and LBGP facilitated the rapid construction of multilayered cell sheets on flat and curved collagen membranes in vitro. Furthermore, the combined cell spray printing and LBGP accelerated the recovery of the rat corneal epithelium in the mechanical injury model. Our findings offer a therapeutic avenue for addressing corneal epithelial injuries and regeneration.


Asunto(s)
Epitelio Corneal , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/lesiones , Animales , Ratas , Lesiones de la Cornea/tratamiento farmacológico , Lesiones de la Cornea/patología , Modelos Animales de Enfermedad , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiología , Apoptosis/efectos de los fármacos , Ratas Sprague-Dawley , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Lycium/química , Bioimpresión/métodos , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Glicoproteínas/farmacología , Masculino , Medicamentos Herbarios Chinos/farmacología
5.
Exp Eye Res ; 246: 110010, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39069000

RESUMEN

This study aimed to develop and evaluate a guinea pig model for glaucoma, comparing resultant eyeball enlargement with an existing myopia model. Thirty guinea pigs underwent intracameral injection of magnetic microspheres to induce chronic ocular hypertension (COH). Intraocular pressure (IOP) was systematically monitored, revealing a successful induction of COH in 73.33% of the guinea pigs. The mean IOP increased from a baseline of 18.04 ± 1.33 mmHg, reaching a peak at week 3 (36.31 ± 6.13 mmHg) and remaining elevated for at least 7 weeks. All data are presented as mean ± standard deviation of the mean. Subsequently, detailed assessments were conducted to validate the established glaucoma model. Immunofluorescent staining demonstrated a significant decrease in the density of retinal ganglion cells (RGC) in the glaucoma group. Optic disc excavation and notable thinning of the lamina cribrosa (LC) were observed. The quantity of optic nerve ax·ons in glaucoma group gradually decreased from baseline (44553 ± 3608/mm2) to week 4 (28687 ± 2071/mm2) and week 8 (17977 ± 3697/mm2). Moreover, regarding the global enlargement of eyeballs, both the transverse and longitudinal axis in glaucomatous eyes were found to be significantly larger than that in myopic eyes, particularly in the anterior chamber depth (1.758 ± 0.113 mm vs. 1.151 ± 0.046 mm). These findings indicate distinct patterns of structural changes associated with glaucoma and myopia in the guinea pig model. This guinea pig model holds promise for future research aimed at exploring biomechanical mechanisms, therapeutic interventions, and advancing our understanding of the relationship between glaucoma and myopia.


Asunto(s)
Modelos Animales de Enfermedad , Glaucoma , Presión Intraocular , Miopía , Células Ganglionares de la Retina , Animales , Cobayas , Miopía/fisiopatología , Miopía/patología , Presión Intraocular/fisiología , Células Ganglionares de la Retina/patología , Glaucoma/fisiopatología , Glaucoma/patología , Disco Óptico/patología , Masculino , Tomografía de Coherencia Óptica , Tonometría Ocular
6.
J Magn Reson Imaging ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39319502

RESUMEN

BACKGROUND: Traditional neuroimaging studies have primarily emphasized analysis at the group level, often neglecting the specificity at the individual level. Recently, there has been a growing interest in individual differences in brain connectivity. Investigating individual-specific connectivity is important for understanding the mechanisms of major depressive disorder (MDD) and the variations among individuals. PURPOSE: To integrate individualized functional connectivity and structural connectivity with machine learning techniques to distinguish people with MDD and healthy controls (HCs). STUDY TYPE: Prospective. SUBJECTS: A total of 182 patients with MDD and 157 HCs and a verification cohort including 54 patients and 46 HCs. FIELD STRENGTH/SEQUENCE: 3.0 T/T1-weighted imaging, resting-state functional MRI with echo-planar sequence, and diffusion tensor imaging with single-shot spin echo. ASSESSMENT: Functional and structural brain networks from rs-fMRI and DTI data were constructed, respectively. Based on these networks, individualized functional connectivity (IFC) and individualized structural connectivity (ISC) were extracted using common orthogonal basis extraction (COBE). Subsequently, multimodal canonical correlation analysis combined with joint independent component analysis (mCCA + jICA) was conducted to fusion analysis to identify the joint and unique independent components (ICs) across multiple modes. These ICs were utilized to generate features, and a support vector machine (SVM) model was implemented for the classification of MDD. STATISTICAL TESTS: The differences in individualized connectivity between patients and controls were compared using two-sample t test, with a significance threshold set at P < 0.05. The established model was tested and evaluated using the receiver operating characteristic (ROC) curve. RESULTS: The classification performance of the constructed individualized connectivity feature model after multisequence fusion increased from 72.2% to 90.3%. Furthermore, the prediction model showed significant predictive power for assessing the severity of depression in patients with MDD (r = 0.544). DATA CONCLUSION: The integration of IFC and ISC through multisequence fusion enhances our capacity to identify MDD, highlighting the advantages of the individualized approach and underscoring its significance in MDD research. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

