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To explore the effect of acacetin on myocardial mitochondrial dysfunction in spontaneously hypertensive rats (SHR) with insulin resistance (IR), and the possible mechanism. Rapid IR was first induced in fructose-fed SHR, and they were then treated with acacetin (25, 50 mg/kg). After 7 weeks, the rats were tested for hypertension, IR, cardiac function, and mitochondrial damage status. Potential mechanisms of action were explored in terms of oxidative stress, mitochondrial fission and division, apoptosis, and the insulin signaling pathway. Subsequently, the PI3K gene was silenced, after intervention with acacetin (5 μM) for 24 h, and H

A new flavonoid, saffloflavone , along with six known compounds, kaempferol-3-O-rutinoside, kaempferol-3-O-sophoroside, quercetin-3-O-β-d-glucoside, quercetin-7-O-β-d-glucoside, luteolin-7-O-β-d-glucoside and kaempferol 3-O-β-d-glucoside were isolated from the flowers of Carthamus tinctorius L. All the structures were determined by interpretation of their spectroscopic data. The cardioprotective effects of all the isolates against oxidative stress of H9c2 cells induced by H2O2 were investigated. The results showed that compounds 4-6 exhibited protective effects against of H9c2 cells injury induced by H2O2.

In this work, new ACu3Ti4O12 (A = Sr, La2/3, Ca, Y2/3) negative temperature coefficient (NTC) ceramics have been successfully fabricated by traditional solid-state reaction method. XRD analysis shows that the ACu3Ti4O12 ceramics are of the CaCu3Ti4O12 phase with body-centered cubic structure, suggesting that the change of A-site ion does not change the crystal structure. The scanning electron microscope image shows that the difference of A-site ion in ACu3Ti4O12 results in the different micromorphology. The X-ray photoelectron spectroscopy analysis further confirms the coexistence of Cu+/Cu2+ and/or Ti3+/Ti4+ in the compounds, which are one of the important factors for the electrical conductivity in ACu3Ti4O12 ceramics. Electrical performance analysis proves that the effect of grain size on resistivity is greater than that of the A-site ion species. The resistivity decreases with increasing temperature from 25 to 500 °C, indicative of NTC characteristics.

Yang Fu,1,2 Peipei Yuan,1,2 Yajuan Zheng,1 Yaxin Wei,1 Liyuan Gao,1 Yuan Ruan,1 Yi Chen,1 Panying Li,1 Weisheng Feng,1,2 Xiaoke Zheng1,2 1Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China; 2The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, 450046, People’s Republic of ChinaCorrespondence: Xiaoke Zheng; Weisheng Feng, Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China, Email zhengxk.2006@163.com; fwsh@hactcm.edu.cnPurpose: Pseudoephedrine (PSE) has rapid absorption and metabolism, which limits its pharmacologic actions. We postulated that pseudoephedrine nanoparticles (PSE-NPs) with high bioavailability could overcome this limitation. The defensive function of PSE-NPs nanoparticles against adriamycin-induced reproductive toxicity in mice was studied.Methods: We encapsulated PSE in polylactide-polyglycolide nanoparticles (PLGA-NPs) and verified their protective activity against testicular injury in vivo and in vitro.Results: We report a promising delivery system that loads PSE into PLGA-NPs and finally assembles it into a nanocomposite particle. In vitro, PSE-NPs reduced the adriamycin-induced apoptosis of GC-1 cells significantly, improved mitochondrial energy metabolism and promoted expression of the proteins related to the gonadotropin-releasing hormone (GnRh) receptor signaling pathway. In vivo, evaluation of sperm indices and histology showed that adriamycin could induce testicular toxicity. PSE-NPs significantly increased the sperm motility of mice, reduced the percent apoptosis and oxidative stress of testes, increased serum levels of GnRh, activated the GnRhR signaling pathway in testes and promoted expression of meiosis-related factors.Conclusion: In view of their safety and efficiency, these PSE-NPs have potential applications in alleviating adriamycin-induced reproductive toxicity.Graphical Abstract: Keywords: pseudoephedrine nanoparticles, adriamycin, reproductive toxicity, GnRhR signaling pathway, sperm meiosis

