Kushen （Radix Sophorae Flavescentis） has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection （CKI） is a ...mixture of natural compounds extracted from Kushen and Baituling （Rhizoma Smilacis Glabrae）. The main principles of CKI are matrine （MT） and oxymatrine （OMT） that exhibit a variety of pharmacological activities, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrotic and cardiovascular protective effects. Recent evidence shows that these compounds also produce anti-cancer actions, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- and/or radiotherapy-induced toxicity when combined with chemotherapeutic drugs. In this review, we summarize recent progress in studying the anti-cancer activities of MT, OMT and CKI and their potential molecular targets, which provide clues and references for further study.
Background ands Aims
NAFLD is associated with elevation of many cytokines, particularly IL‐6; however, the role of IL‐6 in NAFLD remains obscure. The aim of this study was to examine how ...myeloid‐specific IL‐6 signaling affects NAFLD by the regulation of antifibrotic microRNA‐223 (miR‐223) in myeloid cells.
Approach and Results
Patients with NAFLD or NASH and healthy controls were recruited, and serum IL‐6 and soluble IL‐6 receptor α (sIL‐6Rα) were measured. Compared to controls, serum IL‐6 and sIL‐6Rα levels were elevated in NAFLD/NASH patients. IL‐6 levels correlated positively with the number of circulating leukocytes and monocytes. The role of IL‐6 in NAFLD was investigated in Il6 knockout (KO) and Il6 receptor A (Il6ra) conditional KO mice after high‐fat diet (HFD) feeding. HFD‐fed Il6 KO mice had worse liver injury and fibrosis, but less inflammation, compared to wild‐type mice. Hepatocyte‐specific Il6ra KO mice had more steatosis and liver injury, whereas myeloid‐specific Il6ra KO mice had a lower number of hepatic infiltrating macrophages (IMs) and neutrophils with increased cell death of these cells, but greater liver fibrosis (LF), than WT mice. Mechanistically, the increased LF in HFD‐fed, myeloid‐specific Il6ra KO mice was attributable to the reduction of antifibrotic miR‐223 and subsequent up‐regulation of the miR‐223 target gene, transcriptional activator with PDZ‐binding motif (TAZ), a well‐known factor to promote NASH fibrosis. In vitro, IL‐6 treatment up‐regulated exosome biogenesis‐related genes and subsequently promoted macrophages to release miR‐223‐enriched exosomes that were able to reduce profibrotic TAZ expression in hepatocytes by exosomal transfer. Finally, serum IL‐6 and miR‐223 levels were elevated and correlated with each other in NAFLD patients.
Conclusions
Myeloid‐specific IL‐6 signaling inhibits LF through exosomal transfer of antifibrotic miR‐223 into hepatocytes, providing therapeutic targets for NAFLD therapy.
Institutional diversity characterizing state-owned enterprises (SOEs) from emerging economies holds critical but under-examined implications for their internationalization activities. Different types ...of SOEs can exhibit distinct motivations, strategic resources, and adaptive capabilities for penetrating foreign markets. To understand how such idiosyncratic differences emerge, we conceptualize the heterogeneity of SOEs as an outcome of multiple institutional reform processes – administrative and fiscal decentralization, industrial restructuring, and market liberalization – which create diversity between SOEs affiliated with central and local levels of government. Building on the idea of "institutions-asconfigurations", we elucidate how such reforms reconfigure SOEs' constellation of resources, capabilities, and priorities which shape the parameters of their ability to negotiate for home and host country institutional legitimacy. Specifically, we propose that the restructuring of central SOEs into "national champions" exposes them to stronger institutional pressures from home and host country governments while local SOEs which have fewer obligations to serve national strategic prerogatives display greater managerial autonomy and market orientation, but lower levels of monopolistic behavior. We discuss how such contrasting attributes contribute to variations in SOEs' international business diversification patterns, foreign subsidiary establishment and ownership modes, and overseas location preferences. Recognition of SOEs' organizational diversity holds important implications for theories on state-owned multinationals.
•This paper entitled “Time-variant reliability analysis for industrial robot RV reducer under multiple failure modes using Kriging model” has three highlights:•A time-variant reliability analysis ...with multiple failure modes is performed for industrial robot RV reducer using Kriging model.•The multiple response Gaussian process is adopted to depict the correlation of multiple time-variant limit state functions.•Three learning functions are used to choose the new point and the effectiveness is also testified.
