Search

In this work, a new treatment method combining ultrasonic vibration with FeCoNiCrCu high entropy alloy (HEA) coating was used to prepared Al/Mg bimetal through the lost foam compound casting. The effects of composite treatment involving ultrasonic vibration and HEA coating on interfacial microstructure and mechanical properties of Al/Mg bimetal were studied. Results demonstrate that the interface thickness of the Al/Mg bimetal with composite treatment significantly decreases to only 26.99% of the thickness observed in the untreated Al/Mg bimetal. The HEA coating hinders the diffusion between Al and Mg, resulting the significant reduction in Al/Mg intermetallic compounds in the interface. The Al/Mg bimetal interface with composite treatment is composed of Al3Mg2and Mg2Si/AlxFeCoNiCrCu+FeCoNiCrCu/δ-Mg+Al12Mg17eutectic structures. The interface resulting from the composite treatment has a lower hardness than that without treatment. The acoustic cavitation and acoustic streaming effects generated by ultrasonic vibration promote the diffusion of Al elements within the HEA coating, resulting in a significant improvement in the metallurgical bonding quality on the Mg side. The fracture position shifts from the Mg side of the Al/Mg bimetal only with HEA coating to the Al side with composite treatment. The shear strength of the Al/Mg bimetal increases from 32.16 MPa without treatment to 63.44 MPa with ultrasonic vibration and HEA coating, increasing by 97.26%.

Diltiazem and glibenclamide are commonly used hypotensive and antidiabetic drugs. This study reports the discovery of the potential antitumor and antimetastatic effects of these two drugs using a structural dynamics-driven virtual screening targeting urokinase receptor (uPAR). Owing to uPAR’s high flexibility, currently resolved crystal structures of uPAR, all in ligand-bound states, provide limited representations of its physiological conformation. To improve the accuracy of screening, we performed a long-timescale molecular dynamics simulation and obtained the representative conformations of apo-uPAR as the targets for our screening. Experimentally, we demonstrated that diltiazem and glibenclamide bound uPAR with KDvalues in the micromolar range. In addition, both compounds effectively suppressed tumor growth and metastasis in a uPAR-dependent manner in vitroand in vivo. This work not only provides two potent uPAR inhibitors but also reports a proof-of-concept study on the potential off-label antitumor and antimetastatic uses of diltiazem and glibenclamide.

Triple-negative breast cancer (TNBC) is highly aggressive and causes a higher proportion of metastatic cases. However, therapies directed to specific molecular targets have rarely achieved clinically meaningful improvements in the outcome of TNBC therapy. A urokinase-type plasminogen activator (uPA), one of the best-validated biomarkers of breast cancer, is an extracellular proteolytic serine protease involved in many pathological and physiological processes, including tumor cell invasion and metastasis. Nafamostat mesylate (NM) is a synthetic compound that inhibits various serine proteases and has been used as a therapeutic agent for the treatment of TNBC. Nevertheless, NM has poor specificity for serine proteases and is easy be hydrolyzed; moreover, the inhibitory mechanism of TNBC therapy is unclear. In this study, we combine NM with a macromolecular drug delivery vehicle, mouse amino-terminal fragment of urokinase–human serum albumin (mATF–HSA), to form a complex (mATF–HSA:NM) using the dilution–incubation–purification method. mATF specifically targets uPAR overexpressed on the surface of TNBC cells; moreover, HSA prevents NM from being hydrolyzed by numerous serine proteases. mATF–HSA:NM showed stronger inhibitory effects on the proliferation and metastasis of TNBC in vitro and in vivo without significant cytotoxicity on normal cells and tissues. In addition, we demonstrated that NM mediates metastasis of TNBC cells through inhibition of uPA using a stable uPA knockdown cell line (MDA-MB231 shuPA). Overall, we have developed a macromolecular complex targeted to treat high uPAR-expressing tumor types, and mATF–HSA can potentially be used to load other types of drugs with tumor-targeting specificity for mouse tumor models and is a promising tool to study tumor biology in mouse tumor models.

Drought and salt stresses, the major environmental abiotic stresses in agriculture worldwide, affect plant growth, crop productivity, and quality. Therefore, developing crops with higher drought and salt tolerance is highly desirable. This study reported the isolation, biological function, and molecular characterization of a novel maspardin gene, OsMas1, from rice. The OsMas1 protein was localized to the cytoplasm. The expression levels of OsMas1were up-regulated under mannitol, PEG6000, NaCl, and abscisic acid (ABA) treatments in rice. The OsMas1gene was introduced into the rice cultivar Zhonghua 11 (wild type, WT). OsMas1-overexpression (OsMas1-OE) plants exhibited significantly enhanced salt and drought tolerance; in contrast, OsMas1-interference (OsMas1-RNAi) plants exhibited decreased tolerance to salt and drought stresses, compared with WT. OsMas1-OE plants exhibited enhanced hypersensitivity, while OsMas1-RNAi plants showed less sensitivity to exogenous ABA treatment at both germination and post-germination stages. ABA, proline and K+contents and superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and photosynthesis activities were significantly increased. In contrast, malonaldehyde (MDA), hydrogen peroxide (H2O2), superoxide anion radical (O2-·), and Na+contents were significantly decreased in OsMas1-OE plants compared with OsMas1-RNAi and WT plants. Overexpression of OsMas1up-regulated the genes involved in ABA signaling, proline biosynthesis, reactive oxygen species (ROS)-scavenging system, photosynthesis, and ion transport under salt and drought stresses. Our results indicate that the OsMas1gene improves salt and drought tolerance in rice, which may serve as a candidate gene for enhancing crop resistance to abiotic stresses.

