The canine anti-tumor necrosis factor-alpha (TNF-α) monoclonal antibody is a potential therapeutic option for treating canine arthritis. The current treatments for arthritis in dogs have limitations ...due to side effects, emphasizing the need for safer and more effective therapies. The crystal structure of canine TNF-α (cTNF-α) was successfully determined at a resolution of 1.85 Å, and the protein was shown to assemble as a trimer, with high similarity to the functional quaternary structure of human TNF-α (hTNF-α). Adalimumab (Humira), a known TNF-α inhibitor, effectively targets and neutralizes TNF-α to reduce inflammation and has been used to manage autoimmune conditions such as rheumatoid arthritis. By comparing the structure of cTNF-α with the complex structure of hTNF-α and adalimumab-Fab, the epitope of adalimumab on cTNF-α was identified. The significant structural similarities of epitopes in cTNF-α and hTNF-α indicate the potential of using adalimumab to target cTNF-α. Therefore, a canine/human chimeric antibody, Humivet-R1, was created by grafting the variable domain of adalimumab onto a canine antibody framework derived from ranevetmab. Humivet-R1 exhibits potent neutralizing ability (IC
= 0.05 nM) and high binding affinity (EC
= 0.416 nM) to cTNF-α, comparable to that of adalimumab for both hTNF-α and cTNF-α. These results strongly suggest that Humivet-R1 has the potential to provide effective treatment for canine arthritis with reduced side effects. Here, we propose a structure-guided antibody design for the use of a chimeric antibody to treat canine inflammatory disease. Our successful development strategy can speed up therapeutic antibody discovery for animals and has the potential to revolutionize veterinary medicine.
A molecular nano‐floating gate (NFG) of pentacene‐based transistor memory devices is developed using conjugated polymer nanoparticles (CPN) as the discrete trapping sites embedded in an insulating ...polymer, poly (methacrylic acid) (PMAA). The nanoparticles of polyfluorene (PF) and poly(fluorene‐alt‐benzo2,1,3thiadiazole (PFBT) with average diameters of around 50–70 nm are used as charge‐trapping sites, while hydrophilic PMAA serves as a matrix and a tunneling layer. By inserting PF nanoparticles as the floating gate, the transistor memory device reveals a controllable threshold voltage shift, indicating effectively electron‐trapping by the PF CPN. The electron‐storage capability can be further improved using the PFBT‐based NFG since their lower unoccupied molecular orbital level is beneficial for stabilization of the trapped charges, leading a large memory window (35 V), retention time longer than 104 s with a high ON/OFF ratio of >104. In addition, the memory device performance using conjugated polymer nanoparticle NFG is much higher than that of the corresponding polymer blend thin films of PF/polystyrene. It suggests that the discrete polymer nanoparticles can be effectively covered by the tunneling layer, PMAA, to achieve the superior memory characteristics.
A molecular nano‐floating gate approach using conjugated polymer nanoparticles is developed for achieving high performance transistor memory devices. The transistor memory device using discrete polyfluorene and poly(fluorene‐alt‐benzo2,1,3thiadiazole nanoparticles as the floating gates can effectively trap the electrons and lead to a large memory window, long retention time, and a high ON/OFF ratio of >104.
Polymers with an abundant amorphous domain should facilitate energy dissipation upon stretching, making near amorphous π-conjugated polymers have immense potential in realizing intrinsically ...stretchable field-effect transistor (FET) devices. In this study, high mobility preservation under the stretched state is attempted by replacing typical alkyl-monothienyl (T-R) on a benzo1,2-b:4,5-b’dithiophene-difluorobenzothiadiazole backbone with three other biaxially extended side-chains, including alkyl-dithienyl (2T-R), branching alkyl-trithienyl (3T-R), and alkyl-benzotrithienyl (B3T-R) groups. Despite showing near amorphous features, the semi-2D BDT-based polymers with bulkier biaxially extended side chains (PBDT-2T, PBDT-3T, and PBDT-B3T) still present comparable mobility to the reference semicrystalline polymer (PBDT-T). Although these four polymers yield comparable mobility, they show distinctly different mobility retention in the stretched state. From the study of their mobility-stretchability relationship, the interdigitating and/or entanglement of these biaxially extended conjugated side chains are shown to play a nontrivial role in the resultant mechanical robustness against the stretching force. Owing to the proper spatial mobility and geometry, the branched 3T-R side chain possesses a more intense interdigitating and/or entanglement capability than the linear 2T-R one and the fused B3T-R one, providing better mechanical strength under stretched states. Meanwhile, it maintains sufficient interchain connectivity for intermittent interchain hopping to compensate for the 1D charge transport along the backbone, ensuring good charge transport even in the stretched state. As a result, the printed PBDT-3T film is demonstrated to deliver a high mobility retention of 73% at a 60% strain exerted parallel to the charge-transporting direction and a very stable mobility retention of 88% after 1000 stretching-releasing cycles at a 60% strain, being one of the best stretchable near amorphous conjugated polymers reported thus far. Our result underlines the effectiveness of using biaxially extended conjugated side chains to realize high-performance stretchable polymers.