The aim of the work was to investigate the effects of acacetin on endothelial dysfunction and aortic fibrosis in insulin-resistant SHR rats and explore its mechanism. Seven-week-old male spontaneously hypertensive rats (SHR) were selected to establish a rat model of hypertension with insulin resistance induced by 10% fructose. The nuclear factor kappa B p65 (NF-κB p65) and Collagen I were observed by Immunohistochemistry. Immunofluorescence was used to observe estrogen receptor-alpha (ERα), estrogen receptor-beta (ERβ), and G protein-coupled receptor 30 (GPR30). Western blotting was used to detect interleukin (IL-1β), Arginase 2 (ARG2), Nostrin, endothelial nitric oxide synthase (eNOS), TGF-β, Smad3, ERK pathway proteins such as p-c-Raf, p-MEK1/2, p-ERK, ERK, p-P90RSK and p-MSK1. We found that acacetin did have an improvement on endothelial dysfunction and fibrosis. Meanwhile, it was also found to have a significant effect on the level of estrogen in this model by accident. Then, the experiment of uterine weight gain in mice confirmed that acacetin had a certain estrogen-like effect in vivo and played its role through the estrogen receptors pathway. In vitro experience HUVEC cells were stimulated with 30 mM/L glucose and 100 mM/L NaCl for 24 h to establish the endothelial cell injury model. HUVEC cells were treated with 1 μM/L estrogen receptors antagonist (ICI 182780) for 30 min before administration. Cell experiments showed that acacetin could reduce the apoptosis of HUVEC cells, the levels of inflammatory cytokines and the expression of TGF-β, Collagen I and Smad3 in endothelial cell injury model. After treatment with ICI 182780, the improvement of acacetin was significantly reversed. The results showed that acacetin relieved endothelial dysfunction and reduced the aortic fibrosis in insulin-resistant SHR rats by reducing the release of inflammatory factors and improving vasodilatory function through estrogen signaling pathway.

Context In the antihypertensive study of phenylacetamide (PA) on spontaneously hypertensive rats (SHR), it was occasionally found that PA prevents myocardial injury. Objective Clarify the protective mechanism of PA on myocardial injury in SHR rats. Materials and methods In vivo, SHR rats were treated with or without PA (15, 30, 45 mg/kg) for 3 weeks (12 per group). In vitro, H9c2 cells were treated with PA (1, 5, 10 μM) for 24 h, and then stimulated with H2O2 (300 μM) for 4 h. Molecular mechanisms were explored through cardiac pathology, cardiac function and biochemical markers. Results In vivo, PA (15, 30, 45 mg/kg) reduced CVF from 14.8 ± 1.62 to 9.94 ± 1.56, 8.6 ± 1.33, 8.14 ± 1.45%; increased the LVEF relative level from 0.8 ± 0.06 to 0.83 ± 0.04, 0.86 ± 0.05, 0.9 ± 0.04. All three doses can improve the cardiac pathological structure and function (LVEDD, LVESD, LVFS, heart index, NT-proBNP, CKMB, SBP); however, 45 mg/kg works best. But different doses show different molecular mechanisms. PA (15 mg/kg) improves RAAS system (REN, ACE), inflammation (ET-1, IL-1β) and MAPK pathway (p-ERK/ERK, p-JNK/JNK) better. PA (45 mg/kg) improves oxidative stress (SOD, NOX1) and TGF-β pathway (Smad3) better. In vitro, PA improved cell viability, oxidative stress (SOD, NOX1) and Smad3 protein expression. Discussion and conclusions: PA regulates different mechanisms at different concentrations to improve myocardial injury, and high dose is the best. This experiment provides a theoretical basis for the development of new clinical drugs for cardiovascular disease.