Al/Mg bimetal was prepared by lost foam solid-liquid compound casting, and the effects of mechanical vibration on the filling and solidification behavior, microstructure and performance of the bimetal were investigated. Results show that the mechanical vibration has a remarkable influence on the filling and solidification processes. It is found that after mechanical vibration, the filling rate increases and the filling rate at different times is more uniform than that without vibration. In addition, the mechanical vibration also increases the wettability between liquid AZ91D and A356 inlays. The mechanical vibration reduces the horizontal and vertical temperature gradient of the casting and makes the temperature distribution of the whole casting more uniform. Compared to the Al/Mg bimetal without vibration, the shear strength is improved by 39.76% after the mechanical vibration is applied, due to the decrease of the inclusions and Al12Mg17dendrites, and the refinement and uniform distribution of the Mg2Si particles in the interface of the Al/Mg bimetal.

Air pollution caused by bacteria and viruses has posed a serious threat to public health. Commercial air purifiers based on dense fibrous filters can remove particulate matter, including airborne pathogens, but do not kill them efficiently. Here, we developed a double-grafted antibacterial fiber material for the high-efficiency capture and inactivation of airborne microorganisms. Tetracarboxyl phthalocyanine zinc, a photosensitizer, was first grafted onto the polyester (PET) fiber, followed by coating with chitosan on the surface of PET fiber to make a double-grafted fiber material. Under the irradiation of light with a specific wavelength (680 nm), double-grafted fiber materials killed up to 99.99% of Gram-positive bacteria and Gram-negative bacteria and had a significant antibacterial effect on drug-resistant bacteria. The double-grafted PET fiber showed broad-spectrum antibacterial activities and was capable to inactivate drug-resistant bacteria. Notably, in filtration experiments for airborne bacteria, this double-grafted PET fiber demonstrated a high bacteria capture efficiency (95.68%) better than the untreated PET fiber (64.87%). Besides, the double-grafted PET fiber was capable of efficiently killing airborne bacteria. This work provides a new idea for the development of air filtration materials that can efficiently kill airborne pathogen and has good biosafety.

Two raw coals and their washery products were collected from two coal-washing plants of Ningwu coal field, Shanxi, China. The migration behaviors of sulfur (S) and arsenic (As) during coal washing process were investigated by the microwave digestion method together with hydride generation-atomic fluorescence spectrometry. Based on the checked mass balance of As, a sequential-chemical-extraction method was used to explore the dependence between speciation transformation and release characteristics of S and As during the combustion process of raw coal, cleaned coal, coal gangue, middling coal, or coal slime. The results show that 20%–28% of S and As in raw coal are migrated to the cleaned coal, and 46%–61% of them to gangue. Pearson correlation coefficient identifies that the inorganic minerals in samples control the migration behavior of S and As. Compared with the elements in raw coal, the proportions of organic S and As in cleaned coal increase to 30%–50%, while the inorganic S and As in coal gangue account for more than 90%, which indicates the dependence between the species of S and As in raw coal and its washery products. The relatively large amount of organic S and As in the cleaned coal obviously release together with water and volatile matters below 500 ℃. While the inorganic bonded As and S in gangue mainly release during the decomposition process of pyrite, sulfate and other inorganic minerals between 500 and 1000 ℃, which shows the consistency of S and As release characteristics during combustion of raw coal or washery product. The release rates of S and As from the cleaned coal are the fastest among all samples and the corresponding maximum release ratios are 80%–95% at 300 s and 60%–75% at 200 s, respectively, whilst their release rates from gangue are the slowest and As reaches the maximum release ratio of 40%–45% at 300 s but S doesn’t get to the maximum release ratio even at 600 s. The release rates of S and As from the middling coal or raw coal are between the cleaned coal and gangue. The different release rates of S and As during the sample combustion are mainly depended on their speciation distributions in nature.

Protein disulfide isomerase (PDI) is a vital oxidoreductase. Extracellular PDI promotes thrombus formation but does not affect physiological blood hemostasis. Inhibition of extracellular PDI has been demonstrated as a promising strategy for antithrombotic treatment. Herein, we focused on the major substrate binding site, a unique pocket in the PDI b′ domain, and identified four natural products binding to PDI by combining virtual screening with tryptophan fluorescence-based assays against a customized natural product library. These hits all directly bound to the PDI-b′ domain and inhibited the reductase activity of PDI. Among them, galangin showed the most prominent potency (5.9 μM) against PDI and as a broad-spectrum inhibitor for vascular thiol isomerases. In vivostudies manifested that galangin delayed the time of blood vessel occlusion in an electricity-induced mouse thrombosis model. Molecular docking and dynamics simulation further revealed that the hydroxyl-substituted benzopyrone moiety of galangin deeply inserted into the interface between the PDI-b′ substrate-binding pocket and the a′ domain. Together, these findings provide a potential antithrombotic drug candidate and demonstrate that the PDI b′ domain is a critical domain for inhibitor development. Besides, we also report an innovative high-throughput screening method for the rapid discovery of PDI b′ targeted inhibitors.

