A long-standing challenge in optical neuroimaging has been the assessment of hemodynamics and oxygen metabolism in the awake rodent brain at the microscopic level. Here, we report first-of-a-kind head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin, and blood flow in awake mice. Combining these hemodynamic measurements allows us to derive two key metabolic parameters—oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2). This enabling technology offers the first opportunity to comprehensively and quantitatively characterize the hemodynamic and oxygen-metabolic responses of the mouse brain to isoflurane, a general anesthetic widely used in preclinical research and clinical practice. Side-by-side comparison of the awake and anesthetized brains reveals that isoflurane induces diameter-dependent arterial dilation, elevated blood flow, and reduced OEF in a dose-dependent manner. As a result of the combined effects, CMRO2 is significantly reduced in the anesthetized brain under both normoxia and hypoxia, which suggests a mechanism for anesthetic neuroprotection. The head-restrained functional and metabolic PAM opens a new avenue for basic and translational research on neurovascular coupling without the strong influence of anesthesia and on the neuroprotective effects of various interventions, including but not limited to volatile anesthetics, against cerebral hypoxia and ischemia.

We report a new type of carbon nanotube ring (CNTR) coated with gold nanoparticles (CNTR@AuNPs) using CNTR as a template and surface attached redox-active polymer as a reducing agent. This nanostructure of CNTR bundle embedded in the gap of closely attached AuNPs can play multiple roles as a Raman probe to detect cancer cells and a photoacoustic (PA) contrast agent for imaging-guided cancer therapy. The CNTR@AuNP exhibits substantially higher Raman and optical signals than CNTR coated with a complete Au shell (CNTR@ AuNS) and straight CNT@AuNP. The extinction intensity of CNTR@AuNP is about 120-fold higher than that of CNTR at 808 nm, and the surface enhanced Raman scattering (SERS) signal of CNTR@AuNP is about 110 times stronger than that of CNTR, presumably due to the combined effects of enhanced coupling between the embedded CNTR and the plasmon mode of the closely attached AuNPs, and the strong electromagnetic field in the cavity of the AuNP shell originated from the intercoupling of AuNPs. The greatly enhanced PA signal and photothermal conversion property of CNTR@AuNP were successfully employed for imaging and imaging-guided cancer therapy in two tumor xenograft models. Experimental observations were further supported by numerical simulations and perturbation theory analysis.

Capitalizing on the optical absorption of hemoglobin, photoacoustic microscopy (PAM) is uniquely capable of anatomical and functional characterization of the intact microcirculation in vivo. However, PAM of the metabolic rate of oxygen (MRO₂) at the microscopic level remains an unmet challenge, mainly due to the inability to simultaneously quantify microvascular diameter, oxygen saturation of hemoglobin (sO₂), and blood flow at the same spatial scale. To fill this technical gap, we have developed a multi-parametric PAM platform. By analyzing both the sO₂-encoded spectral dependence and the flow-induced temporal decorrelation of photoacoustic signals generated by the raster-scanned mouse ear vasculature, we demonstrated-for the first time-simultaneous wide-field PAM of all three parameters down to the capillary level in vivo.

A simple process to prepare monodisperse ferrimagnetic cobalt-substituted magnetite Co(x)Fe(3-x)O4 nanoparticles is reported. These ferrimagnetic nanoparticles are readily dispersed in hexane, forming a stable ferrimagnetic nanoparticle dispersion, and allowing easy nanoparticle self-assembly. When assembled under an external magnetic field (5.5 kOe), these nanoparticles show preferred magnetic alignment with their H(c) reaching 2.49 kOe.

Solid templates have been long regarded as one of the most promising ways to achieve single-shelled hollow nanostructures; however, few effective methods for the construction of multishelled hollow objects from their solid template counterparts have been developed. We report here, for the first time, a novel and convenient route to synthesizing double-shelled hollow spheres from the solid templates via programming the reaction-temperature procedures. The programmed temperature strategy developed in this work then provides an essential and general access to multishelled hollow nanostructures based on the designed extension of single-shelled hollow objects, independent of their outside contours, such as tubes, hollow spheres, and cubes. Starting from the V(OH)(2)NH(2) solid templates, we show that the relationship between the hollowing rate and the reaction temperature obey the Van't Hoff rule and Arrhenius activation-energy equation, revealing that it is the chemical reaction rather than the diffusion process that guided the whole hollowing process, despite the fact that the coupled reaction/diffusion process is involved in the hollowing process. Using the double-shelled hollow spheres as the PCM (CaCl(2).6H(2)O) matrix grants much better thermal-storage stability than that for the nanoparticles counterpart, revealing that the designed nanostructures can give rise to significant improvements for the energy-saving performance in future "smart house" systems.

