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The current view of nucleic acid–mediated innate immunity is that binding of intracellular sensors to nucleic acids is sufficient for their activation. Here, we report that endocytosis of virus or foreign DNA initiates a priming signal for the DNA sensor cyclic GMP-AMP synthase (cGAS)–mediated innate immune response. Mechanistically, viral infection or foreign DNA transfection triggers recruitment of the spleen tyrosine kinase (SYK) and cGAS to the endosomal vacuolar H + pump (V-ATPase), where SYK is activated and then phosphorylates human cGAS Y214/215 (mouse cGas Y200/201 ) to prime its activation. Upon binding to DNA, the primed cGAS initiates robust cGAMP production and mediator of IRF3 activation/stimulator of interferon genes-dependent innate immune response. Consistently, blocking the V-ATPase-SYK axis impairs DNA virus- and transfected DNA-induced cGAMP production and expression of antiviral genes. Our findings reveal that V-ATPase-SYK–mediated tyrosine phosphorylation of cGAS following endocytosis of virus or other cargos serves as a priming signal for cGAS activation and innate immune response.

Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors significantly reduce low-density lipoprotein cholesterol (LDL-C) and improve the prognosis of patients with acute coronary syndrome (ACS). However, the feasibility and safety of early application of PCSK9 inhibitors on the basis of statins combined with ezetimibe to strengthen lipid lowering in extremely high-risk coronary heart disease populations are still unknown.This study was a prospective, randomized controlled study. A total of 136 patients with extremely high-risk ACS with LDL-C ≥ 3.0 mmol/L after percutaneous coronary intervention (PCI) treatment were randomly assigned 1:1 to the control group (atorvastatin 40 mg/day and ezetimibe 10 mg/day) or the evolocumab group (evolocumab 140 mg every 2 weeks combined with atorvastatin 40 mg/day and ezetimibe 10 mg/day). We compared the blood lipid profiles, major adverse cardiovascular events (MACEs), and adverse reactions. MACEs included cardiogenic death, nonfatal myocardial infarction, nonfatal stroke, and readmission due to angina. Adverse reactions included allergies, myalgia, poor blood glucose control, and liver damage.Within 1 month, the average level of LDL-C in the evolocumab group decreased from 3.54 to 0.57 mmol/L and that in the control group decreased from 3.52 to 1.26 mmol/L. The LDL-C compliance (1.0 mmol/L) rate was significantly increased in the evolocumab group compared with the control group (82.35% versus 22.06%, P0.01). The average level of lipoprotein (a) (Lp (a) ) in the control group increased by 9.94 ± 51.93% from baseline after treatment, but evolocumab reduced the Lp (a) level (-38.84 ± 32.40%). Additionally, evolocumab further reduced the levels of apolipoprotein B/A1 (-70.56 ± 22.38% versus -51.29 ± 18.14%), cholesterol (-54.76 ± 18.10% versus -41.16 ± 18.14%), and apolipoprotein B (-66.47 ± 26.89% versus -46.78 ± 24.12%) compared with those in the control group, all P0.01. The blood lipid levels of both control and evolocumab groups stabilized after 1 month. During the 3-month follow-up, the incidence of MACEs after PCI was lower in the evolocumab group than in the control group (8.82% versus 24.59%, P = 0.015), and evolocumab combined with statins and ezetimibe did not increase the occurrence of adverse reactions (13.24% versus 11.48%, P = 0.762).In patients with extremely high-risk ACS with high levels of LDL-C, adding evolocumab to their treatment regimen as early as possible may enhance lipid lowering, increase the patient's LDL-C compliance rate in the short term, and improve cardiovascular prognosis but will not increase adverse reactions.

