The discovery of a novel IκB kinase β inhibitor based on pharmacophore modeling, virtual screening and biological evaluation

suppl info</p

Table_1_Applications of nanobodies in brain diseases.docx

Nanobodies are antibody fragments derived from camelids, naturally endowed with properties like low molecular weight, high affinity and low immunogenicity, which contribute to their effective use as research tools, but also as diagnostic and therapeutic agents in a wide range of diseases, including brain diseases. Also, with the success of Caplacizumab, the first approved nanobody drug which was established as a first-in-class medication to treat acquired thrombotic thrombocytopenic purpura, nanobody-based therapy has received increasing attention. In the current review, we first briefly introduce the characterization and manufacturing of nanobodies. Then, we discuss the issue of crossing of the brain-blood-barrier (BBB) by nanobodies, making use of natural methods of BBB penetration, including passive diffusion, active efflux carriers (ATP-binding cassette transporters), carrier-mediated influx via solute carriers and transcytosis (including receptor-mediated transport, and adsorptive mediated transport) as well as various physical and chemical methods or even more complicated methods such as genetic methods via viral vectors to deliver nanobodies to the brain. Next, we give an extensive overview of research, diagnostic and therapeutic applications of nanobodies in brain-related diseases, with emphasis on Alzheimer’s disease, Parkinson’s disease, and brain tumors. Thanks to the advance of nanobody engineering and modification technologies, nanobodies can be linked to toxins or conjugated with radionuclides, photosensitizers and nanoparticles, according to different requirements. Finally, we provide several perspectives that may facilitate future studies and whereby the versatile nanobodies offer promising perspectives for advancing our knowledge about brain disorders, as well as hopefully yielding diagnostic and therapeutic solutions.</p

Design of Light-Driven Biocompatible and Biodegradable Microrobots Containing Mg-Based Metallic Glass Nanowires

Light-driven microrobots capable of moving rapidly on water surfaces in response to external stimuli are widely used in a variety of fields, such as drug delivery, remote sampling, and biosensors. However, most light-driven microrobots use graphene and carbon nanotubes as photothermal materials, resulting in poor biocompatibility and degradability, which greatly limits their practical bioapplications. To address this challenge, a composition and microstructure design strategy with excellent photothermal properties suitable for the fabrication of light-driven microrobots was proposed in this work. The Mg-based metallic glass nanowires (Mg-MGNWs) were embedded with polyhydroxyalkanoates (PHA) to fabricate biocompatible and degradable microrobots with excellent photothermal effect and complex shapes. Consequently, the microrobot can be precisely driven by a near-infrared laser to achieve high efficiency and remote manipulation on the water surface for a long period of time, with a velocity of 9.91 mm/s at a power density of 2.0 W/cm2. Due to the Marangoni effect, programmable and complex motions of the microrobot such as linear, clockwise, counterclockwise, and obstacle avoidance motions can be achieved. The biocompatible and degradable microrobot fabrication strategy could have great potential in the fields of environmental detection, targeted drug delivery, disease diagnosis, and detection

Design of Light-Driven Biocompatible and Biodegradable Microrobots Containing Mg-Based Metallic Glass Nanowires

Light-driven microrobots capable of moving rapidly on water surfaces in response to external stimuli are widely used in a variety of fields, such as drug delivery, remote sampling, and biosensors. However, most light-driven microrobots use graphene and carbon nanotubes as photothermal materials, resulting in poor biocompatibility and degradability, which greatly limits their practical bioapplications. To address this challenge, a composition and microstructure design strategy with excellent photothermal properties suitable for the fabrication of light-driven microrobots was proposed in this work. The Mg-based metallic glass nanowires (Mg-MGNWs) were embedded with polyhydroxyalkanoates (PHA) to fabricate biocompatible and degradable microrobots with excellent photothermal effect and complex shapes. Consequently, the microrobot can be precisely driven by a near-infrared laser to achieve high efficiency and remote manipulation on the water surface for a long period of time, with a velocity of 9.91 mm/s at a power density of 2.0 W/cm2. Due to the Marangoni effect, programmable and complex motions of the microrobot such as linear, clockwise, counterclockwise, and obstacle avoidance motions can be achieved. The biocompatible and degradable microrobot fabrication strategy could have great potential in the fields of environmental detection, targeted drug delivery, disease diagnosis, and detection