Capable of mediating efficient transfection and protein production without eliciting innate immune responses, chemically modified mRNA holds great potential to produce paracrine factors at a physiologically beneficial level, in a spatiotemporally controlled manner, and with low toxicity. Although highly promising in cardiovascular medicine and wound healing, effects of this emerging therapeutic on the microvasculature and its bioactivity in disease settings remain poorly understood. Here, we longitudinally and comprehensively characterize microvascular responses to AZD8601, a modified mRNA encoding vascular endothelial growth factor A (VEGF-A), in vivo. Using multi-parametric photoacoustic microscopy, we show that intradermal injection of AZD8601 formulated in a biocompatible vehicle results in pronounced, sustained and dose-dependent vasodilation, blood flow upregulation, and neovessel formation, in striking contrast to those induced by recombinant human VEGF-A protein, a non-translatable variant of AZD8601, and citrate/saline vehicle. Moreover, we evaluate the bioactivity of AZD8601 in a mouse model of diabetic wound healing in vivo. Using a boron nanoparticle-based tissue oxygen sensor, we show that sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing.

High-resolution quantitative imaging of cerebral oxygen metabolism in mice is crucial for understanding brain functions and formulating new strategies to treat neurological disorders, but remains a challenge. Here, we report on our newly developed ultrasound-aided multi-parametric photoacoustic microscopy (PAM), which enables simultaneous quantification of the total concentration of hemoglobin (C Hb ), the oxygen saturation of hemoglobin (sO 2 ), and cerebral blood flow (CBF) at the microscopic level and through the intact mouse skull. The three-dimensional skull and vascular anatomies delineated by the dual-contrast (i.e., ultrasonic and photoacoustic) system provide important guidance for dynamically focused contour scan and vessel orientation-dependent correction of CBF, respectively. Moreover, bi-directional raster scan allows determining the direction of blood flow in individual vessels. Capable of imaging all three hemodynamic parameters at the same spatiotemporal scale, our ultrasound-aided PAM fills a critical gap in preclinical neuroimaging and lays the foundation for high-resolution mapping of the cerebral metabolic rate of oxygen (CMRO 2 )-a quantitative index of cerebral oxygen metabolism. This technical innovation is expected to shed new light on the mechanism and treatment of a broad spectrum of neurological disorders, including Alzheimer's disease and ischemic stroke. The brain accounts for more than 20% of our oxygen consumption at the resting state 1 . Disruptions in cerebral oxygen metabolism play a key role in the initiation and progression of multiple life-threatening brain disorders, in particular Alzheimer's disease and ischemic stroke 2,3 . High-resolution imaging of the cerebral metabolic rate of oxygen (CMRO 2 ) in mice-a species with abundant disease models and genetic manipulations available-is crucial for understanding elusive pathogenic mechanisms and formulating new therapeutic strategies. However, existing techniques have yet to achieve this goal. Positron emission tomography (PET) allows quantifying CMRO 2 in absolute values, but lacks the spatial resolution to image the mouse brain 4,5 . Combining optical intrinsic signal and laser speckle imaging allows measuring CMRO 2 at the mesoscopic level, but rather qualitative 6,7 . Functional ultrasound enables high resolution imaging of the cerebral blood flow across the entire rodent brain 8,9 , but does not have access to the functional information of blood oxygenation.Photoacoustic microscopy (PAM) 10-12 holds great potential to address this long-standing challenge. Capitalizing on the optical absorption of hemoglobin-the primary carrier of oxygen in the circulation, PAM allows in vivo characterization of vascular anatomy 13,14 , hemodynamics 15 , and vasoactivity [16][17][18] . By measuring the total concentration of hemoglobin (C Hb ), the oxygen saturation of hemoglobin (sO 2 ), and blood flow at selected locations in feeding arteries and draining veins, Yao et al. previously demonstrated PAM of the total metabolic rate of oxygen ...

We study real-time correlators in the warped AdS/CFT correspondence. We apply the prescription used in the usual AdS/CFT correspondence and obtain the retarded Green's functions for the scalar and vector fields in the spacelike warped and the null warped black hole backgrounds. We find that the retarded Green's functions and the cross sections are well consistent with the predictions from dual CFT. Our results not only support strongly the conjectured warped AdS/CFT correspondence, but also show that the usual relativistic AdS/CFT prescription of obtaining the real-time correlators remain effective in more general backgrounds with anisotropic conformal infinity.Comment: 27 page