Quercetin-3-rutinoside (rutin) is a bioflavonoid that is common in foods. The finding that quercetin-3-rutinoside inhibits protein disulfide isomerase (PDI) and potently blocks thrombosis in vivohas enabled the evaluation of PDI inhibition in multiple animal models of thrombus formation and has prompted clinical studies of PDI inhibition in thrombosis. Nonetheless, how quercetin-3-rutinoside blocks PDI activity remains an unanswered question. Combining NMR spectroscopy, site-directed mutagenesis, and biological assays, we identified H256 as the key residue for PDI interacting with quercetin-3-rutinoside. Quercetin-3-rutinoside inhibited the activity of PDI (WT) but not PDI (H256A). Molecular dynamic simulations indicated that the flavonoid skeleton, but not the rutinoside conjugate, is embedded in the major binding pocket on the b′ domain. Among several quercetin-3-rutinoside analogues tested, only compounds with a phenoxyl group at position 7 showed direct binding to PDI, further supporting our molecular model. Studies using purified coagulation factors showed that quercetin-3-rutinoside inhibited the augmenting effects of PDI (WT), but not PDI (H256A), on tissue factor (TF) activity. Quercetin-3-rutinoside also inhibited chemotherapy-induced TF activity enhancement on endothelial cells. Together, our studies show that residue H256 in PDI and the phenoxyl group at position 7 in quercetin-3-rutinoside are essential for inhibition of PDI by quercetin-3-rutinoside. These results provide new insight into the molecular mechanism by which flavonoids block PDI activity.

No-bake resin-bonded sand is commonly used in casting production. However, its air pollution is relatively serious, especially in the molding and pouring process. For this reason, it is necessary to study the gas evolution characteristics of no-bake resin-bonded sand from room temperature to high temperatures, and not only the amount of gaseous products, but also the composition of the gaseous products. No-bake furan resin-bonded sand (#1), phenolic urethane no-bake resin-bonded sand (#2), and alkaline phenolic no-bake resin-bonded sand (#3) are the three most common no-bake resin-bonded sands in casting. The gas evolution volume and rate of these three no-bake resin-bonded sands were studied. Thermogravimetry-mass spectrometer (TG-MS), headspace-gas chromatography/mass spectrometer (HS-GC/MS), and pyrolysis-gas chromatography/mass spectrometer (PY-GC/MS) were used to measure the composition of the gaseous products emitted from binders at room temperature and high temperatures. The differences between formaldehyde, heterocyclic aromatic compounds (HAC), monocyclic aromatic hydrocarbons (MAH), and polycyclic aromatic hydrocarbons (PAHs) gaseous products from the three types of no-bake resin-bonded sands during the molding and casting process were compared. From the perspective of environmental protection, alkaline phenolic no-bake resin-bonded sand and no-bake furan resin-bonded sand are better than phenolic urethane no-bake resin-bonded sand.

As a typical electron deficient element, beryllium is potentially suitable for designing the species with novel non-classical planar hypercoordinate carbon due to high preference for the planar structures by small beryllium-containing clusters. In particular, the CBe54–cluster with a planar pentacoordinate carbon (ppC) had been proved by many previous studies to be an excellent template structure for the systematic design of ppC species through attaching various monovalent atoms on the bridging position of Be–Be edges. In this work, based on the analysis and extension on our recently reported CBe4Mnn–2(M = Li, Au, n= 1~3) species, we propose that ptC cluster CBe42–is similar to CBe54–in that it can also be employed as a template structure to systematically design the ptC species through binding various monovalent atoms on the bridging position of Be–Be edges. Our extensive screening suggests that the feasible bridging atoms (E) can be found in group 1 (H, Li, Na), group 11 (Cu, Ag, Au), and group 17 (F, Cl, Br, I) elements, leading to total thirty eligible ptC species with CBe4core moiety (CBe4Enn–2). The ptC atoms in these species are involved into three delocalized σ bonds and a delocalized π bond, thereby not only obeying the octet rule, but also possessing novel 6σ +2π double aromaticity, which significantly stabilizes the ptC arrangement. In addition, the attached bridging atoms can stabilize the CBe4core ptC moiety by replacing the highly diffused Be–Be two-center two-electron bonds with the much less diffused Be–E two-center two-electron bonds or Be–E–Be three-center two-electron bonds, as reflected by the increasing HOMO-LUMO gaps when the number of bridging atoms increases. Remarkably, the stochastic search algorithm in combination with high level CCSD(T) calculations revealed that twenty-six of the thirty-one ptC species (including previously reported six species) were global energy minima on their corresponding potential energy surfaces, in which twenty-five of them were also confirmed to be dynamically viable. They are suitable for the generation and characterization in gas phase experiments and followed spectroscopic studies.

ABSTRACTPeptidic inhibitors of proteases are attracting increasing interest not only as drug candidates but also for studying the function and regulation mechanisms of these enzymes. Previously, we screened out a cyclic peptide inhibitor of human uPA and found that Ala substitution of P2 residue turns upain-1 to a substrate. To further investigate the effect of P2 residue on the peptide behavior transformation, we constructed upain-1-W3F, which has Phe replacement in the P2 position. We determined KDand Kiof upain-1-W3F and found that upain-1-W3F might still exist as an inhibitor. Furthermore, the high-resolution crystal structure of upain-1-W3F·uPA reveals that upain-1-W3F indeed stays as an intact inhibitor bind to uPA. We thus propose that the P2 residue plays a nonnegligible role in the conversion of upain-1 to a substrate. These results also proposed a strategy to optimize the pharmacological properties of peptide-based drug candidates by hydrophobicity and steric hindrance.Abbreviations: uPA: urokinase-type plasminogen activator; SPD: serine protease domain; S1 pocket: specific substrate-binding pocket

