Search

BACKGROUND Tissue dynamics of von Willebrand factor (VWF) that are vital to its biological function have not been fully characterized. OBJECTIVE To develop a new fluorescent protein--VWF chimera (FP-VWF) that has similar hematologic function to wild-type VWF and use it to monitor the tissue dynamics of VWF distribution. METHODS Genotyping, platelet counting, tail bleeding time assay, agarose gels, western blot, platelet aggregation, proteolytic analysis, and ELISA were applied in characterizing the function of FP-VWF; fluorescence spectrometer and confocal fluorescence microscope were used to monitor the plasma and tissue distribution of FP-VWF. RESULTS The transgenic mice that carry the FP-VWF retain hematologic activity of VWF with plasma levels of FP-VWF reduced by 50% and there are reduced high molecular weight FP-VWF multimers compared to the wild-type mice. The GPIb-binding and ADAMTS-13 (A Disintegrin and Metalloprotease with ThrombSpondin type 1 motif, member 13) proteolytic efficiency of FP-VWF are similar to wild-type VWF. The tissue distribution of FP-VWF was probed directly through its intrinsic fluorescence at normal or stimulated status, which indicated that the medicine-stimulated endogenous FP-VWF seems primarily released from the aorta and cleared in the spleen. Similar results were observed in non-fluorescent mice through a standard immunofluorescence approach. The fluorescence signals of FP-VWF were also similar to the standard dye-based approach in detecting the FeCl3 -induced blood clotting in vivo. CONCLUSIONS Together, these results suggest that this novel FP-VWF chimera is valuable in probing the tissue dynamics of VWF in quite a few biological and pharmaceutical applications.

Aims Apelin is the endogenous ligand of G protein-coupled receptor APJ and play an important role in the regulation of cardiovascular homeostasis. We aimed to investigate whether apelin ameliorates vascular calcification (VC) by inhibition of endoplasmic reticulum stress (ERS). Methods and results VC model in rats was induced by nicotine plus vitamin D, while calcification of vascular smooth muscle cell (VSMC) was induced by beta-glycerophosphate. Alizarin Red S staining showed dramatic calcium deposition in the aorta of rats with VC, while calcium contents and ALP activity also increased in calcified aorta. Protein levels of apelin and APJ were decreased in the calcified aorta. In rats with VC, apelin treatment significantly ameliorated aortic calcification, compliance and stimulation of ERS. The ameliorative effect of apelin on VC and ERS was also observed in calcified VSMCs. ERS stimulator (tunicamycin or DTT) blocked the beneficial effect of apelin. Apelin treatment activated the PI3K/Akt signaling, blockage of which by wortmannin or inhibitor IV prevented the ameliorative effect of apelin, while ERS inhibitor 4-PBA rescued the blockade effect of wortmannin. Akt-induced GSK inhibition prevented the phosphorylation of PERK and IRE1, and the activation of these two major ERS branches. F13A blocked the ameliorative effect of apelin on VC and ERS, which was reversed by treatment with 4-PBA or Akt activator SC79 Conclusions Apelin ameliorated VC by binding to APJ and then prevented ERS activation by stimulating Akt signaling. These results might provide new target for therapy and prevention of VC.

This study aimed to investigate whether inhibition of endoplasmic reticulum stress (ERS) mediated the ameliorative effect of apelin on acute heart failure (AHF). Rabbit model of AHF was induced by sodium pentobarbital. Cardiac dysfunction and injury were detected in the rabbit models of AHF, including impaired hemodynamic parameters and increased levels of CK-MB and cTnI. Apelin treatment dramatically improved cardiac impairment caused by AHF. ERS, indexed by increased GRP78, CHOP, and cleaved-caspase12 protein levels, was simultaneously attenuated by apelin. Apelin also could ameliorate increased protein levels of cleaved-caspase3 and Bax, and improved decreased protein levels of Bcl-2. Two common ERS stimulators, tunicamycin (Tm) and dithiothreitol (DTT) blocked the ameliorative effect of apelin on AHF. Phosphorylated Akt levels increased after apelin treatment in the rabbit models of AHF. The Akt signaling inhibitors wortmannin and LY294002 could block the cardioprotective effect of apelin, which could be relieved by ERS inhibitor 4-phenyl butyric acid (4-PBA). The aforementioned beneficial effects of apelin could all be blocked by APJ receptor antagonist F13A. 4-PBA and SC79, an Akt activator, can restore the ameliorative effect of apelin on AHF blocked by F13A. Apelin treatment dramatically ameliorated cardiac impairment caused by AHF, which might be mediated by APJ/Akt/ERS signaling pathway. These results will shed new light on AHF therapy.

Bacterial sigma (σ) factor, along with RNA polymerase core enzyme, initiates gene transcription from specific promoter regions and therefore regulates clusters of genes in response to a particular situation. The extracytoplasmic function (ECF) σ factors are a class of alternative σ factors that are often associated with environmental signal transduction across the bacterial membrane, in which external signal triggers the release of active σ from the membrane-anchored anti-σ factor. Gram-positive model organism Bacillus subtilis (B. subtilis) has seven ECF σ factors: σM, σV, σX, σW, σY, σZ and σYlaC. Although all these ECF σ factors were found to be involved in B. subtilis antibiotic resistance, σW is among the most studied and considered to play a pivotal role in responding to antimicrobial stresses. σW is under tight control and remains deactivated until exposure to external stimuli, after which proteases PrsW and RasP cleave the specific anti-sigma factor-RsiW to release and activate σW. Membrane anchored protein YsdB is a negative regulator of this activation, possibly via its direct interaction with PrsW and/or RsiW. Importantly, YsdB is well conserved among Bacilli, including pathogenic bacteria like Bacillus cereus. In this study, we describe the chemical shift assignments of the cytoplasmic domain of YsdB (29-130) of B. subtilis in solution as a basis for further interaction studies and structure determination. The near-complete assignment and the solution structure that will follow could provide a further understanding in σW regulation.

