The development of stimuli‐responsive soft actuators, a task largely undertaken by material scientists, has become a major driving force in pushing the frontiers of microrobotics. Devices made of ...soft active materials are oftentimes small in size, remotely and wirelessly powered/controlled, and capable of adapting themselves to unexpected hurdles. However, nowadays most soft microscale robots are rather simple in terms of design and architecture, and it remains a challenge to create complex 3D soft robots with stimuli‐responsive properties. Here, it is suggested that kirigami‐based techniques can be useful for fabricating complex 3D robotic structures that can be activated with light. External stress fields introduce out‐of‐plane deformation of kirigami film actuators made of liquid crystal networks. Such 2D‐to‐3D structural transformations can give rise to mechanical actuation upon light illumination, thus allowing the realization of kirigami‐based light‐fuelled robotics. A kirigami rolling robot is demonstrated, where a light beam controls the multigait motion and steers the moving direction in 2D. The device is able to navigate along different routes and moves up a ramp with a slope of 6°. The results demonstrate a facile technique to realize complex and flexible 3D structures with light‐activated robotic functions.
Kirigami, an art that transforms 2D sheets into designable 3D sculptures, is applied in a light‐responsive thin film based on liquid crystal network actuators. Versatile 3D shapes are obtained in cut films upon external stress fields, and a multigait rolling robot is demonstrated. The device is capable of light‐induced locomotion steering, climbing up slopes, and human‐friendly interaction, thus offering new alternatives to microrobotics with complex shapes and actuations.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in countless infections and caused millions of deaths since its emergence in 2019. Coronavirus disease 2019 ...(COVID-19)-associated mortality is caused by uncontrolled inflammation, aberrant immune response, cytokine storm, and an imbalanced hyperactive immune system. The cytokine storm further results in multiple organ failure and lung immunopathology. Therefore, any potential treatments should focus on the direct elimination of viral particles, prevention strategies, and mitigation of the imbalanced (hyperactive) immune system. This review focuses on cytokine secretions of innate and adaptive immune responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, and other chemokines. In addition to the review focus, we discuss potential immunotherapeutic approaches based on relevant pathophysiological features, the systemic immune response against SARS-CoV-2, and data from recent clinical trials and experiments on the COVID-19-associated cytokine storm. Prompt use of these cytokines as diagnostic markers and aggressive prevention and management of the cytokine storm can help determine COVID-19-associated morbidity and mortality. The prophylaxis and rapid management of the cytokine storm appear to significantly improve disease outcomes. For these reasons, this study aims to provide advanced information to facilitate innovative strategies to survive in the COVID-19 pandemic.
The bone regeneration efficiency of bone marrow mesenchymal stem cells (BMSCs) and dental pulp mesenchymal stem cells (DPSCs) combined with xenografts in the craniofacial region remains unclear. ...Accordingly, this study commenced by comparing the cell morphology, cell proliferation, trilineage differentiation, mineral synthesis, and osteogenic gene expression of BMSCs and DPSCs in vitro. Four experimental groups (empty control, Bio-Oss only, Bio-Oss+BMSCs, and Bio-Oss+DPSCs) were then designed and implanted in rabbit calvarial defects. The BMSCs and DPSCs showed a similar morphology, proliferative ability, surface marker profile, and trilineage-differentiation potential in vitro. However, the BMSCs exhibited a higher mineral deposition and expression levels of osteogenic marker genes, including alkaline phosphatase (ALP), runt related transcription factor 2 (RUNX2), and osteocalcin (OCN). In the in vivo studies, the bone volume density in both MSC groups was significantly greater than that in the empty control or Bio-Oss only group. Moreover, the new bone formation and Collagen I / osteoprotegerin protein expressions of the scaffold+MSC groups were higher than those of the Bio-Oss only group. Finally, the Bio-Oss+BMSC and Bio-Oss+DPSC groups had a similar bone mineral density, new bone formation, and osteogenesis-related protein expression. Overall, the DPSCs seeded on Bio-Oss matched the bone regeneration efficacy of BMSCs in vivo and hence appear to be a promising strategy for craniofacial defect repair in future clinical applications.
Polarizers play a key role in generating polarized light for display, imaging, and data communication, but adoption often suffers from high optical loss. Recently, due to superior optoelectronic ...properties, halide perovskites have been widely developed for lighting applications; however, highly polarized emission (polarization degree >0.8) has not yet been realized with perovskites. Herein, by incorporating inkjet printing and an anodic aluminum oxide (AAO) confinement strategy, highly ordered perovskite nanowire (NW) arrays are demonstrated for anisotropic optical applications. The optical device based on perovskite NW arrays reveals a high photoluminescence external quantum efficiency of 21.6% and emits highly polarized light with polarization degree up to 0.84. The highly polarized emission from perovskite NW arrays has potential to considerably reduce the optical loss of polarizers, which may attract great interest in developing polarized light sources for next‐generation optoelectronic applications.