This paper proposes a time-variant reliability method for an industrial robot rotate vector (RV) reducer with multiple failure modes using a Kriging model. Firstly, the limit state functions of the industrial robot RV reducer are built by considering time-variant load and material degradation based on the failure physic method. Secondly, a time-variant reliability analysis method for multiple failure modes is proposed based on a double-loop Kriging model. The inner loop is the extremal optimization for each limit state function based on the efficient global optimization (EGO). The outer loop is the active learning reliability analysis by combining multiple response Gaussian process model (MRGP) and the Monte Carlo simulation (MCS). Furthermore, three learning functions (U-function, EFF-function and H-function) are individually adopted to choose a new sample point until the convergence is satisfied. Case studies are finally provided to illustrate the effectiveness of the proposed method.
Background and Aims
Fibroblast growth factor (FGF) 1 demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. This study ...investigated the therapeutic activity and mechanism of a nonmitogenic FGF1 variant carrying 3 substitutions of heparin‐binding sites (FGF1△HBS) against NAFLD.
Approach and Results
FGF1△HBS administration was effective in 9‐month‐old diabetic mice carrying a homozygous mutation in the leptin receptor gene (db/db) with NAFLD; liver weight, lipid deposition, and inflammation declined and liver injury decreased. FGF1△HBS reduced oxidative stress by stimulating nuclear translocation of nuclear erythroid 2 p45‐related factor 2 (Nrf2) and elevation of antioxidant protein expression. FGF1△HBS also inhibited activity and/or expression of lipogenic genes, coincident with phosphorylation of adenosine monophosphate–activated protein kinase (AMPK) and its substrates. Mechanistic studies on palmitate exposed hepatic cells demonstrated that NAFLD‐like oxidative damage and lipid accumulation could be reversed by FGF1△HBS. In palmitate‐treated hepatic cells, small interfering RNA (siRNA) knockdown of Nrf2 abolished only FGF1△HBS antioxidative actions but not improvement of lipid metabolism. In contrast, AMPK inhibition by pharmacological agent or siRNA abolished FGF1△HBS benefits on both oxidative stress and lipid metabolism that were FGF receptor (FGFR) 4 dependent. Further support of these in vitro findings is that liver‐specific AMPK knockout abolished therapeutic effects of FGF1△HBS against high‐fat/high‐sucrose diet–induced hepatic steatosis. Moreover, FGF1△HBS improved high‐fat/high‐cholesterol diet–induced steatohepatitis and fibrosis in apolipoprotein E knockout mice.
Conclusions
These findings indicate that FGF1△HBS is effective for preventing and reversing liver steatosis and steatohepatitis and acts by activation of AMPK through hepatocyte FGFR4.
Supramolecular rather than covalent molecular engineering on Feringa motors can provide an alternative toolkit for tuning the properties of motorized materials through appropriate supramolecular ...structural perturbations, which are underexplored. Herein, a multicomponent supramolecular gel system is successfully prepared by employing an ultra‐low molecular weight gelator and a modulator‐Feringa motor. The electron microscopic, spectroscopic, and rheological data revealed that the morphology and mechanical properties of the gel can be tuned via a crystallographic mismatch branching (CMB) mechanism simply by adding varied amounts of motor modulators. Notably, the rotary motion of the motor is preserved in such a multicomponent gel system, and the morphology and rheology of the gel can be further altered by the motor's rotary motion that promotes the structural perturbation, resulting in seldomly seen gel‐to‐gel transition events. The work shown here offers prospects to utilize a supramolecular perturbation strategy to deliver responsiveness from molecular motors to the corresponding bulk materials.
A multicomponent supramolecular gel containing a Feringa motor as the modulator is successfully prepared. The rotary motion of the motor is preserved in such a multicomponent gel system, and the morphology and rheology of the gel can be altered by the light‐activated motor's rotary motion that leads to the supramolecular structural perturbation, resulting in seldomly seen gel‐to‐gel transition event.
Since 2003, the discovery of chiral dienes as steering ligands in asymmetric processes has opened the field of chiral chelating olefin catalysis. However, despite the impressive advances, the ...development of readily accessible and catalytically promising chiral olefins has been much less successful. In very recent years, chiral sulfur-containing olefins have emerged as a new exciting class of hybrid ligands for asymmetric catalysis. This article summarizes our efforts in developing extremely simple chiral sulfur-olefins as ligands for a variety of transition-metal-catalyzed asymmetric transformations, and the recent progress by other groups in the design and use of sulfinamide- or sulfoxide-based olefins in asymmetric catalysis.
