Wave of single-impulse-stimulated fast initial dip in single vessels of mouse brains imaged by high-speed functional photoacoustic microscopy

Significance: The initial dip in hemoglobin-oxygenation response to stimulations is a spatially confined endogenous indicator that is faster than the blood flow response, making it a desired label-free contrast to map the neural activity. A fundamental question is whether a single-impulse stimulus, much shorter than the response delay, could produce an observable initial dip without repeated stimulation. Aim: To answer this question, we report high-speed functional photoacoustic (PA) microscopy to investigate the initial dip in mouse brains. Approach: We developed a Raman-laser-based dual-wavelength functional PA microscope that can image capillary-level blood oxygenation at a 1-MHz one-dimensional imaging rate. This technology was applied to monitor the hemodynamics of mouse cerebral vasculature after applying an impulse stimulus to the forepaw. Results: We observed a transient initial dip in cerebral microvessels starting as early as 0.13 s after the onset of the stimulus. The initial dip and the subsequent overshoot manifested a wave pattern propagating across different microvascular compartments. Conclusions: We quantified both spatially and temporally the single-impulse-stimulated microvascular hemodynamics in mouse brains at single-vessel resolution. Fast label-free imaging of single-impulse response holds promise for real-time brain–computer interfaces

Wave of single-impulse-stimulated fast initial dip in single vessels of mouse brains imaged by high-speed functional photoacoustic microscopy

Significance: The initial dip in hemoglobin-oxygenation response to stimulations is a spatially confined endogenous indicator that is faster than the blood flow response, making it a desired label-free contrast to map the neural activity. A fundamental question is whether a single-impulse stimulus, much shorter than the response delay, could produce an observable initial dip without repeated stimulation. Aim: To answer this question, we report high-speed functional photoacoustic (PA) microscopy to investigate the initial dip in mouse brains. Approach: We developed a Raman-laser-based dual-wavelength functional PA microscope that can image capillary-level blood oxygenation at a 1-MHz one-dimensional imaging rate. This technology was applied to monitor the hemodynamics of mouse cerebral vasculature after applying an impulse stimulus to the forepaw. Results: We observed a transient initial dip in cerebral microvessels starting as early as 0.13 s after the onset of the stimulus. The initial dip and the subsequent overshoot manifested a wave pattern propagating across different microvascular compartments. Conclusions: We quantified both spatially and temporally the single-impulse-stimulated microvascular hemodynamics in mouse brains at single-vessel resolution. Fast label-free imaging of single-impulse response holds promise for real-time brain–computer interfaces

The bidirectional interation between pancreatic cancer and diabetes

Abstract The bidirectional interation between pancreatic cancer (PanCa) and diabetes has been confirmed by epidemiological studies, which provide evidence-based medical support for further research into the mechanisms involved in the interaction. We reviewed the literature regarding the role of diabetes in the generation and progression of PanCa and the mechanism by which PanCa induces diabetes for its malignant progression. The effect of antidiabetic drugs on the occurrence and prognosis of PanCa was also reviewed. Diabetes may directly promote the progression of PanCa by pancreatic duct enlargement and hypertension, as well as by enabling an increased tumor volume. Hyperinsulinemia, insulin resistance, cytokines, hyperglycemia and genotype change are also important factors in the progression of PanCa with diabetes. Hyperglycemia may be the first clinical manifestation and is helpful in the early diagnosis of PanCa. Furthermore, antidiabetic drugs can have different effects on the occurrence and prognosis of PanCa. The bidirectional interation between PanCa and diabetes is involved in the occurrence, proliferation, invasion, metastasis and prognosis of PanCa with diabetes. The discovery of biomarkers for the early diagnosis of PanCa, as well as the novel usage of metformin for its antitumor effects and determining the potential mechanisms of these effects, may be the next direction for PanCa research and treatment.</p

A Truncated IL‐17RC Peptide Ameliorates Synovitis and Bone Destruction of Arthritic Mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134880/1/adhm201600668_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134880/2/adhm201600668-sup-0001-S1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134880/3/adhm201600668.pd

Rapid and Visual Detection of Monkey B Virus Based on Recombinase Polymerase Amplification

Monkey B virus (BV) infection in humans and other macaque species has a mortality rate of approximately 80%. Because BV infects humans through bites, scratches, and other injuries inflicted by macaques, the simple and rapid diagnosis of BV in field laboratories is of great importance to protect veterinarians, laboratory researchers, and support personnels from the threat of infection. Two recombinase polymerase amplification (RPA) assays with a closed vertical flow (VF) visualization strip (RPA-VF-UL27 and RPA-VF-US6) were developed that target two conserved genes combined with a one-off, closed visualization strip device. We compared the sensitivities and specificities of the two assays after optimization of the reaction conditions. The performance of RPA-VF-US6 at room temperature was determined to evaluate its potential in point-of-care (POC) testing. RPA-VF-US6 specifically detected the positive plasmid control (rather than nucleic acids of herpesviruses) with a detection limit of 28 copies, while RPA-VF-UL27 had cross-reactivity with HSV-1, but even 3.4 copies of plasmid standards were readout by this assay. Moreover, RPA-VF-US6 had excellent performance at room temperature (the detection limit was 2,800 plasmid copies), indicating the potential of RPA-VF-US6 in POC testing. We developed two RPA assays for BV visualization diagnosis. RPA-VF-US6 is a simple, rapid, and specific detection method for BV. The entire reaction can be performed at a constant temperature within 30 min, suggesting the potential of RPA-VF-US6 for POC testing in field laboratories without sophisticated instruments

Confined conversion of CuS nanowires to CuO nanotubes by annealing-induced diffusion in nanochannels

Copper oxide (CuO) nanotubes were successfully converted from CuS nanowires embedded in anodic aluminum oxide (AAO) template by annealing-induced diffusion in a confined tube-type space. The spreading of CuO and formation of CuO layer on the nanochannel surface of AAO, and the confinement offered by AAO nanochannels play a key role in the formation of CuO nanotubes

Analysis of the Constituents in Rat Serum after Oral Administration of Fufang Zhenzhu Tiaozhi Capsule by UPLC–Q–TOF–MS/MS

A rapid and sensitive UPLC/Q–TOF–MS method has been established for analysis of the constituents in rat serum after oral administration of Fufang Zhenzhu Tiaozhi (FTZ) capsule, an effective compound prescription for treating hyperlipidemia in the clinic. The UPLC/MS information of samples was obtained first in FTZ preparation and FTZ-treated rat serum. Mass spectra were acquired in both negative and positive ion modes. Thirty-six constituents in rat serum after oral administration of FTZ were detected, including the alkaloids, ginsenosides, pentacyclic triterpenes, and their metabolites. These chemicals were identified based on the retention time and mass spectrometry data with those of authentic standards or comparison of the literatures reports. Twenty-seven prototype components originated from FTZ and nine were the metabolites of the FTZ constituents. These results shed light on the potential active constituents of the complex traditional Chinese medicinal formulas

Dual inhibition of AKT‐mTOR and AR signaling by targeting HDAC3 in PTEN‐ or SPOP‐mutated prostate cancer

Abstract AKT‐mTOR and androgen receptor (AR) signaling pathways are aberrantly activated in prostate cancer due to frequent PTEN deletions or SPOP mutations. A clinical barrier is that targeting one of them often activates the other. Here, we demonstrate that HDAC3 augments AKT phosphorylation in prostate cancer cells and its overexpression correlates with AKT phosphorylation in patient samples. HDAC3 facilitates lysine‐63‐chain polyubiquitination and phosphorylation of AKT, and this effect is mediated by AKT deacetylation at lysine 14 and 20 residues and HDAC3 interaction with the scaffold protein APPL1. Conditional homozygous deletion of Hdac3 suppresses prostate tumorigenesis and progression by concomitant blockade of AKT and AR signaling in the Pten knockout mouse model. Pharmacological inhibition of HDAC3 using a selective HDAC3 inhibitor RGFP966 inhibits growth of both PTEN‐deficient and SPOP‐mutated prostate cancer cells in culture, patient‐derived organoids and xenografts in mice. Our study identifies HDAC3 as a common upstream activator of AKT and AR signaling and reveals that dual inhibition of AKT and AR pathways is achievable by single‐agent targeting of HDAC3 in prostate cancer

Optical Properties of Magnetic Monopole Excitons

Here we consider theoretically an exciton-like dipole formed by a magnetic monopole and a magnetic antimonopole. This type of quasiparticles may be formed in a magnetic counterpart of a one dimensional semiconductor crystal. We use the familiar Lorentz driven damped harmonic oscillator model to find the eigenmodes of magnetic monopole dipoles strongly coupled to light. The proposed model allows predicting optical signatures of magnetic monopole excitons in crystals