Lipid deposition in the kidney can cause serious damage to the kidney, and there is an obvious epithelial–mesenchymal transition (EMT) and fibrosis in the late stage. To investigate the interventional effects and mechanisms of phenolic compounds from Mori Cortex on the EMT and fibrosis induced by sodium oleate-induced lipid deposition in renal tubular epithelial cells (NRK-52e cells), and the role played by CD36 in the adjustment process, NRK-52e cells induced by 200 μmol/L sodium oleate were given 10 μmoL/L moracin-P-2″-O-β-d-glucopyranoside (Y-1), moracin-P-3′-O-β-d-glucopyranoside (Y-2), moracin-P-3′-O-α-l-arabinopyranoside (Y-3), and moracin-P-3′-O-[β-glucopyranoside-(1→2)arabinopyranoside] (Y-4), and Oil Red O staining was used to detect lipid deposition. A Western blot was used to detect lipid deposition-related protein CD36, inflammation-related protein (p-NF-κB-P65, NF-κB-P65, IL-1β), oxidative stress-related protein (NOX1, Nrf2, Keap1), EMT-related proteins (CD31, α-SMA), and fibrosis-related proteins (TGF-β, ZEB1, Snail1). A qRT-PCR test detected inflammation, EMT, and fibrosis-related gene mRNA levels. The TNF-α levels were detected by ELISA, and the colorimetric method was used to detects SOD and MDA levels. The ROS was measured by flow cytometry. A high-content imaging analysis system was applied to observe EMT and fibrosis-related proteins. At the same time, the experiment silenced CD36 and compared the difference between before and after drug treatment, then used molecular docking technology to predict the potential binding site of the active compounds with CD36. The research results show that sodium oleate can induce lipid deposition, inflammation, oxidative stress, and fibrosis in NRK-52e cells. Y-1 and Y-2 could significantly ameliorate the damage caused by sodium oleate, and Y-2 had a better ameliorating effect, while there was no significant change in Y-3 or Y-4. The amelioration effect of Y-1 and Y-2 disappeared after silencing CD36. Molecular docking technology showed that the Y-1 and Y-2 had hydrogen bonds to CD36 and that, compared with Y-1, Y-2 requires less binding energy. In summary, moracin-P-2″-O-β-d-glucopyranoside and moracin-P-3′-O-β-d-glucopyranoside from Mori Cortex ameliorated lipid deposition, EMT, and fibrosis induced by sodium oleate in NRK-52e cells through CD36.

Glomerular mesangial cell (MC) proliferation and extracellular matrix deposition are the main pathological changes in diabetic nephropathy. Hydrogen sulfide (H2S) inhibits the proliferation of MCs. Dopamine 1 receptors (DR1) are expressed in MCs and serve important physiological roles. However, it is unclear whether DR1 activation inhibits MC proliferation by increasing endogenous H2S. The present study found that the production of H2S and the expression of DR1 and cystathionine-γ-lyase (CSE) were decreased in the renal tissues of diabetic mice and high glucose (HG)-induced MCs. SKF38393 (a DR1 agonist) increased the production of H2S and the expression of DR1 and CSE and NaHS (an exogenous H2S donor) only increased H2S production and CSE expression but not DR1 expression. HG increased the thickness of the glomerular basement membrane, cell viability and proliferation, the expression of cyclin D1, PCNA, collagen 1 and α-smooth muscle actin and the activity of phosphorylated ERK1/2 and decreased the expression of P21 and MMP9. SKF38393 and NaHS reversed the effects of HG. PPG (a CSE inhibitor) abolished the beneficial effects of SKF38393. The beneficial effects of SKF38393 were similar to those of PD98059 (an ERK1/2 inhibitor). Taken together, the findings suggested that the DR1-CSE/H2S pathway activation attenuated diabetic MC proliferation and extracellular matrix deposition by downregulating the ERK1/2 signaling pathway.

