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We performed a double-blind, double-dummy controlled study to compare the efficacy between recombinant human thrombopoietin (rhTPO) and eltrombopag in rapidly increasing the platelet counts in Chinese patients with immune thrombocytopenia (ITP). A total of 96 patients diagnosed with ITP for ≥6 months who had baseline platelet counts of

The epithelial-to-mesenchymal transition (EMT)-based tubulointerstitial fibrosis is the major pathological feature of diabetic kidney disease (DKD). While several studies have linked cell cycle dysregulation to various kidney injuries in recent years, its involvement in fibrosis of DKD is far from being clarified. ING2 (inhibitor of growth 2) is the second member of the inhibitor of growth family and participates in the regulation of many cellular processes. So far the role of ING2 in DKD remains largely unknown. In the present study, ING2 expression was detected by western blotting and immunofluorescent staining both in vitro high glucose-stimulated human proximal tubular epithelial cells (HK-2) and in vivo streptozotocin-induced diabetic mice. Cell proliferation was analyzed by CCK-8 and EdU assay, and cell cycle arrest was measured by flow cytometry. Quantitative polymerase chain reaction (qPCR) and western blotting were used to detect the EMT markers, and the p53 signaling activation was evaluated by chromatin immunoprecipitation (ChIP), qPCR, and western blotting. We found that the proliferation of the cells was reduced upon high glucose stimulation, which was accompanied by cell cycle arrest. The expression of ING2 was increased in hyperglycemia conditions both in vivo and in vitro. ING2 suppression ameliorated the reduced proliferation and cell cycle arrest induced by high glucose in HK-2 cells. Moreover, ING2 knockdown suppressed p21 expression by reducing p53 acetylation and finally alleviated the EMT progress in the high glucose-stimulated HK-2 cells. Our study demonstrated that cell cycle regulation is bound up with the kidney fibrosis in DKD, suggesting a novel function of ING2 as a potential therapeutic strategy targeting cell cycle arrest for DKD.

A photonic quasi-crystal fiber (PQF) methane sensor based on surface plasmon resonance (SPR) is designed and described. The double-side polished six-fold photonic quasi-crystal fiber coated with a silver film produces enhanced SPR effects and sensitivity. A nanostructured thin film with cryptophane-E-doped polysiloxane is deposited on silver as the methane-sensitive surface layer and to mitigate oxidation of silver. The sensor is analyzed and optimized numerically by the full-vector finite element method. For methane concentrations in the range of 0% to 3.5%, the maximum sensitivity of the sensor is 8 nm/%, and the average sensitivity is 6.643 nm/%. Compared to traditional gas sensors, this sensor provides accurate sensing of methane besides offering advantages such as the low cost, miniaturized size, online monitoring, and immunity to electromagnetic field interference.

We recently identified oncologic miR-182 as a new regulator of pulmonary artery hypertension (PAH) that targets myeloid-associated differentiation marker (Myadm), which is expressed in bone marrow stem cells and multipotent progenitors. Both miR-182 and Myadm are expressed in the cardiopulmonary system and correlated with the balance between the bone morphogenetic protein (BMP) and the transforming growth factor (TGF)-β signalling pathways, which are disturbed in PAH. We hypothesize that miR-182/Myadm are involved in BMP-TGF-β-signalling way in PAH. Hypoxia triggered pathological progression in cardiopulmonary PAH in vivo and in vitro; these changes were accompanied by strongly dowregulated BMP/SMAD1/5/8 expression and enhanced TGF-β/SMAD2/3 signalling pathway, favouring SMAD4/SMAD2 transcript formation and inhibiting the PAH negative regulator Id1 expression. miR-182 gain-of-function significantly inhibited the pathological progression in hypoxia-induced PAH (HPH) in vivo and in vitro, with a restoration of the balance in BMP-TGF-β signalling pathway. This recovery was abrogated by overexpression of Myadm. Conversely, loss-of-function of miR-182 increased the pathological progression of HPH followed by severe disturbance of BMP and TGF-β signal transduction and reduced Id1 expression, which was restored by Myadm knockdown. We also showed that the miR-182/Myadm relate BMP-TGF-β pathway is associated with NOS3/NO/cGMP via the crosstalk between endothelial cells and smooth muscle cells. Our findings further support the therapeutic significance of miR-182/Myadm in PAH via the balance of BMP- and TGF-β-associated mechanisms.

Dyslipidemia is a common risk factor of chronic kidney disease (CKD). Current notion suggests that insufficient intracellular fatty acid oxidation (FAO) and subsequently enhanced fatty acid esterification within renal resident cells, a process termed as renal lipotoxicity, is the key pathogenic event responsible for dyslipidemia-induced kidney injury. However, the detailed mechanism is not fully elucidated. Recently, accumulating data indicated that acetylation modification is an important regulating manner for both mitochondrial function and energy metabolism, while whether acetylation modification is involved in renal lipotoxicity is of little known. In the present study, the expression level of global lysine acetylation was detected by immunohistochemistry in high-fat diet mice and western blot in palmitic acid (PA) stimulated HK-2 cells. The acetylation levels of long-chain acyl-CoA dehydrogenases (LCAD) and β-hydroxyacyl-CoA dehydrogenase (β-HAD) were measured by immunoprecipitation. And a multifunction microplate reader was applied to detect FAO rate, triglyceride and acyl-CoA contents, and the enzyme activities, with cellular lipid accumulation identified by Oil Red O staining. We evidenced the acetylation levels of LCAD and β-HAD that were enhanced, which led to decreased enzymatic activities and impaired FAO rate. Furthermore, renal protein hyperacetylation induced by lipid overload was associated with increased expression of GCN5L1. And the silence of GCN5L1 in tubular epithelial cells resulted in deacetylation and activation of LCAD and β-HAD. Finally, excess lipids induced lipotoxicity and epithelial-mesenchymal transition (EMT) were ameliorated by GCN5L1 suppression, suggesting GCN5L1-mediated mitochondrial LCAD and β-HAD acetylation might be a key pathogenic event underlying excess lipids induced FAO impairment.