Transport of fluid through a pipe is essential for the operation of macroscale machines and microfluidic devices. Conventional fluids only flow in response to external pressure. We demonstrate that ...an active isotropic fluid, composed of microtubules and molecular motors, autonomously flows through meter-long three-dimensional channels. We establish control over the magnitude, velocity profile, and direction of the self-organized flows and correlate these to the structure of the extensile microtubule bundles. The inherently three-dimensional transition from bulk-turbulent to confined-coherent flows occurs concomitantly with a transition in the bundle orientational order near the surface and is controlled by a scale-invariant criterion related to the channel profile. The nonequilibrium transition of confined isotropic active fluids can be used to engineer self-organized soft machines.
Abstract
The demand for sustainable energy has motivated the development of artificial photosynthesis. Yet the catalyst and reaction interface designs for directly fixing permanent gases (e.g. CO
2
, ...O
2
, N
2
) into liquid fuels are still challenged by slow mass transfer and sluggish catalytic kinetics at the gas-liquid-solid boundary. Here, we report that gas-permeable metal-organic framework (MOF) membranes can modify the electronic structures and catalytic properties of metal single-atoms (SAs) to promote the diffusion, activation, and reduction of gas molecules (e.g. CO
2,
O
2
) and produce liquid fuels under visible light and mild conditions. With Ir SAs as active centers, the defect-engineered MOF (e.g. activated NH
2
-UiO-66) particles can reduce CO
2
to HCOOH with an apparent quantum efficiency (AQE) of 2.51% at 420 nm on the gas-liquid-solid reaction interface. With promoted gas diffusion at the porous gas-solid interfaces, the gas-permeable SA/MOF membranes can directly convert humid CO
2
gas into HCOOH with a near-unity selectivity and a significantly increased AQE of 15.76% at 420 nm. A similar strategy can be applied to the photocatalytic O
2
-to-H
2
O
2
conversions, suggesting the wide applicability of our catalyst and reaction interface designs.
Development of specific antiviral agents is an urgent unmet need for SARS-coronavirus 2 (SARS-CoV-2) infection. This study focuses on host proteases that proteolytically activate the SARS-CoV-2 spike ...protein, critical for its fusion after binding to angiotensin-converting enzyme 2 (ACE2), as antiviral targets. We first validate cleavage at a putative furin substrate motif at SARS-CoV-2 spikes by expressing it in VeroE6 cells and find prominent syncytium formation. Cleavage and the syncytium are abolished by treatment with the furin inhibitors decanoyl-RVKR-chloromethylketone (CMK) and naphthofluorescein, but not by the transmembrane protease serine 2 (TMPRSS2) inhibitor camostat. CMK and naphthofluorescein show antiviral effects on SARS-CoV-2-infected cells by decreasing virus production and cytopathic effects. Further analysis reveals that, similar to camostat, CMK blocks virus entry, but it further suppresses cleavage of spikes and the syncytium. Naphthofluorescein acts primarily by suppressing viral RNA transcription. Therefore, furin inhibitors may be promising antiviral agents for prevention and treatment of SARS-CoV-2 infection.
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•The furin cleavage site in the SARS-CoV-2 spike protein mediates syncytium formation•The SARS-CoV-2 spike-mediated syncytium is suppressed by specific furin inhibitors•Furin inhibitors block SARS-CoV-2 virus entry and virus replication•Furin inhibitors are potential antiviral agents for SARS-CoV-2 infection and pathogenesis
Development of effective antiviral agents is an urgent unmet need for SARS-CoV-2 infection. Cheng et al. find that cleavage of the furin substrate site in the viral spike protein is critical for virus production and cytopathic effects. Two inhibitors targeting furin are potential antiviral agents to control SARS-CoV-2 infection and pathogenesis.