Paclitaxel (PTX) is a widely used anticancer drug that works by inhibiting microtubule disassembly. PTX safety was greatly enhanced by embedding it with human albumin. Here, we study the synergistic effects of PTX with photodynamic therapy (PDT) both in vitro and in vivo by constructing photosensitizer–PTX nanotheranostics (PPNTs). PPNTs were fabricated via noncovalent hydrophobic interactions and π–π stacking between an amphipathic photosensitizer and PTX with an average diameter of ∼80 nm, and these showed high stability in biological conditions. In a tumor-bearing mouse model, PPNTs were shown to accumulate at the tumor site based on three-dimensional fluorescence tomographic imaging. Under 680 nm light irradiation, PPNTs exhibited a superior solid tumor ablation effect in a mouse model, with a dose of PTX (0.2 mg/kg) that is 10-fold lower than that typically used. Mechanistically, PPNTs induced a strong apoptotic response in cells under light illumination and showed an increased antitumor efficacy that is 47.2-fold and 57.6-fold higher than that of the photosensitizer nanoparticles (PNTs) and free PTX, respectively. In addition, PPNTs showed enhanced cellular uptake with focused mitochondria and lysosome colocalization compared to that of PNTs and the amount of PTX delivered in PPNTs was sufficient to induce cell cycle arrest in the G2/M phase. These findings indicated that the current combination therapy has advantages over monotherapy in promoting tumor regression and ultimately achieving tumor elimination.

The Holliday junction (HJ) is a key intermediate during homologous recombination and DNA double-strand break repair. Timely HJ resolution by resolvases is critical for maintaining genome stability. The mechanisms underlying sequence-specific substrate recognition and cleavage by resolvases remain elusive. The monokaryotic chloroplast 1 protein (MOC1) specifically cleaves four-way DNA junctions in a sequence-specific manner. Here, we report the crystal structures of MOC1 from Zea mays, alone or bound to HJ DNA. MOC1 uses a unique β-hairpin to embrace the DNA junction. A base-recognition motif specifically interacts with the junction center, inducing base flipping and pseudobase-pair formation at the strand-exchanging points. Structures of MOC1 bound to HJ and different metal ions support a two-metal ion catalysis mechanism. Further molecular dynamics simulations and biochemical analyses reveal a communication between specific substrate recognition and metal ion-dependent catalysis. Our study thus provides a mechanism for how a resolvase turns substrate specificity into catalytic efficiency.

Detection of the transition between the two myosin isoforms α- and β-myosin in living cardiomyocytes is essential for understanding cardiac physiology and pathology. In this study, the differences in symmetry of polarization spectra obtained from α- and β-myosin in various mammalian ventricles and propylthiouracil-treated rats are explored through polarization-dependent second harmonic generation microscopy. Here, we report for the, to our knowledge, first time that α- and β-myosin, as protein crystals, possess different symmetries: the former has C6 symmetry, and the latter has C3v. A single-sarcomere line scan further demonstrated that the differences in polarization-spectrum symmetry between α- and β-myosin came from their head regions: the head and neck domains of α- and β-myosin account for the differences in symmetry. In addition, the dynamic transition of the polarization spectrum from C6 to C3v line profile was observed in a cell culture in which norepinephrine induced an α- to β-myosin transition.

Detecting the structural changes caused by volume and pressure overload is critical to comprehending the mechanisms of physiologic and pathologic hypertrophy. This study explores the structural changes at the crystallographic level in myosin filaments in volume- and pressure-overloaded myocardia through polarization-dependent second harmonic generation microscopy. Here, for the first time, we report that the ratio of nonlinear susceptibility tensor components d33/d15 increased significantly in volume- and pressure-overloaded myocardial tissues compared with the ratio in normal mouse myocardial tissues. Through cell stretch experiments, we demonstrated that mechanical tension plays an important role in the increase of d33/d15 in volume- and pressure-overloaded myocardial tissues.

•Nanostructured three-dimensional porous multi-walled carbon nanotubes functionalized graphene nanocomposite has been prepared via a facile and controllable hydrothermal synthetic strategy.•Developed a reliable and inexpensive pretreatment procedure based on β2-agonists in pork using dispersive solid phase extraction with multi-walled carbon nanotube functionalized graphene nanocomposite.•The multiwalled carbon nanotube functionalized graphene nanocomposite can strongly adsorb hydrophobic organic contaminants due to their very high surface hydrophobicity. Particularly, those π-electron bearing compounds are capable of interacting with carbon nanomaterials via π–π electron coupling.

The mechanical properties of resin-bonded sand mixtures at high temperatures significantly affect the quality of casting. However, the existing instruments for high-temperature performances testing mainly focus on inorganic binder-bonded sands no matter the test items or the atmospheric protection, while the instrumentss specially designed for resin-bonded sand are not yet available. A new instrument for testing the high-temperature performance of resin sand was designed including the confirmation of the testing parameters, loading, measurement and control systems, and the design of the frame shape and heating furnace. This instrument can test the compressive strength, heat tolerance time and restraining load of phenol-formaldehyde resin coated sand, self-hardened furan resin sand, and trimethylamine (TEA)-based resin bonded sand at high temperatures. The developed instrument has a high accuracy offering smaller than 0.3% deviation at a full scale in the measurement of the high temperature compressive strength and the restraining load over the range of 0–6.8 MPa and 0–2,000 N, respectively. The high temperature heat tolerance time range is 0–300 s and its measurement accuracy is ±1 s.

