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The etiology of primary Sjogren's syndrome (pSS) remains unknown, and there is no complete curative drug. In this study, we treated a mouse model of the submandibular gland (SG) protein-immunized experimental Sjogren's syndrome (ESS) with paeoniflorin-6'-O-benzene sulfonate (termed CP-25) to evaluate the potential therapeutic effects of CP-25. Through in vivo experiments, we found that CP-25 increased saliva flow, alleviated the salivary gland indexes, and improved tissue integrity in the ESS model. The viability of splenocytes and B-lymphocyte migration from spleen were reduced in ESS mice. Furthermore, CP-25 decreased the expression of IgG antibodies, anti-SSA and anti-SSB antibodies and modulated the levels of cytokines in the serum of SS mice. The numbers of total B lymphocytes, plasma cells (PCs), and memory B cells diminished in the salivary gland. Increased expression of the JAK1-STAT1-CXCL13 axis and IFNα was found in human tissue isolated from pSS patients. In vitro, after stimulation with IFNα, the levels of CXCL13 mRNA and CXCL13 in human salivary gland epithelial cells (HSGEC) increased, while CP-25 counteracted the secretion of CXCL13 and downregulated the expression of CXCL13. IFN-α activated the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which was negatively regulated by additional CP-25. As a consequence, B-cell migration was downregulated in coculture with IFN-α-stimulated HSGEC. Taken together, this study demonstrated that the therapeutic effects of CP-25 were associated with the inhibition of the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which impedes the migration of B cells into the salivary gland. We identified the underlying mechanisms of the therapeutic effect of CP-25 and provided an experimental foundation for CP-25 as a potential drug in the treatment of the human autoimmune disorder pSS.

We present a novel generating function (GF) method for the self-condensing vinyl polymerization (SCVP) system with any initial distribution of preexisted polymers. Such a method was proven to be especially useful to investigate the semi-batch SCVP system allowing a sequence of feeding operations during the polymerization. Consequently, the number-, weight-, and z-average molecular weights as well as polydispersity index of hyperbranched polymers can be explicitly given, which are determined by predetermined feeding details and conversions in each polymerization step. These analytical results are further confirmed by the corresponding Monte Carlo simulation. Therefore the present GF method has provided a unified treatment on the semi-batch SCVP system. Accordingly, hyperbranched polymers with desired properties can be prepared by designing feeding details and presetting conversions at each step based on the present GF method.

Bioactive peptides are an emerging area of biomedical research in the study of numerous human diseases, including acute alcoholic liver injury (AALI). To study the role and mechanism of the milk‑derived hexapeptide Pro‑Gly‑Pro‑Ile‑Pro‑Asn (PGPIPN) in preventing and reducing AALI, the present study established a mouse model of AALI. PGPIPN was used as a therapeutic drug, and glutathione (GSH) was used as a positive control. The body and liver weights of mice were measured, and the liver indexes were calculated to observe mice health. The pathological morphology of liver tissues stained with hematoxylin and eosin were examined to analyze hepatic injury, and hepatocyte apoptosis was measured with a TUNEL assay. The concentrations or activities of alanine aminotransferase (ALT), aspartate aminotransferase, tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6, triglyceride, total cholesterol, malondialdehyde, superoxide dismutase and GSH peroxidase (GSH‑PX) were detected in serum and/or liver homogenates. The 78 kDa glucose‑regulated protein (GRP78), protein kinase R‑like (PKR) endoplasmic reticulum kinase (PERK), phosphorylated (p)‑PERK, eukaryotic initiation factor 2α (eIF‑2α), p-eIF-2α, inositol‑requiring enzyme 1α (IRE‑1α), spliced X‑box binding protein 1 (XBP‑1s), C/EBP homologous protein (CHOP), caspase‑3 and cleaved caspase‑3 proteins associated with endoplasmic reticulum stress in hepatocytes were assessed by western blotting, and RNA levels of XBP‑1s, CHOP and caspase‑3 genes were assessed by reverse transcription‑quantitative PCR. The results suggested that PGPIPN attenuated alcoholic hepatocyte damage in animal models and reduced hepatocyte oxidative stress in a dose‑dependent manner. Moreover, PGPIPN reduced endoplasmic reticulum stress by regulating the expression levels of p‑PERK, p‑eIF‑2α, XBP‑1s, CHOP, caspase‑3 and cleaved caspase‑3. Collectively, the present results indicated that PGPIPN, as a potential therapeutic drug for AALI, exerted a protective effect on the liver and could reduce liver damage.

Electrochemical reduction of CO2 to valuable fuels is appealing for CO2 fixation and energy storage. However, the development of electrocatalysts with high activity and selectivity in a wide potential window is challenging. Herein, atomically thin bismuthene (Bi-ene) is pioneeringly obtained by an in situ electrochemical transformation from ultrathin bismuth-based metal-organic layers. The few-layer Bi-ene, which possesses a great mass of exposed active sites with high intrinsic activity, has a high selectivity (ca. 100 %), large partial current density, and quite good stability in a potential window exceeding 0.35 V toward formate production. It even deliver current densities that exceed 300.0 mA cm-2 without compromising selectivity in a flow-cell reactor. Using in situ ATR-IR spectra and DFT analysis, a reaction mechanism involving HCO3- for formate generation was unveiled, which brings new fundamental understanding of CO2 reduction.