Design of Light-Driven Biocompatible and Biodegradable Microrobots Containing Mg-Based Metallic Glass Nanowires

Light-driven microrobots capable of moving rapidly on water surfaces in response to external stimuli are widely used in a variety of fields, such as drug delivery, remote sampling, and biosensors. However, most light-driven microrobots use graphene and carbon nanotubes as photothermal materials, resulting in poor biocompatibility and degradability, which greatly limits their practical bioapplications. To address this challenge, a composition and microstructure design strategy with excellent photothermal properties suitable for the fabrication of light-driven microrobots was proposed in this work. The Mg-based metallic glass nanowires (Mg-MGNWs) were embedded with polyhydroxyalkanoates (PHA) to fabricate biocompatible and degradable microrobots with excellent photothermal effect and complex shapes. Consequently, the microrobot can be precisely driven by a near-infrared laser to achieve high efficiency and remote manipulation on the water surface for a long period of time, with a velocity of 9.91 mm/s at a power density of 2.0 W/cm2. Due to the Marangoni effect, programmable and complex motions of the microrobot such as linear, clockwise, counterclockwise, and obstacle avoidance motions can be achieved. The biocompatible and degradable microrobot fabrication strategy could have great potential in the fields of environmental detection, targeted drug delivery, disease diagnosis, and detection

Generalizable, Electroless, Template-Assisted Synthesis and Electrocatalytic Mechanistic Understanding of Perovskite LaNiO₃ Nanorods as Viable, Supportless Oxygen Evolution Reaction Catalysts in Alkaline Media

The oxygen evolution reaction (OER) is a key reaction for water electrolysis cells and air-powered battery applications. However, conventional metal oxide catalysts, used for high-performing OER, tend to incorporate comparatively expensive and less abundant precious metals such as Ru and Ir, and, moreover, suffer from poor stability. To attempt to mitigate for all of these issues, we have prepared one-dimensional (1D) OER-active perovskite nanorods using a unique, simple, generalizable, and robust method. Significantly, our work demonstrates the feasibility of a novel electroless, seedless, surfactant-free, wet solution-based protocol for fabricating “high aspect ratio” LaNiO₃ and LaMnO₃ nanostructures. As the main focus of our demonstration of principle, we prepared as-synthesized LaNiO₃ rods and correlated the various temperatures at which these materials were annealed with their resulting OER performance. We observed generally better OER performance for samples prepared with lower annealing temperatures. Specifically, when annealed at 600 °C, in the absence of a conventional conductive carbon support, our as-synthesized LaNiO₃ rods not only evinced (i) a reasonable level of activity toward OER but also displayed (ii) an improved stability, as demonstrated by chronoamperometric measurements, especially when compared with a control sample of commercially available (and more expensive) RuO₂

Chemical Strategies for Enhancing Activity and Charge Transfer in Ultrathin Pt Nanowires Immobilized onto Nanotube Supports for the Oxygen Reduction Reaction

Multiwalled carbon nanotubes (MWNTs) represent a promising support medium for electrocatalysts, especially Pt nanoparticles (NPs). The advantages of using MWNTs include their large surface area, high conductivity, as well as long-term stability. Surface functionalization of MWNTs with various terminal groups, such as −COOH, −SH, and −NH₂, allows for rational electronic tuning of catalyst–support interactions. However, several issues still need to be addressed for such systems. First, over the course of an electrochemical run, catalyst durability can decrease, due in part to metal NP dissolution, a process facilitated by the inherently high surface defect concentration within the support. Second, the covalent functionalization treatment of MWNTs adopted by most groups tends to lead to a loss of structural integrity of the nanotubes (NTs). To mitigate for all of these issues, we have utilized two different attachment approaches (i.e., covalent versus noncovalent) to functionalize the outer walls of pristine MWNTs and compared the catalytic performance of as-deposited ultrathin (<2 nm) 1D Pt nanowires with that of conventional Pt NPs toward the oxygen reduction reaction (ORR). Our results demonstrated that the electrochemical activity of Pt nanostructures immobilized onto functionalized carbon nanotube (CNT) supports could be dramatically improved by using ultrathin Pt nanowires (instead of NPs) with noncovalently (as opposed to covalently) functionalized CNT supports. Spectroscopic evidence corroborated the definitive presence of charge transfer between the metal catalysts and the underlying NT support, whose direction and magnitude are a direct function of (i) the terminal chemistry as well as (ii) the attachment methodology, both of which simultaneously impact upon the observed electrocatalytic performance. Specifically, the use of a noncovalent π–π stacking method coupled with a −COOH terminal moiety yielded the highest performance results, reported to date, for any similar system consisting of Pt (commercial NPs or otherwise) deposited onto carbon-based supports, a finding of broader interest toward the fabrication of high-performing electrocatalysts in general