Acute kidney injury (AKI) is common in patients with acute myocardial infarction. AKI in this setting is associated with short- and long-term adverse events. The aim of this study was to develop a simple score to predict AKI in patients presenting with acute myocardial infarction based on data available at time of admission. This was a retrospective analysis of data collected as part of the Acute Coronary Treatment and Intervention Outcomes Network (ACTION) registry at a tertiary care center between 1/1/2011 and 12/31/2013. Data were collected prospectively for all patients who presented within 24 h of the onset of myocardial infarction. AKI was defined as an increase in creatinine from admission level to peak level of ≥0.3 mg/dl or by ≥50 %. Patients with history of end-stage renal disease requiring renal replacement therapy were excluded. Of 1107 patients included in the study, 147 (13.3 %) developed AKI. The following factors were independently associated with increased risk for AKI: cardiac arrest, decompensated heart failure on presentation, diabetes mellitus, hypertension, anemia, impaired renal function on presentation, and tachycardia on presentation. These factors were combined to form a new predictive tool. The new score showed excellent discrimination for AKI: the area under the receiver operating characteristic curve (AUROC) was 0.76 (95 % confidence interval 0.72–0.80). A simple score using clinical and laboratory data available on admission can predict the risk of AKI in patients presenting with acute myocardial infarction.

Protein–protein interactions drive every aspect of cell signaling, yet only a few small-molecule inhibitors of these interactions exist. Despite our ability to identify critical residues known as hot spots, little is known about how to effectively engage them to disrupt protein–protein interactions. Here, we take advantage of the ease of preparation and stability of pyrrolinone 1, a small-molecule inhibitor of the tight interaction between the urokinase receptor (uPAR) and its binding partner, the urokinase-type plasminogen activator uPA, to synthesize more than 40 derivatives and explore their effect on the protein–protein interaction. We report the crystal structure of uPAR bound to previously discovered pyrazole 3and to pyrrolinone 12. While both 3and 12bind to uPAR and compete with a fluorescently labeled peptide probe, only 12and its derivatives inhibit the full uPAR·uPA interaction. Compounds 3and 12mimic and engage different hot-spot residues on uPA and uPAR, respectively. Interestingly, 12is involved in a π–cation interaction with Arg-53, which is not considered a hot spot. Explicit-solvent molecular dynamics simulations reveal that 3and 12exhibit dramatically different correlations of motion with residues on uPAR. Free energy calculations for the wild-type and mutant uPAR bound to uPA or 12show that Arg-53 interacts with uPA or with 12in a highly cooperative manner, thereby altering the contributions of hot spots to uPAR binding. The direct engagement of peripheral residues not considered hot spots through π–cation or salt-bridge interactions could provide new opportunities for enhanced small-molecule engagement of hot spots to disrupt challenging protein–protein interactions.

Four different concentrations of alkaline solution for pretreatment of Paulownia biomass were comparatively studied. The extracted celluloses were characterized using Fourier Transform Infrared spectra (FTIR) for changes of the chemical group, as well as X-ray Diffraction (XRD), Scanning Electron Microscope (SEM). The four samples were untreated biomass, treated with 2%, 4% and 6%peroxide alkaline, and thena comparison between alkaline and dilute acid pretreatment on those indexes were conducted. FTIR spectra results suggested that NaOH could mainly work on lignin of the raw material while the dilute acid work on hemicellulose. The CrI of acid pretreatment and alkaline pretreatment increased to 0.5467 and 0.6395 respectively comparing with the value of 0.4347 of raw material. The XRD results suggested that both of them could act on amorphous region firstly. The SEM micrographs showed the visual structure changes of this progress. The results of enzyme hydrolysis showed 93.3% and 90.6% of the potential glucose and xylose were recovered in the pretreated biomass at 6% NaOH that proved the effects of the NaOH on cellulose structural.

In the present study, a processing technique for recycling investment casting ceramic shell waste was proposed to separate valuable refractory aggregate zircon sand. The microstructure and phase constituents of the shell waste and separation process were investigated. The results show that the characteristics of microstructure and phase constituents of the shell waste can meet the conditions for preferentially separating zircon sand, and zircon sand can be separated by gravity separation on a shaking table. The separated zircon sand has good shape and high purity, and can be used for the production of castings and other applications.

Water soluble cores (WSCs) have been widely applied in manufacture of complex metal components with hollow configurations or internal channels. However, the WSCs without any additons have low tensile strength and low humidity resistance. The purpose of this study is to prepare a water-soluble potassium carbonate sand core with addition of kaolin by the hot-temping method. The effects of kaolin on tensile strength, humidity resistance, fracture mechanism, as well as the gas evolution and collapsibility of WSCs were investigated. Results show that both the crystal morphology and the fracture mechanism of the inorganic salt are changed under the participation of kaolin, contributing to the increase of the tensile strength and the humidity resistance of the core. With the addition of 3wt.% kaolin, the tensile strength could be increased by a factor of 2, reached 1.50 MPa and the hygroscopic rate could be decreased by 14%, achieved 0.559% (after stored for 8 h), respectively. As the addition amount of kaolin increases from 0wt.% to 3wt.%, the main fracture mechanism changes from a adhesive to a cohesive fracture mechanism. The water-soluble potassium carbonate core obtained has the low gas evolution and excellent collapsibility, which makes it suitable for casting low melting metal with complex cavities and crooked channels.

