Ethnopharmacokinetic- and Activity-Guided Isolation of a New Antidepressive Compound from Fructus Aurantii Found in the Traditional Chinese Medicine Chaihu-Shugan-San: A New Approach and Its Application

Aims. We aimed to identify an antidepressive compound found in traditional Chinese medicine (TCM) by a new approach called ethnopharmacokinetic- and activity-guided isolation (EAGI). Methods. The new approach targets an unknown chromatographic peak produced by an absorbed compound found in oral Chaihu-Shugan-San (CSS) taken by patients with depression. Once the compound was isolated from Fructus Aurantii (FA), spectral data was employed to identify the compound. The effects of this compound, FA, and CSS on depressive behaviors were investigated. Results. The identified compound was merazin hydrate (MH) according to the new approach. MH, FA, and CSS significantly reduced immobility time and increased locomotor activity. The effects of MH, FA and CSS were similar to Fluoxetine at high doses. Conclusion. MH, a compound whose antidepressive effect is similar to FA and CSS, was isolated for the first time from FA via targeting its corresponding unknown chromatographic peak, and its antidepressive effect was compared with FA or CSS. These findings highlight the potential for drug R&D and pharmacological research of ∼100,000 TCMs

Bioinspired Ultrathin Piecewise Controllable Soft Robots

In nature, animals or plants often use soft organs to move and hunt. Research works on bioinspired materials and devices have attracted more and more interest as which show the potential for future intelligent robots. As key components of soft robots, biomimetic soft actuators are adapted to greater requirements for convenient, accurate, and programmable controlling robots. Here, a class of materials and processing routes of ultrathin actuators are reported for bioinspired piecewise controllable soft robots, where the actuators associate with thermal-responsible soft silicone thin film with thickness as thin as 45 µm and electrically driven by well mechanical designed metallic thin film electrodes. Multiple electrodes in the robots in charge of individual segments control allow the soft robots exhibiting similar functionalities of animals or plants (for example, imitating the tongue of a reptile, such as chameleon to hunt moving preys, and mimicking vines to tightly wind around objects). These bionic results in the soft robots demonstrate their advantages in precise and flexible operation, which provides a good reference for the future research of intelligent soft actuators and robots.acceptedVersionPeer reviewe

Complex 3D microfluidic architectures formed by mechanically guided compressive buckling.

Microfluidic technologies have wide-ranging applications in chemical analysis systems, drug delivery platforms, and artificial vascular networks. This latter area is particularly relevant to 3D cell cultures, engineered tissues, and artificial organs, where volumetric capabilities in fluid distribution are essential. Existing schemes for fabricating 3D microfluidic structures are constrained in realizing desired layout designs, producing physiologically relevant microvascular structures, and/or integrating active electronic/optoelectronic/microelectromechanical components for sensing and actuation. This paper presents a guided assembly approach that bypasses these limitations to yield complex 3D microvascular structures from 2D precursors that exploit the full sophistication of 2D fabrication methods. The capabilities extend to feature sizes <5 μm, in extended arrays and with various embedded sensors and actuators, across wide ranges of overall dimensions, in a parallel, high-throughput process. Examples include 3D microvascular networks with sophisticated layouts, deterministically designed and constructed to expand the geometries and operating features of artificial vascular networks

Mechanical characteristics of groundnut shell particle reinforced polylactide nano fibre

ABSTRACT The PLA-groundnut shell solution is electrospun to produce nanocomposite fibre. The spinneret containing the composite solution was placed 24.7 cm away from the aluminium collector, tilted at an angle of 30 °, and the solution flow rate kept at 1 mL/min. Groundnut Shell particle (GSP) weight fraction used was varied from 3 - 8 wt. %. Particle reinforced nanofibres were formed on the collector from the composite solution at 26 kV. These nanofibres were subjected to tensile test and the result indicates that at 6 wt. % untreated GSP reinforced fibre possessed the best tensile stiffness of 24.62 MPa. This corresponds to 2.201 % increase in Modulus of Elasticity over the unreinforced PLA (1.07 MPa). The 7 wt. % treated GSP fibre showed the least stiffness (0.33 MPa), which is 69 % reduction over that of unreinforced fibre. PLA fibre reinforced with 5 wt. % untreated GSP displayed best blend of properties over the unreinforced with increase of 286 % (4.43 x 10-4 HB), 1,502 % (1.07 MPa), 286 % (0.22 MPa), 6.8 % (0.05 J) and 1,081 % (~ 0.15 MPa) in hardness, stiffness, UTS, energy at break and stress at break respectively. However, ductility decreased by ~33.3 % when compared to the unreinforced (18.27). The 5 wt. % untreated GSP PLA reinforced fibre showed the highest UTS (0.855 MPa). The micrographs showed beads on reinforced fibres, while the virgin PLA showed no beads