Doxorubicin (DOX) is a highly effective chemotherapeutic that is effective for various tumours. However, the clinical application of DOX has been limited by adverse reactions such as cardiotoxicity and heart failure. Since DOX-induced cardiotoxicity is irreversible, drugs to prevent DOX-induced cardiotoxicity are needed.This study aimed to investigate the effect of total flavonoids of Selaginella tamariscina (P.Beauv.) Spring (TFST) on doxorubicin-induced cardiotoxicity.The present study established DOX-induced cardiotoxicity models in C57BL/6 mice treated with DOX (cumulative dose: 20 mg/kg body weight) and H9c2 cells incubated with DOX (1 μM/l) to explore the intervention effect and potential mechanism of TFST. Echocardiography was performed to evaluate left ventricular functions. Heart tissue samples were collected for histological evaluation. Myocardial injury markers and oxidative stress markers were examined. Mitochondrial energy metabolism pathway associated proteins PPARα/PGC-1α/Sirt3 were detected. We also explored the effects of TFST on endoplasmic reticulum (ER) stress and apoptosis. To further investigate the protective mechanism of TFST, we used the specific small interfering RNA MFN2 (siMFN2) to explore the effect of MFN2 on TFST against DOX-induced cardiotoxicity in vitro. Flow cytometry detected reactive oxygen species, mitochondrial membrane potential and apoptosis. Cell mitochondrial stress was measured by Seahorse XF analyser.Both in vivo and in vitro studies verified that TFST observably alleviated DOX-induced mitochondrial dysfunction and ER stress. However, these effects were reversed after transfected siMFN2.Our results indicated that TFST ameliorates DOX-induced cardiotoxicity by alleviating mitochondrial dysfunction and ER stress by activating MFN2/PERK. MFN2/PERK pathway activation may be a novel mechanism to protect against DOX-induced cardiotoxicity.

With the development and progress of automobile industry, the automobile electronic control system has put forward higher and higher requirements to the controller. From the realization of the controller to vehicle test, all need hardware in loop test, and ensure the real test results of core is to run in real-time processor on the real-time operating system, at the same time with a single core processor in the operation of the real-time system bottlenecks, this paper USES the multi-core processor platform to build real-time problems of real-time system research. The Linux system is studied in this paper after the defects in real time, this paper proposes a by adding preemption patch solution to realize real- time Linux system, at the same time, using the advantages of multi-core processors, the CPU resources of real-time and non- real-time tasks are divided, and the number of interrupts on the CPU where the real-time task is located is reduced. Finally, a specific RTOS development case based on the PREEMPT_RT patch is given, and on this basis, the effectiveness of the proposed scheme in the real-time performance of the system is verified.

Ying Hou,1,* Peipei Yuan,1,* Yang Fu,1 Qi Zhang,1 Liyuan Gao,1 Yaxin Wei,1 Xiaoke Zheng,1,2 Weisheng Feng1,2 1College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Engineering and Technology Center for Chinese Medicine Development of Henan Province, Henan Science and Technology Department, Zhengzhou, 450046, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoke Zheng; Weisheng FengCollege of Pharmacy, Henan University of Chinese Medicine, No. 156, Jinshui East Road, Zhengzhou, 450046, People’s Republic of ChinaTel +86-371-6019-0296Email zhengxk.2006@163.com; fwsh@hactcm.edu.cnIntroduction: Hypertension is closely related to myocardial injury. Long-term hypertension can cause myocardial injury. Therefore, it is very important to find drugs to treat myocardial injury caused by hypertension. The aim of present study is to investigate the effects and mechanisms of geniposide on myocardial injuries in spontaneously hypertensive rats (SHR) and H9c2 cells induced by NaCl solution.Materials and Methods: Male Wistar–Kyoto (WKY) and SHR rats were given different doses of geniposide (25 mg/kg/d or 50 mg/kg/d) or distilled water for three consecutive weeks. Meanwhile, an H9c2 cell line-injury model was established using a solution of 150 μmol/L NaCl for 8 h. The cardiac function and related indexes of rats were detected.Results: The results showed that geniposide decreased the levels of COI and COIII, which promoted the phosphorylation of AMPK (p-AMPK) and enhanced the energy metabolism pathway. Geniposide improved myocardial apoptosis by regulating apoptotic proteins (p38, BAX and Bcl-2). Finally, heart function was regulated, and the markers of myocardial injury were decreased. Geniposide increased the viability of H9c2 cells treated with the NaCl solution and decreased the rate of apoptosis by regulating the levels of apoptotic proteins. Geniposide could activate energy metabolism signalling pathway (AMPK/SirT1/FOXO1) and reduce H9c2 cell apoptosis.Conclusion: Our results showed that the mechanisms by which geniposide improves myocardial injury in SHR may be through regulating the energy metabolism signalling pathway (AMPK/SirT1/FOXO1) and improving myocardial apoptosis by regulating apoptotic proteins.Keywords: geniposide, SHR, myocardial injury, apoptosis, energy metabolism