This paper aimed at present situation of exploitation and utilization of water resource protection and tourism in wuhan city, analyses the reason of its existing problems, and then for the existing problems of water pollution in wuhan city, has carried on the thorough analysis and discussion, in order to realize the good governance of water pollution in wuhan city, and puts forward countermeasures of water pollution in wuhan city

Along with the main rivers and lakes of China are polluted inordinately, water environment issues in China have been becomingincreasingly severe. The cross-domain water pollution contradictions cannot be well settled by the government-centered river and watercourse control, which means that,urgently, a new river and watercourse control mechanism needs to be established. With continuous changes of water management, in order to get along with water even more harmoniously, the mankind has formed the concept of water resource management through cross-domain consultation. Combining traditional, historical and social culturefactors, ancient and modern, this paper analyzes influences of the cross-domain consultation upon water culture, proposes detailed countermeasures of establishing the water culture featuring“harmoniousco-existence between mankind and water”by cross-domain consultation, so as to effectively settle contradictions triggered by water pollution amongdifferent administrative regions, and improve the efficiency ofwatercontrol.

Direct thrombus imaging contributes to early detection of thrombosis, and animal models with clinical relevance are vital in the development of new thrombolytics. Here, a facile clot‐homing strategy is developed based on the finding that blood clot is negatively charged. Positively charged pentalysine moiety is coupled with phthalocyanine‐based fluorophore , and its applications in murine thromboembolic models are described. The probe efficiently stains the cryosection of intracranial thrombi retrieved from patients with cardioembolic stroke. In vitro, the fibrin‐rich clot is labeled by the probe at sub‐nanomolar concentration. The probe‐labeled clot is formed into microparticles (1–5 µm) and intravenously injected into mice for pulmonary embolism modeling. In vivo imaging demonstrates fast accumulation and retention of fluorescent clot microparticles in pulmonary vessels. Recombinant tissue‐type plasminogen activator (rtPA) administration greatly reduces near‐infrared signal in the lungs in a time‐dependent manner. This probe is also tested in a stroke model. Middle cerebral artery is occluded by autologous thrombi formed under electric stimulation. In vivo imaging shows that the probe efficiently homes to thrombus at early stage. Hence, this probe has great potential in real‐time imaging of thromboembolism in clinically relevant models, promoting bench‐to‐bedside translation. This clot‐homing principle can be used in other applications. Blood clot, composed of condense fibrin network, platelets, and red blood cells, carries many negative charges. A near‐infrared fluorophore (ZnPc5K, 680 nm) with positively charged pentalysine moiety can efficiently bind to blood clot, enabling in vivo 3D and real‐time imaging of thromboembolic disorders, e.g., pulmonary embolism and ischemic stroke.

Due to uniquely ordered nanoporous structure and high surface area as well as large pore volume, mesoporous materials have exhibited excellent performance in both controlled drug delivery with sustained release profiles and formulation of poorly aqueoussoluble drugs with enhanced bioavailability. Compared with other bulk excipients, mesoporous materials could achieve a higher loading of active ingredients and a tunable drug release profile, as the high surface density of surface hydroxyl groups offered versatility to be functionalized. With drug molecules stored in nano sized channels, the pore openings could be modified using functional polymers or nano-valves performing as stimuli-responsive release devices and the drug release could be triggered by environmental changes or other external effects. In particular, mesoporous silica nanoparticles (MSN) have attracted much attention for application in functional target drug delivery to the cancer cell. The smart nano-vehicles for drug delivery have showed obvious improvements in the therapeutic efficacy for tumor suppression as compared with conventional sustained release systems, although further progress is still needed for eventual clinical applications. Alternatively, unmodified mesoporous silica also exhibited feasible application for direct formulation of poorly water-soluble drugs to enhance dissolution rate, solubility and thus increase the bioavailability after administration. In summary, mesoporous materials offer great versatility that can be used both for on-demand oral and local drug delivery, and scientists are making great efforts to design and fabricate innovative drug delivery systems based on mesoporous drug carriers.

Both Eubacteria and Archaea community diversity and dynamicity were studied during PCP-degrading micro-aerobic granular sludge cultivation using 16S rDNA ribosomal RNA approach. Main bands of DGGE were compared with sequences. The results showed that Eubacteria and Archaea community were closely related to uncultured microorganisms. There were aerobic, micro-aerobic and anaerobic bacterium in micro-aerobic granular sludge simultaneously. After granular sludge was domesticated by PCP, the dominant Eubacteria and Archaea for PCP degradation were related to Proteobacteria, Sphingomonas, Methanogenic bacterium and so on.

We present both theoretically and experimentally the thermo-optic characteristics of micro-structured optical fiber (MOF) filled with mixed liquid. The performance of MOF depends on the efficient interaction between the fundamental mode of the transmitted light wave and the tunable thermo-optic materials in the cladding. The numerical simulation indicates that the confinement loss of MOF presents higher temperature dependence with higher air-filling ratios d/Λ, longer incident wavelength and fewer air holes in the cladding. For the 4cm liquid-filled grapefruit MOF, we demonstrate from experiments that different proportions of solutions lead to tunable temperature sensitive ranges. The insertion loss and the extinction ratio are 3~4 dB and approximate 20 dB, respectively. The proposed liquid-filling MOF will be developed as thermo-optic sensor, attenuator or optical switch with the advantages of simple structure, compact configuration and easy fabrication.

To develop a new industrial briquette composite binder, response surface methodology was used to arrange experiments, with modified peat(MP），mixed wastes(WS)，modified clay 2(C2) and clay 1(C1) as raw materials. The experimental data was firstly processed utilizing the method of multi-factorial total probability formula evaluation. Then based on the regression analysis and model building, the optimum formula was obtained. Finally, the bonding mechanism was analyzed through a systematical study by means of both ESEM and TG-DTA. The results indicated that the briquette prepared according to the optimum formula, namely 4.4% of MP, 6.5% of WS, 2% of C1, 1% of C2, and correlative key parameters of briquetting technics, namely forming water 13%, drying temperature 180℃ and drying time 2.5h had excellent performances, which could meet the demand of industrial production in enterprises.

