Transition metal oxides for high-temperature lithium-ion batteries have captivated orchestrated efforts for next-generation high-energy-density anodes. However, due to inherent low tap density, poor conductivity, and structural instability, their poor cyclability capacity and rate performance at elevated temperatures hinder further implementation. Oxygen vacancies (Ov) engineered by manipulating the active sites and electrical conductivity is a promising method for superior lithium storage. Herein, hierarchical MnO/Co nanoparticle-embedded N-doped carbon nanotube (CNT)-assembled carbonaceous micropolyhedrons (Ov-MnO/Co NCPs) are constructed by a “4S” self-assembly, self-template, self-adaptive, and self-catalytic metal–organic framework template method with in situ oxygen vacancies introduced. Impressively, the internal nanoparticles with metallic Co and the external N-doped carbonaceous matrix entangled by fluffy self-generated CNTs synchronously constructed hierarchical micro/nano-secondary hybrids, facilitating highly compacted density, staggered conductive network, multidirectional diffusion pathways, and accelerated electrochemical kinetics. Experimental and density functional theory investigations systematically manifested that the Ov alongside the local built-in electric field within the crystal lattice induced the boosted electrical conductivity, additional active sites, and alleviated structural expansion, further achieving the exceptional diffusivity coefficient and pseudocapacitive capacity. Benefiting from the integrated structural and compositional optimization, the Ov-MnO/Co NCPs achieved distinguished “3C” performance with superior ultralong cyclability (a volumetric capacity of 1713.5 mAh cm–3 at 1 A g–1 up to 1000 cycles), good rate capacity (a well-maintained capacity of 670.2 mAh g–1 even at 10 A g–1), and considerable high-temperature capability at 60 °C.
Photodynamic therapy (PDT) is an established therapeutic method, first approved by the FDA for certain kinds of cancer in 1998. There are also increasing data to show that a related procedure, sonodynamic therapy (SDT), is a promising new modality for cancer treatment. Here, the authors report clinical results in 3 advanced refractory breast cancer patients who were treated using a combination of sonodynamic and photodynamic therapy (SPDT), along with conventional therapies. All 3 patients had pathologically proven metastatic breast carcinoma. These widely disseminated carcinomas had ultimately failed to respond to conventional therapy. A new sensitizing agent, Sonoflora 1™ (SF1) was administered sublingually; then, after a 24-hour delay, patients were treated with a combination of light and ultrasound. All patients had significant partial or complete responses. SPDT is a promising new therapeutic combination for the treatment of breast cancer.
Metal–organic frameworks (MOFs) have potential application prospects in electrochemical energy storage and conversion area on account of their high specific surface area, high porosity, tunable pore size, and structural diversity...
Bamboo particles (BP) were treated with 0.3N (1.20 wt %) low‐concentration alkali solution for different times (0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 24 h) as reinforcements in poly(lactic acid) (PLA) biodegradable composites. Characteristics of BP by composition analysis, scanning electron microscopy, Brunauer‐Emmett Teller test, and Fourier transform infrared spectroscopy, showed that low‐concentration alkali treatment had a significant influence on the microstructure, specific surface area, and chemical groups of BP. PLA/treated‐BP and PLA/untreated‐BP composites were both produced with 30 wt % BP contents. Mechanical measurements showed that tensile strength, tensile modulus, and elongation at break of PLA/BP composites increased when the alkali treatment time reached 3.0 h with maximal values of 44.21, 406.41 MPa, and 6.22%, respectively. Maximal flexural strength and flexural modulus of 83.85 MPa and 4.50 GPa were also found after 3.0‐h alkali treatment. Differential scanning calorimetric analysis illustrated that PLA/BP composites had a better compatibility and larger PLA crystallinity after 3.0‐h treatment. Overall, low concentration alkali treatment was a feasible technology in creating BP reinforced PLA composites. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1667–1674, 2013
COP1 and COP9 signalosome (CSN) are the substrate receptor and deneddylase of CRL4 E3 ligase, respectively. How they functionally interact remains unclear. Here, we uncover COP1–CSN antagonism during glucose-induced insulin secretion. Heterozygous Csn2WT/K70E mice with partially disrupted binding of IP6, a CSN cofactor, display congenital hyperinsulinism and insulin resistance. This is due to increased Cul4 neddylation, CRL4COP1 E3 assembly, and ubiquitylation of ETV5, an obesity-associated transcriptional suppressor of insulin secretion. Hyperglycemia reciprocally regulates CRL4-CSN versus CRL4COP1 assembly to promote ETV5 degradation. Excessive ETV5 degradation is a hallmark of Csn2WT/K70E, high-fat diet-treated, and ob/ob mice. The CRL neddylation inhibitor Pevonedistat/MLN4924 stabilizes ETV5 and remediates the hyperinsulinemia and obesity/diabetes phenotypes of these mice. These observations were extended to human islets and EndoC-βH1 cells. Thus, a CRL4COP1-ETV5 proteolytic checkpoint licensing GSIS is safeguarded by IP6-assisted CSN-COP1 competition. Deregulation of the IP6-CSN-CRL4COP1-ETV5 axis underlies hyperinsulinemia and can be intervened to reduce obesity and diabetic risk.