Many researches aim at materials promoting osteogenesis, but few of these articles focus on serum. Here, we made Poly(lactic-co-glycolic acid)-Hydroxyapatite (PLGA/HA) scaffolds using 3D printing technology, and evaluated the effect of scaffolds promoting osteogenesis by serum detection and other tests. Sixty Sprague Dawley (SD) rats were selected to grind out a 4 mm long fullthickness bone defect of the bilateral femurs and were randomly divided into a PLGA/HA group which implanted with PLGA/HA scaffolds and a control group with no scaffolds implanted. Bone specimens and serum were collected on the 3rd day and 1st, 2nd, 3rd, 4th, and 5th week after operation and then detected respectively. Three-point bending test indicated that the bone strength of the control group was significantly lower than the PLGA/HA group in the later stage of the experiment. In terms of serum indexes, the calcium (Ca) and alkaline phosphatase (ALP) expressions were much higher in the PLGA/HA group, while the tartrate-resistant acid phosphatase (TRAP) level in the PLGA/HA group was lower in the early stage of the experiment. The level of bone morphogenetic protein 2 (BMP2) in the PLGA/HA group was significantly higher than that of the control group on the 1st, 2nd, and 4th weeks. These results revealed that 3D printing PLGA/HA scaffolds can effectively promote bone tissue formation and inhibit bone absorption. The scaffold has a good potential application prospect at clinic as a kind of bone tissue engineering material.

Using self-consistent field calculations, we examine the effect of brush polydispersity on conformational transitions of single adsorption-active diblock copolymer chains embedded in inert polydisperse brushes. To represent the polydispersity, we adopt the continuous Schulz–Zimm chain length distributions, and three typical distributions are chosen such that a wide range of polydispersity is covered. A phase diagram of the diblock copolymer switches has been constructed showing that the first order phase transitions occupy a larger space in the case of polydisperse brushes. We further characterize these first order phase transitions by specifying their transition points, transition widths and transition barriers, where the latter two are particularly important as they determine the performance of the polymer switches. Our calculation indicates that polydispersity has different effect on the switching behavior depending on the lengths of both the active block and the inert block of the copolymer switch chain. In general, polydispersity improves the switching performance in the case of short active blocks, i.e. shorter or not very longer than the average length of the brush chains, and the corresponding energy barrier is smaller than a few kBT. In contrast, monodisperse brushes have the advantages when these two blocks are particularly long, i.e., lower transition barriers and fast switching. Notably, when the inert block approaches the average length of the brush chains, the transition barrier becomes almost zero in any case for monodisperse brushes, while a large finite value is still observed for that in polydisperse brushes. The complex interplay between the brush polydispersity and the switch behavior is attributed to the wide-range repulsions generated by the polydisperse brushes.

An innovative model of the mechanism for peeling defect in inter metal dielectric(IMD) process induced by poor adhesion between metal and oxide film on wafer bevel is presented. Peeling defect is inspected by dark field inspection (DFI) tool of KLA. Scanning electron microscopy (SEM) and Transmission electron microscope (TEM) are used to study the stack and composition of wafer edge film. Peeling defect source will be discussed in this paper, and the tests demonstrated metal film and oxide film's growth ability varied at wafer bevel, that induce metal film accumulate approach to wafer bottom bevel, when the thick oxide film of next layer deposition, they cannot bond firming, the films peel off with the mechanical transfer or high temperature. Solution of to avoid peeling defects with bevel clean also was demonstrated as well.

A Monte Carlo simulation on the ternary self-condensing vinyl polymerization system under the semi-batch mode is presented, where reactants are composed of comonomers (inimers and monomers) and multi-functionality core initiators. For the semi-batch process in the system, we mainly consider the influence of three feeding ways on the average polymeric quantities (weight-average molecular weight and polydispersity index) of hyperbranched polymers, where core initiators and comonomers are fed into the reactor at different time (or equivalently, at different conversions of vinyl group). As expected, the semi-batch process has a significant effect on the average properties of polymers, and therefore the feeding schedule can be predetermined to prepare polymers with desired properties.

In this study, the argon gas and argon arc plasma are chosen as two typical examples of cold and hot flow fields, respectively, to investigate on the physical nature of the refractive index gradient in moire tomography diagnosis. The results indicate that refractive index gradient is mainly determined by refractive index sensitivity to the pressure change and the pressure gradient for the cold flow field. However, in the case of hot flows, refractive index gradient mainly depends on refractive index sensitivity to changes in pressure and temperature as well as to pressure and temperature gradients. The involved results can improve the use of moire tomography for characterizing various complicated flow fields. This may extend the range of application of all methods that determine flow field's key parameters from refractive index distributions.

Background and Objective: Transient ischemic attack (TIA) is a serious condition that is often called a warning stroke. The risk of cerebral infarction in patients with TIA and positive DWI finding...

The determination of band offsets is crucial in the optimization of Ga2O3-based devices, since the band alignment types could determine the operations of devices due to the restriction of carrier transport across the heterogeneous interfaces. In this work, the band offsets of the Ga2O3/FTO heterojunction are studied using x-ray photoelectron spectroscopy (XPS) based on Kraut’s method, which suggests a staggered type-II alignment with a conduction band offset (Δ E C) of 1.66 eV and a valence band offset (Δ E V) of –2.41 eV. Furthermore, the electronic properties of the Ga2O3/FTO heterostructure are also measured, both in the dark and under ultraviolet (UV) illuminated conditions (254 nm UV light). Overall, this work can provide meaningful guidance for the design and construction of oxide hetero-structured devices based on wide-bandgap semiconducting Ga2O3.

Esophageal cancer is one of the leading causes of cancer related mortality across the globe. The current treatment options are insufficient and are associated with number of side effects. Therefore there is a pressing need to develop effective and more efficient strategies for the treatment of esophageal cancer. Consistently, natural products are considered potential candidates for develop of cancer chemotherapy. Icariin is a naturally occurring flavonol glucoside and has been reported to possess tremendous pharmacological potential ranging from neuroprotection to anticancer activity. However, the pharmacological role of icariin in esophageal cancer is still largely unclear. Here in the present study, icariin was evaluated for its anticancer activity against KYSE70 esophageal cancer cells and the possible underlying mechanism was determined. Icariin induced cytotoxicity with an IC50 of 40μM in esophageal cancer cells. These inhibitory effects were due to apoptosis through reactive oxygen species (ROS) mediated alterations in mitochondrial membrane potential (MMP). The results indicated that icariin enhanced the accretion of ROS upto 260% and reduced the MMP upto 48% at 100μM. Icariin also induced G2/M cell cycle arrest as evident from the significant increase in the G2 cell populations of KYSE70 esophageal cancer cells. Additionally, icariin inhibited esophageal cancer cell migration, invasion and metastasis by regulating the expression of epithelial to mesenchymal transition (EMT) markers. Results also indicated that icariin reduced cell viability and migration in part through suppression of the PI3K/AKT and STAT3 pathways. Taken together, our results indicate that icariin may prove a potential natural anticancer molecule against esophageal cancer.

Primary Sjogren's syndrome (pSS) is an autoimmune disease of unresolved aetiology that affects the exocrine glands. Clinical symptoms frequently also involve skin, liver, kidney and neurovascular components. The pathogenesis of pSS is still unclear but B cell hyperactivity has been identified as a hallmark of pSS. Currently, a curative therapeutic agent is lacking. In this study, we explored whether paeoniflorin-6′-O-benzene (CP-25) exerted therapeutic effects through regulating B lymphocyte migration via CXCR5-GRK2-MAPK mediated signaling pathways in a mouse model of antigen-induced, experimental Sjogren's syndrome (ESS). We found that CP-25 increased the salivary flow and alleviated the histopathology of ESS. Furthermore, CP-25 reduced the viability of B lymphocyte and limited the target organs index. In the peripheral blood and salivary gland of ESS mice, CP-25 down-regulated the proportion of total B cells, CXCR5+ B cells and PDCA1 + CD19- and limited the presence of phosphorylated (p-) p38 and ERK (p-ERK). Besides, CP-25 increased the percentage of memory B cells in the peripheral blood and reduced it in salivary gland. Furthermore, in vitro, CP-25 down-regulated p-p38, p-ERK, CXCR5 and membrane GRK2, and increased cytoplasm GRK2 in Maver-1 cells, a mantle cell lymphoma cell line, causing a lower migration ability of Maver-1 cells. Thus, we define CP-25 as a novel compound that is a potent therapeutic agent for pSS which modulates B lymphocyte subsets and impacts the migration of B lymphocytes through regulating the CXCR5-GRK2-ERK/p38 signaling pathway.

The detection of hypochlorite (ClO-) content in tap water is extremely important because excess amounts of hypochlorite can convert into highly toxic species and inadequate amounts of hypochlorite cannot fully kill bacteria and viruses. Although several metal-organic frameworks (MOFs) have been successfully employed as fluorescent sensors for hypochlorite detection, all these sensors are based on single emission that responds to the dose of hypochlorite. Ratiometric sensors are highly desirable, which can improve the sensitivity, accuracy, and reliability via self-calibration. Herein, a nanoscale dual-emission multivariate 5-5-Eu/BPyDC@MOF-253-NH2 was synthesized by sequential mixed-ligand self-assembly and postsynthesis method. Among the two emission bands of 5-5-Eu/BPyDC@MOF-253-NH2, the strong blue emitting derived from ligands is sensitive to hypochlorite, while the red emitting derived from Eu(III) almost keeps invariable. Therefore, 5-5-Eu/BPyDC@MOF-253-NH2 was exploited as a fluorescent ratiometric nanosensor for "on-off" sensing of hypochlorite. Notably, the proposed sensing system showed an excellent performance including fast response (within 15 s), relative high specificity, wide linear range (0.1-30 μM), and low detection limit (0.094 μM). Besides, the suppressed blue emitting was recovered after the addition of ascorbic acid (AA) that consumes ClO- via the redox reaction. Therefore, 5-5-Eu/BPyDC@MOF-253-NH2 was further employed as a fluorescent ratiometric nanosensor for the "on-off-on" sensing of AA. This work represents the first MOF-based fluorescent "switch" for the ratiometric sensing of hypochlorite and the second for ratiometric sensing of AA.

Oxidative stress is a major cause of adverse outcomes in preeclampsia (PE). Ferroptosis, i.e. programmed cell death from iron-dependent lipid peroxidation, likely mediates PE pathogenesis. We evaluated specific markers for ferroptosis in normal and PE placental tissues, using in vitro (trophoblasts) and in vivo (rat) models. Increase in malondialdehyde content and total Fe2+ along with reduced the glutathione content and glutathione peroxidase activity was observed in PE placenta. While the trophoblasts experienced death under hypoxia, inhibitors of ferroptosis, apoptosis, autophagy, and necrosis increased the cell viability. Microarrays, bioinformatic analysis, and luciferase reporter assay revealed that upregulation of miR-30b-5p in PE models plays a pivotal role in ferroptosis, by downregulating Cys2/glutamate antiporter and PAX3 and decreasing ferroportin 1 (an iron exporter) expression, resulting in decreased GSH and increased labile Fe2+. Inhibition of miR-30b-5p expression and supplementation with ferroptosis inhibitors attenuated the PE symptoms in rat models, making miR-30b-5p a potential therapeutic target for PE. Keywords: miR-30-5p, Ferroptosis, Preeclampsia, SLC7A11, Ferroportin 1

A core-shell structured chitosan (CS)-based gene vector with a sustainable gene transfection effect was designed and successfully prepared in this study. The pEGFP was first combined with the thiolated and N-alkylated chitosan (TACS). Then, hydroxybutyl chitosan grafted with poly(ethylene glycol) (EG-HBC) was coated on the pEGFP-loaded TACS particles. The prepared pEGFP-loaded TACS@EG-HBC particles have a size of about 200 nm and little cytotoxicity. The in vitro and in vivo gene transfection experiments indicate that the pEGFP-loaded TACS@EG-HBC particles possess a better sustainable gene transfection capacity and a high transfection efficiency, which should be attributed to the biodegradation of the CS-based shell, the thiolation and N-alkylation modification on CS cores, and the grafted PEG chains with better biocompatibility. The in vivo gene expression of the loaded pEGFP can persist up to 60 days. This novel gene vector has a theoretical and practical significance for gene therapy with sustained transfection effect.

By using means of density functional theory calculations, we reported the heterostructure consisting of monolayer MoSSe and graphene, as a promising anode material for lithium ion batteries. We investigated the adsorption and diffusion of lithium atoms in the MoSSe and MoSSe_graphene heterostructures, and we found that the combination with graphene makes the lithium atoms’ adsorption more stable, meanwhile, the diffusion barriers on the surface are lower than that at the interface, which are comparable to the barriers on the corresponding monolayers. The maximum lithium storage capacity of the heterostructure is enhanced to 390 mAh/g. Our work made a comparison with all the typical structures of MoSSe and MoSSe_graphene, and suggests that the S side of MoSSe-2 combined with graphene and the Se side of MoSSe-2 combined with graphene are the promising materials for their higher lithium capacity and charge/discharge rates.

It is imperative to remove organicarsenic acids (OAAs) from water because they can convert into highly toxic inorganic arsenic compounds in natural environment via biotic and abiotic degradation routes. Herein, seven Zr-based metal-organic frameworks (Zr-MOFs) including DUT-67, UiO-66, UiO-67, MOF-808, MOF-808F, NU-1000, NU-1000B with various structures were screened for the adsorptive removal of representative OAAs including p-arsanilic acid (ASA) and roxarsone (ROX) in water media. Initial screening found that MOF-808 and MOF-808F have the largest adsorption capacities. Therefore, their adsorption behaviors including adsorption kinetics, isotherms, specificity and effects of pH were fully investigated. Remarkably, MOF-808F had the second largest maximum adsorption capacities of ASA (621.1 mg g−1) and ROX (709.2 mg g−1) among the reported MOF-based adsorbents. In addition, MOF-808F showed excellent selectivity and reusability and no observable drop of adsorption efficiency was found in the presence of equimolar competing ions (Cl−, OAc− or SO42−) or after three successive adsorptive runs. By contrast, MOF-808 had inferior adsorption specificity and reusability in spite of the very similar structure with MOF-808F. The structure-dependent adsorption performances can be explained by the distinct adsorptive mechanisms, which were revealed by zeta potential measurements, X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculation etc. The dominant interaction between MOF-808 and ASA was coordination interactions, while ASA adsorption over MOF-808F was governed by the synergistic effect of π-π stacking, hydrogen bonding, and electrostatic interactions. This work no only presented an excellent adsorbent (MOF-808F) toward OAAs, but also revealed the structure dependent adsorption performances/mechanisms.

Phase equilibria of hydrogen bonding (HB) fluid confined in a slit pore with broken symmetry were investigated by the density functional theory incorporated with modified fundamental measure theory, where the symmetry breaking originated from the distinct interactions between fluid molecules and two walls of the slit pore. In terms of adsorption-desorption isotherms and the corresponding grand potentials, phase diagrams of HB fluid under various conditions are presented. Furthermore, through phase coexistences of laying transition and capillary condensation, the effects of HB interaction, pore width, fluid-pore interaction and the broken symmetry on the phase equilibrium properties are addressed. It is shown that these factors can give rise to apparent influences on the phase equilibria of confined HB fluid because of the competition between intermolecular interaction and fluid-pore interaction. Interestingly, a significant influence of broken symmetry of the slit pore is found, and thus the symmetry brea...

An equation of state (EOS) was established by combining the perturbed-chain polar statistical associating fluid theory (PCP-SAFT) with density-gradient theory (DGT). The bulk and interfacial properties of carbon dioxide (CO 2 )–butane, CO 2 –decane, CO 2 –benzene, CO 2 –cyclohexane and CO 2 –tetradecane binary mixtures were investigated. To illustrate the effect of the quadrupolar contribution of CO 2 on the bulk and interfacial properties, the calculated vapor–liquid equilibria (VLE) and surface tensions were compared with those calculated from the perturbed-chain statistical associating fluid theory (PC-SAFT) and DGT, in which CO 2 was treated as non-polar molecule. Results showed that by taking into account the quadrupolar contribution of CO 2 , both the VLE and surface tensions of CO 2 –hydrocarbon binary mixtures can be significantly improved compared with the experimental data.

A microemulsion electrokinetic capillary (MEEKC) chromatography method was online-coupled with field-amplified sample injection (FASI) for the analysis of nucleosides and nucleobases, namely cytidine, guanosine, N6-methyladenosine, fluorouracil, thymine, adenine, mercaptopurine, 6-hydroxypurine, and guanine. A microemulsion background electrolyte containing 10 mM sodium dodecyl sulfate (SDS), 0.6% (v/v) 1-butanol, 0.5% (v/v) ethyl acetate and 98.9% (v/v) borate buffer (10 mM; pH 9.0) was used as the running buffer. An online field-amplified sample injection (FASI) technique was adopted to improve the detection sensitivity. Baseline separation of nine nucleosides was achieved within 12 min with detection limits (S/N = 3) between 0.22 and 2.97 μg mL−1 with the DAD detector at 200 nm under optimized conditions. The proposed method was applied to the determination of nine nucleoside compounds in spiked urine and serum samples with the recoveries ranging 91.2–113% and 85.2–112% and the relative standard deviations (RSDs, n = 3) at less than 5.90% and 8.22%, respectively.

A high molecular weight protein (HMWP) was isolated and purified from sow milk, and some of its biochemical characteristics and biological functions were identified. The origin of HMWP was also investigated. The molecular weight of HMWP was determined to be about 115 000 and 114 800 by SDS-PAGE and gel filtration, respectively. The sequence of 10 amino acids in N-terminal of HMWP was Ala-Leu-Val-Gln-Ser-Cys-Leu-Asn-Leu-Val. The sequence was blasted against GenBank. No protein showed significant similarity with this sequence suggesting the HMWP may be novel. The result of liquid chromatography mass spectrometry (LC-MS) also proved HMWP could be a novel protein. By amino acid assay, HMWP was rich in glutamate (including glutamine), cysteine, glycine, aspartic acid (including asparagines) and proline. The content of hydrophobic amino acids (Ala, Val, Leu, Ile, Met, Phe and Pro) was lower at 18.59% of the total amino acids suggesting HMWP has high solubility in water. Western blots of lectins were used to identify the kinds of carbohydrate residues attached to HMWP qualitatively. The result showed that HMWP was a kind of glycoprotein containing N-acetylneuraminic acid (NeuNAc), mannose (Man) and/or N-acetylglucosamine (GlcNAc). By isoelectric focusing, HMWP pI was found to be 5.1. Compared with milk fat globule membrane protein (MFGMP) isolated from the sow milk in SDS-PAGE, MFGMP did not contain HMWP. HMWP was assumed to be a secretory milk protein. HMWP was not found in bovine, goat, rabbit or human milk in SDS-PAGE gel suggesting HMWP may be unique to sow milk. By Western blot, HMWP could be detected in sow milk, not in sow serum, which suggests it is synthesized and secreted by the mammary gland. HMWP concentrations in sows milk were the lowest in the first day of lactation, rose significantly during lactation 1 to 7 days. The HMWP content of sows milk remained relatively constant ((1.95±0.13) g/l) during lactation 7 to 20 days. HMWP significantly inhibited Escherichia coli in a dose related manner in vitro. Overall, HMWP could be a novel sow milk protein with implications for the mammary gland and the piglet.

Inhibition of the rennin-angiotensin system (RAS) could reduce insulin resistance in patients with hypertension and diabetic kidney disease (DKD), but whether the effect of losartan on insulin resistance is associated with reduction of oxidative stress and enhancement of insulin signaling transduction has not been fully elucidated.130 patients with type 2 DKD were randomly assigned into 2 groups, the losartan group (n=65, 100 mg orally daily for 12 months) and the amlodipine group (n=65, 10 mg orally daily for 12 months). Oxidative stress markers in plasma, urine concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine (NT) as well as SOD activity were measured by ELISA. After in vitro treatment with different doses of losartan (10, 100 μmol/L) or amlodipine for 48 h, the size of H2O2-induced adipocytes and glucose consumption were measured. Western blot was performed to investigate IRS-1 serine phosphorylation level as well as the protein expressions of phosphorylated insulin receptor (pIR), phosphatidylinositol 3- kinase (PI3K) and insulin receptor substrate 1 (IRS-1) in 3T3-L1 adipocytes.After 12-month treatment, there were no significant differences in systolic and diastolic blood pressures decreases, plasma fasting blood glucose and HbA1c between the 2 groups. Compared with amlodipine group, fasting blood insulin levels and insulin resistance index (HOMA-IR) were significantly decreased in losartan group, and in addition, the circulating levels of 8-OHdG and NT were significantly decreased in losartan group, while the serum SOD activity was enhanced. There were significant positively correlations of HOMA-IR with inflammatory oxidative stress markers. In vitro study showed that losartan could increase glucose uptake in 3T3-L1 adipocytes (P0.01) and decrease adipocyte size (P0.01), while amlodipine can't. Losartan can also enhance adiponectin (P0.05) and decrease TNF-α (P0.05) and IL-6 (P0.01) secretion, while amlodipine can't. The protein expressions of pIR, IRS-1 and PI3K were significantly increased after treatment with losartan (P0.01), while the level of IRS-1 serine phosphorylation was decreased (P0.01), which could be blocked by specific PI3K inhibitor wortmannin.These results suggest that the effect of losartan on insulin resistance is associated with the reduction of oxidative stress and inflammation in patients with type 2 DKD as well as the activation of insulin signal pathway in insulin-resistance 3T3-L1 adipocytes through modulation of PI3K pathway. (Clinical Trials. gov number, NCT 00774904).

We present the pressure tensor of an associating Lennard-Jones (LJ) fluid confined in a spherical cavity of hard wall, where a high-order density correlation has been taken into account. To give the two-body association potential for calculating the pressure tensor, an angle-average of site-site attraction over all orientations of two particles is performed. Furthermore, the classical density functional theory is employed to obtain the density profile of the confined fluid, by which the normal and tangential pressure profiles are illustrated under various conditions to show the dependence of the pressure tensor on the association strength, number of associating sites, radius of cavity, and bulk density. As an application, the corresponding surface tension is calculated. It is shown that under a strong association interaction (both association strength and the number of associating sites are large), the pressure profiles are depleted from the wall of the cavity instead of the oscillatory behavior under a weak association interaction. Such a tendency is mainly determined by the competition between association interaction and excluded volume interaction. Therefore, the aggregation state and related properties of an associating LJ fluid within a confinement of nanoscale can be efficiently regulated by the association interaction.

the PEG with the molecular weights(MW) ranging from 200 to 2000 have been extensively investigated for Fenton oxidation. The affectingfactors such as pH, dosage of hydrogen peroxide and FeSO4•7H2O was studied in the experiment. The experimental results showed that the dosage of Fenton's reagent ( FeSO4•7H2O was 0.3g/L and 30%H2O2 was 0.5ml/L）was 3:5 and the pH was 3 at the room temperature, the highest CODcr removal ratio can be up to 84%.

High-molecular-weight penicillin-binding proteins (PBPs) are essential integral membrane proteins of the bacterial cytoplasmic membrane responsible for biosynthesis of peptidoglycan. They are the targets of antibacterial β-lactam drugs, including penicillins, cephalosporins, and carbapenems. β-Lactams covalently acylate the active sites of the PBP transpeptidase domains. Because β-lactams are time-dependent inhibitors, quantitative assessment of the inhibitory activity of these compounds ideally involves measurement of their second-order acylation rate constants. We previously described a fluorescence anisotropy-based assay to measure these rate constants for soluble constructs of PBP3 (Anal. Biochem. 439 (2013) 37–43). Here we report the expression and purification of a soluble construct of Pseudomonas aeruginosa PBP2 as a fusion protein with NusA. This soluble PBP2 was used to measure second-order acylation rate constants with the fluorescence anisotropy assay. Measurements were obtained for mecillinam, which reacts specifically with PBP2, and for several carbapenems. The assay also revealed that PBP2 slowly hydrolyzed mecillinam and was used to measure the rate constant for this deacylation reaction.

LptA is a soluble periplasmic component of the lipopolysaccharide (LPS) transport system of Gram-negative bacteria that transports newly synthesized LPS from the inner membrane to the outer leaflet of the outer membrane. LptA links the inner membrane components (LptBFGC) to the outer membrane components (LptDE), but it is uncertain whether LptA is a freely moving LPS shuttle or part of a stable trans-periplasm structure. Escherichiacoli LptA forms highly polymerized head-to-tail oligomers in solution, but dimers in vivo. We studied the oligomerization of purified Pseudomonasaeruginosa LptA. Size-exclusion chromatography showed that P. aeruginosa LptA, unlike E. coli LptA, is a dimer over a wide range of concentrations. Chemical crosslinking with bis(sulfosuccinimidyl) suberate confirmed that dimers were the predominant species even at sub-micromolar LptA concentrations, which was unaffected by LPS binding. Mass spectrometry of crosslinked dimers showed that crosslinks occurred between the N-terminal α-amino group and either Lys-172 or Lys-173 near the C-terminus. These results support a hypothetical structure for the dimer of isolated P. aeruginosa LptA in which the N-terminus of one monomer is in close proximity to the C-terminus of the other, and the same surface of each monomer forms the interface between them, preventing further oligomerization.

A new enzyme-free and ultrasensitive electrochemical Pb 2+ biosensor was developed. By coupling the DNA-assisted cascade of hybridization reaction with the quantum dots (QDs) for signal amplification, a detection limit as low as 6.1 pM can be obtained for Pb 2+ . In this study, the “8-17” DNAzyme was used for specific recognition of Pb 2+ . In the presence of Pb 2+ , the DNAzyme was activated and cleaved the substrate strand. And then, the hybridization between the linker probe and signal probe was initiated, which resulted in formation of a long cascade DNA structure as well as assemble of numerous QDs at last. By the use of magnetic beads, the free signal probe can be easily removed by external magnetic field. After acid lysis, a great amount of redox cations can be released from the QDs and eventually result in significantly amplified electrochemical signals. This method is highly sensitive, selective and simple without the participation of any protein based enzyme (nuclease), thereby holds great potential for real sample analysis.

An argon arc jet plasma flowing into air is chosen as a practical example to study the multiple species jet plasma's optical computerized tomography (OCT) diagnosis. The refractive index models of the pure argon and the multiple species arc plasmas are supplied. On the basis of which, the temperature reconstruction model of the multiple species arc plasma is further derived. By theoretical calculation, the effect of mixed air on the refractive index is given. For the sake of better proving the effect of directly omitting the mixed air on flow field's temperature reconstruction from the refractive index, a simulated experiment is supplied. Finally, the condition, which can be adopted to estimate that whether the pure argon arc plasma refractive index model still can be used as the temperature reconstruction model of the argon arc plasma jet flowing into air, is proposed.

Against the problem of calculating gas content rapidly, this article studied the desorption characteristics of coal by measuring the characteristic parameters of coal in the laboratory. With the actually measured amount of desorption and the desorption rule of the coal within the first 30min, through theoretical derivation and Multiple Linear Regression, the gas content desorbs within the first 120min and the residual amount after a 120min of coal desorption is studied and confirmed Based on the rapid determination model of gas content in the coal seam is established, and the new model is verified, whose accuracy rate reaches above 85%. If relevant electronic equipments were made, this method would be able to give a result within 40min, thereby realizing the rapid determination of gas content in the coal seam within the gas belt.

In this study, uniformly distributed leaf-like ZnO nanostructure on glass substrates had been prepared by a simple two-step method. The structural properties were analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The photocatalytic activity of the leaf-like ZnO nanostructure had been investigated through the degradation of Rhodamine B under UV illumination and using a ZnO thin film and ZnO nanorods as the references. The results show that the photocatalytic activity of leaf-like ZnO nanostructure is higher than that of the ZnO thin film or ZnO nanorods. This is mainly because the leaf-like ZnO nanostructure has a larger surface area than ZnO thin films or ZnO nanorods. What is more, the leaf-like ZnO nanostructure is very firm on the substrate and its photocatalytic activity can be recycled and is stable.

In this paper, moire and emission tomography are integrated to visualize and diagnose the arc plasma jet flowing into air, and the argon arc plasma jet is chosen as a practical example for experiment. The refractive index distribution and structure of the measured flow field are simultaneously obtained by moire and emission tomography respectively. As a result, the mixed flow field—arc plasma jet flowing into air can be divided into two regions. Finally, the different reconstruction models are adopted to obtain the temperature and electron number density distributions for the two different regions.

A simple and sensitive method, based on surface-enhanced Raman scattering (SERS), for immunoassay and label-free protein detection is reported. A series of bowl-shaped silver cavity arrays were fabricated by electrodeposition using a self-assembled polystyrene spheres template. The reflection spectra of these cavity arrays were recorded as a function of film thickness, and then correlated with SERS enhancement using sodium thiophenolate as the probe molecule. The results reveal that SERS enhancement can be maximized when the frequency of both the incident laser and the Raman scattering approach the frequency of the localized surface plasmon resonance. The optimized array was then used as the bottom layer of a silver nanoparticle-protein-bowl-shaped silver cavity array sandwich. The second layer of silver was introduced by the interactions between the proteins in the middle layer of the sandwich architecture and silver nanoparticles. Human IgG bound to the surface of this microcavity array can retain its recognition function. With the Raman reporter molecules labeled on the antibody, a detection limit down to 0.1 ng mL(-1) for human IgG is easily achieved. Furthermore, the SERS spectra of label-free proteins (catalase, cytochrome C, avidin and lysozyme) from the assembled sandwich have excellent reproducibility and high quality. The results reveal that the proposed approach has potential for use in qualitative and quantitative detection of biomolecules.

The general treatment is proposed to investigate the explicit expressions of the average number of subchains with definite monomer sequences on the polymer skeleton, in which the AB + A f type polycondensation is chosen as the classical model of polymerization. The linear homo-polymers and star-shape co-polymers are examined to derive the z-average mean-square radius of gyration, respectively, where the mass of monomers are taken into consideration. Furthermore, the z-average mean-square radius of gyration of mixture sample is calculated, in which the weight factors of the co-polymer and homo-polymer for the non-fractionated samples are examined analytically.

A generation function method is used to obtain some average polymer physical quantities in the self-condensing vinyl polymerization (SCVP) system with any initial distribution. For the system under study, the generation function is explicitly derived in terms of the corresponding differential kinetic equations. As an application, two SCVP systems with uniform and dispersed prepolymers were discussed, respectively. As a result, the number-, weight- and Z-average degrees of polymerization and polydispersity index were presented. It is shown that, on the one hand, the initial distribution plays an important role in these physical quantities, and on the other hand, the generation function method is found to be very convenient in the calculations of average polymer quantities. It is expected that the present method can be applied in more complex SCVP systems with such as semi-batch process, multi-components and unequal reactivity.