The synchronization and adaptation of Neurospora crassa circadian and conidiation rhythms to short light-dark cycles

These are supplementary materials for the paper submitted to a journal

Ultrathin Pt_<i>x</i>Sn_1–<i>x</i> Nanowires for Methanol and Ethanol Oxidation Reactions: Tuning Performance by Varying Chemical Composition

Pt-based alloys denote promising catalysts for the methanol oxidation reaction (MOR) and the ethanol oxidation reaction (EOR), due to their enhanced activity toward alcohol-oxidation reactions and reduced cost as compared with Pt alone. Among all of these binary systems, PtSn has been reported to exhibit superior methanol/ethanol oxidation activity. In this study, we deliberatively tailor chemical composition, reduce size, and optimize morphology of the catalyst in an effort to understand structure–property correlations that can be used to improve upon the electrocatalytic activity of these systems. Previous work performed by our group suggested that Pt-based catalysts, possessing an ultrathin one-dimensional (1D) structure, dramatically promote both cathodic and anodic reactions with respect to their zero-dimensional (0D) counterparts. Herein, a novel set of ultrathin binary Pt–Sn 1D nanowire (NW) catalysts with rationally controlled chemical compositions, i.e., Pt₉Sn₁, Pt₈Sn₂, and Pt₇Sn₃, has been synthesized using a facile, room-temperature, wet-solution-based method. The crystallinity and chemical composition of these as-prepared samples were initially characterized using XRD, XPS, and EDX. Results revealed that this synthetic protocol could successfully generate PtSn alloys with purposely tunable chemical compositions. TEM and HRTEM verified the structural integrity of our ultrathin 1D NW morphology for our Pt₉Sn₁, Pt₈Sn₂, and Pt₇Sn₃ samples. The effects of varying Sn content within these alloy samples toward the electro-oxidation reaction of methanol and ethanol were probed using cyclic voltammetry (CV) in acidic media. Within this series, we find that the optimized chemical composition for both the MOR and the EOR is Pt₇Sn₃

DataSheet_1_Toward the development of smart capabilities for understanding seafloor stretching morphology and biogeographic patterns via DenseNet from high-resolution multibeam bathymetric surveys for underwater vehicles.docx

The increasing use of underwater vehicles facilitates deep-sea exploration at a wide range of depths and spatial scales. In this paper, we make an initial attempt to develop online computing strategies to identify seafloor categories and predict biogeographic patterns with a deep learning-based architecture, DenseNet, integrated with joint morphological cues, with the expectation of potentially developing its embedded smart capacities. We utilized high-resolution multibeam bathymetric measurements derived from MBES and denoted a collection of joint morphological cues to help with semantic mapping and localization. We systematically strengthened dominant feature propagation and promoted feature reuse via DenseNet by applying the channel attention module and spatial pyramid pooling. From our experiment results, the seafloor classification accuracy reached up to 89.87%, 82.01%, and 73.52% on average in terms of PA, MPA, and MIoU metrics, achieving comparable performances with the state-of-the-art deep learning frameworks. We made a preliminary study on potential biogeographic distribution statistics, which allowed us to delicately distinguish the functionality of probable submarine benthic habitats. This study demonstrates the premise of using underwater vehicles through unbiased means or pre-programmed path planning to quantify and estimate seafloor categories and the exhibited fine-scale biogeographic patterns.</p