7.
Surg Endosc ; 38(2): 640-647, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38012439

RESUMEN

BACKGROUND: Lymph node status is an important factor in determining preoperative treatment strategies for stage T1b-T2 esophageal cancer (EC). Thus, the aim of this study was to investigate the risk factors for lymph node metastasis (LNM) in T1b-T2 EC and to establish and validate a risk-scoring model to guide the selection of optimal treatment options. METHODS: Patients who underwent upfront surgery for pT1b-T2 EC between January 2016 and December 2022 were analyzed. On the basis of the independent risk factors determined by multivariate logistic regression analysis, a risk-scoring model for the prediction of LNM was constructed and then validated. The area under the receiver operating characteristic curve (AUC) was used to assess the discriminant ability of the model. RESULTS: The incidence of LNM was 33.5% (214/638) in our cohort, 33.4% (169/506) in the primary cohort and 34.1% (45/132) in the validation cohort. Multivariate analysis confirmed that primary site, tumor grade, tumor size, depth, and lymphovascular invasion were independent risk factors for LNM (all P < 0.05), and patients were grouped based on these factors. A 7-point risk-scoring model based on these variables had good predictive accuracy in both the primary cohort (AUC, 0.749; 95% confidence interval 0.709-0.786) and the validation cohort (AUC, 0.738; 95% confidence interval 0.655-0.811). CONCLUSION: A novel risk-scoring model for lymph node metastasis was established to guide the optimal treatment of patients with T1b-T2 EC.


Asunto(s)
Neoplasias Esofágicas , Humanos , Metástasis Linfática/patología , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología
8.
J Opt Soc Am A Opt Image Sci Vis ; 41(3): 406-413, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38437428

RESUMEN

We present a dish spliced concentrator (DSC) featuring hexagonal spherical sub-mirrors of uniform size. The DSC offers advantages over traditional parabolic dish concentrators, including a compact layout, cost-effectiveness, higher concentration ratio, and improved light uniformity. Its versatility allows for both uniform and focused light concentration by adjusting parameters like the focal length of the DSC, making it suitable for concentrating photovoltaic (CPV) and concentrating solar thermal (CST) applications. We design the DSC using three-dimensional (3D) vector rotation theory, implementing ray tracing and transmission characteristic analysis based on three-dimensional vector reflection theory. We establish a simulation model to evaluate the impact of geometric parameters on the DSC's optical performance.

9.
J Nanobiotechnology ; 22(1): 496, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164723

RESUMEN

Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell-cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H2O2) catalyzed by intracellular GOx into oxygen (O2), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery.


Asunto(s)
Glucosa Oxidasa , Hidrogeles , Hidrogeles/química , Hidrogeles/farmacología , Animales , Humanos , Línea Celular Tumoral , Ratones , Glucosa Oxidasa/farmacología , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/química , Recurrencia Local de Neoplasia , Ratones Desnudos , Ratones Endogámicos BALB C , Nanocompuestos/química , Nanocompuestos/uso terapéutico , Polietilenglicoles/química , Polietilenglicoles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Cobre/química , Cobre/farmacología , Hemostasis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Peróxido de Hidrógeno/farmacología
10.
J Nanobiotechnology ; 22(1): 151, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575943

RESUMEN

BACKGROUND: As the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects. METHODS AND RESULTS: In this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination. CONCLUSION: Tumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma.