Recycling of the shell of investment casting is meaningful. However，there are many factors which hamper the progress of this work, and one of these is that the Fe content is difficult to reach the standard under the present technological conditions. Through investigating and analyzing the sources of Fe in three factories which produce steel casting and a factory which is engaging in recycling of the shell of investment casting, a new idea which suggested to remove iron through controlling import of Fe form sources was put forward in this paper. To realize this idea, corresponding measures was suggested, such as classifying the shell, picking iron out manually, storing the shell appropriately, and selecting reasonable equipment for recycling processing.

This study is to discuss the reaction pathways of vanillin (3-methoxy-4-hydroxy-benzaldehyde) degradation by Gordonia sp.The product structure was analyzed by spectroscopic technique. Vanillin removal kinetics could be best described by a simple recalcitrant first order model:-dS/dt=k s,1 X(S-S∞),k s,1 is the vanillin removal rate constant.

Paulownia that is widely distributed in china has the potential for fuel ethanol production because of its relative high cellulose and hemicellulose content and high growth rate. The dilute acid pretreatment hydrolysis process was optimized by developing a respond surface methodology to research the optimum condition of pretreatment. Cellulose conversion ratio and furfural concentration were conducted as the response results of the RSM. The optimal condition of pretreatment is the reaction temperature 145.5℃, the sulfuric acid concentration 1.14% and the residence time 39.3min, the highest cellulose conversion ratio 89.48% was achieved and furfural concentration was smaller than 1g/L. The chemical compositions of untreated paulownia were investigated and their structures were detected by SEM.

Combine with the practice of Kunming city first-phase subway project construction, detailedly introduce the success construction experiences of shield crossing the dense buildings in the unfavorable conditions of shallow soil covering, big gradient, curve in small radius, complex geological condition and upgrade excavation etc. in the paper. Reasonable choosing the grout of synchronization grouting and the main technical parameters of shield tunneling on supporting pressure of working chamber, tunneling speed, total thrust, cutter head torque and excavation quantity etc., and strengthen the link of secondary grouting and technology management, the amount of settlement and uplift of the ground and the buildings can be effectively controlled.

Experiment with intensity level for the LC30 ceramsite concrete as the research object, changing the content of cement, GRT fiber, rubber powder by the orthogonal test to configure GRT fiber—rubberized haydite concrete samples, maintenance samples 7d and 28d in standard conditions and respectively testing their bend strength. Through the analysis of the test data, using multiple regression analysis established the GRT fiber—rubberized haydite concrete 7d and 28d bend strength regression formulas.By means of BP neural network theory combine MATLAB programme established GRT fiber—rubberized haydite concrete 7d and 28d bend strength neural network model.Finally using 3 groups new test data to compare the value of multiple regression equations and BP neural network’s predicted value.The results indicate that the multiple regression equations of 28d’s and 28d’s BP neural network model are availabled.But because of the water and cement which in the GRT fiber—rubberized haydite concrete can not hydration reaction sufficiently during the 7d’s,so the multiple regression equations of 7d’s is unavailabled.

By this method of adding fly ash of equal amount in the mortar, making analysis including the decreasing water change、7d and 28d compressive strength as well as flexural strength. Results show that exists the optimum proportion of fly ash cement mortar, that is C：F：S：W=220：55：1410：275.On the basis of mixing only 20% fly ash and epoxy resin-polymer, doing analysis about the decreasing water change、7d compressive strength and flexural strength、application property. At the same time, this paper fits the regression equation which using the 7d compressive strength and flexural strength、decreasing water rate as the dependent variables, polymer cement ratio as the independent variable. More important is that the credibility of regression equation is much high.

Experiment with intensity level for the LC30 ceramsite concrete as the research object, changing the content of cement, GRT fiber, rubber powder by the orthogonal test to configure GRT fiber—rubberized haydite concrete samples, maintenance samples 7d and 28d in standard conditions and respectively testing their standard compressive strength. Through the analysis of the test data, using multiple regression analysis established the GRT fiber—rubberized haydite concrete 7d and 28d standard compressive strength regression formulas.By means of BP neural network theory combine MATLAB programme established GRT fiber—rubberized haydite concrete 7d and 28d standard compressive strength neural network model.Finally using 3 groups new test data to compare the value of multiple regression equations and BP neural network’s predicted value.The results indicate that the multiple regression equations and BP neural network model are availabled.

Kunming dian chi lake to pick to: the main southern culvert-pipe CFG pile composite foundation, illustrates the application of CFG pile mechanism, design calculation, construction process and the detection principle and its application effect is analyzed.

Experiment with intensity level for the LC30 ceramsite concrete as the research object, changing the content of cement, GRT fiber, rubber powder by the orthogonal test to configure GRT fiber—rubberized haydite concrete samples, maintenance samples 28d in standard conditions and respectively testing their modulus of elasticity、standard compressive strength and apparent density. Through the analysis of the test data, using regression method to establish the GRT fiber—rubberized haydite concrete static compression modulus of elasticity experiential formula and use new test data to compare the value of calculation. By comparing test values and calculated values proved availability of the regression formula.