A 2-pyridone modified zinc phthalocyanine (denoted ZnPc-PYR) achieves a one stone for three birds outcome in the photodynamic therapy (PDT) treatment of cancer. ZnPc-PYR can be excited by both 665 and 808 nm light to treat superficial and deep tumors, store and slowly release singlet oxygen (1O2) to improve its utilization and downregulate the HIF-1 (hypoxia-inducible factor 1) expression level to enhance the tumor cell's sensitivity to PDT treatment under hypoxic conditions.

Stimulator of interferon genes (STING) has been shown to play a critical role in orchestrating immune responses to various pathogens through sensing cyclic dinucleotides. However, how STING regulates intestinal homeostasis is still not completely understood. In this study, we found that STING(−/−) mice were more susceptible to enteric infection with Citrobacter rodentium compared to WT mice evidenced by more severe intestinal inflammation and impaired bacterial clearance. STING(−/−) mice demonstrated lower expression of REG3γ, but not β-defensins and Cramp, in IECs. Consistently, STING(−/−) IECs showed reduced capacity to inhibit bacterial growth. STING agonists, both 10-carboxymethyl-9-acridanone (CMA) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA), promoted REG3γ expression IECs. Furthermore, STING agonists promoted WT but not REG3γ-deficient IEC bacterial killing. Mechanistically, STING agonists activated STAT3 and promoted glycolysis in IECs. Inhibition of STAT3 pathway and glycolysis suppressed STING induced REG3γ production in IECs, and abrogated STING-mediated IEC killing of Citrobactor rodentium. Additionally, treatment with the STING ligand, 2,3-cGAMP, inhibited Citrobactor rodentium-induced colitis in vivo. Overall, STING promotes IEC REG3γ expression to inhibit enteric infection and intestinal inflammation, thus, maintaining the intestinal homeostasis.

Biochemical and structural characterizations of a protein are the prerequisite for the further understanding of its biological role and potential applications. The expression of recombinant protein is almost unavoidable to produce the amount of the protein required for these studies, especially at the industrial level. Escherichia coli is the single most used system for recombinant protein expression and the first choice for a trial expression. Besides the inherited defects of its prokaryotic origin, the E. coli system has problems like low protein solubility and formation of inclusion bodies. To improve the solubility while assisting correct folding of the target protein, fusing a tag protein prior to its N-terminus is one of the common approaches. GST, MBP, Trx and SUMO proteins are among the most used tags by providing different advantages during recombinant protein expression. Msyb, a small and acidic protein native to E. coli, is another example that could improve the solubility of the target protein. While the biophysical and biochemical properties of these common tag proteins have been studied to a great extent, Msyb protein remains largely uncharacterized. Here, using solution-state NMR, our near-complete resonance assignment of Msyb provides a basis for future structure determination which would help to expand its usage as a common tag protein.

Erastin was initially discovered as a small molecule compound that selectively kills tumor cells expressing ST and RASV12 and was later widely investigated as an inducer of ferroptosis. Ferroptosis is a recently discovered form of cell death caused by peroxidation induced by the accumulation of intracellular lipid reactive oxygen species (L-ROS) in an iron-dependent manner. Erastin can mediate ferroptosis through a variety of molecules including the cystine-glutamate transport receptor (system XC -), the voltage-dependent anion channel (VDAC), and p53. Erastin is able to enhance the sensitivity of chemotherapy and radiotherapy, suggesting a promising future in cancer therapy. We hope that this review will help to better understand the role of erastin in ferroptosis and lay the foundation for further research and the development of erastin-based cancer therapies in the future.

By taking advantage of electronic influence of ligand design, the novel neutral nickel complexes bearing strong electron-donating N-acylated imidazolin-2-imine ligand were synthesized and characterized. The nickel catalysts conducted ethylene polymerization with high activity and good thermal stability, affording semicrystalline polyethylene with short chain branches (32–46/1000 C atoms). The complex Ni2 bearing adamantyl substituent on the imidazoline ligand showed higher activity than phenyl substituted complex Ni1, and highest activity was observed at 60 °C (up to ~106 g⋅mol−1⋅h−1). Most importantly, the catalysts were also effective for the copolymerization of ethylene and 5-hexenyl acetate with moderate activity (~105 g⋅mol−1⋅h−1). The microstructure analyses by the 13C NMR spectroscopy indicated that the 5-hexenyl acetate was successfully incorporated into the polyethylene main chain with reasonable comonomer content.

The incorporation of even a small number of polar functional groups in the polyolefin backbone is sufficient to improve the polyolefin properties. Compared with palladium catalyzed direct copolymerization of olefins with polar vinyl monomers, the development of low-cost nickel-based catalysts is more challenging because of their higher oxophilicity. On the basis of the advantage of reducing the electrophilicity of the nickel center by the installation of strongly electron-donating ligands, we herein report the synthesis of novel bis(N-acylated imidazolin-2-imine) nickel complexes for norbornene polymerization and copolymerization with polar monomers. Moreover, the phenyl substituent on the imidazoline ligand is expected to enhance the tolerance of the nickel catalyst toward polar functional groups, thus allowing the copolymerization of norbornene with commercial methyl acrylate to afford high molecular weight functionalized cyclic olefin copolymers (COCs) with moderate activity and reasonable comonomer content.