Photocatalytic nitrogen fixation reaction can harvest the solar energy to convert the abundant but inert N2 into NH3. Here, utilizing metal–organic framework (MOF) membranes as the ideal assembly of ...nanoreactors to disperse and confine gold nanoparticles (AuNPs), we realize the direct plasmonic photocatalytic nitrogen fixation under ambient conditions. Upon visible irradiation, the hot electrons generated on the AuNPs can be directly injected into the N2 molecules adsorbed on Au surfaces. Such N2 molecules can be additionally activated by the strong but evanescently localized surface plasmon resonance field, resulting in a supralinear intensity dependence of the ammonia evolution rate with much higher apparent quantum efficiency and lower apparent activation energy under stronger irradiation. Moreover, the gas-permeable Au@MOF membranes, consisting of numerous interconnected nanoreactors, can ensure the dispersity and stability of AuNPs, further facilitate the mass transfer of N2 molecules and (hydrated) protons, and boost the plasmonic photocatalytic reactions at the designed gas–membrane–solution interface. As a result, an ammonia evolution rate of 18.9 mmol gAu –1 h–1 was achieved under visible light (>400 nm, 100 mW cm–2) with an apparent quantum efficiency of 1.54% at 520 nm.
Traditional anticancer treatments have several limitations, but cancer is still one of the deadliest diseases. As a result, new anticancer drugs are required for the treatment of cancer. The use of ...metal nanoparticles (NPs) as alternative chemotherapeutic drugs is on the rise in cancer research. Metal NPs have the potential for use in a wide range of applications. Natural or surface-induced anticancer effects can be found in metals. The focus of this review is on the therapeutic potential of metal-based NPs. The potential of various types of metal NPs for tumor targeting will be discussed for cancer treatment. The in vivo application of metal NPs for solid tumors will be reviewed. Risk factors involved in the clinical application of metal NPs will also be summarized.
Heavy metal ions are highly toxic and widely spread as environmental pollutants. New strategies are being developed to simultaneously detect and remove these toxic ions. Herein, we take the intrinsic ...advantage of covalent organic frameworks (COFs) and develop fluorescent COFs for sensing applications. As a proof-of-concept, a thioether-functionalized COF material, COF-LZU8, was “bottom-up” integrated with multifunctionality for the selective detection and facile removal of mercury(II): the π-conjugated framework as the signal transducer, the evenly and densely distributed thioether groups as the Hg2+ receptor, the regular pores facilitating the real-time detection and mass transfer, together with the robust COF structure for recycle use. The excellent sensing performance of COF-LZU8 was achieved in terms of high sensitivity, excellent selectivity, easy visibility, and real-time response. Meanwhile, the efficient removal of Hg2+ from water and the recycling of COF-LZU8 offers the possibility for practical applications. In addition, X-ray photoelectron spectroscopy and solid-state NMR investigations verified the strong and selective interaction between Hg2+ and the thioether groups of COF-LZU8. This research not only demonstrates the utilization of fluorescent COFs for both sensing and removal of metal ions but also highlights the facile construction of functionalized COFs for environmental applications.
Robots can benefit education in many ways, and robotics holds great promise as a learning technology. However, the use of robots in education remains largely unknown to both researchers and ...educators. Many educators and developers have questions regarding the essential applications for robots used in education. Thus, this study aims to identify the essential applications of educational robots. To gain insight from the perspectives of researchers, experts and educators, we investigate the requirements of educational robots in all levels of education through 3 approaches: systematic literature review, expert interviews and instructor surveys. We review the extant literature that addresses the use of robots in education and adopted data from one of them, and conduct interviews with industry experts, scholars and instructors. We also conduct an online survey that invites instructors from six different levels of education to respond. We find the following to be the top five essential applications for educational robots: language education, robotics education, teaching assistance, social skill development and special education, and guided learning through feedback.
•An investigation that identifies the essential applications of educational robots.•The investigation consists of a systematic literature review, expert interviews and instructor surveys.•Robotics, language education and robot teaching assistant are the top three applications.•Robotics, language education and social and special education are the core applications.•Preschool and primary school group have greater potential to implement educational robots in near future.
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