Mitochondrial stress (mitostress) triggered by viral infection or mitochondrial dysfunction causes the release of mitochondrial DNA (mtDNA) into the cytosol and activates the cGAS-mediated innate immune response. The regulation of mtDNA release upon mitostress remains uncharacterized. Here, we identified mitochondria-associated vaccinia virus-related kinase 2 (VRK2) as a key regulator of this process. VRK2 deficiency inhibited the induction of antiviral genes and caused earlier and higher mortality in mice after viral infection. Upon viral infection, VRK2 associated with voltage-dependent anion channel 1 (VDAC1) and promoted VDAC1 oligomerization and mtDNA release, leading to the cGAS-mediated innate immune response. VRK2 was also required for mtDNA release and cGAS-mediated innate immunity triggered by nonviral factors that cause Ca(2+) overload but was not required for the cytosolic nucleic acid-triggered innate immune response. Thus, VRK2 plays a crucial role in the mtDNA-triggered innate immune response and may be a potential therapeutic target for infectious and autoimmune diseases associated with mtDNA release.

Background/Aim: The role of nuclear respiratory factor 1 (NRF1) on the prostate cancer progression is controversial. We aimed to investigate the effect of NRF1 overexpression on the metastasis potential of PC3 prostate cancer cells and the associated molecular mechanisms. Materials and Methods: Cell survival, migration capacity, mitochondrial biogenesis, the expression of TGF-β signaling and EMT markers were examined after overexpression and silencing of NRF1 in PC3 cells. Results: We found that NRF1-overexpressing cells exhibited a decreased cell viability and proliferation ability as well as a reduced migration capacity compared to control cells. Moreover, ectopic expression of NRF1 increased the mitochondrial biogenesis and inhibited the EMT characteristics, including a decrease in the mesenchymal marker, α-SMA and an increase in the epithelial cell marker, E-cadherin. We also demonstrated that overexpression of NRF1 suppressed the expression of TGF-β signaling in PC3 cells. As expected, silencing of NRF1 reversed the abovementioned effects. Conclusion: This study demonstrated that upregulation of NRF1 holds the potential to inhibit the metastasis of prostate cancer, possibly through an elevation of mitochondrial biogenesis and the subsequent repression of TGF-β-associated EMT. Therapeutic avenues that increase NRF1 expression may serve as an adjunct to conventional treatments of prostate cancer.

Introduction Prostate cancer has significant mortality and metastasis rate in the male. Unfortunately, effective treatment for patients with advanced prostate cancer is still lacking. Verbascoside, a phenylethanoid glycoside, displays various pharmacological properties, such as the anti-cancer activities. The present study aimed to evaluate the effects of purified verbascoside on human prostate cancer and the associated molecular mechanisms. Materials and methods The human prostate cancer cell lines, Du-145 and PC-3, were treated with various concentrations of verbascoside (0.1, 1, 10 μM) for 24 h followed by the examination of cell viability using MTT and trypan blue exclusion assays. Cell migration and invasion capacities were assessed by wound healing assay and transwell system. Western blot and immunofluorescence staining were used to detect the expression of epithelial-mesenchymal transition (EMT)-associated factors, components of transforming growth factor (TGF-β)/Smad signaling, and high-mobility group box (HMGB)/receptor for advanced glycation end-products (RAGE) axis. Results Verbascoside treatment significantly inhibited cell proliferation, migration, and invasion abilities of Du-145 and PC-3 cells. We showed that verbascoside decreased the expression of EMT promotors, Snail and Slug, and increased the expression of E-cadherin. Moreover, the expression level of alpha-smooth muscle actin was downregulated by verbascoside as well. Besides, we found that the TGF-β pathway was suppressed, which was demonstrated by the diminished expression of type I and II TGF-β receptors and phosphorylated Smad2/3 along with the upregulated Smad7. Our data suggested that this downregulation of TGF-β signaling was mediated by repression of HMGB 1 (HMGB1)/RAGE axis. Conclusion Verbascoside mitigated the cell proliferation and aggressiveness of prostate cancer via downregulation of TGF-β-associated EMT progression through HMGB1/RAGE suppression. Collectively, our findings revealed that verbascoside may be a beneficial dietary supplement for prostate cancer patients.

