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Review  |  2019-08-22

Traditional Chinese Medicine as a Treatment for Rheumatoid Arthritis: From Empirical Practice to Evidence-Based Therapy

Rheumatoid arthritis (RA) is a common autoimmune condition with an elusive etiology. Conventional and biological disease-modifying drugs sometimes fail or produce only partial responses. Traditional Chinese medicine (TCM) has long been used in China as a treatment for RA and is achieving everincreasing acceptance worldwide. TCM treatments are traditionally guided by the theory of treatment based on TCM syndrome differentiation; however, they remain a matter of empirical practice relying on TCM theories and doctors’ own experience, which places severe restrictions on worldwide TCM application. Nevertheless, TCM is a treasure trove for drug discovery, particularly as a treatment for complicated human conditions. The discoveries of artemisinin as a treatment for malaria and of TCM–arsenic trioxide (As2O3) combination therapy as a treatment for acute promyelocytic leukemia (APL) are excellent examples of the great value of TCM. Regarding RA treatments, many Chinese medicinal herbs and their formulas, extracts, ingredients, and even single compounds have been used in clinical applications. Several Chinese proprietary medicines (CPMs) derived from TCM formulas or herbal bioactive components, such as the controlled-release tablets of ZhengQingFengTongNing (ZQFTN), tripterygium glycoside tablets, and capsules of total glucosides of peony (TGP), have been included in the National Health Insurance Directory of China, and show comparable therapeutic efficacies to those of western chemical drugs with fewer side effects. As TCM research has advanced, particularly in the use of multidisciplinary technologies, the scientific foundations and characteristics of the use of TCM to treat RA have been revealed, and the quality of TCM treatments have been increasingly enhanced. However, TCM generally lacks sufficient clinical and laboratory data to be consistent with international standards for quality, safety, and efficacy in order to support its application worldwide. Therefore, intensive basic and clinical studies on TCM are required. In particular, investigations that use cutting-edge technologies in analytical chemistry, biology, and biomedical sciences, and the development of randomized clinical trials (RCTs) and personalized pragmatic randomized controlled trials (PPRCTs) are necessary. Researchers should also collaborate to advance TCM from empirical practice to evidence-based therapy, thus consistently promoting TCM development and globalization in a vital, beneficial, and contributable manner.

Hu-Dan Pan

Perspective  |  2019-08-21

Complexity at Mesoscales: A Common Challenge in Developing Artificial Intelligence

Exploring the physical mechanisms of complex systems and making effective use of them are the keys to dealing with the complexity of the world. The emergence of big data and the enhancement of computing power, in conjunction with the improvement of optimization algorithms, are leading to the development of artificial intelligence (AI) driven by deep learning. However, deep learning fails to reveal the underlying logic and physical connotations of the problems being solved. Mesoscience provides a concept to understand the mechanism of the spatiotemporal multiscale structure of complex systems, and its capability for analyzing complex problems has been validated in different fields. This paper proposes a research paradigm for AI, which introduces the analytical principles of mesoscience into the design of deep learning models. This is done to address the fundamental problem of deep learning models detaching the physical prototype from the problem being solved; the purpose is to promote the sustainable development of AI.

Li Guo

Article  |  2019-12-11

Hierarchical ZSM-5 zeolite with radial mesopores: Preparation, formation mechanism and application for benzene alkylation

Hierarchical ZSM-5 zeolite with radial mesopores is controllably synthesized using piperidine in a NaOH solution. The piperidine molecules enter the zeolite micropores and protect the zeolite framework from extensive desilication. The areas containing fewer aluminum atoms contain fewer piperidine protectant molecules and so they dissolve first. Small amounts of mesopores are then gradually generated in areas with more aluminum atoms and more piperidine protectant. In this manner, radial mesopores are formed in the ZSM-5 zeolite with a maximal preservation of the micropores and active sites. The optimal hierarchical ZSM-5 zeolite, prepared with a molar ratio of piperidine to zeolite of 0.03, had a mesopore surface area of 136 m ·g and a solid yield of 80%. The incorporation of the radial mesopores results in micropores that are interconnected which shortened the average diffusion path length. Compared to the parent zeolite, the hierarchical ZSM-5 zeolite possesses more accessible acid sites and has a higher catalytic activity and a longer lifetime for the alkylation of benzene.

Darui Wang

Article  |  2019-12-11

4-Amino-1,8-naphthalimide based fluorescent photoinduced electron transfer (PET) pH sensors as liposomal cellular imaging agents: The effect of substituent patterns on PET directional quenching

Four new fluorescent sensors ( - ) based on the 4-amino-1,8-naphthalimide fluorophores ( ) have been synthesized based on the classical fluorophore-spacer-receptor model. These four compounds all gave rise to emission bands centred at 535 nm, which were found to be highly pH dependent, the emission being ‘switched on’ in acidic media, while being quenched due to PET from the amino moieties to the excited state of the at more alkaline pH. The luminescent pH dependence for these probes was found to be highly dependent on the substitution on the imide site, as well as the polyamine chain attached to the position 4-amino moiety. In the case of sensor the presence of the 4-amino-aniline dominated the pH dependent quenching. Nevertheless, at higher pH, PET quenching was also found to occur from the polyamine site. Hence, is better described as a receptor -spacer -fluorophore-spacer -receptor system, where the dominant PET process is due to (normally less favourable) ‘directional’ PET quenching from the 4-amino-aniline unit to the site. Similar trends and pH fluorescence dependences were also seen for and . These compounds were also tested for their imaging potential and toxicity against HeLa cells (using DRAQ5 as nuclear stain which does now show pH dependent changes in acidic and neutral pH) and the results demonstrated that these compounds have reduced cellular viability at moderately high concentrations (with IC values between ca. 8‒30 µmol∙L ), but were found to be suitable for intracellular pH determination at 1 µmol∙L concentrations, where no real toxicity was observed. This allowed us to employ these as lysosomal probes at sub-toxic concentrations, where the based emission was found to be pH depended, mirroring that seen in aqueous solution for , with the main fluorescence changes occurring within acidic to neutral pH.

Miguel Martínez-Calvo

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