Nitric oxide (NO) can play both prosurvival and prodeath roles in photodynamic therapy (PDT). The generation efficiency of peroxynitrite anions (ONOO-), by NO and superoxide anions (O2•-), significantly influenced the outcome. Reports indicated that such efficiency is closely related to the distance between NO and O2•-. Thus, in this manuscript, l-arginine (Arg) ethyl ester-modified zinc phthalocyanine (Arg-ZnPc) was designed and synthesized as a photosensitizer (PS) and NO donor. Post light irradiation, the guanido of Arg-ZnPc can be effectively oxidized by the generated reactive oxygen species (ROS) in the PDT process to release NO. Such a strategy could ensure O2•- and NO generation in the same place at the same time to guarantee effective ONOO- formation. In addition, NO has other multiple synergistic cancer treatment functions, including tumor tissue vasodilatation for drug extravasation promotion, P-glycoprotein (P-gp) downregulation for drug efflux inhibition, and glutathione depletion for cancer cell endogenous antioxidant defense destruction. In vitro and in vivo results indicated that the effective ONOO- formation and multiple functions of Arg-ZnPc could synergistically enhance its PDT activity and ensure satisfactory cancer treatment outcome.

Chronic pain is a leading health and socioeconomic problem and an unmet need exists for long-lasting analgesics. SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are required for neuropeptide release and noxious signal transducer surface trafficking, thus, selective expression of the SNARE-cleaving light-chain protease of botulinum neurotoxin A (LCA) in peripheral sensory neurons could alleviate chronic pain. However, a safety concern to this approach is the lack of a sensory neuronal promoter to prevent the expression of LCA in the central nervous system. Towards this, we exploit the unique characteristics of Pirt (phosphoinositide-interacting regulator of TRP), which is expressed in peripheral nociceptive neurons. For the first time, we identified a Pirt promoter element and cloned it into a lentiviral vector driving transgene expression selectively in peripheral sensory neurons. Pirt promoter driven-LCA expression yielded rapid and concentration-dependent cleavage of SNAP-25 in cultured sensory neurons. Moreover, the transcripts of pain-related genes (TAC1, tachykinin precursor 1, &nbsp, CALCB, calcitonin gene-related peptide 2, HTR3A, 5-hydroxytryptamine receptor 3A, NPY2R, neuropeptide Y receptor Y2, GPR52, G protein-coupled receptor 52, SCN9A, sodium voltage-gated channel alpha subunit 9, TRPV1 and TRPA1, transient receptor potential cation channel subfamily V member 1 and subfamily A member 1) in pro-inflammatory cytokines stimulated sensory neurons were downregulated by viral mediated expression of LCA. Furthermore, viral expression of LCA yielded long-lasting inhibition of pain mediator release. Thus, we show that the engineered Pirt-LCA virus may provide a novel means for long lasting pain relief.

Utilizing catalase-mimicking nanozymes to produce O2 is an effective method to overcome tumor hypoxia. However, it is challenging to fabricate nanozymes with ultrahigh catalytic activity. Palladium nanosheet (Pd NS), a photothermal agent for photothermal therapy (PTT), has superior catalase-mimicking activity. Here, titanium dioxide (TiO2 ) is used to modify Pd NS (denoted Pd@TiO2 ) by a simple one-step method to improve its catalytic activity about 8 times. The enhancement mechanism's fundamental insights are discussed through experiments and density functional theory calculations. Next, zinc phthalocyanine is loaded on Pd@TiO2 to form a nanomotor (denoted PTZCs) with the synergistic activities of photodynamic therapy and PTT. PTZCs inherit the catalase activity of Pd@TiO2 to facilitate the decomposition of endogenous H2 O2 to O2 , which can relieve tumor hypoxia and propel PTZC migration to expand the reach of PTZCs, further enhancing its synergistic treatment outcome both in vitro and in vivo. It is proposed that this work can provide a simple and effective strategy for catalytic activity enhancement and bring a critical new perspective to studying and guiding the nanozyme design.

Dracorhodin perchlorate (DP), a synthetic analogue of the anthocyanin red pigment dracorhodin, has been shown to exert various pharmacological effects, including anticancer activity. However, its effects on human esophageal squamous cell carcinoma (ESCC) cells have not been previously investigated, and the molecular mechanisms underlying its anticancer activity remain unclear. In the present study, it was demonstrated that DP significantly reduced the viability of ESCC cells compared with that noted in normal human liver LO2 cells. Treatment with DP induced G2/M phase cell cycle arrest through upregulation of p21 and p27, and downregulation of cyclin B1 and Cdc2. Furthermore, DP treatment induced caspase‑dependent apoptosis, which could be reversed by exposure to Z‑VAD‑FMK, a caspase inhibitor. Western blotting demonstrated that DP induced apoptosis through extrinsic and intrinsic pathways by upregulating death receptor 4 (DR4), DR5, cleaved caspase‑3/‑7/‑9 and cleaved poly (ADP‑ribose) polymerase (PARP), and by decreasing total PARP, total caspase‑3/7, Bcl‑2 and caspase‑9/‑10. Moreover, DP treatment decreased the phosphorylation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), AKT, and forkhead box O3a (FOXO3a) in ESCC cells, indicating that the activity of the JAK2/STAT3 and AKT/FOXO3a signaling pathways was inhibited. Therefore, DP is a promising therapeutic agent for ESCC.

The carbon fiber reinforced thermoplastics (CFRTP) was successfully joined to aluminum using a laser-induced Al Ti C powder interlayer. The selection principle of the composition and content of the interlayer was studied. We calculate the composition and content of the interlayer material is Al54Ti32C14. The influence of connection temperature and connection pressure on the mechanical properties of the joint is studied. The results show that the connection temperature is 1600 °C and the connection pressure is 30 N, the maximum shear strength of the joint can reach 5.2 MPa. This experiment uses exothermal reaction of Al Ti C powder by laser induces self-propagating reaction to connect aluminum and CFRTP. In the aluminum side, the metallurgical reaction between interlayer and aluminum produces Al3Ti. In the CFRTP side, under the action of pressure, using the heat generated by the self-propagating reaction to melt the CFRTP, the molten CFRTP into the micro-hole of interlayer to form mechanical interlock. At the same time, element diffusion occurs at the interface, thus forming mechanical interlocking and diffusion connections.

High quality perovskite films with large columnar grains are greatly desired for efficient perovskite solar cells. Here, low volatility N-methyl-2-pyrrolidone (NMP) was added in MAI/IPA solution in a two-step spin-coating method, which promoted the conversion of lead iodide to perovskite. The perovskite films were annealed by a closed-steam annealing method to prolong the recrystallization process of perovskite films assisted by the residual NMP. It leaded to high quality CH3NH3PbI3 perovskite films with large columnar grains due to its enhancement of the Oswald ripening. The large grain perovskite film leaded to efficient carrier transformation and injection, and low recombination. The photovoltaic performance of the perovskite solar cells was improved significantly.

Blueberry anthocyanin (BA) have strong health benefits as an active natural antioxidant and perfluorooctanoic acid (PFOA) can result in oxidative stress in animals. In our study, the protective effects of BA against stress induced by PFOA was investigated in the planarian Dugesia japonica using oxidative stress biomarkers, ATP contents, ATPase activity, DNA methylation and mRNA expression. PFOA exposure could resulted in malondialdehyde production. At the same time, treatment with BA decreased the production of malondialdehyde in BA-exposed and co-treatment planarians. PFOA caused activities increase in glutathione peroxidase (GPx), glutathione S-transferase (GST) and activities decrease in glutathione reductase (GR). PFOA exposure decreased the GSH and ATP contents. Additionally, it increased the GSSG contents and ATPase activity. BA administration increased the activities of GPx, GST and GR in BA and co-treatment planarians. Meanwhile BA maintained the contents of ATP, ATPase activity, GSH and GSSG by alleviating PFOA toxicity. Moreover, PFOA and BA increased the contents of 5-methylcytosine and decreased 5-hydroxymethylcytosine in all group. In addition, PFOA and BA treated planarians significantly altered the expression of genes associated with above biochemical parameters. The results showed that the mRNA expression of gpx, Djgst, gr, Djnak and dnmt1 were significantly elevated in all groups. Alterations in the mRNA expression levels indicated a stress response to PFOA exposure and anthocyanin protection. These alterations regulated biomarkers of oxidative stress, energy metabolism and DNA methylation levels in planarians. These results indicate that BA attenuated PFOA-induced oxidative stress, energy metabolism, DNA methylation and gene expression disorders.

High-quality perovskite films with large grains and long carrier lifetime are crucial for efficient solar cells. It is a simple and effective way to increase the perovskite grain size by adding some additives in the precursor solution. Here, we use a low-toxicity and low-volatility organic compound of 1-ethyl-2-pyrrolidone (NEP) as an additive in the PbI2(PbBr2)/dimethylformamide precursor solution to form a Lewis adduct of PbI2·NEP, which facilitate forming perovskite intermediate embedded with NEP molecules. The residual NEP molecules are kept in the narrow space between the intermediate film and substrate during annealing by using a closed-steam annealing method, which prolong the dissolution-recrystallization process. With assistance of the residual NEP, high-quality perovskite films with smooth surface, PbI2 free, high crystallinity, large columnar grains, and long carrier lifetime are fabricated. Correspondingly, the power conversion efficiency of the best perovskite solar cells is enhanced signific...

The introduction of even low amount of polar functional group is important to expand the range of polyolefin properties. The palladium-catalyzed copolymerization of olefins with polar monomers is a valuable method for the direct synthesis of polar functionalized polyolefins, while low-cost nickel-based catalysts for these copolymerizations still have been limited. Here we report a series of mono- and dinuclear nickel complexes based on structurally simple anilinoanthraquinone ligand for the ethylene copolymerization and norbornene copolymerization with polar monomers. The dinickel catalysts exhibit higher activity and polar monomer incorporation than corresponding mononuclear analogue, owing to the electronic cooperativity effects between the two nickel centers through conjugated ligand.

DNA mimicry by proteins is a strategy that employed by some proteins to occupy the binding sites of the DNA-binding proteins and deny further access to these sites by DNA. Such proteins have been found in bacteriophage, eukaryotic virus, prokaryotic, and eukaryotic cells to imitate non-coding functions of DNA. Here, we report another phage protein Gp44 from bacteriophage SPO1 of Bacillus subtilis, employing mimicry as part of unusual strategy to inhibit host RNA polymerase. Consisting of three simple domains, Gp44 contains a DNA binding motif, a flexible DNA mimic domain and a random-coiled domain. Gp44 is able to anchor to host genome and interact bacterial RNA polymerase via the β and β′ subunit, resulting in bacterial growth inhibition. Our findings represent a non-specific strategy that SPO1 phage uses to target different bacterial transcription machinery regardless of the structural variations of RNA polymerases. This feature may have potential applications like generation of genetic engineered phages with Gp44 gene incorporated used in phage therapy to target a range of bacterial hosts.

Lactate, one of the most common primary metabolites of bacteria and human cells, has been shown to play essential roles in the regulation of inflammatory diseases, including inflammatory bowel diseases. However, whether and how host-derived lactate affects intestinal epithelial homeostasis is still not completely understood. Here, we investigated how L-lactate, mainly produced by host cells, regulates intestinal epithelial cell (IEC) migration to promote intestinal wound healing. Using video microscopy and tracking individual cells, we found that L-lactate enhanced IEC migration in direction persistence and speed. Mechanistically, L-lactate promoted IEC mitochondrial ATP production. The mitochondrial ATP synthase inhibitor, oligomycin, significantly decreased IEC persistence and speed, which inhibited cell migration induced by L-lactate. Furthermore, administering mice with L-lactate suppressed colitis induced by dextran sulfate sodium. In conclusion, our study demonstrates that host-derived L-lactate promotes IEC mitochondrial ATP production to drive cell migration, promoting intestinal wound healing to alleviate intestinal inflammation.

Mitochondrial apoptosis is one of the main mechanisms for cancer cells to overcome chemoresistance. Hexokinase 2 (HK2) can resist cancer cell apoptosis by expressing on mitochondria and binding to voltage-dependent anion channel 1 (VDAC1). We previously reported that peroxisome proliferator-activated receptor coactivator 1 α (PGC1α) is highly expressed in ovarian cancer cisplatin-resistant cells. However, the underlying mechanism remains unclear. Therefore, we evaluated the interaction between PGC1α and HK2 in ovarian cancer cisplatin-resistant cells. We found that the knockdown of PGC1α promotes the apoptosis of ovarian cancer cisplatin-resistant cells and increases their sensitivity to cisplatin. In addition, we found that the knockdown of PGC1α affects the mitochondrial membrane potential and the binding of HK2 and VDAC1. As the heat shock protein 70 (HSP70) family can help protein transport, we detected it and found that PGC1α can promote HSP70 gene transcription. Furthermore, HSP70 can promote an increase of HK2 expression on mitochondria and an increase of binding to VDAC1. Based on these results, PGC1α may reduce apoptosis through the HSP70/HK2/VDAC1 signaling pathway, thus promoting cisplatin resistance of ovarian cancer. These findings provide strong theoretical support for PGC1α as a potential therapeutic target of cisplatin resistance in ovarian cancer.

Triptolide is widely used in the clinical treatment of various diseases. Side effects, including reproductive toxicity to male patients, limit its application. However, no detailed mechanisms or potential intervention targets have been reported. In this study, we show that triptolide activated the mitochondrial apoptosis pathway in rat testicular Leydig cells and induced apoptosis both in vivo and in vitro, which may cause hypoleydigism and impair spermatogenesis. Mechanistically, triptolide-induced dynamin-related protein 1 (Drp1) overexpression, which interfered with mitochondrial dynamic stability to activate the mitochondrial apoptosis pathway. Mdivi-1, a selective Drp1 inhibitor, partially reversed the mitochondrial dynamic disturbance and rat testicular Leydig cell apoptosis induced by triptolide. Inhibiting Drp1 over-activation may be a new strategy for mitigating the reproductive toxicity of triptolide.

The present study aimed to investigate the impact of the degradation of cytoskeletal proteins (desmin, integrin, vinculin, and talin) on the formation of intracellular gap and drip channel and water-holding capacity in pork. The intensity of intact cytoskeletal proteins and the width of intracellular gap and drip channel were measured in high drip loss and low drip loss groups. The data indicate that the width of intracellular gap and drip channel explained 17% and 62% variation in drip loss, respectively, while the intensity of intact desmin, integrin, and vinculin explained 47%, 34%, and 47% variation in drip loss, respectively. The postmortem formation of intracellular gap is mainly affected by the changes in integrin and vinculin, while the formation of the drip channel is influenced by the changes in desmin. These findings suggest that postmortem formation of wide intracellular gap and drip channels is linked to increased drip loss.

Liver cancer is a disease with high mortality; it is often diagnosed at intermediate and advanced stages and has a high recurrence rate. ROS restriction and adequate energy supply play significant roles in liver cancer. SLC25A11, a member of the malate-aspartate shuttle (MAS), regulates electroneutral exchange between 2-oxoglutarate and other dicarboxylates. It transports glutathione (GSH) from the cytoplasm into mitochondria to maintain GSH levels to limit ROS production. Moreover, SLC25A11 is essential for ATP generation in cancers as it regulates NADH transportation from the cytoplasm to mitochondria. The purpose of this research was to investigate the prognostic value of SLC25A11 in liver cancer. The Cancer Genome Atlas database was used to analyze the levels of SLC25A11 in liver cancer. Fisher’s exact and chi-square tests were used to evaluate the relationship between SLC25A11 expression and clinical characteristics. Finally, we explored the value of SLC25A11 in prognosis by Cox analysis and Kaplan-Meier curves. Our results revealed that SLC25A11 was downregulated in liver cancer compared to normal controls. Low expression of SLC25A11 was associated with clinical stage, vital status, histologic grade, overall survival (OS) and relapse-free survival (RFS). Liver cancer patients with low SLC25A11 expression had shorter OS and RFS than patients with high SLC25A11 expression. Multivariate analysis showed that the expression of SLC25A11 was an independent predictor of RFS and OS. In conclusion, this study identified that SLC25A11 serves as a new prognostic marker for liver cancer.

Radon exposure is the most frequent cause of lung cancer in non-smokers. The high linear energy transfer alpha-particles from radon decay cause the accumulation of multiple genetic changes and lead to cancer development. Epithelial-mesenchymal transition (EMT) plays an important role in oncogenesis. However, the mechanisms underlying chronic radon exposure-induced EMT attributed to carcinogenesis are not understood. This study aimed to explore the EMT and potential molecular mechanisms induced by repeated radon exposure. The EMT model of 16HBE and BEAS-2B cells was established with radon exposure (20000 Bq/m3, 20 min each time every 3 days). We found repeated radon exposure facilitated epithelial cell migration, proliferation, reduced cell adhesion and ability to undergo EMT through a decrease in epithelial markers and an increase in mesenchymal markers. Radon regulated the expression of matrix metalloproteinase 2 (MMP2) and tissue inhibitors of metalloproteinase 2 (TIMP2) to disrupt the balance of MMP2/TIMP2. In vivo, BALB/c mice were exposed to 105 Bq/m3 radon gas for cumulative doses of 60 and 120 Working Level Months (WLM). Radon inhalation caused lung damage and fibrosis in mice, which was aggravated with the increase of exposure dose. EMT-like transformation also occurred in lung tissues of radon-exposure mice. Moreover, radon radiation increased p-PI3K, p-AKT and p-mTOR in cells and mice. Radon reduced the GSK-3β level and elevated the active β-catenin in 16HBE cells. The m-TOR and AKT inhibitors attenuated radon exposure-induced EMT by regulation related biomarkers. These data demonstrated that radon exposure induced EMT through the PI3K/AKT/mTOR pathway in epithelial cells and lung tissue.

A novel fluorescent probe O-hNRSel based on tetralin-xanthene fused dye O-hNR was designed and synthesized by introducing 2,4-dinitrobenzenesulfonate functionality. This probe is able to detect selenocysteine (Sec) with rapid response time (2 min) and a large fluorescence enhancement at 624 nm (124-fold). O-hNRSel exhibited selective response to Sec over many other analy and high sensitivity with the detection limit as low as 17 nM. Furthermore, O-hNRSel has been used for fluorescent imaging of Sec in living cells with good biocompatibility.

Perovskite solar cells (PSCs) have great potentials in photovoltaics due to their high power conversion efficiency and low processing cost. PSCs are usually fabricated from PbI2/dimethylformamide solution with some toxic additives, such as N-methyl pyrrolidone and hexamethylphosphoramide. Here, we use an environmental friendly aprotic polar solvent, 1,3-dimethyl-2-imidazolidinone (DMI), to fabricate perovskite films. By adding 10 vol% DMI in the precursor solution, high-quality perovskite films with smooth surface are obtained. By increasing annealing temperature from 100 to 130 °C, the average grain size of the perovskite increases from ~ 216 to 375 nm. As a result, the efficiency of the PSCs increases from 10.72 to 14.54%. Electronic supplementary material The online version of this article (10.1186/s11671-017-2391-3) contains supplementary material, which is available to authorized users.

Cellulose nanofibers (CNFs) aerogel was prepared via simple covalent crosslinking and freeze-drying method. The porous cellulose aerogel possessed high specific surface area and high metal-chelating capacity, which showed fast adsorption kinetics and high adsorption capacity (440.60 mg g−1) in static uranium adsorption process. In the dynamic filtration system, the maximum adsorption capacity reached 194 mg g−1 with the initial concentration of 10 mg L−1. In addition, the CNFs aerogel possessed excellent selectivity and good regeneration ability for uranium adsorption. The integrated analyses of attenuated total reflection Fourier transform infrared (ATR-FTIR), X-Ray photoelectron spectroscopy (XPS) and extended X-ray absorption fine structure (EXAFS) suggested that the predominant UO22+ species formed inner-sphere surface complexes with two active carboxyl groups in the coordination model. This strategy may provide a sustainable route for development of efficient biomass-based adsorbents for selective uranium removal from aqueous solution.

Oily wastewater pollution is considered as one of the most serious global environmental problems. Treating oily wastewater is particularly important and challenging because emulsified oil was difficult to be effectively and economically removed from wastewater. In this work, a novel rough poly(vinylidene fluoride) (PVDF)-SiO2 nanofibrous membrane based on the commercial nylon medium was developed via a facile one-step electrospinning approach by assembling SiO2 nanoparticles for effective coalescence separation of oily wastewater. The PVDF-SiO2 nanofibrous membrane showed high hydrophobicity with water contact angle 135o in air and poor oleophilicity with oil contact angle 87° under water. The membrane performed high coalescence separation efficiency of 98.6% for hexadecane-in-water emulsion. Besides, the nanofibrous membrane exhibited good separation performances with different flow velocities, initial oil concentrations and types of oil-water systems, which showed high potentials in oily wastewater treatment.

For a HVDC transformer, the cellulose particles bridging phenomenon under the DC electric field needed to be analyzed. This is useful for further understanding the insulation failure and partly guiding the transformer structure design. The images of cellulose particles accumulation and the conduction current for contaminated mineral oil and natural ester were compared under different DC electrical field strength and different electrode distance using plate-plate electrode system. The cellulose particles bridging model under the DC electrical stress was constructed. The bridging process of cellulose particles in mineral oil is much easier compared with that in natural ester, and the bridges in mineral oil were also thicker than that in natural ester. The contaminated mineral oil has much higher conduction current than the contaminated natural ester at the same electrical stress. The saturate conduction current of contaminated mineral oil decreases in a non-linear way with the electrode distance increasing, while the saturate conduction current for contaminated natural ester increases in a linear way. The completed bridges contribute a lot to the conduction current. The effect of cellulose particles on the conduction property of natural ester is weaker than that of mineral oil..

Two coumarin-based boron complexes (HBN and MBN) with aggregation-induced emission were designed and synthesized. The photophysical properties of the complexes were investigated in different solvents and in the solid state. Results showed that the inhibited C═N isomerization by N,O-chelated BF2 caused the significant enhancement of fluorescence in THF. In particular, the complexes displayed red-shifted emissions (>60 nm) in mixed solvents of CH3CN and water because of the aggregation-induced charge-transfer enhancement. In the solid state, the bright red emission appeared at 650 nm (620 nm), with a Stokes shift of 170 nm. Cell-imaging experiments indicated that the complexes have good membrane permeability and can be used as lysosome trackers.

Enzyme-linked immunosorbent assay (ELISA) has been one of the main methods for detecting an antigen in an aqueous sample for more than four decades. Nowadays, one of the biggest concerns for ELISA is still how to improve the sensitivity of the assay, and the luciferase-luciferin reaction system has been noticed as a new detection method with high sensitivity. In this study, a luciferin-luciferase reaction system was used as the detection method for a sandwich ELISA system. It was shown that this new system led to an increase in the detection sensitivity of at least two times when compared with the traditional horseradish peroxidase (HRP) detection method. Lastly, the serum levels of the human extracellular matrix 1 protein of breast cancer patients were determined by the new system, which were overall similar to the HRP chemiluminescent system. Furthermore, this new luciferase reporter can be implemented into other ELISA systems for the purpose of increasing the assay sensitivity.

After a century of practice, cellulose insulating polymer (insulating paper/pressboard) has been shown to be one of the best and most widely used insulating materials in power transformers. However, with the increased voltage level of the transformer, research has focused on improving the insulation performance of the transformer&rsquo, s cellulose insulation polymer. Considering the complex environment of the transformer, it is not enough to improve the single performance of the insulating polymer. In this study, a nano-structured ZnO-Al2O3-PTFE (polytetrafluoroethylene) multifunctional film was deposited on the surface of insulating pressboard by radio frequency (RF) magnetron sputtering. The effect of the multilayered ZnO-Al2O3-PTFE functional film on the dielectric and water contact angle of the cellulose insulating polymer was investigated. The scanning electron microscopy/energy dispersive spectrometry (SEM/EDS) showed that the nano-structured ZnO-Al2O3-PTFE functional film was successfully deposited on the cellulose insulation pressboard surface. The functional film presented an obvious stratification phenomenon. By analyzing the result of the contact angle, it was found that the functional film shields the hydroxyl group of the inner cellulose and improves hydrophobicity. The AC breakdown field strength of the treated samples was obviously increased (by 12 to ~17%), which means that the modified samples had a better dielectric insulation performance. This study provides a surface modification method to comprehensively improve electrical properties and the ability to inhibit the moisture of the cellulose insulating polymer, used in a power transformer.

Simple Summary Feed efficiency strongly influences the productivity and profitability in modern swine farming enterprises. Residual feed intake (RFI) as a measure of feed efficiency has been extensively studied, which is defined as the differing value between observed feed intake and expected feed intake based on growth and backfat. There is a potential that the porcine vitronectin plays a role in RFI through affecting the energy metabolism within muscles. Using sequencing technology, we found that rich variations and amino acid changes existed in key regions of vitronectin. In addition, a difference in variant frequencies was observed between local Chinese breeds (Sujiang, Jiangqu-hai, and Jiaxing-black) and three well characterized breeds (American Duroc, Canadian Duroc, and Berkshire) derived from the overseas. We suggest that the porcine vitronectin gene can be studied further and may be developed as a gene marker to select high feed-efficiency swines. Abstract Vitronectin plays a role in the blood homeostasis and has been implicated in cell adhesion, migration, and proliferation. Vitronectin has a potential role affecting the residual feed intake (RFI) or feeding efficiency in swine production. Its variations have not been reported in Chinese swine breeds. In this study, two regions of porcine vitronectin were analyzed using PCR and sequencing. The sequence analysis revealed thirteen nucleotide substitutions in region 1 (exon 2- exon 3) and three nucleotide substitutions in region 2 (exon 5- intron 5), which would result in five amino acid changes (p.Ala52Thr, p.Leu94Pro, p.Leu94Gln, p.Gln94Pro, and p.Glu126Gly). In region 1, c.156C/T, c.281A/T, and c.377A/G were the most common (at a total frequency of 49.3%, 31.3% and 31.9% respectively), whereas c.153C/T and c.180C/G were rare (at a total frequency of 1.39%). In region 2, c.597 + 12A/G was the most common (at a total frequency of 39.6%), followed by c.597 + 15A/G (at a total frequency of 31.3%) and c.459A/G (at a total frequency of 16.0%). There was a difference (p < 0.05) in variant frequencies between Chinese breeds and overseas breeds. These results indicate that the porcine vitronectin gene is polymorphic and suggest further analysis is required to see if the variation detected affects RFI or feed efficiency in swines.