The clinical outcome of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors is limited by the ambiguous molecular subtypes of non-small cell lung cancer (NSCLC) patients and the emergence of drug-resistance. Here, a nanotheranostic agent ECMI, which is indocyanine green (ICG)-loaded mesoporous silica nanoparticles lidded with ZnO QDs and wrapped with erlotinib-modified chitosan, was developed for accurately determination of molecular subtypes and synergistic therapy. The erlotinib could guide ECMI into EGFR-mutated NSCLC cells and acquire a pH/redox dual-responsive release of ICG for precise fluorescent imaging. The ECMI could exert synergistic photodynamic/molecular targeted therapeutic effects under near-infrared irradiation in either erlotinib-sensitive or erlotinib-resistant EGFR-mutated NSCLC cells. In vivo experiments further showed that ECMI had distinct distribution behaviors in different NSCLC models and demonstrated synergistic anticancer effects. These results indicated that ECMI could be a promising nanotheranostic agent to treat EGFR-mutated NSCLC, and could provide a new perspective for individualized treatment.

A photonic quasi-crystal fiber (PQF) with high birefringence based on ZrF4-BaF2-LaF3-AlF3-NaF (ZBLAN) is described. There are two elliptical air holes in the core to increase birefringence and the outer air hole array has a twelve-fold Stampfli-type quasi-crystal structure. ZBLAN reduces absorption loss in the infrared region resulting in higher birefringence. The birefringence and confinement loss of the PQF are analyzed numerically by the full-vector finite element method. Birefringence is higher than that of conventional polarization-maintaining fibers due to the two elliptical air holes in the center and reaches the maximum of 4.15×10−2 at a wavelength of 2 μm. The novel structure has great potential in high-performance optical devices.

Pd–Cu/Palygorskite catalysts were prepared by a deposition precipitation method using palygorskite (PC/Pal) and carbon modified palygorskite (PC/Pal-C) as supports, respectively. Their catalytic activities toward CO oxidation at room temperature and in humid circumstances were investigated. It is found that PC/Pal-C exhibits much higher catalytic activity and stability than PC/Pal for room-temperature CO oxidation under moisture-rich conditions. X-ray photoelectron spectroscopy (XPS) and H2-TPR results indicate that the more active Pd2+ and highly dispersed Cu2Cl(OH)3 species present on the PC/Pal-C, which promotes the higher catalytic activity. The thermogravimetric (TG) and water contact angles (CA) results suggest that the slightly enhanced hydrophobicity of PC/Pal-C could properly restrain the moisture condensation on the catalyst surface, which may account for the excellent catalytic stability. The more surface active species and the proper hydrophobicity may be responsible for the excellent catalytic performance of PC/Pal-C.

Titanium dioxide (TiO2)/fluorine-doped tin dioxide (FTO) bilayer films were deposited on glass substrates by spray pyrolysis. The effects of hydrogen plasma exposure on structure, morphology and optical properties of the films were studied. The distribution of elements in the double layer film was investigated by glow discharge spectrometer. The results indicate that the TiO2 film provides effective protection of the underlying FTO film from the bombardment with hydrogen ions and radicals. Without the TiO2 protective layer, SnO2 will be reduced to sub-oxidized SnO and metallic Sn by hydrogen ions and radicals with increasing the exposure time. In addition, the TiO2/FTO film presents a nano-flower shaped appearance due to the small particles (TiO2) agglomerated on the surface of large particles (SnO2), the novel textured morphology is preferred for improving light scattering and haze of the film. A high haze value of 36.7% was obtained when the approximate thickness of the prepared TiO2 layer is 213 nm. This work may provide an alternative for improving performance of a-Si based solar cells.

Diabetic kidney disease (DKD) is the major cause of end-stage renal disease (ESRD). In the past few decades, there has been a large amount of evidence to highlight the pivotal role of oxidative stress in the development and progression of DKD. However, the detailed molecular mechanisms are not fully elucidated. A new sight has been established that the mitochondrial acetyltransferase GCN5L1 participates in cellular redox homeostasis maintenance in DKD. Firstly, we found that the expression of GCN5L1 is significantly elevated both in human and mouse kidney tissues with DKD and in hyperglycemic renal tubular epithelial cells (TECs), while deletion of GCN5L1 could effectively ameliorate oxidative stress-induced renal injury in DKD. Furthermore, deletion of GCN5L1 could reduce MnSOD acetylation on lysine 68 and activate its activity, thereby scavenging excessive ROS and relieving oxidative stress-induced renal inflammation and fibrosis. In general, GCN5L1-mediated acetylation of MnSOD exacerbated oxidative stress-induced renal injury, suggesting that GCN5L1 might be a potential intervention target in DKD.

Bexarotene (BEX), a specific retinoic acid X receptor (RXR) agonist granted by Food and Drug Administration (FDA) approval for the clinical treatment of T cell lymphoma, has now been found to exert pharmacological effects in the nervous system, with low bioavailability and poor cerebral distribution limiting its application in treatment on neurological disorders. Pharmaceutical co-crystal was a helpful method to improve the bioavailability and tissue distribution of active pharmaceutical ingredients (APIs). Here, 2bexarotene-ligustrazine (2BEX-LIG), a novel co-crystal system of BEX and ligustrazine (LIG) of which with BEX is an API, was constructed with satisfactory stability and enhanced solubility. The pharmacokinetics characteristics of BEX were detected, and the results showed that the absolute bioavailability and the cerebral concentration of BEX in rats administrated with 2BEX-LIG were enhanced from 22.89% to 42.86% and increased by 3.4-fold, respectively, compared with those in rats administrated an equivalent of BEX. Hence, our present study indicated that the novel co-crystal of 2BEX-LIG contributed to improving BEX oral bioavailability and cerebral distribution, thereby providing significant advantages for clinical application of brain tumors and other neurological diseases.