Background With the development of tissue engineering, enhanced tendon regeneration could be achieved by exploiting suitable cell types and biomaterials. The accessibility, robust cell amplification ability, superior tendon differentiation potential, and immunomodulatory effects of human periodontal ligament stem cells (hPDLSCs) indicate their potential as ideal seed cells for tendon tissue engineering. Nevertheless, there are currently no reports of using PDLSCs as seed cells. Previous studies have confirmed the potential of silk scaffold for tendon tissue engineering. However, the biomimetic silk scaffold with tendon extracellular matrix (ECM)-like structure has not been systematically studied for in situ tendon regeneration. Therefore, this study aims to evaluate the effects of hPDLSCs and biomimetic silk scaffold on in situ tendon regeneration. Methods Human PDLSCs were isolated from extracted wisdom teeth. The differentiation potential of hPDLSCs towards osteo-, chondro-, and adipo-lineage was examined by cultured in different inducing media. Aligned and random silk scaffolds were fabricated by the controlled directional freezing technique. Scaffolds were characterized including surface structure, water contact angle, swelling ratio, degradation speed and mechanical properties. The biocompatibility of silk scaffolds was evaluated by live/dead staining, SEM observation, cell proliferation determination and immunofluorescent staining of deposited collagen type I. Subsequently, hPDLSCs were seeded on the aligned silk scaffold and transplanted into the ruptured rat Achilles tendon. Scaffolds without cells served as control groups. After 4 weeks, histology evaluation was carried out and macrophage polarization was examined to check the repair effects and immunomodulatory effects. Results Human PDLSCs were successfully isolated, and their multi-differentiation potential was confirmed. Compared with random scaffold, aligned silk scaffold had more elongated and aligned pores and promoted the proliferation and ordered arrangement of hPDLSCs. After implantation into rat Achilles tendon defect, hPDLSCs seeded aligned silk scaffold enhanced tendon repair with more tendon-like tissue formation after 4 weeks, as compared to the scaffold-only groups. Higher expression of CD206 and lower expression of iNOS, IL-1β and TNF-α were found in the hPDLSCs seeded aligned silk scaffold group, which revealed its modulation effect of macrophage polarization from M1 to M2 phenotype. Conclusions In summary, this study demonstrates the efficacy of hPDLSCs as seed cells and aligned silk scaffold as a tendon-mimetic scaffold for enhanced tendon tissue engineering, which may have broad implications for future tendon tissue engineering and regenerative medicine researches.
Osteochondral defects are characterized by injuries to both cartilage and subchondral bone, which is a result of trauma, inflammation, or inappropriate loading. Due to the unique biological properties of subchondral bone and cartilage, developing a tissue engineering scaffold that can promote dual-lineage regeneration of cartilage and bone simultaneously remains a great challenge. In this study, a microporous nanosilicate-reinforced enzymatically crosslinked silk fibroin (SF) hydrogel is fabricated by introducing montmorillonite (MMT) nanoparticles via intercalation chemistry. In vitro studies show that SF-MMT nanocomposite hydrogel has improved mechanical properties and hydrophilicity, as well as the bioactivities to promote the osteogenic differentiation of bone marrow mesenchymal stem cells and maintain chondrocyte phenotype compared with SF hydrogel. Global proteomic analysis verifies the dual-lineage bioactivities of SF-MMT nanocomposite hydrogel, which are probably regulated by multiple signaling pathways. Furthermore, it is observed that the biophysical interaction of cells and SF-MMT nanocomposite hydrogel is partially mediated by clathrin-mediated endocytosis and its downstream processes. In vivo, the SF-MMT nanocomposite hydrogel effectively promotes osteochondral regeneration as evidenced by macroscopic, micro-CT, and histological evaluation. In conclusion, a functionalized SF-MMT nanocomposite hydrogel is developed with dual-lineage bioactivity for osteochondral regeneration, indicating its potential in osteochondral tissue engineering.
Background: The management of ground glass nodules (GGNs) remains a distinctive challenge. This study is aimed at comparing the predictive growth trends of radiomic features against current clinical features for the evaluation of GGNs.Methods: A total of 110 GGNs in 85 patients were included in this retrospective study, in which follow up occurred over a span ≥2 years. A total of 396 radiomic features were manually segmented by radiologists and quantitatively analyzed using an Analysis Kit software. After feature selection, three models were developed to predict the growth of GGNs. The performance of all three models was evaluated by a receiver operating characteristic (ROC) curve. The best performing model was also assessed by calibration and clinical utility. Results:After using a stepwise multivariate logistic regression analysis and dimensionality reduction, the diameter and five specific radiomic features were included in the clinical model and the radiomic model. The rad-score [odds ratio (OR) = 5.130; P < 0.01] and diameter (OR = 1.087; P < 0.05) were both considered as predictive indicators for the growth of GGNs. Meanwhile, the area under the ROC curve of the combined model reached 0.801. The high degree of fitting and favorable clinical utility was detected using the calibration curve with the Hosmer-Lemeshow test and the decision curve analysis was utilized for the nomogram.Conclusions: A combined model using the current clinical features alongside the radiomic features can serve as a powerful tool to assist clinicians in guiding the management of GGNs.
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