99 research outputs found
The Antihistamine Drugs Carbinoxamine Maleate and Chlorpheniramine Maleate Exhibit Potent Antiviral Activity Against a Broad Spectrum of Influenza Viruses
Influenza A viruses (IAV) comprise some of the most common infectious pathogens in humans, and they cause significant mortality and morbidity in immunocompromised people as well as children and the elderly. After screening an FDA-approved drug library containing 1280 compounds by cytopathic effect (CPE) reduction assay using the Cell Counting Kit-8, we found two antihistamines, carbinoxamine maleate (CAM) and S-(+)-chlorpheniramine maleate (SCM) with potent antiviral activity against A/Shanghai/4664T/2013(H7N9) infection with IC50 (half-maximal inhibitory concentration) of 3.56 and 11.84 μM, respectively. Further studies showed that CAM and SCM could also inhibit infection by other influenza A viruses, including A/Shanghai/37T/2009(H1N1), A/Puerto Rico/8/1934(H1N1), A/Guizhou/54/1989(H3N2), and one influenza B virus, B/Shanghai/2017(BY). Mice were challenged intranasally with A/H7N9/4664T/2013 (H7N9) virus and intraperitoneally injected with CAM (10 mg/kg per day) or SCM (1 mg/kg per day) for 5 days. CAM or SCM (10 mg/kg per day) were fully protected against challenge with A/Shanghai/4664T/2013(H7N9). The results from mechanistic studies indicate that both could inhibit influenza virus infection by blocking viral entry into the target cell, the early stage of virus life cycle. However, CAM and SCM neither blocked virus attachment, characteristic of HA activity, nor virus release, characteristic of NA activity. Such data suggest that these two compounds may interfere with the endocytosis process. Thus, we have identified two FDA-approved antihistamine drugs, CAM and SCM, which can be repurposed for inhibiting infection by divergent influenza A strains and one influenza B strain with potential to be used for treatment and prevention of influenza virus infection
IgG Fc-binding motif-conjugated HIV-1 fusion inhibitor exhibits improved potency and in vivo half-life: Potential application in combination with broad neutralizing antibodies
The clinical application of conventional peptide drugs, such as the HIV-1 fusion inhibitor enfuvirtide,
is limited by their short half-life in vivo. To overcome this limitation, we developed a
new strategy to extend the in vivo half-life of a short HIV-1 fusion inhibitory peptide, CP24, by
fusing it with the human IgG Fc-binding peptide (IBP). The newly engineered peptide IBPCP24
exhibited potent and broad anti-HIV-1 activity with IC50 values ranging from 0.2 to
173.7 nM for inhibiting a broad spectrum of HIV-1 strains with different subtypes and tropisms,
including those resistant to enfuvirtide. Most importantly, its half-life in the plasma of
rhesus monkeys was 46.1 h, about 26- and 14-fold longer than that of CP24 (t1/2 = 1.7 h) and
enfuvirtide (t1/2 = 3 h), respectively. IBP-CP24 intravenously administered in rhesus monkeys
could not induce significant IBP-CP24-specific antibody response and it showed no obvious
in vitro or in vivo toxicity. In the prophylactic study, humanized mice pretreated with IBPCP24
were protected from HIV-1 infection. As a therapeutic treatment, coadministration of
IBP-CP24 and normal human IgG to humanized mice with chronic HIV-1 infection resulted in
a significant decrease of plasma viremia. Combining IBP-CP24 with a broad neutralizing antibody
(bNAb) targeting CD4-binding site (CD4bs) in gp120 or a membrane proximal external
region (MPER) in gp41 exhibited synergistic effect, resulting in significant dose-reduction of
the bNAb and IBP-CP24. These results suggest that IBP-CP24 has the potential to be further
developed as a new HIV-1 fusion inhibitor-based, long-acting anti-HIV drug that can be used
alone or in combination with a bNAb for treatment and prevention of HIV-1 infection
Outcomes of thoracic endovascular aortic repair with fenestrated surgeon-modified stent-graft for type B aortic dissections involving the aortic arch