As one of the main energy metabolism organs, kidney has been proved to have high energy requirements and are more inclined to fatty acid metabolism as the main energy source. Long-chain acyl-CoA dehydrogenases (LCAD) and beta-hydroxyacyl-CoA dehydrogenase (beta-HAD), key enzymes involved in fatty acid oxidation, has been identified as the substrate of acetyltransferase GCN5L1 and deacetylase Sirt3. Acetylation levels of LCAD and beta-HAD regulate its enzymes activity and thus affect fatty acid oxidation rate. Moreover, immunoprecipitation is a key assay for the detection of LCAD and beta-HAD acetylation levels. Here we describe a protocol of immunoprecipitation of acetyl-lysine and western blotting of LCAD and beta-HAD in palmitic acid treated HK-2 cells (human renal tubular epithelial cells). The scheme provides the readers with clear steps so that this method could be applied to detect the acetylation level of various proteins.

Background Inflammation, oxidative stress and epithelial barrier dysfunction have been implicated in inflammatory bowel disease (IBD) pathology. The targeted inhibition of these features may represent a promising therapeutic strategy for IBD. Polydatin is an effective natural antioxidant that possesses strong antioxidant and anti-apoptotic properties. Thus, we studied the protective effects of polydatin treatments on a mouse model of experimental colitis. Methods Acute colitis was experimentally induced by adding 3% dextran sulfate sodium (DSS) to the drinking water provided to mice for 7 days and by administering different doses of polydatin (15, 30, or 45 mg/kg) during the same period. Mice were also treated with the Sonic hedgehog (Shh) pathway inhibitor cyclopamine to estimate the efficacy of polydatin and Shh inhibitors on colitis. The disease activity index (DAI), colon length, histology, levels of oxidative and apoptotic mediators and levels of Shh pathway components were evaluated. Results The polydatin treatment significantly attenuated the DAI, colon shortening and histological damage. In addition, polydatin administration effectively decreased malondialdehyde (MDA) levels and increased the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Polydatin also inhibited apoptosis in mice with colitis by downregulating the expression of the pro-apoptotic proteins Bax, caspase 3 and cleaved caspase 3 and increasing the expression of the anti-apoptotic protein Bcl-2. Furthermore, polydatin modulated Shh signaling pathway activation. After polydatin treatment, the main components of the Shh pathway, including Shh, Patched (Ptc), Smoothened (Smo), and glioblastoma-1 (Gli1), were upregulated at the mRNA and protein levels. Blockade of the Shh pathway using cyclopamine abolished the effects of polydatin on mice with colitis. Conclusion Based on these observations, polydatin may suppress experimental colitis at least partially by regulating the Shh signaling pathway.

Chemotherapy is currently one of the promising therapeutic methods for non-small-cell lung cancer (NSCLC), but the emergence of multidrug resistance (MDR) is the greatest obstacle to efficient drug delivery for successful chemotherapy. Nanotechnology-based drug delivery holds great promise to promote intracellular drug delivery to reverse MDR. In this work, we used our previously synthesized ursolic acid (UA) derivative, FZU-03,010 (F3), to prepare nanodrugs of F3 with different architectures and study the role of the structure on the physiochemical properties and the biological effects against A549 and its PTX-resistant A549/PTX lung cancer cells. Using different preparation methods, amphiphilic F3 could self-assemble into different structures such as nanoaggregates (F3-NA), vesicles (F3-VC), or nanoparticles (F3-NP) with different physiochemical properties. The self-assembled nanodrugs could be utilized for the entrapment of fluorophores and showed different cellular uptake efficiencies. The cytotoxicity results demonstrated that compared with UA, F3-NA and F3-NP could suppress A549 and A549/PTX cells viability more potently at lower concentration. In addition, F3-NA and F3-NP could induce G1 cell cycle arrest, cell apoptosis and caspase-3 activation more efficiently than that of UA. Furthermore, F3-NA and F3-NP could effectively inhibit PI3K/Akt pathway and decrease the expression of Bcl-2 and the cell cycle-dependent kinase inhibitors p-ERK1/2 and Cyclin D1 in both A549 and A549/PTX cells. In conclusion, our results suggest that the UA derivative F3 is more potent in inhibiting cancer cell proliferation, and F3-NA and F3-NP have the potential to be developed as a therapeutic agent for resistant NSCLC cells.

Photodynamic therapy (PDT) was hindered by the poor water solubility and long-enduring photoactivities of photosensitizers. Here, we developed a novel controllable photodynamic agent CPHI based on β-cyclodextrin modified polyamidoamine (PAMAM) dendrimer (CP) co-delivery of indocyanine green (ICG) and hematoporphyrin (HP). The CPHI possessed appropriate particle sizes and zeta potentials, considerable photostability, and NIR-triggered release property. The fluorescence of HP could be quenched by ICG when HP and ICG were co-loaded inside the CP, and the quenching efficiency was related with the weight ratio of HP and ICG. When the feeding weight proportion of HP and ICG is 1/10, the fluorescence of HP was quenched by 87.3% in CPHI. Under 808 nm laser irradiation, the ICG in CP was degraded, and the fluorescence of HP could recover. The recovered HP was capable of generating reactive oxygen species (ROS) for PDT with 606 nm laser irradiation. The cytotoxicity and cell apoptosis studies showed that CPHI could effectively induce MCF-7 cells apoptosis with PDT effects under 808/660 nm laser. These results suggested that CPHI could be an efficient cancer therapeutic agent for controllable PDT with low dark toxicity.