By incorporating inkjet printing with anodic aluminum oxide nanoporous confinement, highly ordered perovskite nanowire arrays are fabricated, which can emit extremely polarized light with a polarization degree up to 0.84.
Identification of patients at risk of death from cancer surgery should aid in preoperative preparation. The purpose of this study is to assess and adjust the age-adjusted Charlson comorbidity index ...(ACCI) to identify cancer patients with increased risk of perioperative mortality.
We identified 156,151 patients undergoing surgery for one of the ten common cancers between 2007 and 2011 in the Taiwan National Health Insurance Research Database. Half of the patients were randomly selected, and a multivariate logistic regression analysis was used to develop an adjusted-ACCI score for estimating the risk of 90-day mortality by variables from the original ACCI. The score was validated. The association between the score and perioperative mortality was analyzed.
The adjusted-ACCI score yield a better discrimination on mortality after cancer surgery than the original ACCI score, with c-statics of 0.75 versus 0.71. Over 80 years of age, 70-80 years, and renal disease had the strongest impact on mortality, hazard ratios 8.40, 3.63, and 3.09 (P < 0.001), respectively. The overall 90-day mortality rates in the entire cohort varied from 0.9%, 2.9%, 7.0%, and 13.2% in four risk groups stratifying by the adjusted-ACCI score; the adjusted hazard ratio for score 4-7, 8-11, and ≥ 12 was 2.84, 6.07, and 11.17 (P < 0.001), respectively, in 90-day mortality compared to score 0-3.
The adjusted-ACCI score helps to identify patients with a higher risk of 90-day mortality after cancer surgery. It might be particularly helpful for preoperative evaluation of patients over 80 years of age.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recombinant adeno‐associated virus (rAAV) is among the most commonly used in vivo gene delivery vehicles and has seen a number of successes in clinical application. Current manufacturing processes of ...rAAV employ multiple plasmid transfection or rely on virus infection and face challenges in scale‐up. A synthetic biology approach was taken to generate stable cell lines with integrated genetic modules, which produced rAAV upon induction albeit at a low productivity. To identify potential factors that restrained the productivity, we systematically characterized virus production kinetics through targeted quantitative proteomics and various physical assays of viral components. We demonstrated that reducing the excessive expression of gene of interest by its conditional expression greatly increased the productivity of these synthetic cell lines. Further enhancement was gained by optimizing induction profiles and alleviating proteasomal degradation of viral capsid protein by the addition of proteasome inhibitors. Altogether, these enhancements brought the productivity close to traditional multiple plasmid transfection. The rAAV produced had comparable full particle contents as those produced by conventional transient plasmid transfection. The present work exemplified the versatility of our synthetic biology‐based viral vector production platform and its potential for plasmid‐ and virus‐free rAAV manufacturing.
Recombinant adeno‐associated virus producer cell lines were established by integrating the inducible essential viral genes into the HEK293 cell genome. Reduced gene of interest expression greatly increased productivity. Further enhancements guided by systematic characterization were achieved by optimizing induction profiles and alleviating capsid protein degradation and brought the productivity close to that of triple transfection.
Interleukin‐2 (IL‐2) is one of the first FDA‐approved immunotherapeutics, but its use is limited by toxicity and low efficacy. In addition, all immunotherapies are limited by the immunosuppressive ...and desmoplastic microenvironment of “immunologically cold” tumors, such as pancreatic ductal adenocarcinoma (PDAC) or hepatocellular carcinoma (HCC) with advanced liver fibrosis. Here, a new chemoimmunotherapy nanogel (IL2‐Pt@Nanogel) for dual delivery of IL‐2 and the type II immunogenic cell death inducer Pt‐NHC that reduces the immunosuppressive phenotype of tumor‐associated macrophages and diminishes regulatory T cell infiltration by inducing the production of type I interferon (IFN) by cancer cells is reported. Combining the angiotensin II receptor blocker losartan with IL2‐Pt@Nanogel treatment reduces desmoplasia and reprogrammes the microenvironment of PDAC and HCC toward an immunostimulatory one. These effects result in potent anti‐tumor efficacy in models of primary and metastatic PDAC and HCC with underlying liver fibrosis. This study presents a strategy for IL‐2‐based chemoimmunotherapy with the potential for clinical translation to treat solid tumors.