ObjectivesThis retrospective analysis aimed to evaluate the early and midterm outcomes of thoracic endovascular aortic repair (TEVAR) with fenestrated surgeon-modified stent-graft (f-SMSG) for type B aortic dissections (TBAD) involving the aortic arch.MethodsFrom March 2016 to April 2021, 47 consecutive patients were treated using TEVAR with f-SMSG. All patients were diagnosed with TBAD involving the aortic arch.ResultsIn total, 47 patients with TBAD involving the aortic arch were treated with f-SMSGs. There were 21 zone 1 and 26 zone 2 TEVAR, and 65 arteries were revascularized successfully with fenestrations. Technical success was achieved in 46 patients (97.88%). The 30-day estimated survival (± SE) and reintervention was 93.6 ± 1.0% (95% Confidence Interval [CI], 92.6–94.6%) and 91.5 ± 1.2% (95% CI, 90.3–92.7%), respectively. During a median follow-up of 51 months (range, 16–71 months), 1 patient died of rupture of aortic dissection (AD) and 3 patients died of non-aortic-related reasons. Reintervention was performed for four patients, including two patients of type IA entry flow and two patients of type IB entry flow. No occlusion of the supra-aortic trunk was observed. The estimated survival and reintervention (± SE) at 4 years was 88.7 ± 1.4% (95% CI, 87.3–90.1%) and 84.8 ± 1.5% (95% CI, 83.3–86.3%), respectively.ConclusionThoracic endovascular aortic repair with f-SMSG is an alternative treatment option for TBAD involving the aortic arch in high-volume centers
Toward General-Purpose Robots via Foundation Models: A Survey and Meta-Analysis
Building general-purpose robots that can operate seamlessly, in any
environment, with any object, and utilizing various skills to complete diverse
tasks has been a long-standing goal in Artificial Intelligence. Unfortunately,
however, most existing robotic systems have been constrained - having been
designed for specific tasks, trained on specific datasets, and deployed within
specific environments. These systems usually require extensively-labeled data,
rely on task-specific models, have numerous generalization issues when deployed
in real-world scenarios, and struggle to remain robust to distribution shifts.
Motivated by the impressive open-set performance and content generation
capabilities of web-scale, large-capacity pre-trained models (i.e., foundation
models) in research fields such as Natural Language Processing (NLP) and
Computer Vision (CV), we devote this survey to exploring (i) how these existing
foundation models from NLP and CV can be applied to the field of robotics, and
also exploring (ii) what a robotics-specific foundation model would look like.
We begin by providing an overview of what constitutes a conventional robotic
system and the fundamental barriers to making it universally applicable. Next,
we establish a taxonomy to discuss current work exploring ways to leverage
existing foundation models for robotics and develop ones catered to robotics.
Finally, we discuss key challenges and promising future directions in using
foundation models for enabling general-purpose robotic systems. We encourage
readers to view our living GitHub repository of resources, including papers
reviewed in this survey as well as related projects and repositories for
developing foundation models for robotics
The Protective Role of Hyaluronic Acid in Cr(VI)-Induced Oxidative Damage in Corneal Epithelial Cells
Cr(VI) exposure could produce kinds of intermediates and reactive oxygen species, both of which were related to DNA damage. Hyaluronan (HA) has impressive biological functions and was reported to protect corneal epithelial cells against oxidative damage induced by ultraviolet B, benzalkonium chloride, and sodium lauryl sulfate. So the aim of our study was to investigate HA protection on human corneal epithelial (HCE) cells against Cr(VI)-induced toxic effects. The HCE cell lines were exposed to different concentrations of K2Cr2O7 (1.875, 3.75, 7.5, 15.0, and 30 μM) or a combination of K2Cr2O7 and 0.2% HA and incubated with different times (15 min, 30 min, and 60 min). Our data showed that Cr(VI) exposure could cause decreased cell viability, increased DNA damage, and ROS generation to the HCE cell lines. But incubation of HA increased HCE cell survival rates and decreased DNA damage and ROS generation induced by Cr(VI) in a dose- and time-dependent manner. We report for the first time that HA can protect HCE cells against the toxicity of Cr(VI), indicating that it will be a promising therapeutic agent to corneal injuries caused by Cr(VI)
Search for light dark matter from atmosphere in PandaX-4T
We report a search for light dark matter produced through the cascading decay
of mesons, which are created as a result of inelastic collisions between
cosmic rays and Earth's atmosphere. We introduce a new and general framework,
publicly accessible, designed to address boosted dark matter specifically, with
which a full and dedicated simulation including both elastic and quasi-elastic
processes of Earth attenuation effect on the dark matter particles arriving at
the detector is performed. In the PandaX-4T commissioning data of 0.63
tonneyear exposure, no significant excess over background is observed.