From ancient times to the present, music allows people to listen to music from different periods, understand its structure and expressions, perceive which nationality, region, age, and type of music, and then express its thinking at that time. The unique feeling of music creation is purposeful and connotative, which implies the author's life experience and thoughts, and can bring people beautiful enjoyment and express people's emotions. From the growth of learning, music plays an important role and is an important part of primary education. It is an effective tool for cultivating children's artistic literacy. Generally, music education in kindergartens has begun around the world. In ancient China, music was regarded as one of the six artistic abilities that scholars and scholars should possess. As for the formal music education in China, it continues until the end of nine years of compulsory education, that is, graduation from junior high school. At present, music education is also offered in ordinary high schools. This study found that learners can sing, express emotions and have a happy time with music. Afterwards, the music melody gives the listener motivation, comfort and peace, but from beginning to end, learners often only envy and cannot play. The reason can be summarized as a bunch of musical pokers such as "sprouts", during the period of enlightenment, especially in elementary school. After the learner recognizes the musical poker, it cannot be connected with the Sheet music, resulting in a great sense of distance in the recognition of notes, beats, and melody. Therefore, this study introduces innovative thinking courses combined with music education, which mainly discusses the training of sound sense and beat, and uses cross-field teaching to make musical pokers no longer unfamiliar.

The yield potential of japonica/indica hybrids (JIH) has been achieved over 13.5 t ha−1 in large-scale rice fields, and some physiological traits for yield advantage of JIH over japonica inbred rice (JI) and indica hybrid rice (IH) were also identified. To date, little attention has been paid to morphological traits for yield advantage of JIH over JI and IH. For this reason, three JIH, three JI, and three IH were field-grown at East China (Ningbo, Zhejiang Province) in 2015 and 2016. Compared with JI and IH, JIH had 14.3 and 20.8% higher grain yield, respectively, attributed to its more spikelets per panicle and relatively high percentage of filled grains. The advantage in spikelets per panicle of JIH over JI and IH was shown in number of grains on the upper, middle, and lower branches. Compared with JI and IH, JIH had higher leaf area through leaf width and lower leaf angle of upper three leaves, higher leaf area index and leaf area per tiller at heading and maturity stages, higher stem weight per tiller and K and Si concentrations of stem at maturity, higher dry matter weight in leaf, stem, and panicle at heading and maturity stages, and higher biomass accumulation after heading and lower biomass translocation from stem during ripening. Leaf width of upper three leaves were correlated positively, while leaf angle of upper three leaves were correlated negatively with biomass accumulation after heading, stem weight per tiller, and per unit length. Our results indicated that the grain yield advantage of JIH was ascribed mainly to the more spikelets per panicle and relatively high percentage of filled grains. Higher leaf area through leaf width and more erect leaves were associated with improved biomass accumulation and stem weighing during ripening, and were the primary morphological traits underlying higher grain yield of JIH.

To observe the clinical therapeutic effect on mild and moderate postpartum depression treated with acupuncture ofA total of 116 patients with mild and moderate postpartum depression were divided into an acupuncture group (103 cases) and a non-acupuncture group (13 cases) according to treatment regimen provided. In the acupuncture group, acupuncture ofThe total effective rate of the acupuncture A group was 100.0% (31/31), better than 76.9% (10/13) in the non-acupuncture group and 58.1% in the acupuncture B group (18/31) (Acupuncture of