The Pd–Cu/attapulgite clay catalysts were synthesized using a deposition–precipitation method with different precipitants. The as-synthesized catalysts were characterized by ICP-AES, N2-physisorption, XRD, FT-IR, TEM and TPR. Their catalytic activities for CO oxidation were tested by a fixed-bed continuous flow reactor at room temperature and in humid circumstances. The results illustrated that the activity of CO oxidation strongly depended on the precipitant. The best catalytic performance is achieved by using NH3·H2O (PC-AH) or NH4HCO3 (PC-AHC) as precipitants. The crystalline phase of PC-AH and PC-AHC comprised of Cu2Cl(OH)3 and CuO, while the catalysts prepared with NaOH (PC-SH) or NaHCO3 (PC-SHC) as precipitants were mainly CuO. Combined with FT-IR and TEM results, it could be found that Cu2Cl(OH)3 on PC-AH and PC-AHC possessed higher stability than that on PC-SH and PC-SHC due to the different formation process and morphology of Cu2Cl(OH)3 species. The TPR results showed that the Cu2Cl(OH)3 had a strong interaction with Pd species and enhanced reducibility. Moreover, the residual sodium ions on PC-SH and PC-SHC may have adverse effect on the catalytic activity. A suitable precipitant resulted in the most efficient CO oxidation catalyst at room temperature and in humid circumstances.

In present study, a stable and magnetic metal-organic framework (MOF) material was synthesized by simple solvothermal method as adsorbent to rapid removal of two organic dyes, the Rhodamine B (RB) and Rhodamine 6G (Rh6G), in water samples. The prepared material showed great characteristics of large surface area (519.86 m 2 g −1 ), excellent magnetic responsivity (35.00 emu g −1 ) and rapid removal (within 5 min). Maximum adsorption capacities of the magnetic material toward RB and Rh6G were up to 219.78 and 306.75 mg g −1 , respectively. Adsorption kinetics suggested the adsorption process met the pseudo-second-order kinetic model. The prepared material could be reused at least 10 times by washing with acetonitrile solution, the relative standard deviation (RSD) of these ten cycles removal efficiency was 4.8%. In conclusion, good chemical inertness, a mechanical/water stability and super-hydrophilicity feature made this MOF a promising adsorbent for targets removal from environmental water sample.

Novel methodology for efficient functionalization of tetrahydro-β-carbolines (THβCs) has been established via an unexpected oxidative rearrangement coupling reaction. Treatment of THβCs with photogenerated singlet oxygen (1O2) afforded unstable dioxetanes, followed by further transformation to construct new bond in the presence of TFA. This operationally simple protocol exhibits broadly functional group-tolerant and allows for last-stage functionalization of complex drug-like molecules.

Folate (FA) and heptamethine cyanine (Cy7)-modified chitosan (CF7) was synthesized by click chemistry and its self-assembled nanoparticles (CF7Ns) were developed for tumor-specific imaging and photodynamic therapy. The characterization spectrum confirmed CF7 had a good FA and Cy7 conjugation efficacy. The diameter of CF7Ns measured by DLS was about 291.6 nm, and the morphology observed with AFM showed filamentous clusters of particles. The results of targeting ability of CF7Ns demonstrated enhanced targeting behaviors of CF7Ns compared with non-FA-modified nanoparticles C7Ns in FA receptor-positive HeLa cells. The cytotoxicity and cell apoptosis assay showed that CF7Ns under near-infrared light irradiation led to more apoptotic cell death in HeLa cells to improve the therapeutic efficacy. The mechanisms of the photodynamic effects of CF7Ns were demonstrated through measurement of intracellular reactive oxygen species and the apoptosis-related cytokines. These results suggested that CF7Ns are promising tumor targeting carriers for simultaneous fluorescence imaging and photodynamic therapy.

Soil contamination with arsenic (As) can cause phytotoxicity and elevated As accumulation in rice grain. Here, we used a forward genetics approach to investigate the mechanism of arsenate (As(V)) tolerance and accumulation in rice. A rice mutant hypersensitive to As(V), but not to As(III), was isolated. Genomic resequencing and complementation tests were used to identify the causal gene. The function of the gene, its expression pattern and subcellular localization were characterized. OsHAC4 is the causal gene for the As(V)-hypersensitive phenotype. The gene encodes a rhodanase-like protein that shows As(V) reductase activity when expressed in Escherichia coli. OsHAC4 was highly expressed in roots and was induced by As(V). In OsHAC4pro-GUS transgenic plants, the gene was expressed exclusively in the root epidermis and exodermis. OsHAC4-eGFP was localized in the cytoplasm and the nucleus. Mutation in OsHAC4 resulted in decreased As(V) reduction in roots, decreased As(III) efflux to the external medium and markedly increased As accumulation in rice shoots. Overexpression of OsHAC4 increased As(V) tolerance and decreased As accumulation in rice plants. OsHAC4 is an As(V) reductase that is critical for As(V) detoxification and for the control of As accumulation in rice. As(V) reduction, followed by As(III) efflux, is an important mechanism of As(V) detoxification.

Hyperbranched polymer with epoxide-terminated group was synthesized through end-capping reaction between hyperbranched polymer with hydroxyl-terminated group and epichlorohydrin. The chemical structure of the synthesized polymer was characterized by ATR-IR and 1H NMR spectroscopy. The influence of hyperbranched polymer content on the mechanical properties and fracture toughness of epoxy/polyamide systems was investigated. The toughening mechanism was discussed basing on observing the fracture surface morphologies of epoxy/polyamide/hyperbranched polymer system.

A facile one-pot synthesis of tricyclo-1,4-benzoxazines has been developed via metal-free intramolecular cyclization of indole derivates. These reactions were efficiently achieved at ambient temperature by using visible-light photoredox catalysis in continuous flow. This directed intramolecular cyclization could be easily handled and scaled up in an open flask, enabling construction of a focused compound library for further pharmacological evaluation.

