Abstract:Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or α-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their additional clinical benefits include reducing levels of TNFα and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. The incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products, and their integration with self-care, music and mHealth, expands precision/personalized medicine strategies for chronic diseases via pharmacological-behavioral combination therapies.

Highlights This article firstly reviews the urban traffic situation from 1/23/2020 to 3/8/2020 in China. Between cities, blocking and controlling the traffic are urgent in the early stage of epidemic. Inside a city, it is urgent to suspend the public transports, block roads, restrict private cars. We also give suggestions about the long-term planning and improvement methods. This article offers a valuable reference of urban traffic control now and in the future.

Fiber metal laminate (FML) is a kind of lightweight material with excellent mechanical properties combining advantages of metal laminates and fiber reinforced composites. It has been widely used in the aerospace and transportation fields and is especially used as structural material such as aircraft skins, wings, and tails. However, under complex service conditions, interlaminar failure in FMLs greatly reduced mechanical properties of the material, even leading to serious economic and safety disasters. The failure and destruction of important structural parts of aircraft and other manned transportation vehicles are extremely unsafe for people. Therefore, it is of great significance to summarize the interlaminar failure behavior of FMLs and find ways to avoid these defects. This review paper is a collection of various researches done by many groups, which systematically discuss the interlaminar failure behaviors and their control methods of FMLs. The application status of several common FMLs in aircraft structures was given. The common interlaminar failure modes of FMLs and the testing and evaluation methods of interlaminar properties were stated. The failure mechanisms and the corresponding control methods were analyzed. Finally, the future developments of FMLs were also discussed by the authors. Through this review article, readers can obtain new research progress about the control method, the mechanism and future development on the failure behavior of FMLs in a more efficient way.

We previously reported a novel inhibitor of the ataxia-telangiectasia mutated (ATM) kinase, which is a target for novel radiosensitizing drugs. While our initial lead, compound 4, was relatively potent and nontoxic, it exhibited poor stability to oxidative metabolism and relatively poor selectivity against other kinases. The current study focused on balancing potency and selectivity with metabolic stability through structural modification to the metabolized site on the quinazoline core. We performed extensive structure-activity and structure-property relationship studies on this quinazoline ATM kinase inhibitor in order to identify structural variants with enhanced selectivity and metabolic stability. We show that, while the C-7-methoxy group is essential for potency, replacing the C-6-methoxy group considerably improves metabolic stability without affecting potency. Promising analogues 20, 27g, and 27n were selected based on in vitro pharmacology and evaluated in murine pharmacokinetic and tolerability studies. Compound 27g possessed significantly improve pharmacokinetics relative to that of 4. Compound 27g was also significantly more selective against other kinases than 4. Therefore, 27g is a good candidate for further development as a potential radiosensitizer.

No abstract

Abdominal bleeding is a lethal complication in acute pancreatitis (AP) and it is commonly described as a late event. However, spontaneous intra-abdominal bleeding could occur very early but no study focusing on this phenomenon was published yet. In this study, 1137 AP patients were retrospectively screened and 24 subjects suffering early spontaneous bleeding (ESB) were selected. Meanwhile, a 1:1 well-balanced cohort of non-bleeding patients was generated by propensity score match. The clinical characteristics of these patients were compared and a multiple regression analysis was performed to assess the risk factors for ESB. Besides, patients with massive post-intervention bleeding (PIB) were collected for additional comparison. ESB patients suffered significantly worse outcome than the matched cohort evidenced by dramatically higher mortality than the non-bleeding patients and even the PIB group (54.2% versus 20.8%, P = 0.017; 54.2% versus 31.0%, P = 0.049). The regression analysis demonstrated computer tomography severity index (CTSI; OR, 3.34; 95% CI, 1.995–5.59, P < 0.001) and creatinine (OR, 1.008; 95% CI, 1.004–1.012, P < 0.001) were associated with the occurrence of ESB. In conclusion, ESB is a rare but dangerous complication of moderate-to-severe AP and may result in high mortality. CTSI and creatinine are independent risk factors for the development of ESB.

Non-noble iron-nitrogen-carbon (Fe-N-C) catalysts have been explored as one type of the most promising alternatives of precious platinum (Pt) in catalyzing the oxygen reduction reaction (ORR). However, their catalytic ORR activity and stability still cannot meet the requirement of practical applications. Active sites in such catalysts are the key factors determining the catalytic performance. This review gives a critical overview on identification and understanding of active sties of non-pyrolytic and pyrolytic Fe-N-C catalysts in terms of design strategies, synthesis, characterization, functional mechanisms and performance validation. The diversity and complexity of active sites that greatly dominate the progress of Fe-N-C catalysts include Fe-containing sites (Fe-based nanoparticles and single-atom Fe-species) and metalfree sites (heteroatoms doping and defects). Meanwhile, synergistic effects are also discussed in this review with emphasis on the interaction among multiple active sites. Although substantial endeavors have been devoted to develop the efficient Fe-N-C catalysts, some challenges still remain. To facilitate further research on Fe-N-C catalysts toward practical applications, some research perspectives are prospected in the aspects of innovative synthesis methods, active-sites modulation strategies, high-resolution ex situ/in situ/ operando characterization techniques, theoretical calculations, and so on. This review may provide a guideline for identifying and understanding activesites for developing high-performance Fe-N-C catalysts.

All solid-state lithium-ion batteries based on polymer electrolytes have higher safety and energy density, but the low conductivity of lithium ion restricts its application. This study proposes a new method to promote the ionic conductivity of polyethylene oxide (PEO)-based solid electrolytes. In this method, the PEO-based solid electrolyte was first prepared by casting, and then power ultrasound was exerted on the electrolyte by a sandwich structure to modify the electrolyte structure. Through analysis of the performance and microstructure of the electrolyte, it was found that the ultrasonic treatment increased the ionic conductivity by 78%, improved tensile strength and plastic deformation ability, but did not affect the thermal stability and the chemical composition. The ultrasonic vibration, exerting high energy to the solid electrolyte through high-frequency vibration, broke PEO grains and melted them with the frictional heat at boundary. Due to the slight melting and fast solidifying produced by the pulsed ultrasonic treatment, the crystallization was suppressed. The crystallinity was thus reduced by 6.2%, which increased the migration channels of lithium ions and reduced the tortuosity effect. Furthermore, the ultrasonic vibration compressed the electrolyte to produce plastic flow of the material, which made the electrolyte structure more compact. The density of ethylene oxide (EO) units thus increased in the amorphous phase, providing multiple electron-donor coordination sites for the Li+. The hopping distance of the ion between donors decreased, which also facilitated the migration. In addition, the mechanical performance of the electrolyte membrane improved. This study provides a reference for the improvement of polymer based all-solid-state batteries.