Cancer cells acquire genetic heterogeneity to escape from immune surveillance during tumor evolution, but a systematic approach to distinguish driver from passenger mutations is lacking. Here we investigate the impact of different immune pressure on tumor clonal dynamics and immune evasion mechanism, by combining massive parallel sequencing of immune edited tumors and CRISPR library screens in syngeneic mouse tumor model and co-culture system. We find that the core microRNA (miRNA) biogenesis and targeting machinery maintains the sensitivity of cancer cells to PD-1-independent T cell-mediated cytotoxicity. Genetic inactivation of the machinery or re-introduction of ANKRD52 frequent patient mutations dampens the JAK-STAT-interferon-γ signaling and antigen presentation in cancer cells, largely by abolishing miR-155-targeted silencing of suppressor of cytokine signaling 1 (SOCS1). Expression of each miRNA machinery component strongly correlates with intratumoral T cell infiltration in nearly all human cancer types. Our data indicate that the evolutionarily conserved miRNA pathway can be exploited by cancer cells to escape from T cell-mediated elimination and immunotherapy., Dysregulation of the microRNA machinery has crucial roles in cancer development. Here the authors show that inactivation of proteins involved in microRNA-mediated gene silencing, such as ANKRD52 or AGO2, confers resistance to T cell-mediated immune response in a preclinical cancer model.

Advanced glycation end products (AGE) and angiotensin II were closely correlated with the progression of diabetic nephopathy (DN). Nitric oxide (NO) is a protective mediator of renal tubular hypertrophy in DN. Here, we examined the molecular mechanisms of angiotensin-converting enzyme inhibitor (ACEI) and NO signaling responsible for diminishing AGE-induced renal tubular hypertrophy. In human renal proximal tubular cells, AGE decreased NO production, inducible NOS activity, guanosine 3',5'-cyclic monophosphate (cGMP) synthesis, and cGMP-dependent protein kinase (PKG) activation. All theses effects of AGE were reversed by treatment with ACEIs (captopril and enalapril), the NO donor S-nitroso-N-acetylpenicillamine (SNAP), and the PKG activator 8-para-chlorophenylthio-cGMPs (8-pCPT-cGMPs). In addition, AGE-enhanced activation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) were clearly reduced by captopril, enalapril, SNAP, and 8-pCPT-cGMPs. The abilities of ACEIs and NO/PKG activation to inhibit AGE-induced hypertrophic growth were verified by the observation that captopril, enalapril, SNAP, and 8-pCPT-cGMPs decreased protein levels of fibronectin, p21 Waf1/Cip1 , and receptor for AGE. The results of the present study suggest that ACEIs significantly reduced AGE-increased ERK/JNK/p38 MAPK activation and renal tubular hypertrophy partly through enhancement of the NO/PKG pathway.

Background Osthole has been widely reported to have pharmacological activities such as anti-cancer, anti-inflammation and anti-hyperlipidemic effects. Klotho was identified as an anti-senescence protein in a variety of tissues. Loss of klotho has been associated with chronic kidney disease. However, potential roles and molecular events for osthole and klotho in diabetic nephropathy remain unclear. Purpose In the current study, we undertook to study the effect of osthole on klotho expression in advanced glycation end products (AGE)-cultured human renal proximal tubular cells, and to investigate the molecular mechanisms of osthole and exogenous klotho against AGE-induced renal tubular hypertrophy. Methods Cell viability was elucidated by MTT assay. Protein expression was measured by Western blotting. mRNA level was analyzed by real-time PCR. Cellular hypertrophy growth was evaluated by hypertrophy index. Relative cell size was detected by flow cytometry. Results We found that raising the ambient AGE concentration causes a dose-dependent decrease in klotho synthesis. Osthole significantly increased AGE-inhibited klotho mRNA and protein expression. Osthole and exogenous klotho treatments significantly attenuated AGE-induced Janus kinase 2 (JAK2)-signal transducers and activators of transcription 1 (STAT1) and STAT3 activation. Moreover, protein levels of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 were augmented by osthole and exogenous klotho. The abilities of osthole and exogenous klotho to reverse AGE-induced cellular hypertrophy were verified by the observation that osthole and exogenous klotho inhibited p21Waf1/Cip1/collagen IV/RAGE expression, total protein content, and cell size. Conclusion Consequently, we found that osthole attenuated AGE-induced renal tubular hypertrophy via induction of klotho expression and suppression of the JAK2-STAT1/STAT3 signaling. These results also showed that klotho might be used as a unique molecular target for the treatment of diabetic nephropathy.

