PurposeBerberine (BBR), an alkaloid produced by a traditional Chinese plant, was recently attributed multiple effects on lipometabolism, inflammation, and fibrosis. Thyroid-associated ophthalmopathy ...(TAO) is highly associated with these pathologic changes. Thus, we aimed to examine the potential therapeutic effect of BBR in an in vitro model of TAO. MethodsOrbital fibroblasts (OFs) obtained from control donors (n = 6) or patients with TAO (n = 6) were cultured. The CCK-8 assay was conducted for assessing the optimal concentration range. Oil Red O staining, Western blotting, and quantitative RT-PCR (qRT-PCR) were conducted to assess adipogenesis in OFs. RNA sequencing (RNA-seq) was used to screen the key pathways of the antiadipogenic effect mediated by BBR. Along with incremental concentrations of BBR, IL-1β-induced expression of proinflammatory molecules was determined by ELISA and qRT-PCR. In addition, TGF-β-induced hyaluronan (HA) production and fibrosis were evaluated by ELISA, qRT-PCR, and Western blotting. ResultsTAO-OFs, but not control fibroblasts (CON-OFs), were readily differentiated into adipocytes with the commercial medium. Intracellular lipid accumulation was dose-dependently decreased by BBR, and adipogenic markers were also downregulated. Moreover, the PPARγ and AMPK pathways were screened out by RNA-seq and their downstream effectors were suppressed by BBR. Besides, BBR attenuated IL-1β-induced expression of proinflammatory molecules in both TAO-OFs and CON-OFs by blocking nuclear factor-κB signaling. BBR's inhibitory effect on TGF-β-mediated tissue remodeling was also confirmed in OFs. ConclusionsThese findings demonstrate BBR has outstanding capabilities of controlling adipogenesis, inflammation, HA production, and fibrosis in OFs, highlighting its potential therapeutic role in TAO management.
Compared with the intrinsic ZnO-NWs, the ZnO-ZnS nano-heterostructure material formed by modifying ZnS on ZnO surface shows significant improvement in sensing performance to 5 ppm H2S gas at the ...working temperatures of 100-400 °C, especially in the low temperature range.
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This paper reports a high-performance H2S gas sensing material that is made of ZnO nanowires (NWs) modified by an optimal amount of ZnS to form nano-heterojunctions. Compared with the intrinsic ZnO-NWs, the three differently modified nano-heterostructure material ZnO-ZnS-x (x = 5, 10, 15) shows significant improvement in sensing performance to H2S at the working temperatures of 100−400 °C, especially in the low temperature range (<300 °C). The chemiresistive sensor with ZnO-ZnS-10 sensing-material exhibits the largest response signal to H2S among all the other ZnO-ZnS-x (x = 5, 10, 15, 20) sensors. Its response signal to 5 ppm H2S at 150 °C is about 2.7 times to that of the ZnO-NWs sensor. Besides, the ZnO-ZnS-10 sensor also features satisfactory selectivity and repeatability at 150 °C. With the technical advantage attributed to the reduction of the redesigned band gap at the interface between ZnO and ZnS, the ZnO-ZnS heterostructure sensor rather than the traditional ZnO-NWs sensor can be used for high-sensitivity application at low working temperature.
The mechanism of host--guest interaction driven phase change behavior is still unclear, although many pore-based composite phase change materials (PCMs) have been synthesized and tested. Here, we ...prepared stearic acid (SA)-metal organic framework MIL-101(Cr) composite PCMs. FTIR, PXRD, DSC, and 3ω measurements were used to evaluate the constructional and phase change thermal properties of the obtained composites. With a pseudo-supercritical path (PSCP)-based molecular dynamics method, the melting temperature and enthalpy in a complex restricted space were well predicted, and the radius of gyration, interaction energy, atom-atom radial distribution functions were further analyzed. The results showed that the surface modification highly improved the loading capacity for SA, from 30 wt% to 70 wt%, with a fusion enthalpy increasing from 46.3 J/g to 110.01 J/g, owing to the new formation of hydrogen bonding between modified surface and PCM. Thermal conductivity of the host--guest PCM was increased by 68.2%, which was higher than that of either the MIL-101(Cr)NH2 or the SA alone. It was important to study the underlying mechanism of modified surface on energy storage in confined nanopores. The discussion suggested a controllable design and preparation for high performance PCM composite.
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•Amino groups were successfully grated onto MILs by surface modification.•The PSCP method was first applied for well-prediction of complex composites melting point.•There was a great improvement on loading capacity, due to the newly formed hydrogen bonding.