Asunto(s)
Neoplasias Óseas , Nanopartículas , Neoplasias , Osteosarcoma , Niño , Humanos , Adolescente , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/terapia , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/tratamiento farmacológico , Inmunoterapia , Línea Celular Tumoral , Fototerapia
11.
Molecules ; 29(13)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38998912

RESUMEN

Managing chronic non-healing wounds presents a significant clinical challenge due to their frequent bacterial infections. Mesoporous silica-based materials possess robust wound-healing capabilities attributed to their renowned antimicrobial properties. The current study details the advancement of mesoporous silicon-loaded MnO and CaO molecules (HMn-Ca) against bacterial infections and chronic non-healing wounds. HMn-Ca was synthesized by reducing manganese chloride and calcium chloride by urotropine solution with mesoporous silicon as the template, thereby transforming the manganese and calcium ions on the framework of mesoporous silicon. The developed HMn-Ca was investigated using scanning electron microscopy (SEM), transmission electron microscope (TEM), ultraviolet-visible (UV-visible), and visible spectrophotometry, followed by the determination of Zeta potential. The production of reactive oxygen species (ROS) was determined by using the 3,3,5,5-tetramethylbenzidine (TMB) oxidation reaction. The wound healing effectiveness of the synthesized HMn-Ca is evaluated in a bacterial-infected mouse model. The loading of MnO and CaO inside mesoporous silicon enhanced the generation of ROS and the capacity of bacterial capture, subsequently decomposing the bacterial membrane, leading to the puncturing of the bacterial membrane, followed by cellular demise. As a result, treatment with HMn-Ca could improve the healing of the bacterial-infected wound, illustrating a straightforward yet potent method for engineering nanozymes tailored for antibacterial therapy.


Asunto(s)
Compuestos de Manganeso , Nanopartículas , Óxidos , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Ratones , Nanopartículas/química , Óxidos/química , Óxidos/farmacología , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Porosidad , Especies Reactivas de Oxígeno/metabolismo , Antiinfecciosos/farmacología , Antiinfecciosos/química , Compuestos de Calcio/química , Compuestos de Calcio/farmacología , Oxidación-Reducción , Antibacterianos/farmacología , Antibacterianos/química , Manganeso/química , Manganeso/farmacología , Pruebas de Sensibilidad Microbiana
12.
J Am Chem Soc ; 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36952390

RESUMEN

Mechanistic understanding of asymmetric induction plays a crucial role in designing new catalytic asymmetric reactions. Reported herein is atroposelective access to C-N axially chiral isoquinolones via rhodium-catalyzed C-H activation of N-alkoxy benzamides and annulation with imidoyl sulfoxonium ylides. The coupling system proceeded with excellent functional group tolerance, and different conditions were identified to afford one or the other enantiomeric product each in excellent enantioselectivity for a representative class of the sulfoxonium ylide reagent, thus making both enantiomers readily available using the same catalyst. Experimental and computational studies revealed a pathway of C-H alkylation and enantio-determining formal nucleophilic substitution-C-N cyclization that is mediated by the rhodium catalyst via σ-bond metathesis as the asymmetric induction mechanism. Computational studies indicated that the solvent-dependent enatiodivergence originated from different levels of σ-bond metathesis mediated by neutral versus cationic rhodium species.