The present study aimed to investigate the regulatory roles of miR-142-3p on the aggressive phenotypes of rheumatoid arthritis (RA) human fibroblast-like synoviocytes (RA-HFLSs), and reveal the potential mechanisms relating with nuclear factor-κB (NF-κB) signaling. miR-142-3p expression was detected in RA synovial tissues and RA-HFLSs by quantitative real-time PCR (qRT-PCR) and Northern blot analysis. RA-HFLSs were transfected with miR-142-3p inhibitor and/or treated with 10 µg/l tumor necrosis factor α (TNF-α). The viability, colony formation, apoptosis, migration, invasion, and the levels of interleukin (IL)-6, and matrix metalloproteinase 3 (MMP-3) were detected. The mRNA expressions of B-cell lymphoma-2 (Bcl-2), Bax, Bad, IL-6, and MMP-3 were detected by qRT-PCR. Moreover, the expression of Bcl-2, IL-1 receptor-associated kinase 1 (IRAK1), Toll-like receptor 4 (TLR4), NF-κB p65, and phosphorylated NF-κB p65 (p-NF-κB p65) were detected by Western blot. The interaction between IRAK1 and miR-142-3p was identified by dual luciferase reporter gene assay. MiR-142-3p was up-regulated in RA synovial tissues and RA-HFLSs. TNF-α activated the aggressive phenotypes of RA-HFLSs, including enhanced proliferation, migration, invasion, and inflammation, and inhibited apoptosis. miR-142-3p inhibitor significantly decreased the cell viability, the number of cell clones, the migration rate, the number of invasive cells, the contents and expression of IL-6 and MMP-3, and increased the apoptosis rate and the expressions of Bax and Bad, and decreased Bcl-2 expression of TNF-α-treated RA-HFLSs. MiR-142-3p inhibitor significantly reversed TNF-α-induced up-regulation of IRAK1, TLR4, and p-NF-κB p65 in TNF-α-treated RA-HFLSs. Besides, IRAK1 was a target of miR-142-3p. The down-regulation of miR-142-3p inhibited the aggressive phenotypes of RA-HFLSs through inhibiting NF-κB signaling.

Salidroside (Sal), the active ingredient of Rhodiola rosea L, has various pharmacological activities, including antioxidant, anti-inflammatory and anti-tumor activities. Recently, studies have shown that oxidative stress and apoptosis are related to the pathogenesis of inflammatory bowel disease. Therefore, we evaluated the effects of Sal on oxidative stress and apoptosis in colitis mice through the SIRT1/FoxOs pathway. To induce the colitis model, mice continuously consumed water containing 3% DSS for 7 days; some mice were also treated with Sal and the SIRT1/FoxOs pathway blocker selisistat (Ex527). Changes in body weight, DAI, colon length and colon tissue histology as well as SOD, GSH-Px and CAT activities were measured. The expression of SIRT1, FoxO1, FoxO3a, FoxO4, caspase-3, cleaved-caspase-3, Bax and Bcl-2 in colorectal tissues was detected by RT-PCR and Western blotting. The study showed that Sal decreased the DAI score, weight loss, colon shortening and colon tissue damage in colitis mice. Sal inhibited oxidative stress by upregulating SOD, GSH-Px and CAT while suppressing colonic apoptosis by downregulating the expression of Bax, caspase-3, and cleaved-caspase-3 and upregulating the expression of Bcl-2. Sal also activated SIRT1/FoxOs signaling, which increased the expression of SIRT1, FoxO1, FoxO3a and FoxO4 in colon tissue. Furthermore, SIRT1/FoxOs pathway inhibition using Ex527 partially eliminated the effect of Sal on colitis mice. The study manifested that Sal may protect colitis mice by activating the SIRT1/FoxOs pathway, which is related to oxidative stress and apoptosis in colon tissues.

The role of CD147 in regulation of rheumatoid arthritis (RA) is not fully elucidated. The aim of this study was to investigate the effect of cell-to-cell contact of activated CD14+ monocytes with CD4+ T cells, and the modulatory role of CD147 on T-helper 17 (Th17) cells differentiation in patients with RA. Twenty confirmed active RA patients and twenty normal controls were enrolled. CD4+ T cells and CD14+ monocytes were purified by magnetic beads cell sorting. Cells were cultured under different conditions in CD4+ T cells alone, direct cell-to-cell contact co-culture of CD4+ and CD14+ cells, or indirect transwell co-culture of CD4+ /CD14+ cells in response to LPS and anti-CD3 stimulation with or without anti-CD147 antibody pretreatments. The proportion of IL-17-producing CD4+ T cells (defined as Th17 cells) was determined by flow cytometry. The levels of interleukin (IL)-17, IL-6, and IL-1β in the supernatants of cultured cells were measured by ELISA. The optimal condition for in vitro induction of Th17 cells differentiation was co-stimulation with 0.1 μg/mL of LPS and 100 ng/mL of anti-CD3 for 3 days under direct cell-to-cell contact co-culture of CD4+ and CD14+ cells. Anti-CD147 antibody reduced the proportion of Th17 cells, and also inhibited the productions of IL-17, IL-6, and IL-1β in PBMC culture from RA patients. The current results revealed that Th17 differentiation required cell-to-cell contact with activated monocytes. CD147 promoted the differentiation of Th17 cells by regulation of cytokine production, which provided the evidence for pathogenesis and potential therapeutic targets for RA.