Background. Duzhong Butiansu (DZBTS) prescription contains many traditional Chinese medicines and has been shown to have a curative effect on male fertility. However, the efficacy and mechanism of DZBTS in the treatment of male infertility induced by heat stress have not been reported. The aim of the present study is to elucidate the effect and mechanism of DZBTS on spermatogenic function of a heat stress model in rats. Methods. Male Wistar rats (280–320 g) were given different doses of DZBTS (0.4853 g/kg/d or 0.9707 g/kg/d), Shengjing capsule (0.56 g/kg/d), or double distilled water for 15 days. A 43°C hot water bath for 30 minutes was used to stimulate the testis of rats. Sperm count, sperm motility, the organ index of kidney and gonadal organs, serum sex hormone levels, and serum oxidising reaction index were measured. Haematoxylin and eosin (HE) staining was used to observe the morphology of the testis and kidney. The expression of Hsp70 in testes was observed by immunofluorescence. The changes in heat stress, reproductive-related protein, and mRNA were measured by western blot assay and RT-qPCR. Results. Heat stress downregulated the levels of sex hormone (P<0.05 or P<0.01) and its receptor androgen receptor (AR) protein expression and mRNA (P<0.01) in rats. Meanwhile, heat stress downregulated the levels of CAMP-responsive element-binding (CREB1) protein and mRNA (P<0.01), which are involved with spermatogenesis. Heat stress also decreased the oxidative damage index. Furthermore, Hsp70 and the heat shock transcription factor 1 (HSF1) protein pathway and mRNA level were overactivated (P<0.05 or P<0.01). Finally, the organ coefficients of the kidney and gonadal organs of rats were decreased. The sperm concentration and motility also decreased significantly (P<0.01). DZBTS could recover these changes induced by heat stress. Conclusions. Our results for the first time have found that DZBTS can improve spermatogenesis disorder in a heat stress model in rats, which may be mainly by regulating AR, sperm regulatory protein CREB1, and the HSF/Hsp70 signaling pathway to decrease oxidative stress.

In this paper, high thermal stability of Mn doped Y2/3Cu3Ti4O12 negative temperature coefficient (NTC) ceramics have been successfully fabricated by the combination of Pechini powder synthesis and solid-state reaction sintering. The substitution of Mn for Ti plays a critical role in controlling the phase structure, microstructure, electrical properties, and stability. The structure of as-sintered ceramics is a single Y2/3Cu3Ti4O12 phase at x ​≤ ​0.5, while the CuO phase begins to appear at x ​≥ ​0.7. X-ray photoelectron spectroscopy further confirms the change of cation concentration, one of the critical factors for electrical conductivity in Y2/3Cu3Ti4-xMnxO12 ceramics. In the temperature of −50–250 ​°C, the resistivity all decreases with increasing temperature and Mn content, the aging coefficient of all samples is within 0.4%, and the minimum can reach 0.2%. We strongly propose that the Mn substitution and Pechini method are highly desirable for the fabrication of high stability NTC thermistors for medi-temperature region application.

Aims Our study was designed to explore the function and mechanism of taxifolin on glucose metabolism and water-salt metabolism in kidney with metabolic syndrome (MS) rats. Main methods Spontaneous hypertensive rats were induced by fructose to establish MS model. Systolic blood pressure (SBP) and homeostasis model assessment of insulin resistance (HOMA-IR) were measured after 7 weeks of continuous administration with taxifolin. Kidney injury indices and histopathological evaluation were done. The apoptosis rate of primary kidney cells was detected by flow cytometry. Insulin signaling pathway related proteins and renal glucose transport-related proteins were detected by western blotting. We assessed the effects of taxifolin on sodium water retention and renin-angiotensin-aldosterone system (RAAS) in MS rats. We examined not only changes in urine volume, osmotic pressure, urinary sodium and urinary chloride excretion, but also the effects on NA+/K+-ATPase and RAAS indicators. We also detected changes in inflammatory factors by immunohistochemical staining and immunofluorescence. In vitro experiment, high glucose and salt stimulated NRK-52E cells. By adding the PI3K inhibitor (wortmannin) to inhibit the PI3K, the effects of inhibiting the PI3K/AKT signaling pathway on glucose metabolism, water-sodium retention and inflammatory response were discussed. Key findings Taxifolin effectively reversed SBP, HOMA-IR, the kidney indices and abnormal histopathological changes induced by MS. Besides, taxifolin called back the protein associated with the downstream glucose metabolism pathway of PI3K/AKT. It also inhibited overactivation of RAAS and inflammatory response. In vitro experiments have demonstrated that the PI3K/AKT signaling pathway plays an important role in this process. Significance Taxifolin can improve homeostasis of glucose, inhibit overactivation of RAAS and reduce inflammatory response by PI3K/AKT signaling pathway.

