Preclinical Absorption, Distribution, Metabolism, and Excretion of Sodium Danshensu, One of the Main Water-Soluble Ingredients in Salvia miltiorrhiza, in Rats

In this study, the absorption, distribution, metabolism and excretion (ADME) of sodium danshensu (Sodium DL-β-(3, 4-dihydroxyphenyl)lactate), one of the main water-soluble active constituents in Salvia miltiorrhiza, were evaluated in rats. Pharmacokinetic study was evaluated in doses of 15, 30, and 60 mg/kg after intravenous administration of sodium danshensu. Bioavailability study was evaluated by comparing between 30 mg/kg (I.V.) and 180 mg/kg (P.O.) of sodium danshensu. Tissue distribution, metabolism, and excretion were evaluated at 30 mg/kg (I.V.) of sodium danshensu. Following intravenous administration, sodium danshensu exhibited linear pharmacokinetics in the dose range of 15–60 mg/kg. Sodium danshensu appeared to be poorly absorbed after oral administration, with an absolute bioavailability of 13.72%. The primary distribution tissue was kidney, but it was also distributed to lung, stomach, muscle, uterus, heart, etc. Within 96 h after intravenous administration, 46.99% was excreted via urine and 1.16% was excreted via feces as the parent drug. Biliary excretion of sodium danshensu was about 0.83% for 24 h. Metabolites in urine were identified as methylation, sulfation, both methylation and sulfation, and acetylation of danshensu. Sodium danshensu can be developed as an injection because of its poor oral bioavailability. In conclusion, sodium danshensu is widely distributed, mainly phase II metabolized and excreted primarily in urine as an unchanged drug in rats

Self-Similar Tilings of Fractal Blow-Ups

New tilings of certain subsets of $\mathbb{R}^{M}$ are studied, tilings associated with fractal blow-ups of certain similitude iterated function systems (IFS). For each such IFS with attractor satisfying the open set condition, our construction produces a usually infinite family of tilings that satisfy the following properties: (1) the prototile set is finite; (2) the tilings are repetitive (quasiperiodic); (3) each family contains self-similartilings, usually infinitely many; and (4) when the IFS is rigid in an appropriate sense, the tiling has no non-trivial symmetry; in particular the tiling is non-periodic

Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes

AbstractVisual impairment due to glaucoma currently impacts 70 million people worldwide. While disease progression can be slowed or stopped with effective lowering of intraocular pressure, current medical treatments are often inadequate. Fortunately, three new classes of therapeutics that target the diseased conventional outflow tissue responsible for ocular hypertension are in the final stages of human testing. The rho kinase inhibitors have proven particularly efficacious and additive to current therapies. Unfortunately, non-contact technology that monitors the health of outflow tissue and its response to conventional outflow therapy is not available clinically. Using optical coherence tomographic (OCT) imaging and novel segmentation software, we present the first demonstration of drug effects on conventional outflow tissues in living eyes. Topical netarsudil (formerly AR-13324), a rho kinase/ norepinephrine transporter inhibitor, affected both proximal (trabecular meshwork and Schlemm’s Canal) and distal portions (intrascleral vessels) of the mouse conventional outflow tract. Hence, increased perfusion of outflow tissues was reliably resolved by OCT as widening of the trabecular meshwork and significant increases in cross-sectional area of Schlemm’s canal following netarsudil treatment. These changes occurred in conjunction with increased outflow facility, increased speckle variance intensity of outflow vessels, increased tracer deposition in conventional outflow tissues and decreased intraocular pressure. This is the first report using live imaging to show real-time drug effects on conventional outflow tissues and specifically the mechanism of action of netarsudil in mouse eyes. Advancements here pave the way for development of a clinic-friendly OCT platform for monitoring glaucoma therapy

A global monthly field of seawater pH over 3 decades: a machine learning approach

The continuous uptake of anthropogenic CO2 by the ocean leads to ocean acidification, which is an ongoing threat to the marine ecosystem. The ocean acidification rate was globally documented in the surface ocean but limited below the surface. Here, we present a monthly four-dimensional 1°×1° gridded product of global seawater pH, derived from a machine learning algorithm trained on pH observations at total scale and in-situ temperature from the Global Ocean Data Analysis Project (GLODAP). The constructed pH product covers the years 1992–2020 and depths from the surface to 2 km on 41 levels. Three types of machine learning algorithms were used in the pH product construction, including self-organizing map neural networks for region dividing, a stepwise algorithm for predictor selection, and feed-forward neural networks (FFNN) for non-linear relationship regression. The performance of the machine learning algorithm was validated using real observations by a cross validation method, where four repeating iterations were carried out with 25 % varied observations for each evaluation and 75 % for training. The constructed pH product is evaluated through comparisons to time series observations and the GLODAP pH climatology. The overall root mean square error between the FFNN constructed pH and the GLODAP measurements is 0.028, ranging from 0.044 in the surface to 0.013 at 2000 m. The pH product is distributed through the data repository of the Marine Science Data Center of the Chinese Academy of Sciences at http://dx.doi.org/10.12157/IOCAS.20230720.001 (Zhong et al., 2023)