Hyperbranched polymer with amino end groups (HBPA) and core-shell particle (CSP, which is fabricated through grafting HBPA onto the surface of silica nanoparticle) were incorporated into an epoxy matrix to fabricate a high performance composite. The effects of CSPs contents on the mechanical properties of composites were studied, discussing the results from tensile, flexural, and impact tests. The composites revealed noticeable improvements in tensile strength, elongation, flexural strength and impact strength in comparison to the neat epoxy or epoxy/HBPA system. The glass transition temperature (Tg) was also improved by the addition of CSP. Field emission scanning electron micrograph (FESEM) indicated that HBPA could favorable improve the compatibility between CSP and epoxy matrix. And the toughening mechanisms were the synergic effect of shearing deformation, phase separation, crack propagation, crack deflection, and crack pinning.

The performance of a magnetic ion-imprinted chitosan resins (MICR) have been investigated for the adsorption processes of Th(IV) ions from aqueous solution. Infrared spectra (IR) and energy dispersive spectrometer (EDS) show that it is a successful cross-linking and ion-imprinting process, and Th(IV) has been adsorbed onto the MICR. Experimental equilibrium data has been obtained and the results have shown that the Langmuir isotherm model better fits the experimental data compared with the Freundlich isotherm. Two simplified models including pseudo-first order and pseudo-second order equations were selected to simulate the adsorption process.

In this study, glass-fiber, grafted by epoxide-terminated hyperbranched polymer (GF-HBPE), was incorporated into epoxy resins for reinforcement purpose. The effects of GF-HBPE content on mechanical properties of the resulting epoxy-based composites, such as tensile strength, percentage elongation at break, flexural strength, and impact strength, were investigated. The experimental results revealed that GF-HBPE substantially outperformed impact resistance in both tensile and flexural tests. For instance, the tensile strength, percentage elongation at break, flexural strength, and impact strength of the epoxy composite with 1 wt% GF-HBPE increase by about 23.6%, 125%, 26%, and 74.5%, respectively, compared to the unmodified epoxy thermoset.

A novel amino-terminated hyperbranched polymer (ATHBP) was synthesized through the end-capping reaction between hyperbranched polymer with hydroxyl group (HBPH) and diethylenetriamine. The chemical structure of ATHBP was characterized by attenuated total internal reflectance infrared spectroscopy (ATR-IR) and 1H nuclear magnetic resonance spectroscopy (1H NMR). The effect of ATHBP content (0–30 wt%) on the impact resistance and glass transition temperature (Tg) of diglycidyl ether of bisphenol-A epoxy resin was studied. The toughness mechanism was discussed by observing the fracture surface morphologies of epoxy thermosets using field emission scanning electron microscopy (FESEM). The results showed that the degree of branching of ATHBP was 0.56. And the introduction of ATHBP could favorably improve the impact strength but not sacrifice the Tg of epoxy resin. For example, the impact strength of 25 wt% formulation was 60.7 % higher than that of the neat epoxy thermoset. FESEM analysis indicated that the toughening mechanism may be attributed to plastic deformation mechanism.

To ascertain the number and percentage of angiogenic T (Tang) cell subsets by flow cytometry in systemic sclerosis (SSc), and their relation with specific clinical features. Thirty SSc patients and 15 healthy controls (HCs) were included. Luminex was performed to analyze the levels of interleukin (IL)-17A, vascular endothelial growth factor (VEGF), tumor necrosis factor-α, and vascular cell adhesion molecule (VCAM). The ratio of circulating CD3 + CD31 + CXCR4 + T (CD3 + Tang) cells and CD8+ CD31 + CXCR4 + T (CD8+ Tang) cells in SSc patients was enlarger than in HCs, while CD4 + CD31 + CXCR4 + T cells (CD4 + Tang) exhibited no difference between SSc patients and HCs. The number and percentage of Tang cells were higher in SSc patients with pulmonary artery hypertension (PAH) than in non-PAH SSc patients and HCs. The ratios of Tang cell subsets in nucleolar pattern-positive SSc patients were markedly raised as compared with their negative ones and HCs. Additionally, the percentage of circulating CD3 + Tang cells was positively associated with VEGF serum levels in SSc patients. Meanwhile, the rate of CD8+ tang cells might have been emphatically corresponded to VEGF and VCAM serum levels in SSc patients. These results imply that the increase in Tang cells in peripheral blood are associated with immunoregulatory disturbances in SSc patients.

Ghrelin is a circulating peptide hormone, which involved in promoting feeding and regulating energy metabolism in human and rodents. Abnormal synovial hyperplasia is the most important pathologic hallmark of rheumatoid arthritis (RA), which is characterised by tumor-like expansion. Existing studies indicated that there may exist some relation between the decreased ghrelin and the abnormally proliferating synovial cells in RA. Therefore, the aim of this study is to explore the apoptotic effects of ghrelin on MH7A synovial cells in vitro. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the effects of ghrelin on the viability of MH7A cells. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) and flow cytometry were used to test the apoptotic effects of ghrelin. At last, Western blot and real-time PCR were performed to explore the expression of caspases-8, -9, and -3 after the treatment of ghrelin. MTT experiments showed that ghrelin could inhibit viability of MH7A cells. The results of flow cytometry and TUNEL showed that ghrelin could induce apoptosis of MH7A synovial cells. Western blot showed that expression of cleaved-caspases-8, -9, and -3 were increased in ghrelin stimulation group compared with the control group, while expression of pro-caspases-8, -9, and -3 had no significant difference. In mRNA levels, ghrelin can decrease pro-caspases-8, -9, and -3 mRNA expression, which confirmed the results of protein levels. Then these apoptotic effects were significantly reversed by [D-Lys3] GHRP-6 (ghrelin receptor antagonist). This study found that ghrelin can induce apoptosis of MH7A cells through caspase signaling pathways.