IL2‐Pt@Nanogel, a chemoimmunotherapy nanogel delivering IL‐2 and Pt‐NHC, diminishes the immunosuppressive phenotype of tumor‐associated macrophages and reduces regulatory T cell infiltration. When combined with the angiotensin II receptor blocker, losartan, this nanogel reduces desmoplasia and shifts the PDAC and HCC microenvironments towards an immunostimulatory state. This approach has shown significant anti‐tumor efficacy in primary and metastatic PDAC and HCC models, indicating a promising IL‐2‐based chemoimmunotherapy strategy for solid tumor treatment.
The neuromorphic and in‐memory computing using memristors are promising for the building of the next generation computing systems. However, the diffusion dynamics of metal ions/atoms inside the ...switching medium impose variability in conducting filament (CF) formation, thus limiting their use in von‐Neumann architecture. The precise modulation on the diffusion of metal ions/atoms and their reduction/oxidation probability holds promise to overcome the speed, size, and energy issues of present‐day computers. Here, this study shows that the diffusion of metal ions can be modulated by defects inside the switching medium and confines metal filaments in a precise 1D channel. This filament confinement by the defect engineering leads to an anomalous switching mechanism with two interchangeable modes: unipolar threshold and bipolar modes. The variation between two modes can be modulated by controlling defects in the structures, leading to a uniform switching with low SET/RESET voltage variations of 17.3% and −17.6%, respectively. Moreover, the convolutional neural network is implemented to emulate synaptic plasticity and image recognition to achieve recognition accuracy of 87% due to a highly linear weight update, demonstrating its potential for in‐memory computing.
Three-dimensional bicontinuous porous materials formed by dealloying contribute significantly to various applications including catalysis, sensor development and energy storage. This work studies a ...method of molten salt dealloying via real-time in situ synchrotron three-dimensional X-ray nano-tomography. Quantification of morphological parameters determined that long-range diffusion is the rate-determining step for the dealloying process. The subsequent coarsening rate was primarily surface diffusion controlled, with Rayleigh instability leading to ligament pinch-off and creating isolated bubbles in ligaments, while bulk diffusion leads to a slight densification. Chemical environments characterized by X-ray absorption near edge structure spectroscopic imaging show that molten salt dealloying prevents surface oxidation of the metal. In this work, gaining a fundamental mechanistic understanding of the molten salt dealloying process in forming porous structures provides a nontoxic, tunable dealloying technique and has important implications for molten salt corrosion processes, which is one of the major challenges in molten salt reactors and concentrated solar power plants.
Lung cancer is a leading cause of cancer-related mortality worldwide, and effective therapies are limited. Lung cancer is a leading cause of cancer-related mortality worldwide with limited effective ...therapy. Sorafenib is a multi-tyrosine kinase inhibitor frequently used to treat numerous types of malignant tumors. However, it has been demonstrated that sorafenib showed moderate antitumor activity and is associated with several side effects in lung cancer, which restricted its clinical application. This study aimed to examine the antitumor effect of the combination treatment of sorafenib and 5-methoxytryptophan (5-MTP) on cell growth and metastasis of Lewis lung carcinoma (LLC) cells.
The anticancer effect of the combination treatment of sorafenib and 5-MTP was determined through cytotoxicity assay and colony forming assays. The mechanism was elucidated using flow cytometry and western blotting. Wound healing and Transwell assays were conducted to evaluate the impact of the combination treatment on migration and invasion abilities. An in vivo model was employed to analyze the effect of the combination treatment on the tumorigenic ability of LLC cells.
Our results demonstrated that the sorafenib and 5-MTP combination synergistically reduced viability and proliferation compared to sorafenib or 5-MTP treatment alone. Reduction of cyclin D1 expression was observed in the sorafenib alone or combination treatments, leading to cell cycle arrest. Furthermore, the sorafenib-5-MTP combination significantly increased the inhibitory effect on migration and invasion of LLC cells compared to the single treatments. The combination also significantly downregulated vimentin and MMP9 levels, contributing to the inhibition of metastasis. The reduction of phosphorylated Akt and STAT3 expression may further contribute to the inhibitory effect on proliferation and metastasis. In vivo, the sorafenib-5-MTP combination further reduced tumor growth and metastasis compared to the treatment of sorafenib alone.
In conclusion, our data indicate that 5-MTP sensitizes the antitumor activity of sorafenib in LLC cells in vitro and in vivo, suggesting that sorafenib-5-MTP has the potential to serve as a therapeutic option for patients with lung cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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