On the Morphology, Structure and Field Emission Properties of Silver-Tetracyanoquinodimethane Nanostructures

Silver-tetracyanoquinodimethane(Ag-TCNQ) nanostructured arrays with different morphologies were grown by an organic vapor-transport reaction under different conditions. The field emission properties of nanostructured arrays were studied systematically. Their morphology and crystal structure were characterized by SEM and XRD, respectively. It was found that the field emission properties were strongly dependent on the reaction temperature and the initial Ag film thickness. The lowest turn-on field with 10-nm-thick silver film is about 2.0 V/μm, comparable to that of carbon nanotubes. The film crystal structure and the morphology are contributed to the final emission performance

Sodium Dichloroacetate Stimulates Angiogenesis by Improving Endothelial Precursor Cell Function in an AKT/GSK-3β/Nrf2 Dependent Pathway in Vascular Dementia Rats

Sodium dichloroacetate (DCA) is a mitochondrial pyruvate dehydrogenase kinase inhibitor, and has been shown to display vasoprotective effects in chronic ischemic stroke. The purpose of this study was to evaluate the therapeutic effect of DCA on vascular dementia (VD) and endothelial progenitor cell (EPC)-mediated angiogenesis. After cerebral ischemia-reperfusion in rats, DCA was administered continuously for 21 days; following which, histological analysis, and cognitive functional tests were conducted. Rat bone marrow-derived EPCs were isolated, their function and quantity were measured, and the effects of long-term administration of DCA on EPCs in a rat model of VD was studied. We found that long-term DCA administration improved cognitive function in VD rats, reduced brain infarct size and brain atrophy, increased VEGF and bFGF levels in vivo, promoted angiogenesis in damaged areas, and significantly improved EPC function in VD rats. Compared with the VD group, AKT, Nrf2, eNOS expression, and intracellular NO levels were elevated in EPCs of DCA-treated VD rats. In addition, GSK3β and intracellular ROS levels were decreased. Simultaneously, it was found that DCA directly acted on EPCs, and improved EPC functional behavior. Taken together, these findings suggested that long-term DCA administration improved cognitive function in a rat model of VD, and did so in part, by improving EPC function. Observations suggest that prolonged DCA administration might be beneficial in treating VD

An assessment of multimodal imaging of subsurface text in mummy cartonnage using surrogate papyrus phantoms

Ancient Egyptian mummies were often covered with an outer casing, panels and masks made from cartonnage: a lightweight material made from linen, plaster, and recycled papyrus held together with adhesive. Egyptologists, papyrologists, and historians aim to recover and read extant text on the papyrus contained within cartonnage layers, but some methods, such as dissolving mummy casings, are destructive. The use of an advanced range of different imaging modalities was investigated to test the feasibility of non-destructive approaches applied to multi-layered papyrus found in ancient Egyptian mummy cartonnage. Eight different techniques were compared by imaging four synthetic phantoms designed to provide robust, well-understood, yet relevant sample standards using modern papyrus and replica inks. The techniques include optical (multispectral imaging with reflection and transillumination, and optical coherence tomography), X-ray (X-ray fluorescence imaging, X-ray fluorescence spectroscopy, X-ray micro computed tomography and phase contrast X-ray) and terahertz-based approaches. Optical imaging techniques were able to detect inks on all four phantoms, but were unable to significantly penetrate papyrus. X-ray-based techniques were sensitive to iron-based inks with excellent penetration but were not able to detect carbon-based inks. However, using terahertz imaging, it was possible to detect carbon-based inks with good penetration but with less sensitivity to iron-based inks. The phantoms allowed reliable and repeatable tests to be made at multiple sites on three continents. The tests demonstrated that each imaging modality needs to be optimised for this particular application: it is, in general, not sufficient to repurpose an existing device without modification. Furthermore, it is likely that no single imaging technique will to be able to robustly detect and enable the reading of text within ancient Egyptian mummy cartonnage. However, by carefully selecting, optimising and combining techniques, text contained within these fragile and rare artefacts may eventually be open to non-destructive imaging, identification, and interpretation

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe