Z-ligustilide reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling pathways

Purpose: To investigate the effect of Z-ligustilide (Z-lig) on cisplatin-induced nephrotoxicity and examine whether NRF2 signaling mediates the underlying mechanism of action.Methods: Human proximal tubular epithelial cells (HK-2) were pretreated with 20 or 100 μM Z-lig for 2 h, followed by 10 μM cisplatin treatment for 24 h. Cell viability was measured using (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A commercial kit was used todetermine lactate dehydrogenase (LDH) release. Apoptosis was determined by flow cytometry while Western blotting was used to evaluate protein levels. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) were assessed by enzymelinked immunosorbent assay (ELISA).Results: Cisplatin decreased HK-2 cell viability and increased LDH release, while Z-lig increased cell viability and decreased LDH release in a dose-dependent manner (p < 0.05). Moreover, Z-lig reduced cisplatin-induced apoptosis (p < 0.01), and alleviated cellular oxidative stress caused by cisplatin (p < 0.05). Furthermore, Z-lig activated NRF2/HO-1 signaling in cells treated with cisplatin (p < 0.05).Conclusion: Z-lig reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling. Thus, Z-lig is a potential drug for the treatment of nephrotoxicity caused by cisplatin. Keywords: Z-ligustilide, Cisplatin, Nephrotoxicity, Oxidative stress, Apoptosis, Nuclear factor erythroid 2-related factor 2, Heme oxygenase-

Potentialities of Hubble parameter and expansion rate function data to alleviate Hubble tension

Taking advantage of Gaussian process (GP), we obtain an improved estimate of the Hubble constant, $H_0=70.41\pm1.58$ km s$^{-1}$ Mpc$^{-1}$, using Hubble parameter [$H(z)$] from cosmic chronometers (CCH) and expansion rate function [$E(z)$], extracted from type Ia supernovae, data. This result is higher than those obtained by directly reconstructing CCH data with GP. In order to estimate the potential of future CCH data, we simulate two sets of $H(z)$ data and use them to constrain $H_0$ by either using GP reconstruction or fitting them with $E(z)$ data. We find that simulated $H(z)$ data alleviate $H_0$ tension by pushing $H_0$ values higher towards $\sim70$ km s$^{-1}$ Mpc$^{-1}$. We also find that joint $H(z)$ + $E(z)$ data favor higher values of $H_0$, which is also confirmed by constraining $H_0$ in the flat concordance model and 2-order Taylor expansion of $H(z)$. In summary, we conclude that more and better-quality CCH data as well as $E(z)$ data can provide a new and useful perspective on resolving $H_0$ tension.Comment: 11 pages, 8 figure

Sharper Asymptotically Optimal CDC Schemes via Combinatorial Designs

Coded distributed computing (CDC) was introduced to greatly reduce the communication load for MapReduce computing systems. Such a system has $K$ nodes, $N$ input files, and $Q$ Reduce functions. Each input file is mapped by $r$ nodes and each Reduce function is computed by $s$ nodes. The architecture must allow for coding techniques that achieve the maximum multicast gain. Some CDC schemes that achieve optimal communication load have been proposed before. The parameters $N$ and $Q$ in those schemes, however, grow too fast with respect to $K$ to be of great practical value. To improve the situation, researchers have come up with some asymptotically optimal cascaded CDC schemes with $s+r=K$ from symmetric designs. In this paper, we propose new asymptotically optimal cascaded CDC schemes. Akin to known schemes, ours have $r+s=K$ and make use of symmetric designs as construction tools. Unlike previous schemes, ours have much smaller communication loads, given the same set of parameters $K$, $r$, $N$, and $Q$. We also expand the construction tools to include almost difference sets. Using them, we have managed to construct a new asymptotically optimal cascaded CDC scheme

A Construction of Asymptotically Optimal Cascaded CDC Schemes via Combinatorial Designs

A coded distributed computing (CDC) system aims to reduce the communication load in the MapReduce framework. Such a system has $K$ nodes, $N$ input files, and $Q$ Reduce functions. Each input file is mapped by $r$ nodes and each Reduce function is computed by $s$ nodes. The objective is to achieve the maximum multicast gain. There are known CDC schemes that achieve optimal communication load. In some prominent known schemes, however, $N$ and $Q$ grow too fast in terms of $K$, greatly reducing their gains in practical scenarios. To mitigate the situation, some asymptotically optimal cascaded CDC schemes with $r=s$ have been proposed by using symmetric designs. In this paper, we put forward new asymptotically optimal cascaded CDC schemes with $r=s$ by using $1$-designs. Compared with earlier schemes from symmetric designs, ours have much smaller computation loads while keeping the other relevant parameters the same. We also obtain new asymptotically optimal cascaded CDC schemes with more flexible parameters compared with previously best-performing schemes

Dark structures in sunspot light bridges

We present unprecedented high-resolution TiO images and Fe I 1565 nm spectropolarimetric data of two light bridges taken by the 1.6-m Goode Solar Telescope at Big Bear Solar Observatory. In the first light bridge (LB1), we find striking knot-like dark structures within the central dark lane. Many dark knots show migration away from the penumbra along the light bridge. The sizes, intensity depressions and apparent speeds of their proper motion along the light bridges of 33 dark knots identified from the TiO images are mainly in the ranges of 80$\sim$200~km, 30\%$\sim$50\%, and 0.3$\sim$1.2~km~s$^{-1}$, respectively. In the second light bridge (LB2), a faint central dark lane and striking transverse intergranular lanes were observed. These intergranular lanes have sizes and intensity depressions comparable to those of the dark knots in LB1, and also migrate away from the penumbra at similar speeds. Our observations reveal that LB2 is made up of a chain of evolving convection cells, as indicated by patches of blue shift surrounded by narrow lanes of red shift. The central dark lane generally corresponds to blueshifts, supporting the previous suggestion of central dark lanes being the top parts of convection upflows. In contrast, the intergranular lanes are associated with redshifts and located at two sides of each convection cell. The magnetic fields are stronger in intergranular lanes than in the central dark lane. These results suggest that these intergranular lanes are manifestations of convergent convective downflows in the light bridge. We also provide evidence that the dark knots observed in LB1 may have a similar origin.Comment: 6 figure

An Ear Wearable Device System for Facial Emotion Recognition Disorders

A wearable device system was proposed in the present work to address the problem of facial emotion recognition disorders. The proposed system could comprehensively analyze the user’s own stress status, emotions of people around, and the surrounding environment. The system consists of a multi-dimensional physiological signals acquisition module, an image acquisition and transmission module, a user interface of the user mobile terminal, and a cloud database for data storage. Moreover, a deep learning based multi-model physiological signal pressure recognition algorithm and a facial emotion recognition algorithm were designed and implemented in the system. Some publicly available data sets were used to test the two algorithms, and the experiment results showed that the two algorithms could well realize the expected functions of the system

Mechanism of Guilu Erxian ointment based on targeted metabolomics in intervening in vitro fertilization and embryo transfer outcome in older patients with poor ovarian response of kidney-qi deficiency type

ObjectiveTo study the effect of Guilu Erxian ointment on the outcome of IVF-ET in older patients with poor ovarian response infertility of kidney-qi deficiency type, and to verify and analyze the mechanism of action of traditional Chinese medicine on improving older patients with poor ovarian response infertility of kidney-qi deficiency type from the perspective of metabolomics using targeted metabolomics technology, identify the related metabolic pathways, and provide metabolic biomarker basis and clinical treatment ideas for improving older patients with poor ovarian response infertility.MethodsThis study was a double-blind, randomized, placebo-controlled trial, and a total of 119 infertile patients who underwent IVF-ET at Shandong Center for Reproduction and Genetics of Integrated Traditional Chinese and Western Medicine were selected. Eighty older patients with infertility undergoing IVF were randomly divided into older treatment group and older placebo group, and another 39 young healthy women who underwent IVF-ET or ICSI due to male factors were selected as the normal control group. Flexible GnRH antagonist protocol was used for ovulation induction in all three groups, and Guilu Erxian ointment and placebo groups started taking Guilu Erxian ointment and placebo from the third day of menstruation until IVF surgery. And ultra-high performance liquid chromatography-triple quadrupole mass spectrometer (UHPLC-QTRAP MS) was used to detect metabolites in the three groups of samples.ResultsCompared with the placebo group, the number of oocytes retrieved, 2PN fertilization, high-quality embryos, total number of available embryos and estrogen on HCG day were increased in the treatment group, and the differences were statistically significant (P > 0.05), but the clinical pregnancy rate of fresh embryos and frozen embryos were not statistically significant (P > 0.05). The results of targeted metabolomics analysis showed that follicular fluid in the treatment group clustered with the normal young group and deviated from the placebo group. A total of 55 significant differential metabolites were found in the follicular fluid of older patients with poor ovarian response of kidney-qi deficiency type and patients in the normal young group, after Guilu Erxian ointment intervention, Metabolites such as L-Aspartic acid, Glycine, L-Serine, Palmitoleic Acid, Palmitelaidic acid, L-Alanine, Gamma-Linolenic acid, Alpha-Linolenic Acid, and N-acetyltryptophan were down-regulated, mainly involving amino acid metabolism and fatty acid metabolism.ConclusionGuilu Erxian ointment can effectively improve the clinical symptoms and IVF outcomes of older patients with poor ovarian response of kidney-qi deficiency type. There were differences in follicular fluid metabolites between older patients with poor ovarian response of kidney-qi deficiency type and normal women. L-Aspartic acid, L-Alanine, Aminoadipic acid, L-Asparagine, L-Arginine, L-Serine, Gamma- Linolenic acid, Pentadecanoic acid and Alpha-Linolenic Acid are closely related to older patients with poor ovarian response due to deficiency of kidney-qi and may be inferred as biomarkers. The mechanism of Guilu Erxian ointment intervention may be mainly through amino acid metabolism and fatty acid metabolism regulation