Compliant and stretchable thermoelectric coils for energy harvesting in miniature flexible devices

With accelerating trends in miniaturization of semiconductor devices, techniques for energy harvesting become increasingly important, especially in wearable technologies and sensors for the internet of things. Although thermoelectric systems have many attractive attributes in this context, maintaining large temperature differences across the device terminals and achieving low–thermal impedance interfaces to the surrounding environment become increasingly difficult to achieve as the characteristic dimensions decrease. Here, we propose and demonstrate an architectural solution to this problem, where thin-film active materials integrate into compliant, open three-dimensional (3D) forms. This approach not only enables efficient thermal impedance matching but also multiplies the heat flow through the harvester, thereby increasing the efficiencies for power conversion. Interconnected arrays of 3D thermoelectric coils built using microscale ribbons of monocrystalline silicon as the active material demonstrate these concepts. Quantitative measurements and simulations establish the basic operating principles and the key design features. The results suggest a scalable strategy for deploying hard thermoelectric thin-film materials in harvesters that can integrate effectively with soft materials systems, including those of the human body

The protective role of DOT1L in UV-induced melanomagenesis

The DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role in MLL-rearranged leukemogenesis. Here, we demonstrate that, in contrast to MLL-rearranged leukemia, DOT1L plays a protective role in ultraviolet radiation (UVR)-induced melanoma development. Specifically, the DOT1L gene is located in a frequently deleted region and undergoes somatic mutation in human melanoma. Specific mutations functionally compromise DOT1L methyltransferase enzyme activity leading to reduced H3K79 methylation. Importantly, in the absence of DOT1L, UVR-induced DNA damage is inefficiently repaired, so that DOT1L loss promotes melanoma development in mice after exposure to UVR. Mechanistically, DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 involvement in binding and recruiting XPC to the DNA damage site for nucleotide excision repair (NER). This study indicates that DOT1L plays a protective role in UVR-induced melanomagenesis

Structure-guided vaccine, antibody and drug discovery

Thesis (Ph.D.)--University of Washington, 2022The current pandemic, COVID19, will remain engraved in our history. However, if not the rapid response for vaccine and antibody development has been made from the outset, this wound might be even deeper and more anguished. Advances in mRNA vaccine delivery and pre-fusion spike stabilization were the cornerstones of this success. And this footstone cannot be made without the structure information we gathered in the past several years. Here, I will show how important and necessary the structure information is for facilitating and even initiating vaccine, antibody and drug development. To illustrate this argument, I am going to cover several examples across coronavirus, henipavirus and orthopoxvirus structure studies using CryoEM and CryoET techniques complemented with biochemical and biophysical assays, such as ELISA, BLI and pseudovirus neutralization. The results from these studies are great examples of how structure information can reshape our understanding of diverse biological systems. And for the virology field, these new understandings are so valuable for potential pandemic preparation. If the disaster reemerges, we will never be more prepared by that time

Improving Circular Supply Chain Performance through Green Innovations: The Moderating Role of Economic Policy Uncertainty

The sudden outbreak and long-term trend of COVID-19 have brought huge attacks and uncertainty to the global economy, forcing countries to introduce various policies frequently to stimulate economic recovery. To realize sustainable development, firms established an environment-friendly economic development model by building a circular supply chain and implementing a green innovation strategy, which is expected to save resources and protect the environment by recycling resources. Based on this background, this study aims to determine the relationship between the uncertainty of economic policy, green innovation strategy, and circular supply chain performance. It divides green innovation strategies into green product innovation, green process innovation, green service innovation, and green logistics innovation to explore their different impacts on the performance of the circular supply chain. Simultaneously, the moderating effect of uncertainty of economic policy between green innovation and the performance of the circular supply chain is explored. Using survey data collected from 308 manufacturing firms in China, we empirically test the theoretical model and proposed hypotheses through the structural equation modeling approach. Our findings demonstrate that green product innovation, green process innovation, green logistics innovation, and green service innovation have a positive impact on the performance of the circular supply chain. Moreover, we also find that, contrary to our expectations, economic policy uncertainty plays a positive role in moderating the relationship between green innovation and circular supply chain performance. We believe that this paper has a clear contribution to the research on green innovation and circular supply chain management. This study provides a new perspective for the research on the integration of green innovation and circular supply chain, deepens firms’ understanding of green innovation strategy and circular supply chain, and provides important implications and guidance for manufacturing firms to better manage green innovation and circular supply chain practice as well as the risk of economic policy uncertainty