Effective isolation of 1,2,4-butanetriol (BT) from the fermentation broth with low BT concentration was achieved based on anionic reactive extraction with a combined extractant consisted of boronic acid carrier and trioctylmetylammonium Aliquat® 336 (A336) dissolved in the organic phase. The influence of various diluents, pH values, the ratio of phenylboronic acid derivatives (PBAD) to BT (αPBAD/BT), and A336 to BT (βA336/BT) on extraction property was investigated in detail. For model BT solutions, satisfactory extraction efficiency of 92% was obtained under the conditions of αPBAD/BT = 1.5, βA336/BT = 2, with dichloromethane as a diluent. Aqueous hydrochloric acid solutions were employed to strip BT from the organic phase. For actual fermentation broth, the extraction and stripping efficiency under the optimum conditions were 74% and 69%, respectively. Besides, compared with the original fermentation broth, 1,2,4-butanetriol has been concentrated by 4.6 times with the reactive extraction coupled hydrolysis.

Biotransformation of steroid compounds: androst-4-ene-3, 17-dione (1), 19-nor-4-androstene-3, 17-dione (2), 13β-ethyl-4-gonene-3, 17-dione (3) using Penicillium decumbens as biocatalyst was investigated, and selective hydroxylation of 1–3 was observed. Biotransformation of 1 afforded 1α-hydroxy-androst-4-ene-3, 17-dione (4) and 1α, 6β-dihydroxy-androst-4-ene-3, 17-dione (5). Incubation of 19-nor-4-androstene-3, 17-dione (2) with P. decumbens culture resulted in the isolation of compounds 1α-hydroxy-19-nor-4-androstene-3, 17-dione (6) and 1α, 15β-dihydroxy-19-nor-4-androstene-3, 17-dione (7). Biotransformation of 3 gave one product 1α-hydroxy-13β-ethyl-4-gonene-3, 17-dione (8) at the same condition. The four metabolic products 5–8 were reported for the first time and the identified C1-α hydroxylation reaction of steroid by P. decumbens provides an another possibility to perform chemical modifications on C-1.

Human extracellular matrix protein-1 (hECM1), a secreted glycoprotein, is widely expressed in different tissues and organs. ECM1 has been implicated in multiple biological functions, which are potentially mediated by the interaction of different ECM1 domains with its ligands. However, the exact biological functions of ECM1 have not been elucidated yet, and the functional study of ECM1 has been partially hampered by the lack of sensitive and specific antibodies, especially those targeting different ECM1 domains. In this study, six strains of monoclonal antibody (MAb) against hECM1 were generated using purified, prokaryotically-expressed hECM1 as an immunogen. The MAbs were shown to be highly sensitive and specific, and suitable for western blot, immunoprecipitation assays and immunohistochemistry. Furthermore, the particular ECM1 domains recognized by different MAbs were identified. Lastly, the MAbs were found to have neutralizing activities, inhibiting the proliferation, migration and metastasis of MDA-MB-231 cells. In conclusion, the domain-specific anti-ECM1 MAbs produced in this study should provide a useful tool for investigating ECM1's biological functions, and cellular pathways in which it is involved.

The converter transformer is a key equipment in high voltage direct current (HVDC) transmission system. Its oil-paper insulation system in the valve winding and outlet bushing experiences AC, DC, AC/DC, and transient impulse voltages simultaneously. The oil contamination problem is more serious under DC electric field. Therefore, it is significant to investigate the characteristic of particles motion and accumulation under DC electric field. In this paper, first, the movement and accumulation behavior of fiber particles and copper particles in mineral oil and natural ester were recorded and simulated. Then, the influence of fiber and copper particles on the oil conductivity was analyzed. Finally, the DC breakdown strength of mineral oil and natural ester with different particles concentration was compared. Results show that the movement speed of copper particles was larger than that of fiber particles. Fiber impurities were easy to form bridges in mineral oil, while there was no impurity bridge in natural ester. The current density of mineral oil containing particles is larger than that of the natural ester at the same testing time. The DC 50% probability breakdown voltages of oil samples containing fiber and copper particles decreased linearly with the increase of particle concentration, and the decrease rate of DC 50% probability breakdown voltages of oil containing copper particles were faster than that of oil containing fiber particles. Compared to pure mineral oil, the DC breakdown voltages corresponding to 50% probability of contaminated mineral oil showed a decrease from 11.9% to 22.5% when the fiber particle concentration increased from 0.001% to 0.012%. The DC 50% probability breakdown voltages of contaminated mineral oil with copper particles decreased from 23.8% to 45.0% when the particle concentration increased from 0.1 g/L to 1.5g/L. However, the decline range of the figures for natural ester contaminated by fiber or copper particles showed a smaller drop.

The effects of microcrystalline cellulose (MCC), gellan gum (GG) and mixed emulsifiers on physical stability of cloudy Flos sophorae immaturus (FSI) beverages were studied. The physical stability of FSI beverages characterized by particle size, microstructure, rheological properties, suspension stability index and backscattered light intensity. It occurred an irreversible phase separation during thermal sterilization process in the original FSI beverage. The beverage adding MCC had large (the volume weighted mean diamete [d43]~36 μm) but non-coalesced particles after thermal sterilization step, showing MCC could protect the particles against the coalescence. Moreover, when MCC and GG were added to FSI beverage, the suspension stability index increased, and the particle size and the change of backscattered light intensity (△BS) decreased. Mixed emulsifiers not only enhance the viscosity of beverage but also influence the properties of beverage interface, leading to greater absolute value of zeta potential which rose to 45.5 mV. In the existence of MCC, GG, and mixed emulsifiers, the system displayed greater stability than others. This study provided some suggestions for the industrial production of cloudy beverages with low viscosity and good stability.