Delayed colectomy can be life-threatening for patients with acute severe ulcerative colitis (ASUC). However, few biomarkers can predict the outcomes of ASUC patients before treatment. Serum procalcitonin (PCT) has been observed to be increased in ASUC patients. The aim of this study was to estimate the association between serum PCT and short-term outcomes in patients with ASUC. A single-center observational study was conducted at a referral hospital from January 2012 to January 2018. Hospitalized ASUC patients, who were administered intravenous corticosteroids (IVCS), were enrolled and followed up for 6 months. The primary outcome was IVCS failure; the secondary outcome was colectomy. Relationships between indicators and clinical outcomes were assessed. Of 152 ASUC patients enrolled in this study, 81 responded to IVCS and 71 failed (62 required short-term colectomy and 9 responded to second-line rescue therapy). Serum PCT on admission was significantly higher in IVCS-failure cases and surgical cases than in medical responders. Serum PCT ≥ 0.10 µg/L (OR = 4.134, p = 0.001) predicted IVCS failure with specificity of 0.741, and the combined measurement with fecal calprotectin (FC) ≥ 1500 µg/g improved the sensitivity. Serum PCT correlated significantly with the Ulcerative Colitis Endoscopic Index of Severity (r = 0.416, p

Aims Podocyte migration may lead foot process effacement and proteinuria. Transforming growth factor-β1 (TGF-β1) and integrins are involved in the adhesion and migration of cells. However, the crosstalk of TGF-β1 and integrins is unclear. Here, we examined how TGF-β1 regulates the expression of integrin-β1 and -β3 to modulate podocyte adhesion and migration. Main methods Podocytes were exposed to TGF-β1 and/or the inhibitors of Smad2/3, ERK and p38, then the expression of integrin-β1 and -β3 was assessed by Real-time PCR and western blot analyses. Podocyte adhesion and migration were measured under TGF-β1 treatment and/or anti-integrin-β3 antibody by cell adhesion assay and wound healing assay. Key findings TGF-β1 had no effect on integrin-β1 mRNA expression. In the analysis of protein expression, TGF-β1 decreased the mature form of integrin-β1, but increased both the precursor form and core peptide of integrin-β1. The inhibitors of ERK and p38, but not Smad2/3, abrogated TGF-β1-induced changes in integrin-β1 protein expression. TGF-β1 increased integrin-β3 mRNA and protein levels. The inhibitors of Smad2/3, ERK and p38 attenuated the TGF-β1-induced increase in integrin-β3 mRNA and protein levels. Podocyte adhesion and migration were enhanced under the stimulation of TGF-β1. The blockade of interactions between integrin-αvβ3 and the extracellular matrix by the anti-integrin-β3 antibody abrogated the TGF-β1-induced enhancement in podocyte adhesion and migration. Significance Our results demonstrate that TGF-β1up-regulates integrin-β3 expression and down-regulates integrin-β1 expression through different pathways. The up-regulation of integrin-β3 expression enhances podocyte migration. This study provides a novel mechanism for TGF-β1 signaling in regulating podocyte migration.