13.
J Am Chem Soc ; 145(27): 14963-14980, 2023 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-37379365

RESUMEN

To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Ph2phen)2(OH2)2]2+, was conjugated to the RGD-containing Ac-MRGDH-NH2 peptide by direct coordination of the M and H residues to the metal. This design afforded two diastereoisomers of a cyclic metallopeptide, Λ-[1]Cl2 and Δ-[1]Cl2. In the dark, the ruthenium-chelating peptide had a triple action. First, it prevented other biomolecules from coordinating with the metal center. Second, its hydrophilicity made [1]Cl2 amphiphilic so that it self-assembled in culture medium into nanoparticles. Third, it acted as a tumor-targeting motif by strongly binding to the integrin (Kd = 0.061 µM for the binding of Λ-[1]Cl2 to αIIbß3), which resulted in the receptor-mediated uptake of the conjugate in vitro. Phototoxicity studies in two-dimensional (2D) monolayers of A549, U87MG, and PC-3 human cancer cell lines and U87MG three-dimensional (3D) tumor spheroids showed that the two isomers of [1]Cl2 were strongly phototoxic, with photoindexes up to 17. Mechanistic studies indicated that such phototoxicity was due to a combination of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) effects, resulting from both reactive oxygen species generation and peptide photosubstitution. Finally, in vivo studies in a subcutaneous U87MG glioblastoma mice model showed that [1]Cl2 efficiently accumulated in the tumor 12 h after injection, where green light irradiation generated a stronger tumoricidal effect than a nontargeted analogue ruthenium complex [2]Cl2. Considering the absence of systemic toxicity for the treated mice, these results demonstrate the high potential of light-sensitive integrin-targeted ruthenium-based anticancer compounds for the treatment of brain cancer in vivo.


Asunto(s)
Antineoplásicos , Neoplasias Encefálicas , Complejos de Coordinación , Profármacos , Rutenio , Animales , Humanos , Ratones , Rutenio/farmacología , Rutenio/química , Profármacos/farmacología , Profármacos/uso terapéutico , Profármacos/química , Integrinas , Péptidos Cíclicos , Péptidos , Neoplasias Encefálicas/tratamiento farmacológico , Línea Celular Tumoral , Complejos de Coordinación/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química
14.
Small ; 19(35): e2300392, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37127883

RESUMEN

Second near infrared (NIR-II, 1000-1700 nm) fluorescence lifetime imaging is a powerful tool for biosensing, anti-counterfeiting, and multiplex imaging. However, the low photoluminescence quantum yield (PLQY) of fluorescence probes in NIR-II region limits its data collecting efficiency and accuracy, especially in multiplex molecular imaging in vivo. To solve this problem, lanthanide-doped nanoparticles (NPs) ß-NaErF4 : 2%Ce@NaYbF4 @NaYF4 with high PLQY and tunable PL lifetime through multi-ion doping and core-shell structural design, are presented. The obtained internal PLQY can reach up to 50.1% in cyclohexane and 9.2% in water under excitation at 980 nm. Inspired by the above results, a fast NIR-II fluorescence lifetime imaging of whole-body vascular in mice is successfully performed by using the homebuilt fluorescence lifetime imaging system, which reveals a murine abdominal capillary network with low background. A further demonstration of fluorescence lifetime multiplex imaging is carried out in molecular imaging of atherosclerosis cells and different organs in vivo through NPs conjugating with specific peptides and different injection modalities, respectively. These results demonstrate that the high PLQY NPs combined with the homebuilt fluorescence lifetime imaging system can realize a fast and high signal-to-noise fluorescence lifetime imaging; thus, opening a road for multiplex molecular imaging of atherosclerosis.


Asunto(s)
Aterosclerosis , Elementos de la Serie de los Lantanoides , Nanopartículas , Animales , Ratones , Elementos de la Serie de los Lantanoides/química , Espectroscopía Infrarroja Corta/métodos , Imagen Óptica , Nanopartículas/química
15.
Ophthalmology ; 130(12): 1279-1289, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37499953

RESUMEN

PURPOSE: To develop and validate the performance of a high myopia (HM)-specific normative database of peripapillary retinal nerve fiber layer (pRNFL) thickness in differentiating HM from highly myopic glaucoma (HMG). DESIGN: Cross-sectional multicenter study. PARTICIPANTS: A total of 1367 Chinese participants (2325 eyes) with nonpathologic HM or HMG were included from 4 centers. After quality control, 1108 eyes from 694 participants with HM were included in the normative database; 459 eyes from 408 participants (323 eyes with HM and 136 eyes with HMG) and 322 eyes from 197 participants (131 eyes with HM and 191 eyes with HMG) were included in the internal and external validation sets, respectively. Only HMG eyes with an intraocular pressure > 21 mmHg were included. METHODS: The pRNFL thickness was measured with swept-source (SS) OCT. Four strategies of pRNFL-specified values were examined, including global and quadrantic pRNFL thickness below the lowest fifth or the lowest first percentile of the normative database. MAIN OUTCOMES MEASURES: The accuracy, sensitivity, and specificity of the HM-specific normative database for detecting HMG. RESULTS: Setting the fifth percentile of the global pRNFL thickness as the threshold, using the HM-specific normative database, we achieved an accuracy of 0.93 (95% confidence interval [CI], 0.90-0.95) and 0.85 (95% CI, 0.81-0.89), and, using the first percentile as the threshold, we acheived an accuracy of 0.85 (95% CI, 0.81-0.88) and 0.70 (95% CI, 0.65-0.75) in detecting HMG in the internal and external validation sets, respectively. The fifth percentile of the global pRNFL thickness achieved high sensitivities of 0.75 (95% CI, 0.67-0.82) and 0.75 (95% CI, 0.68-0.81) and specificities of 1.00 (95% CI, 0.99-1.00) and 1.00 (95% CI, 0.97-1.00) in the internal and external validation datasets, respectively. Compared with the built-in database of the OCT device, the HM-specific normative database showed a higher sensitivity and specificity than the corresponding pRNFL thickness below the fifth or first percentile (P < 0.001 for all). CONCLUSIONS: The HM-specific normative database is more capable of detecting HMG eyes than the SS OCT built-in database, which may be an effective tool for differential diagnosis between HMG and HM. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Asunto(s)
Glaucoma , Miopía , Humanos , Estudios Transversales , Pueblos del Este de Asia , Miopía/diagnóstico , Retina , Glaucoma/diagnóstico , Fibras Nerviosas
16.
J Magn Reson Imaging ; 58(5): 1420-1430, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-36797655

RESUMEN

BACKGROUND: Previous studies have found qualitative structural and functional brain changes in major depressive disorder (MDD) patients. However, most studies ignored the complementarity of multisequence MRI neuroimaging features and cannot determine accurate biomarkers. PURPOSE: To evaluate machine-learning models combined with multisequence MRI neuroimaging features to diagnose patients with MDD. STUDY TYPE: Prospective. SUBJECTS: A training cohort including 111 patients and 90 healthy controls (HCs) and a test cohort including 28 patients and 22 HCs. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted imaging, resting-state functional MRI with echo-planar sequence, and single-shot echo-planar diffusion tensor imaging. ASSESSMENT: Recruitment and integration were used to reflect the dynamic changes of functional networks, while gray matter volume and fractional anisotropy were used to reflect the changes in the morphological and anatomical network. We then fused features with significant differences in functional, morphological, and anatomical networks to evaluate a random forest (RF) classifier to diagnose patients with MDD. Furthermore, a support vector machine (SVM) classifier was used to verify the stability of neuroimaging features. Linear regression analyses were conducted to investigate the relationships among multisequence neuroimaging features and the suicide risk of patients. STATISTICAL TESTS: The comparison of functional network attributes between patients and controls by two-sample t-test. Network-based statistical analysis was used to identify structural and anatomical connectivity changes between MDD and HCs. The performance of the model was evaluated by receiver operating characteristic (ROC) curves. RESULTS: The performance of the RF model integrating multisequence neuroimaging features in the diagnosis of depression was significantly improved, with an AUC of 93.6%. In addition, we found that multisequence neuroimaging features could accurately predict suicide risk in patients with MDD (r = 0.691). DATA CONCLUSION: The RF model fusing functional, morphological, and anatomical network features performed well in diagnosing patients with MDD and provided important insights into the pathological mechanisms of MDD. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.