To solve the problems of concrete piston striking cylinder and pumping insufficiency caused by the mismatch between varying loads and system’s open-loop control property, the optimal model of concrete pumping displacement control was built.To be precise, the displacement control signal parameters were taken as control variables, and the location parameter of the main cylinder’s displacement sensor was taken as structure variable. under the physical constraint condition of non-collision between piston and cylinder, the piston stroke maximizing was taken as objective function and the optimal model of concrete pumping displacement control was built.Optimization result shows that piston of concrete pumping system don’t strike cylinder and pump sufficiently under varying loads.This optimal model, which is built in the integration design space of structure variable and control variables, is of guiding significance for solving open-loop system’s engineering control problems.

Urokinase-type plasminogen activator (uPA) is one of the two physiological serine proteases responsible for the activation of plasminongen to plasmin. uPA activity is regulated by its inhibitors (PAI-1 and PAI-2) and its receptor (uPAR), and an expanding list of their interacting proteins. In addition to plasminogen activation, this system also plays important roles in the regulation of many cellular processes including cell proliferation, adhesion and migration. It is beyond reasonable doubt that this enzyme system plays a central role in tumor biology and represents a high potential target for therapeutic intervention of tumor growth and metastasis. During the past fifteen years, crystal structures of uPA and its inhibitors have facilitated the development of uPA inhibitors. Many crystal structures of proteins in the uPA/uPAR system have also been reported recently, especially a series of structures of uPAR and its complexes with vitronectin and uPA, facilitating the development and evaluation of uPAR inhibitors. Recent progress on uPA inhibitors will be summarized in this article. The unique structural features and the druggable potentials of these new structures will also be discussed.

In order to solve the problem of the response time of concrete pump distribution circuit unmatching pumping construcution requirement,which caused by selecting accumulator based on experience, the parameter configuration of the accumulator was quantitatively expressed. The response time of the distribution circuit is divided into switch time of S tube distribution valve and accumulated pressure differential time of the accumulator. In order to meet the requirements of the response time of the pumping construction, based on the existing parameter configuration of the accumulator, with dynamic characteristic equation and gas state equation respectively, the switch time of S tube distribution valve and accumulated pressure differential time of the accumulator is quantitatively calculated, and the parameters of the accumulator is configurated.Compared to the traditional accumulator choice method, namely selecting accumulator according to experience and testing whether the response time of the distribution circuit is reasonable, quantitative calculated parameter configuration of concrete pump accumulator is more accurate, and can fully meet the requirments of pumping construction. This method also provides theoretical basis for design and choice of engineering machinery accumulator.

There is increasing interest in developing peptides for pharmacological intervention with pathophysiological functions of serine proteases. From phage-displayed peptide libraries, we previously isolated peptidylic inhibitors of urokinase-type plasminogen activator, a potential target for intervention with cancer invasion. The two peptides, upain-1 (CSWRGLENHRMC) and mupain-1 (CPAYSRYLDC), are competitive inhibitors of human and murine urokinase-type plasminogen activator, respectively. Both have an Arg as the P1 residue, inserting into the S1 pocket in the active site of the enzymes, but their specificity depends to a large extent on interactions outside the enzymes' active sites, so-called exosite interactions. Here we describe upain-2 (CSWRGLENHAAC) and the synthesis of a number of upain-2 and mupain-1 variants in which the P1 Arg was substituted with novel non-natural Arg analogs and achieved considerable improvement in the affinity of the peptides to their targets. Using chimeras of human and murine urokinase-type plasminogen activator as well as X-ray crystallography, we delineated the relative contribution of the P1 residue and exosite interactions to the affinity and specificity of the inhibitors for their target enzyme. The effect of inserting a particular non-natural amino acid into the P1 position is determined by the fact that changes in interactions of the P1 residue in the S1 pocket lead to changed exosite interactions and vice versa. These findings are of general interest when the affinities and specificities of serine protease inhibitors to be used for pharmacological intervention are considered and could pave the way for potential drug candidates for the treatment of cancer.

Activated carbon supported nano-TiO2 photocatalyst material was prepared with activated carbon as the carrier and carboxyl methyl cellulose (CMC) as the binder. The results indicated that the optimal TiO2 loading percentage could reach 11.46% when the mass concentration of binder in the dipping solution was 15 g/L. Meanwhile, the optimal experimental results showed that the removal percentage of CODCr from papermaking midcourse wastewater could reach 71.43% under the conditions of 10 W of radiation intensity, 240 minutes of radiation time, 15 g/L of photocatalyst dosage, 4.0 of wastewater pH and 3 mL/L of H2O2 dosage. And the effluent was able to reach China national discharge standard Ⅰ. Furthermore, after three times of repeated use, the activated carbon supported nano-TiO2 photocatalyst material still had a relatively high catalytic activity and stability, and the recycle percentage of the photocatalyst could reach 92.80%.

SiO2/TiO2 photocatalyst was prepared by a sol-gel method applying tetrabutyl titanate as the precursor and cullets as the carrier. The optimal preparing conditions of the SiO2/TiO2 composite photocatalyst were optimized. The optimal conditions included 2:1 of the molar ratio of tetraethyl orthosilicate to tetrabutyl titanate, 3 load times, 600℃ of calcinations temperature, 3 h of calcination time, 3 mL of the dosage of CH3COOH and 5:1 of the molar ratio of water to tetrabutyl titanate. The photodegradation percentage of methylene blue could reach 92.26% under the above optimal conditions. Moreover, after three times of the repeated use, the SiO2/TiO2 composite photocatalyst still had a relatively high catalytic activity and stability, and the recycle percentage of the photocatalyst could reach 92.80%.