The outcome of molecular targeted therapies is restricted by the ambiguous molecular subtypes of nonsmall cell lung cancer (NSCLC), which are difficult to be defined with druggable mutations, and the inevitable emergence of drug-resistance. Here we used the Cu-catalyzed click chemistry to synthesize a chitosan-based self-assembled nanotheranostics (CE7Ns) composed of a near-infrared (NIR) fluorescent photosensitizer Cy7 and molecular targeted drug erlotinib. The well-characterized CE7Ns can release erlotinib and Cy7 fast under acidic condition in the presence of lysozyme, distinguish three molecular subtypes of NSCLC, and specifically bind to the erlotinib-sensitive epidermal growth factor receptor (EGFR)-mutated PC-9 cells. The uptake of CE7Ns is much more in PC-9 cells than in other NSCLC cells, thus generating a notable fluorescence signal in PC-9 cells. Upon NIR irradiation, Cy7 in CE7Ns produces high reactive oxygen species in PC-9 cells. The synergistic effect between erlotinib-targeted therapy and photodynamic therapy significantly up-regulates cancer suppressor p53 and inhibits Survivin, which results in more apoptosis and cell cycle arrest. Upon intravenous administration, the erlotinib-guided CE7Ns significantly accumulate in PC-9-seeded mouse lungs and produce strong fluorescence. Upon NIR irradiation, CE7Ns significantly inhibit the subcutaneously implanted PC-9 tumor growth. This study provides, for the first time, a novel strategy to synthesize a multifunctional theranostic entity to simultaneously distinguish and image druggable mutations and combine targeted therapy with photodynamic therapy to overcome drug resistance.

In the basic performance of SF6 high voltage circuit breaker, the breaking performance is the most important technical index to measure the performance of the product, and the breaking performance is mainly depended on the recovery characteristic of the dielectric strength for the arc extinguishing chamber during the opening and breaking process of the circuit breaker. In this paper, based on the theory of gas dynamics and electromagnetic field, the flow characteristics of the air flow and electric field intensity in the arc extinguishing chamber are simulated by the computer simulation software. And a numerical calculation method for the dielectric strength recovery characteristic of the circuit breaker is proposed. The method presented in this paper will provide necessary theoretical basis and technical support for the future application of the SF6 high voltage circuit breaker in high voltage system.

The performance of a cross-linked magnetic chitosan has been investigated for the adsorption of U(VI) from aqueous solutions. The influences of the pH of solution, the initial concentration of U(VI) ions and the contact time on the adsorption amounts have been discussed, and the appropriate process conditions for the adsorption of U(VI) have been obtained. The adsorption experimental equilibrium data was found to fit the Langmuir model well, and the uptake of U(VI) was 161.3 mg g−1. Two simplified models including pseudo-first order and pseudo-second order equations are selected to follow the adsorption process.

β1-Adrenoceptor autoantibodies (β1-AAs) affect the action potential duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The delayed rectifier potassium current (I K) plays a crucial role in APD, but the effects of β1-AAs on I K have not been completely illuminated. This work aimed to observe the effects of β1-AAs on I K and APD and further explore the mechanisms of β1-AA-mediated ventricular arrhythmias. β1-AAs were obtained from sera of patients with coronary heart disease (CHD) and nonsustained ventricular tachycardia. With whole-cell patch clamp technique, action potentials and I K were recorded. The results illustrated 0.1 μmol/L β1-AAs shortened APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01 μmol/L, β1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001 μmol/L, β1-AAs significantly prolonged APD90 and APD50. Moreover, β1-AAs (0.001, 0.01, 0.1 μmol/L) dose-dependently increased the rapidly activating delayed rectifier potassium current (I Kr), but similarly decreased the slowly activating delayed rectifier potassium current (I Ks) and increased L-type calcium currents at the different concentrations. Taken together, the IKr increase induced by high β1-AA concentrations is responsible for a significant APD reduction which would contribute to repolarization changes and trigger the malignant ventricular arrhythmias in CHD patients.

Gastrodia elata (G. elata), as a natural plant with nourishing and edible value, plays a vital role in food and pharmaceutical production. In the present study, a novel approach for the simultaneous determination of six components based on high-performance liquid chromatography (HPLC) coupled with photodiode array detection (PDA) was developed for the quality evaluation of G. elata from different regions. Meanwhile, antioxidant and α-glucosidase inhibitory activities were estimated and compared. The results indicated that the total contents of the six compounds in G. elata from Guizhou and Zhejiang provinces obtained by boiling were higher than those obtained by steaming in Anhui and Yunnan provinces. In addition, samples from Guizhou, Yunnan and Shanxi provinces contained more p-hydroxybenzyl alcohol, and always possessed higher antioxidant activity, while samples collected from Anhui province showed the highest α-glucosidase inhibitory activity with the highest gastrodin content. The results revealed that the quality of G. elata was affected by different regions and different initial processing technologies, which provided a reference for the selection and application of G. elata.

Baicalin (BAI) has been reported to exert antitumor effects. However, BAI has limited water solubility, non-specific tumor targeting, and low bioavailability, which severely limited its clinical application. The aim of this study was to develop folic acid (FA) covalently conjugated-polyamidoamine (PAMAM) dendrimers (PAMAM-FA) as carrier systems for improvement of water solubility and tumor-specificity of BAI, and study the role of generation on the physiochemical properties and biological effects of PAMAM-FA/BAI complexes. In this work, four generations of PAMAM-FA were synthesized to entrap BAI. The average sizes of G3-FA/BAI, G4-FA/BAI, G5-FA/BAI, and G6-FA/BAI complexes were 174.4nm, 184.5nm, 258.8nm, and 247.5nm, respectively, and the zeta potentials of four PAMAM-FA/BAI complexes were -2.9mV, -6.6mV, -9.3mV, -9.0mV, respectively. The entrapment efficiencies of four PAMAM-FA/BAI complexes were 91.1%, 53.5%, 80.3%, and 91.9%, respectively, and the drug loading of PAMAM-FA/BAI complexes were about 22%. The formed PAMAM-FA/BAI complexes allowed sustained release of BAI in acidic PBS (pH5.4). In cellular uptake assay, PAMAM-FA/BAI complexes demonstrated increased drug uptake level in folate receptor (FR)-positive Hela cancer cells than FR-negative A549 cells, and the cellular uptake efficiency of PAMAM-FA is closely related with the generation of PAMAM. The MTT assay results showed that PAMAM-FA/BAI complexes demonstrated enhanced toxicity against Hela cells than non-FA-modified PAMAM/BAI complexes, and the G6-FA/BAI demonstrated the best inhibition efficiency. The cell cycle and cell apoptosis analysis further demonstrated the tumor-specific therapeutic efficacy of PAMAM-FA/BAI. These results suggested that the PAMAM-FA have the potential for targeted delivery of BAI into cancer cells to enhance its anti-tumor efficacy.