Mn-substituted La2/3Cu3Ti4O12 negative temperature coefficient (NTC) ceramics were successfully prepared by the traditional solid-state method, and their microstructures and electrical properties were also investigated. XRD patterns showed that the ceramics before polishing were covered by a layer of Cu-rich phase. As the Mn content increased, the segregation of Cu-rich phase at the grain boundary decreased, which leads to the gradual increase of the grain boundary resistance. The linear electrical behaviors were slightly enhanced with increasing Mn content. The B25/300-value and activation energy (Ea) increased gradually with increasing Mn content. The values of ρ25, B25/300 and Ea of the sintered ceramics were in the range of 7.8 × 105–6.2 × 106 Ω cm, 5751–6235 K and 0.496–0.538 eV, respectively.

The antihypertensive mechanism was studied of the ethyl acetate fraction of the ethanol extract (EAPF) of Gardenia jasminoides var. radicans Makino (GJRM). GJRM is a fake product of Gardenia jasminoides Ellis ( G. jasminoides), but in China’s Henan province, the production of GJRM is much more than G. jasminoides’s, but its traditional usage is as a dye. Gardenia jasminoides can be used to reduce blood pressure and blood glucose levels. The chemical compositions of GJRM and G. jasminoides are similar, and we previously confirmed that GJRM can also reduce blood pressure. Here, we report that the EAPF of GJRM could activate the phosphoinositide 3-kinases (PI3K) pathway in the kidneys of spontaneously hypertensive rats, thus increasing the content of nitric oxide and bradykinin in sera and decreasing endothelin-1 content. EAPF can also decrease the levels of with-no-lysine kinase 1 (WNK1) expression, WNK4 and oxidative stress-responsive kinase 1 messenger ribonucleic acid (mRNA), and Na-K-2Cl cotransporter and sodium chloride cotransporters mRNA and phosphorylation. To investigate the antihypertensive effects of the EAPF of GJRM, 5 monoterpenoids isolated from EAPF were studied for their effects on NRK52e and IMCD3 cells. These compounds inhibited the PI3K-WNK signaling pathway to varying degrees under hypotonic conditions; 4-methoxyrehmapicrogenin had the best effect.

Most Traditional algorithms using only unilateral estimation or bidirectional estimation usually produce poor visual quality because of the fact that the unilateral motion estimation suffers from holes and overlaps and the bidirectional motion estimation suffers from inaccurate motion vector. This paper presents a new improved Frame rate up conversion(FRUC) scheme which combines the unilateral estimation and the bidirectional estimation smartly to avoid holes and inaccurate motion vector problem. The algorithm proposed in this paper outperforms other traditional methods both in objective and subjective performances. The superior performance of the proposed algorithm has been tested extensively and representative examples are given in this work.

OGC protocols have been widely accepted by the geospatial/land science communities, We call this community geospatial community. Others communities such as atmosphere, ocean, and modeling science adopt the other set of data access protocols. We name these protocols as geoscience protocols. Although these two protocols have been used wildly, but unfortunately, there is no interoperability between them. For bridging this cross-protocol and cross-community gap, CSISS have developed a catalog middleware to mediate client/server interactions between OGC catalog clients and THREDDS servers. A prototype system has been implemented to demonstrate the concept and approach.