Aims Macrophage migration inhibitory factor (MIF) is found to increase in proliferative glomerulonephritis. MIF binds to the MIF receptor (CD74) that activates MAP kinase (ERK and p38). Integrins and cyclinD1 regulate cell proliferation, differentiation and adhesion. This study evaluates whether MIF can regulate integrin-β1/cyclin D1 expression and cell adhesion of podocytes. Main methods Expression of integrin-β1 mRNA/protein and cyclin D1 mRNA under stimulation of MIF was evaluated by real-time PCR and Western blotting. MIF receptor (CD74) and MAP kinase under MIF treatment were examined to determine which pathway regulated integrin-β1 and cyclin D1 expression. Cell adhesion was evaluated under MIF treatment and/or anti-integrin-β1 antibody by cell adhesion assay. Key findings Protein levels of integrin-β1 were up-regulated under MIF treatment in a dosage-dependent manner. CD74 protein levels were not changed after MIF treatment. Integrin-β1 and cyclin D1 mRNA levels were up-regulated after MIF 100 ng/ml treatment. ERK inhibitor U0126 reduced MIF-induced the increase in integrin-β1 mRNA and protein expression following MIF stimulation. However, p38 inhibitor SB 203580 did not inhibit MIF-induced increase in integrin-β1 mRNA and protein expression following MIF stimulation. MIF-induced increase in cyclin D1 mRNA level also was inhibited only by U0126 following MIF stimulation. Podocyte adhesion was increased after MIF treatment, but, anti-integrin-β1 antibody decreased MIF-enhanced podocyte adhesion. Significance MIF increases integrin-β1 and cyclin D1 expression through the ERK pathway in podocytes, and the up-regulated expression of integrin-β1 increases podocyte adhesion. These results provide further understanding for the role of MIF in developing proliferative glomerulonephritis.

Background As a substrate of apoER2, Reelin has been verified to exert neuroprotection by preventing memory impairment. Pinocembrin is the most abundant natural flavonoid found in propolis, and it has been used to exert neuroprotection, blood–brain barrier protection, anti-oxidation, and inflammation diminishing, both in vitro and in vivo. However, the roles and molecular mechanisms of pinocembrin in neurobehavioral outcomes and neuronal repair after vascular dementia are still under investigation. Purpose To explore the role of pinocembrin in the involvement of the Reelin-dab1 signaling pathway in improving memory impairment, both in cell culture and animals experiments. Material and Methods Behavioral tests were conducted on day 48 to confirm the protection of pinocembrin against cognitive impairment. Cell and molecular biology experiments demonstrated that the Reelin-dab1 pathway mediates the underlying mechanism of cognitive improvement by pinocembrin. Results It was showed that pinocembrin alleviated learning and memory deficits induced by vascular dementia, by inducing the expression of Reelin, apoER2, and p-dab1 in the hippocampus. The expression of Reelin and p-dab1 was both inhibited following Reelin RNA interference in SH-SY5Y prior to oxygen glucose deprivation (OGD) injury, suggesting that Reelin played a core role in pinocembrin’s effect on OGD in vitro. Conclusion Pinocembrin improves the cognition via the Reelin-dab1 signaling pathway.

It is of great interest to utilize saline fields to promote rice production in China. Previous studies reported greater yield productivity of japonica/indica hybrids (JIH) over indica hybrids (IH) under nonsaline fields. It has still not been established how salinity stress intervenes with rice yield and whether JIH would exhibit superior grain yield than IH under saline field conditions. This study investigated three JIH and three IH cultivars grown at the two sites that differed significantly in soil salinity, namely, nonsaline (Wulie, abbreviated as WL) and saline (Tiaozini, abbreviated as TZN) fields, in Yancheng, Jiangsu, China. The panicles per m2, spikelets per panicle, filled-kernel percentage, and kernel weight of JIH and IH were reduced, and a 36.0 %–43.5 % loss in grain yield was observed with salinity stress at TZN compared with WL. For JIH and IH, the shoot biomass and leaf area index (LAI) at jointing, heading, and maturity were all reduced at TZN compared to those at WL; similar results were also detected for root biomass, root length and volume, and root bleeding rate after heading. Compared with IH, JIH produced a 24.8 % higher grain yield under saline field conditions at TZN across two years. Four agronomic and physiological traits were summarized for superior grain yield of JIH compared to that of IH with salinity stress under field conditions. First, JIH had an enlarged sink size potential of a greater number of spikelets per panicle. Second, a synergistically increased biomass accumulation and harvest index of JIH, supported by higher biomass accumulation and LAI at the main growth stages and improved NSC remobilization after heading. Third, JIH had an improved stay-green characteristic, indicated by a higher leaf area per plant, SPAD values, and leaf photosynthetic rate after heading. Fourth, JIH exhibited a better root morpho-physiology than that of IH after heading, showing a larger and deeper root structure and higher root bleeding rate. These results indicated that the limited shoot and root growth were responsible for the yield penalty of rice under saline field conditions. JIH's improved agronomic and physiological traits facilitated superior yield performance over IH with salinity stress under field conditions.