We numerically demonstrate optically controlled THz response in a hybrid fishscale metamaterial with embedded photoconductive silicon at oblique incidence of TE wave. The oblique incidence allows excitation of Fano-type trapped mode resonance in a 2-fold rotational symmetric metamaterial. The hybrid fishscale metamaterial exhibits an optically controlled redshift switching effect in the THz range. The switching effect is dominated by the conductivity of the silicon instead of mechanically adjusting angles of incidence. The tuning frequency range is up to 0.3THz with a large modulation depth and high transmission in the “ON” state. The fishscale metamaterial-based switching has been experimentally verified by its microwave counterpart integrated by variable resistors. Our work provides an alternative route to realize tunable Fano-type response in metamaterials and is of importance to active manipulation, sensing and switching of THz waves in practical applications.

Polarization properties provide a controlled degree of freedom in the process of light propagation. Efficiently manipulating polarization states plays a pivotal role in the areas of electromagnetic wave detection and information communication. In this work, we propose a chiral metamaterial that is comprised of an array of 90°-twisted E-shaped resonators with incorporated vanadium dioxide films. The hybridized chiral metamaterial allows us to effectively modify the conductivity of vanadium dioxide utilizing a thermal trigger. A thermo-controlled cross-polarization conversion can be realized. The phase transition metamaterials may open an opportunity in the THz regime to acquire a variety of functionalities, such as tunable filters, modulators and switches.

We present an optically controlled terahertz (THz) switch to tune the state of polarization based on single-layer chiral metamaterial. The chiral metamaterial consists of an array of perforated S-shaped slits with incorporated photoactive silicon, which allows us to control dynamically cross-polarization transmission. The switch state can be efficiently controlled by external optical stimuli. The realization of cross-polarization THz switch in a single-layer metamaterial has simple structure design and easy fabrication and therefore the S-shaped metamaterial will be a promising candidate for polarization control devices.

The toxicities of conventional chemotherapeutic agents to normal cells restrict their dosage and clinical efficacy in acute leukemia; therefore, it is important to develop novel chemotherapeutics, including natural products, which selectively target cancer-specific pathways. The present study aimed to explore the effect of the chemopreventive agent asiatic acid (AA) on the proliferation and apoptotic rate of the leukemia cell line HL-60 and investigated the mechanisms underlying its anti-tumor activity. The effect of AA on the proliferation of HL-60 cells was evaluated using the MTT assay. Annexin V-fluorescein isothiocyanate/propidium iodide double staining followed by flow cytometric analysis as well as Hoechst 33258 staining were used to analyze the apoptotic rate of the cells. Furthermore, changes of survivin, B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 expressions were detected by western blot analysis. AA blocked the growth of HL-60 cells in a dose- and time-dependent manner. The IC50-value of AA on HL-60 cells was 46.67 ± 5.08 µmol/l for 24 h. AA induced apoptosis in a dose-dependent manner, which was inhibited in the presence of Z-DEVD-FMK, a specific inhibitor of caspase. The anti-apoptotic proteins Bcl-2, Mcl-1 and survivin were downregulated by AA in a dose-dependent manner. Concurrently, AA inhibited ERK and p38 phosphorylation in a dose-dependent manner, while JNK phosphorylation was not affected. In conclusion, the present study indicated that the p38 and ERK pathways, as well as modulation of Bcl-2 family and survivin proteins were key regulators of apoptosis induced in HL-60 cells in response to AA.

In this paper, a model of Beddington–DeAngelies chemostat involving two species of micro-organism competing for two perfectly complementary growth-limiting nutrients and pulsed input of toxicant in the polluted environment was studied. Using Floquet theory and small amplitude perturbation method, a conclusion was that there exists two-micro-organism eradication periodic solution and which is global asymptotical stability. At the same time, the condition of the permanence for system was obtained. From the biological point of view, the method for protecting species is to improve the amount of impulsive period, and control the amount of toxicant input to the chemostat. Finally, our results are illustrated by numerical simulations.

We sought to elucidate the effects of different concentrations of dietary selenium on calcium ion release, MLCK levels, and muscle contraction in the uterine smooth muscle of rats. The selenium (Se) content of blood and of uterine smooth muscle tissues was detected by fluorescence spectrophotometry. Ca(2+) content was measured by atomic absorption spectroscopy. Calmodulin (CaM) and MLCK RNA and protein levels were analyzed by quantitative real-time polymerase chain reaction and Western blot, respectively. Dietary Se intake increased the Se levels in the blood and in uterine smooth muscle tissues and increased the Ca(2+) concentration in uterine smooth muscle tissues. The addition of Se also promoted CaM expression and enhanced MLCK activation in uterine smooth muscle tissues. In conclusion, Ca(2+), CaM, and MLCK were regulated by Se in uterine smooth muscle; Se plays a major role in regulating smooth muscle contraction in the uterus.