Asunto(s)
Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Neuroimagen , Encéfalo/patología , Aprendizaje Automático
17.
Angew Chem Int Ed Engl ; 62(20): e202219172, 2023 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-36799272

RESUMEN

Redox logic materials offer new avenues to modulate intracellular pathologic redox environment area-specifically, but the unambiguity of redox logic states and their unidirectional and repetitive switchability are challenging to realize. By merging a bistable diisophthalic phenazine dye ligand with CuII salt, a multistable coordination polymer (CP) was constructed, of which the dye-Cu anisotropic junction achieved the diode-like unidirectional electron transfer and logic state ratchet for the first time. Radical cationic CP maintained OFF status with low toxicity in healthy tissues, but was reduced to the neutral SERVO state by the overexpressed glutathione (GSH) in hypoxic tumors. After photoirradiation, the stabilized charge-separated ON status promoted photo-Fenton reaction for reactive oxygen species (ROS) signal transduction, and simultaneously recovered the initial state for catalytic signal amplification of ROS, furnishing intratumor redox photomodulation for therapy.


Asunto(s)
Glutatión , Polímeros , Glutatión/metabolismo , Lógica , Oxidación-Reducción , Especies Reactivas de Oxígeno , Cobre/química
18.
Ophthalmology ; 129(2): 171-180, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34339778

RESUMEN

PURPOSE: To develop and validate a multimodal artificial intelligence algorithm, FusionNet, using the pattern deviation probability plots from visual field (VF) reports and circular peripapillary OCT scans to detect glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional study. SUBJECTS: Two thousand four hundred sixty-three pairs of VF and OCT images from 1083 patients. METHODS: FusionNet based on bimodal input of VF and OCT paired data was developed to detect GON. Visual field data were collected using the Humphrey Field Analyzer (HFA). OCT images were collected from 3 types of devices (DRI-OCT, Cirrus OCT, and Spectralis). Two thousand four hundred sixty-three pairs of VF and OCT images were divided into 4 datasets: 1567 for training (HFA and DRI-OCT), 441 for primary validation (HFA and DRI-OCT), 255 for the internal test (HFA and Cirrus OCT), and 200 for the external test set (HFA and Spectralis). GON was defined as retinal nerve fiber layer thinning with corresponding VF defects. MAIN OUTCOME MEASURES: Diagnostic performance of FusionNet compared with that of VFNet (with VF data as input) and OCTNet (with OCT data as input). RESULTS: FusionNet achieved an area under the receiver operating characteristic curve (AUC) of 0.950 (0.931-0.968) and outperformed VFNet (AUC, 0.868 [95% confidence interval (CI), 0.834-0.902]), OCTNet (AUC, 0.809 [95% CI, 0.768-0.850]), and 2 glaucoma specialists (glaucoma specialist 1: AUC, 0.882 [95% CI, 0.847-0.917]; glaucoma specialist 2: AUC, 0.883 [95% CI, 0.849-0.918]) in the primary validation set. In the internal and external test sets, the performances of FusionNet were also superior to VFNet and OCTNet (FusionNet vs VFNet vs OCTNet: internal test set 0.917 vs 0.854 vs 0.811; external test set 0.873 vs 0.772 vs 0.785). No significant difference was found between the 2 glaucoma specialists and FusionNet in the internal and external test sets, except for glaucoma specialist 2 (AUC, 0.858 [95% CI, 0.805-0.912]) in the internal test set. CONCLUSIONS: FusionNet, developed using paired VF and OCT data, demonstrated superior performance to both VFNet and OCTNet in detecting GON, suggesting that multimodal machine learning models are valuable in detecting GON.


Asunto(s)
Glaucoma de Ángulo Abierto/diagnóstico por imagen , Aprendizaje Automático , Enfermedades del Nervio Óptico/diagnóstico por imagen , Tomografía de Coherencia Óptica , Trastornos de la Visión/fisiopatología , Campos Visuales/fisiología , Adulto , Anciano , Algoritmos , Área Bajo la Curva , Estudios Transversales , Femenino , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Imagen Multimodal , Fibras Nerviosas/patología , Enfermedades del Nervio Óptico/fisiopatología , Curva ROC , Células Ganglionares de la Retina/patología , Pruebas del Campo Visual
19.
Ophthalmology ; 129(7): 803-812, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35288144