The solubility of 3,4-dinitropyrazole (DNP) in four binary solvents (benzene + ethanol, n-propanol, n-butanol and isoamyl alcohol) was measured by a dynamic laser monitoring at the temperature from 283.15 K to 323.15 K at pressure of 0.1 MPa. The solubility of DNP increased positively with increasing temperature, while increased with decreasing molar fraction of benzene in each binary system. Moreover, the experimental solubility values of DNP in this work were correlated well with four thermodynamic models namely “the modified Apelblat equation, Jouyban-Acree model, NRTL model and Wilson model” obtaining average root-mean-square deviation (104RMSD) lower than 98.93 for correlative studies. In addition, Hansen solubility parameters were used to explain and predict the solubility behavior. Finally, mixing thermodynamic properties were estimated and analyzed based on solubility data and the Wilson model, and it's easy to understand that the dissolution was a spontaneous process from the results.

Developing high efficiency rare earth alloy magnets at low cost is an economically hopeful way to expand their application area. In this study, magnetic properties of nanocomposite isotropic exchange coupled systems with the structure of Nd2Fe14B crystalline grains embedded in α-Fe matrices have been simulated by micromagnetic finite element method (FEM). The results have been analyzed by means of the effect of volume fraction of nanosized exchange coupling area between the magnetically hard Nd2Fe14B and soft α-Fe phase on magnetic properties of the exchange coupled Nd2Fe14B/α-Fe magnetic systems. The results show that the magnetic systems with the structure of Nd2Fe14B grains embedded in α-Fe matrices can have comparatively advanced magnetic properties with small amount of Nd2Fe14B components, because of efficient inter-phase exchange coupling between magnetically hard Nd2Fe14B grains and soft α-Fe matrix.

In this study, magnetic properties of exchange coupled nanocomposite multilayer thin films constructed alternately with magnetic hard Nd 2 Fe 14 B layers and soft α -Fe layers have been studied by micromagnetic finite element method (FEM). According to the results, effects of the thicknesses of layers and the magneto-crystalline anisotropy on the magnetic properties of the Nd 2 Fe 14 B/ α -Fe multilayer systems have been estimated. On the other hand, the results have been analyzed by means of efficiency of interphase exchange coupling, which can be estimated by volume ratios of exchange coupled areas between magnetically hard Nd 2 Fe 14 B and soft α -Fe phase layers. The results show that the magnetic properties of exchange coupled Nd 2 Fe 14 B/ α -Fe multilayer systems can be enhanced by efficient interphase exchange coupling between magnetically hard Nd 2 Fe 14 B layers and soft α -Fe layers.

