Engineering extracellular vesicles for therapeutic delivery in ischaemic stroke
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The assessment and aetiology of drug-induced ischaemic priapism
Ischaemic priapism is a urological emergency characterised by a prolonged, painful erection unrelated to sexual stimulation. While several aetiological factors contribute to this condition, the pharmacological causes have gained significant attention in recent years. This narrative review aims to comprehensively assess ischaemic priapism, specifically focusing on its pharmacological aetiology. We propose an approach and assessment strategy to the numerous factors associated with pharmacologically induced ischaemic priapism. By enhancing our understanding of the pharmacological causes of this condition, healthcare professionals can improve patient management and reduce the long-term complications associated with ischaemic priapism.
A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system
Reactive oxygen and nitrogen species (RONS) contribute to the pathogenesis of neurodegeneration, but the inability to detect RONS in vivo in the central nervous system has confounded the interpretation of results of clinical trials of antioxidants. Here we report the synthesis and characterization of a positron emission tomography (PET) probe, [18F]fluoroedaravone ([18F]FEDV), for the in vivo quantification of oxidative stress. Derived from the antioxidant edaravone, the probe can diffuse through the blood–brain barrier and is stable in human plasma. In mice, PET imaging with [18F]FEDV allowed for the detection of RONS after intrastriatal injection of sodium nitroprusside, in the middle cerebral artery after stroke by photothrombosis, and in brains with tauopathy. When using dynamic PET imaging coupled with parametric mapping, the sensitivity of [18F]FEDV-PET to RONS allowed for the detection of increased oxidative stress. [18F]FEDV-PET could be used to quantify RONS longitudinally in vivo and to assess the results of clinical studies of antioxidants.
Catalytic dwell oscillations complete the F1-ATPase mechanism
The F1-ATPase molecular motor rotates subunit-γ in 120° power strokes within its ring of three catalytic sites separated by catalytic dwells for ATP hydrolysis and Pi release. By monitoring rotary position of subunit-γ in E. coli F1 every 5 μs, we resolved Stage-1 catalytic dwell oscillations that extend from -13° to 13° centered at 0° consistent with F1 structures containing transition state inhibitors, which decay by a first order process consistent with ATP hydrolysis. During Stage-2, 80% of the oscillations extend from 3° and 25° centered at 14°, while 20% are centered at 33° and can extend to 27°–44° comparable to the ATP binding position. Remarkably, in Stage-3 subunit-γ returns to 0° to end the catalytic dwell, which keeps the start of power strokes in phase for consecutive rotational events. These newly observed states fit with F1 structures that were inconsistent with the canonical mechanism, and indicate that catalytic dwell oscillations must persist until the correct occupancy of substrates and products occurs at all three catalytic sites. When that condition is met, F1 can proceed to the next power stroke. Understanding the basis of these catalytic dwell oscillations completes the F1-ATPase rotary mechanism.
Determinants of consumer intention to use autonomous delivery vehicles: based on the planned behavior theory and normative activation model
Autonomous delivery vehicles (ADVs) that provide contactless services have attracted much academic and practical attention in China in recent years. Despite this, there is a lack of in-depth research on what motivates customers to embrace ADVs. The study integrates the theory of planned behavior (TPB) and normative activation model (NAM) and explores how environmental factors, situational factors, and individual factors affect original TPB constructs and ultimately consumers’ intention to use ADVs. Structural equation modeling was performed on survey data of 561 Chinese consumers through an online sampling platform. The results show that among the factors affecting consumer intention, word-of-mouth recommendations have the greatest impact, followed by perceived enjoyment, COVID-19 risk, ascription of responsibility, subjective norm, attitude, and perceived behavioral control. The results not only make important theoretical contributions to the technology acceptance fields but also provide helpful references to logistics enterprises, ADVs technology providers, and policymakers.
Universal relations and bounds for fluctuations in quasistatic small heat engines
The efficiency of any heat engine, defined as the ratio of average work output to heat input, is bounded by Carnot’s celebrated result. However, this measure is insufficient to characterize the properties of miniaturized heat engines carrying non-negligible fluctuations, and a study of higher-order statistics of their energy exchanges is required. Here, we generalize Carnot’s result for reversible cycles to arbitrary order moment of the work and heat fluctuations. Our results show that, in the quasistatic limit, higher-order statistics of a small engine’s energetics depend solely on the ratio between the temperatures of the thermal baths. We further prove that our result for the second moment gives universal bounds for the ratio between the variances of work and heat for quasistatic cycles. We test this theory with our previous experimental results of a Brownian Carnot engine and observe the consistency between them, even beyond the quasistatic regime. Our results can be exploited in the design of thermal nanomachines to reduce their fluctuations of work output without marginalizing its average value and efficiency.
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