Abstract
The development of the resistive switching cross-point array as the next-generation platform for high-density storage, in-memory computing and neuromorphic computing heavily relies on the ...improvement of the two component devices, volatile selector and nonvolatile memory, which have distinct operating current requirements. The perennial current-volatility dilemma that has been widely faced in various device implementations remains a major bottleneck. Here, we show that the device based on electrochemically active, low-thermal conductivity and low-melting temperature semiconducting tellurium filament can solve this dilemma, being able to function as either selector or memory in respective desired current ranges. Furthermore, we demonstrate one-selector-one-resistor behavior in a tandem of two identical Te-based devices, indicating the potential of Te-based device as a universal array building block. These nonconventional phenomena can be understood from a combination of unique electrical-thermal properties in Te. Preliminary device optimization efforts also indicate large and unique design space for Te-based resistive switching devices.
The clinical application of breast ultrasound for the assessment of cancer risk and of deep learning for the classification of breast-ultrasound images has been hindered by inter-grader variability ...and high false positive rates and by deep-learning models that do not follow Breast Imaging Reporting and Data System (BI-RADS) standards, lack explainability features and have not been tested prospectively. Here, we show that an explainable deep-learning system trained on 10,815 multimodal breast-ultrasound images of 721 biopsy-confirmed lesions from 634 patients across two hospitals and prospectively tested on 912 additional images of 152 lesions from 141 patients predicts BI-RADS scores for breast cancer as accurately as experienced radiologists, with areas under the receiver operating curve of 0.922 (95% confidence interval (CI) = 0.868-0.959) for bimodal images and 0.955 (95% CI = 0.909-0.982) for multimodal images. Multimodal multiview breast-ultrasound images augmented with heatmaps for malignancy risk predicted via deep learning may facilitate the adoption of ultrasound imaging in screening mammography workflows.
Cancer therapeutic strategies based on angiogenesis attract great attention from fundamental and clinical research. Blocking oxygen and nutrition supply to tumor cells could inhibit the growth of ...tumors based on occlusion of blood vessels in the tumor. Herein, we report a dual-responsive peptide-based nanoparticle, mimicking the laminin fibrillogenesis specifically and highly efficiently in tumor vessels, resulting in the blockage of tumor vessels and the growth inhibition of tumors. The laminin mimic peptide (LMMP) is designed with a fibrillation sequence, a pH-responsive sequence, and a targeting sequence. The LMMP in nanoformulations is delivered to blood vessels in the tumors, where the microenvironment (pH and microthrombus) enable LMMP to process laminin fibrillogenesis, constructing fibrous networks. The laminin-like fibrous networks capture red blood cells
, forming occlusion specifically in the tumor blood vessels to inhibit the growth of the tumor.
MG53 is a muscle-specific TRIM-family protein that presides over the cell membrane repair response. Here, we show that MG53 present in blood circulation acts as a myokine to facilitate tissue ...injury-repair and regeneration. Transgenic mice with sustained elevation of MG53 in the bloodstream (tPA-MG53) have a healthier and longer life-span when compared with littermate wild type mice. The tPA-MG53 mice show normal glucose handling and insulin signaling in skeletal muscle, and sustained elevation of MG53 in the bloodstream does not have a deleterious impact on db/db mice. More importantly, the tPA-MG53 mice display remarkable dermal wound healing capacity, enhanced muscle performance, and improved injury-repair and regeneration. Recombinant human MG53 protein protects against eccentric contraction-induced acute and chronic muscle injury in mice. Our findings highlight the myokine function of MG53 in tissue protection and present MG53 as an attractive biological reagent for regenerative medicine without interference with glucose handling in the body.
Hepatitis B virus (HBV) infection is a prevalent infectious disease with serious outcomes like chronic and acute hepatitis, cirrhosis, and hepatocellular carcinoma. However, the metabolic alteration ...by HBV is rarely taken into consideration. With the high prevalence of alcohol consumption and chronic HBV infection, their overlap is assumed to be an increasing latent hazard; although the extent has not been calculated. Moreover, the impact of chronic alcohol consumption combined with HBV on cholesterol metabolism is unknown. Six-week-old male FVB/Ncrl mice were hydrodynamically injected with a pGEM-4Z-1.3HBV vector and then fed an ethanol diet for 6 weeks. Serum biomarkers and liver histology, liver cholesterol levels, and cholesterol metabolism-related molecules were measured. In vitro assays with HBx, hepatitis B surface (HBs), or hepatitis B core (HBc) protein expression in HepG2 cells costimulated with ethanol were conducted to assess the cholesterol metabolism. HBV expression synergistically increased cholesterol deposition in the setting of alcoholic fatty liver. The increase of intrahepatic cholesterol was due to metabolic alteration in cholesterol metabolism, including increased cholesterol synthesis, decreased cholesterol degradation, and impaired cholesterol uptake. Overexpression of HBV component HBc, but not HBs or HBx, selectively promoted the hepatocellular cholesterol level.
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