The first constraints on the interaction between light dark matter generated in
the atmosphere and nucleus through a light scalar mediator are obtained. The
lowest excluded cross-section is set at for
dark matter mass of MeV and mediator mass of 300 MeV. The
lowest upper limit of to dark matter decay branching ratio is
A Search for Light Fermionic Dark Matter Absorption on Electrons in PandaX-4T
We report a search on a sub-MeV fermionic dark matter absorbed by electrons
with an outgoing active neutrino using the 0.63 tonne-year exposure collected
by PandaX-4T liquid xenon experiment. No significant signals are observed over
the expected background. The data are interpreted into limits to the effective
couplings between such dark matter and electrons. For axial-vector or vector
interactions, our sensitivity is competitive in comparison to existing
astrophysical bounds on the decay of such dark matter into photon final states.
In particular, we present the first direct detection limits for an axial-vector
(vector) interaction which are the strongest in the mass range from 25 to 45
(35 to 50) keV/c
The Detrimental Role of Intraluminal Thrombus Outweighs Protective Advantage in Abdominal Aortic Aneurysm Pathogenesis: The Implications for the Anti-Platelet Therapy
Abdominal aortic aneurysm (AAA) is a common cardiovascular disease resulting in morbidity and mortality in older adults due to rupture. Currently, AAA treatment relies entirely on invasive surgical treatments, including open repair and endovascular, which carry risks for small aneurysms (diameter < 55 mm). There is an increasing need for the development of pharmacological intervention for early AAA. Over the last decade, it has been increasingly recognized that intraluminal thrombus (ILT) is involved in the growth, remodeling, and rupture of AAA. ILT has been described as having both biomechanically protective and biochemically destructive properties. Platelets are the second most abundant cells in blood circulation and play an integral role in the formation, expansion, and proteolytic activity of ILT. However, the role of platelets in the ILT-potentiated AAA progression/rupture remains unclear. Researchers are seeking pharmaceutical treatment strategies (e.g., anti-thrombotic/anti-platelet therapies) to prevent ILT formation or expansion in early AAA. In this review, we mainly focus on the following: (a) the formation/deposition of ILT in the progression of AAA; (b) the dual role of ILT in the progression of AAA (protective or detrimental); (c) the function of platelet activity in ILT formation; (d) the application of anti-platelet drugs in AAA. Herein, we present challenges and future work, which may motivate researchers to better explain the potential role of ILT in the pathogenesis of AAA and develop anti-platelet drugs for early AAA
Research on the Grinding Performance of an Electroplated Coarse-Grained Diamond Grinding Wheel by Dressing
The coarse-grained electroplated diamond grinding wheels is increasingly favored in precision grinding of hard and brittle materials owing to its high material removal efficiency, high wear resistance and steady surface contour accuracy. However, how to determine whether the dressed grinding wheel surface topography can achieve the desired precision ground surface quality is still a huge challenge to this day. In this paper, a novel numerical simulation model, which was established basing on the statistical features of actual electroplated coarse-grained diamond grinding wheel and the kinetics of the grinding process, was proposed for theoretically and thoroughly studying the influence of the surface dressing depth of coarse-grained electroplated diamond grinding wheel on ground workpiece surface morphology. At first, the statistical features of actual electroplated coarse-grained diamond grinding wheel was acquired and a novel numerical grinding wheel surface model was established. Subsequently, a numerical ground workpiece surface simulation model was also developed. And then, the evolving mechanism of the grinding wheel surface topography with the dressed wheel surface abrasive grain protrusion height was theoretically studied by numerical simulation. Moreover, the influence of the wheel surface abrasive grain protrusion height on the ground surface roughness was thoroughly researched by means of theoretical model and experiments. The simulation and experiments results in this paper indicated that precision ground workpiece surface with nano-scale surface roughness can be acquired by grinding with a dressed grinding wheel with a certain abrasive grain protrusion height of 25% of the typical abrasive size. Comparing with the undressed grinding wheel (grinding wheel with original surface topography and not be dressed), the surface roughness Sa and Sq of the surface ground with a well-dressed wheel can achieving a significant decrease of 97.75–99.77% and 97.57–99.73%, respectively. Therefore, carefully dressing the electroplated coarse-grained diamond grinding wheel is of great significance for obtaining a precision ground workpiece surface quality
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