RESUMEN

PURPOSE: To develop a classification system of visual field (VF) abnormalities in highly myopic eyes with and without glaucoma. DESIGN: Secondary analysis of VF data from a longitudinal cohort study. PARTICIPANTS: One thousand eight hundred ninety-three VF tests from 1302 eyes (825 individuals). METHODS: All participants underwent VF testing (Humphrey 24-2 Swedish interactive threshold algorithm standard program; Carl Zeiss Meditec) and detailed ophthalmic examination. A comprehensive set of VF defect patterns was defined via observation of the 1893 VF reports, literature review, and consensus meetings. The classification system comprised 4 major types of VF patterns, including normal type, glaucoma-like defects (paracentral defect, nasal step, partial arcuate defect, arcuate defect), high myopia-related defects (enlarged blind spot, vertical step, partial peripheral rim, nonspecific defect), and combined defects (nasal step with enlarged blind spot). A subset (n = 1000) of the VFs was used to evaluate the interobserver and intraobserver agreement and weighted κ values of the classification system by 2 trained readers. The prevalence of various VF patterns and their associated factors were determined. MAIN OUTCOME MEASURES: The classification of VF in highly myopic eyes and its associated risk factors. RESULTS: We found that normal type, glaucoma-like defects, high myopia-related defects, and combined defects accounted for 74.1%, 10.8%, 15.0%, and 0.1% of all unique VF tests, respectively. The interobserver and intraobserver agreements were > 89%, and the corresponding κ values were 0.86 or more between readers. Both glaucoma-like and high myopia-related VF defects were associated with older age (odds ratios [ORs], 1.07 [95% confidence interval (CI), 1.04-1.10; P < 0.001] and 1.06 [95% CI, 1.04-1.10; P < 0.001]) and longer axial length (ORs, 1.65 [95% CI, 1.32-2.07; P < 0.001] and 1.37 [95% CI, 1.11-1.68; P = 0.003]). Longer axial length showed a stronger effect on the prevalence of glaucoma-like VF defects than on the prevalence of high myopia-related VF defects (P = 0.036). CONCLUSIONS: We propose a new and reproducible classification system of VF abnormalities for nonpathologic high myopia. Applying a comprehensive classification system will facilitate communication and comparison of findings among studies.


Asunto(s)
Glaucoma , Miopía , Disco Óptico , Glaucoma/complicaciones , Humanos , Presión Intraocular , Estudios Longitudinales , Miopía/complicaciones , Miopía/diagnóstico , Miopía/epidemiología , Disco Óptico/patología , Estudios Retrospectivos , Escotoma/diagnóstico , Trastornos de la Visión/patología , Pruebas del Campo Visual , Campos Visuales
20.
Exp Brain Res ; 240(11): 3023-3032, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36227343

RESUMEN

Even though impaired visuospatial abilities can negatively affect daily functioning, there are very few training programs that attempt to improve visuospatial abilities. The purpose of this study was to examine if a single training session with a computerized version of the Corsi Block Tapping Task could improve mental rotation skills. Fifty-three young adults were assigned to one of two groups: (1) control group (mean age = 21.4; 10 females), who had 20 min of rest after their baseline assessment, or (2) training group (mean age = 21.5; 17 females), who had 20 min of training on the Corsi Block Tapping Task after their baseline assessment. The primary outcome was reaction time on a computer-based mental rotation task, and it was assessed both before and after the rest or training. There was a significant interaction between time (pre vs. post) and group (control vs. training) on mental rotation performance (p = 0.04), with the training group performing on average 124 ms faster on accurate trials than the control group at post-test. This preliminary study suggested that improving mental rotation may be feasible through targeted cognitive training. Future studies will consider multiple sessions of Corsi Block Tapping Task training to maximize training benefits (i.e., dose-response), as well as longer term retention in cognitively intact and impaired individuals.


Asunto(s)
Trastornos del Conocimiento , Navegación Espacial , Adulto Joven , Femenino , Humanos , Adulto , Memoria a Corto Plazo/fisiología
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