Background Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. Nuclear respiratory factor 1 (NRF-1) is a transcriptional regulation factor that plays a central role in the regulation of mitochondrial biogenesis. However, the transcription factor of this process in renal fibrosis is unknown. Thus, we hereby discussed the correlations of NRF-1 and renal interstitial fibrosis. Materials and methods In vitro fibrosis model was established by treatment with transforming growth factor-β1 (TGF-β1) in NRK-49F (Normal Rat kidney fibroblast). We investigated the ROS production, mitochondrial biogenesis and fibrogenic marker (e.q. fibronectin) during the progression of renal fibrosis by kit and Western blotting assay. Here, we used that two distinct mechanisms regulate NRF-1 activation and degradation of NRF-1. NRF-1 was transfect by pcDNA-NRF-1 overexpression gene to evaluate the NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by shRNA-NRF-1 to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin, NRF-1). Results Under renal fibrosis conditions, TGF-β1 (5 ng/ml) increased ROS. Simultaneously, TGF-β1-induced extracellular fibronectin by ELISA assay. In addition, TGF-β1 decreased expression of mitochondrial biogenesis. This is the first time to demonstrate that expression of NRF-1 is significantly decreased in renal fibrosis. However, NRK49F was a transfection with pcDNA-NRF-1 (2 μg/ml) expression vector dramatically reverse TGF-β1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin). More importantly, transfection with shRNA-NRF-1 (2 μg/ml) significantly increased the expression of fibronectin of both intercellular and extracellular origins in NRK-49F cells. Discussion These finding suggest that NRF-1 plays a pivotal role on renal cellular fibrosis. Moreover, NRF-1 might act as a novel renal fibrosis antagonist by down-regulating fibrosis signaling in renal fibroblast cells.

In recent years, the serious environmental problems, the depletion of ozone layer, the greenhouse effect, the oil crisis, the development and utilization of new energy sources have become more important issues in the world, and the development of electric vehicles has been the target of global development. In order to meet the demand of the times, and in line with the technical trend of low-carbon life and energy conservation and environmental protection issues, a new management of the battery life of electric vehicles has been carried out in accordance with the technical trend of low-carbon life and energy conservation and environmental protection issues. Because the design of BMS and EMS is different, then its application in series and parallel of batteries is also different because of the state of batteries, which often results in insufficient battery power, especially when the battery is left with 20% or 10% of the battery, People are scared because they don’t know how long the remaining 20% or 10% will be able to use. Therefore, this study not only can make users understand the current power situation, but can give a big data feedback integration of the functions of the Internet in the analysis of PSD curve (developed by ShinnDar), extend battery charging pricing, and have security positioning functions, and so on. It can also be used to protect the battery effectively, avoid damage due to overvoltage or overcurrent, prolong its service life effectively, which let consumers use it at ease.

Four new monoterpenoids, including two new acyclic monoterpenoids (2R, 6R)-2, 6-dimethyl-8-isovaleroxyoctan-1-ol (1) and (2S, 6S)-2, 6-dimethyl-8-isovaleroxyoctan-1-ol (2), as well as two new iridoids stenopterins F-G (3 and 4), together with fifteen known compounds (5–19), were isolated from whole dried material of Valeriana stenoptera. Stenopterin F was the first reported iridoids with n-butoxyl in the Valerianaceae family. The structures of new compounds were established on the basis of extensive spectroscopic analysis.

Background: Acupuncture is widely used for analgesia in China and western countries. Lateral epicondylitis (LE) is a common disease, which influences the quality of life for many patients. The clinical practice indicates that acupuncture has a therapeutic effect on the LE; however, whether acupuncture is superior to sham acupuncture and some conventional therapy methods has been controversial. Hence, we will provide a protocol to explore the effectiveness and safety for acupuncture for LE. Methods: We will search only the randomized controlled trials (RCTs) literatures of acupuncture for LE from the following seven databases, including PubMed, Cochrane Central Register of Controlled Trials (The Cochrane Library), Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang Data, and Chinese Scientific Journals Database (VIP). The Visual Analogue Scale (VAS) will be considered as the primary outcome and the secondary outcome will include effective rate and function recovery. Adverse events incidence caused by acupuncture will also be discussed, such as dizziness, nausea, vomiting, and weariness. The searching strategy, inclusion and exclusion criteria were made according to the principle of evidence-based medicine. The quality was evaluated by Cochrane Handbook for Systematic Reviews of Interventions (V5.1). All analyses will be conducted by Review Manager Software (V5.3). Result: The results of this review will be submitted to a recognized journal for publication. Conclusion: This proposed meta-analysis will assess the efficacy and safety of acupuncture therapy for LE.