Chiral sensors have attracted growing interest due to their application in health monitoring. However, rational design of wearable logic chiral sensors remains a great challenge. In this work, a dual ...responsive chiral sensor RT@CDMOF is prepared through in situ self-assembly of chiral γ-cyclodextrin metal-organic framework (CDMOF), rhodamine 6G hydrazide (RGH), and tetracyanovinylindane (TCN). The embedded RGH and TCN inherit the chirality of host CDMOF, producing dual changes both in fluorescence and reflectance. RT@CDMOF is explored as a dual channel sensor for chiral discrimination of lactate enantiomers. Comprehensive mechanistic studies reveal the chiral binding process, and carboxylate dissociation is confirmed by impedance and solid-state
H nuclear magnetic resonance (NMR). A flexible membrane sensor is successfully fabricated based on RT@CDMOF for wearable health monitoring. Practical evaluation confirms the potential of fabricated membrane sensor in point-of-care health monitoring by indexing the exercise intensity. Based on above, a chiral IMPLICATION logic unit can be successfully achieved, demonstrating the promising potential of RT@CDMOF in design and assembly of novel smart devices. This work may open a new avenue to the rational design of logic chiral sensors for wearable health monitoring applications.
CsPbI2Br is emerging as a promising all‐inorganic material for perovskite solar cells (PSCs) due to its more stable lattice structure and moisture resistance compared to CsPbI3, although its device ...performance is still much behind this counterpart. Herein, a preannealing process is developed and systematically investigated to achieve high‐quality CsPbI2Br films by regulating the nucleation and crystallization of perovskite. The preannealing temperature and time are specifically optimized for a dopant‐free poly(3‐hexylthiophene) (P3HT)‐based device to target dopant‐induced drastic performance degradation for spiro‐OMeTAD‐based devices. The resulting P3HT‐based device exhibits comparable power conversion efficiency (PCE) to spiro‐OMeTAD‐based devices but much enhanced ambient stability with over 95% PCE after 1300 h. A diphenylamine derivative is introduced as a buffer layer to improve the energy‐level mismatch between CsPbI2Br and P3HT. A record‐high PCE of 15.50% for dopant‐free P3HT‐based CsPbI2Br PSCs is achieved by alleviating the open‐circuit voltage loss with the buffer layer. These results demonstrate that the preannealing processing together with a suitable buffer layer are applicable strategies for developing dopant‐free P3HT PSCs with high efficiency and stability.
High‐efficiency and stable dopant‐free poly(3‐hexylthiophene) (P3HT)‐based CsPbI2Br solar cells are achieved by introducing an optimized preannealing process to engineer the nucleation and crystallization of CsPbI2Br films. Further incorporation of an ultrathin wide‐bandgap diphenylamine derivative layer (poly(9,9‐dioctylfluorenyl‐2,7‐diyl)‐co‐(4,4′‐(N‐(4‐sec‐butylphenyl)diphenylamine)) to regulate the band alignment of CsPbI2Br and P3HT delivers a record‐high efficiency of 15.50% for dopant‐free P3HT‐based CsPbI2Br solar cells.
Inorganic cesium lead halide perovskites offer a pathway towards thermally stable photovoltaics. However, moisture‐induced phase degradation restricts the application of hole transport layers (HTLs) ...with hygroscopic dopants. Dopant‐free HTLs fail to realize efficient photovoltaics due to severe electrical loss. Herein, we developed an electrical loss management strategy by manipulating poly(3‐hexylthiophene) with a small molecule, i.e., SMe‐TATPyr. The developed P3HT/SMe‐TATPyr HTL shows a three‐time increase of carrier mobility owing to breaking the long‐range ordering of “edge‐on” P3HT and inducing the formation of “face‐on” clusters, over 50 % decrease of the perovskite surface defect density, and a reduced voltage loss at the perovskite/HTL interface because of favorable energy level alignment. The CsPbI2Br perovskite solar cell demonstrates a record‐high efficiency of 16.93 % for dopant‐free HTL, and superior moisture and thermal stability by maintaining 96 % efficiency at low‐humidity condition (10–25 % R. H.) for 1500 hours and over 95 % efficiency after annealing at 85 °C for 1000 hours.
An electrical loss management strategy by using SMe‐TATPyr molecule manipulating dopant‐free Poly(3‐hexylthiophene) (P3HT) has been developed and employed to fabricate efficient and thermally stable CsPbI2Br solar cells. The P3HT/SMe‐TATPyr presents optimized molecular orientation, favorable energy level alignment and effective defect passivation. Based on P3HT/SMe‐TATPyr HTLs, the fabricated devices yield a record‐high efficiency of 16.93 % for CsPbI2Br solar cells with dopant‐free HTLs.
PDF