Vascular endothelial growth factor (VEGF-A) stimulating angiogenesis is required for tumor growth and progression. The conventional VEGF-A isoforms have been considered as pro-angiogenic factors. Another family of VEGF-A isoforms generated by alternative splicing, termed VEGFxxxb isoforms, has anti-angiogenic property, exemplified by VEGF165b. Here, we identify a new number of VEGFxxx family-VEGF111b induced by mitomycin C, although not detected in mitomycin C-unexposed ovarian cancer cells. SKOV3 cells were transfected with pcDNA3.1 empty vector, pcDNA3.1-VEGF111b or pcDNA3.1-VEGF165b to collect conditioned mediums respectively. VEGF111b overexpression inhibits proliferation, migration and tube formation of endothelial cell by inhibiting VEGF-R2 phosphorylation and its downstream signaling, similar to VEGF165b but slightly lower than VEGF165b. The anti-angiogenic property depends on the six amino acids of exon 8b of the VEGFxxxb isoforms. Our results show that VEGF111b is a novel potent anti-angiogenic agent that can target the VEGF-R2 and its signaling pathway to inhibit ovarian tumor growth.

Cyclodextrin glycosyltransferase (EC 2.4.1.19, CGTase) is an important industrial enzyme in the production of cyclodextrins. However, the working conditions are extreme, which often restrict the usage of CGTase. Thermal stability is of great importance for this enzyme. Besides to screen microorganism for CGTase that fit the requirement of biotechnology, it is also hoped that protein engineering can tailor CGTase to meet demands of industry. In this work, molecular dynamics simulations were performed to study thermal stabilization of CGTase C-terminal structured region. Dynamic motions of salt bridges in thermal unstable regions were monitored during the simulations. In the C-terminal region, salt bridge Arg591-Asp640 and Lys652-Glu664 were proposed to be more important for stability than the others. Sheet1 and Sheet3 through the Arg591-Asp640 salt-bridge formation renders the C-terminal stable. The salt bridge Lys652-Glu664 linking sheet4 and sheet5 terminal also contributes to the structural stability of C-terminal. This study is attempt to observe the dynamic behavior of CGTase C-terminal at high temperatures and to understand the factors conferring thermostability of this protein. The results provide specific knowledge about thermal stability in CGTase C-terminal and may help to design biotechnologically improved thermostable proteins.

Physical properties, such as density, refractive index and morphology of the aerosol particles will be changed when the relative humidity of the environment is relatively high, which leads to a significant variation of the scattered light signal collected by the single particle light scattering measurement system. If the calibration parameters in the condition of low humidity are applied to inverse aerosol mass concentration, the measurement accuracy will certainly be degraded. Therefore, the calibration parameters of the system must be corrected. In this case, the monotonic relationship between the particle size and the scattered light signal collected by the system should be considered carefully. Combining the Mie scattering theory with the humidity growth model of the particle size and the refractive index, the influence of relative humidity on the scattered light signals of spherical particles has been investigated in this paper. The results indicate that the diameters of spherical particles grow exponentially and the refractive index decreases linearly when the relative humidity is increased between 60% and 95%. Consequently, a significant change of the angular distribution of the scattering intensity occurs. The forward-scattered light is getting stronger, while the back-scattered light becomes weaker. Meanwhile, the scattered light flux of the particle within a solid angle displays exponential growth with increasing the relative humidity. Thus, the monotonous relationship between the particle size and the scattered light flux has changed significantly in the case of the high humidity, and their quadratic coefficient decreases clearly assuming the particle density invariant, which causes an obvious increase of the calibrated proportional coefficient. The results of this work provide an important theoretical guidance for the humidity correction of calibration parameters for the inversion of aerosol mass concentration by the single particle light scattering method.

A conventional VMI (velocity map imaging)-TOF (time-of-flight) spectrometer is modified by adding an extra electrode. By this small modification, the longitudinal focus can be realized for TOF mass resolution while maintaining the lateral focus for optimal VMI energy resolution simultaneously. The mass-resolving power by four-electrode ion optics is greatly enhanced. Our design is especially useful in experiment with a non-focused laser beam.

Avibactam is a β-lactamase inhibitor that is in clinical development, combined with β-lactam partners, for the treatment of bacterial infections comprising Gram-negative organisms. Avibactam is a structural class of inhibitor that does not contain a β-lactam core but maintains the capacity to covalently acylate its β-lactamase targets. Using the TEM-1 enzyme, we characterized avibactam inhibition by measuring the on-rate for acylation and the off-rate for deacylation. The deacylation off-rate was 0.045 min −1 , which allowed investigation of the deacylation route from TEM-1. Using NMR and MS, we showed that deacylation proceeds through regeneration of intact avibactam and not hydrolysis. Other than TEM-1, four additional clinically relevant β-lactamases were shown to release intact avibactam after being acylated. We showed that avibactam is a covalent, slowly reversible inhibitor, which is a unique mechanism of inhibition among β-lactamase inhibitors.