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Difficult to effectively densify in a short time is an important issue that limits the application of magnesium (Mg) alloy fabricated by binder jetting additive manufacturing (AM) process. In this study, two-step sintering (TSS) process was utilized to improve the density of printed Mg alloy samples. Results show that the relative density, mechanical properties and corrosion resistance of the samples after different TSS process were dramatically improved in a short time. A suitable sintering temperature of first sintering step can rapidly increase the density of the samples in a short time. During the second step sintering process, little exceeding the liquidus temperature can further increase the density of the sample, but little lower than the liquidus temperature will lead to a sharp increase in grain size. The sample after sintering at 680 °C for 30 min then sintering at 610 °C for 6 h shows the highest relative density (0.995), the highest strength (394 MPa), the lowest corrosion rate (101 mm/year) and the smallest corrosion current density (60.4 μA/cm2). Compared with one-step sintering process, TTS process has higher sintering efficiency.

The integral membrane, Kunitz-type, serine protease inhibitors, HAI-1 and HAI-2, closely resemble one another structurally and with regard to their specificity and potency against proteases. Structural complementarity between the Kunitz domains and serine protease domains renders the membrane-associated serine proteases, matriptase and prostasin, the primary target proteases of the HAIs. The shared biochemical enzyme-inhibitor relationships are, however, at odds with their behavior at the cellular level, where HAI-1 appears to be the default inhibitor of these proteases and HAI-2 a cell-type-selective inhibitor, even though they are widely co-expressed. The limited motility of these proteins caused by their membrane anchorages may require their co-localization within a certain distance to allow the establishment of a cellular level functional relationship between the proteases and the inhibitors. The differences in their subcellular localization with HAI-1 both inside the cell and on the cell surface, compared to HAI-2 predominately in intracellular granules has, therefore, been implicated in the differential manner of their control of matriptase and prostasin proteolysis. The targeting signals present in the intracellular domains of the HAIs are systematically investigated herein. Studies involving domain swap and point mutation, in combination with immunocytochemistry and cell surface biotinylation/avidin depletion, reveal that the different subcellular localization between the HAIs can largely be attributed to differences in the intracellular Arg/Lys-rich and EHLVY motifs. These intrinsic differences in the targeting signal render the HAIs as two independent rather than redundant proteolysis regulators.

This work demonstrates the superior thermostability of silver-based nanoparticle cathodes under continuous solid oxide fuel cell operation by coating the samarium-doped ceria (SDC) thin shell over silver nanoparticles. The Ag-core/SDC-shell (Ag@SDC) nanoparticles prepared by solvothermal synthesis (Ag core diameter = 48 nm; average SDC shell thickness = 2–5 nm) is inkjet-printed on electrolyte substrates as a thin film cathode. The Ag@SDC film survives the 48-h thermal annealing and its most porosities remain visibly un-agglomerated. The results of fuel cell current stability test show that the cell using the Ag@SDC nanoparticle cathode have only 3% of current degradation after 25 h, which is remarkably lower than that of the cell using the bare Ag nanoparticle cathode (96.1%). In addition, the electrochemical performance of the bare silver cathode in oxygen reduction reaction has significantly improved because of the enhanced surface oxygen adsorption/dissociation process provided by the SDC thin shell.

A facile and environmentally-friendly strategy for increasing antioxidant activity is a crucial issue for value-added lignin and lignin-carbohydrate complex (LCC) as alternative antioxidants. However, the antioxidant activities of lignin and LCC by the traditional solid-liquid extraction (SLE) methods were restricted by the relatively lower solubility induced from high molecular weight (Mw), and the less functional groups including, phenolic hydroxyl and carboxyl. To improve the antioxidantion of lignin and LCC, lithium chloride/dimethyl sulfoxide (LiCl/DMSO) solvent fractionation (LDSF) was conducted to increase the functional groups and reduce Mw, in which LiCl/DMSO acted triple roles as solvent, acid, and metal chloride catalyst for the depolymerization reaction synchronously. The β-O-4′ linkages were cleaved to release the phenolic hydroxyl, resulting in decreasing Mw; the hydroxyl of the side-chain of lignin was oxidized into carboxyl. Thus, the lignin (LD-RL) and LCC (LD-LCC) samples from LDSF had a higher syringyl (S)/guaiacyl (G) ratio, phenolic hydroxyl, and carboxyl contents, but less Mw than control groups from SLE. Consequently, they presented more excellent scavenging rates toward DPPH and ABTS radicals, up to 90%. This work provided panoramic perspectives and basics of the green and convenient approach to isolate and modify lignin and LCC for great antioxidantion with LDSF.

Drought is a critical abiotic stressor that modulates soybean yield. Drought stress drastically enhances reactive oxygen species (ROS) formation, and maintaining ROS content above a cytostatic level but below a cytotoxic level is essential for normal biology processes in plants. At present, most of the known ROS-scavenging systems are in the cytoplasm, and the mechanism of ROS regulation in the nucleus remains unclear. GmNTF2B-1 is a member of the IV subgroup in the nucleus transporter family. Its expression is localized to the roots and is stimulated by drought stress. In this study, the overexpression of GmNTF2B-1 was found to improve the drought tolerance of transgenic soybean by influencing the ROS content in plants. An oxidoreductase, GmOXR17, was identified to interact with GmNTF2B-1 in the nucleus through the yeast two-hybrid, coimmunoprecipitation and bimolecular fluorescence complementation assays. The drought tolerance of GmOXR17 transgenic soybean was similar to that of GmNTF2B-1. GmNTF2B-1 was expressed in both cytoplasm and nucleus, and GmOXR17 transferred from the cytoplasm to the nucleus under drought stress. The overexpression of GmNTF2B-1 enhanced the nuclear entry of GmOXR17, and the overexpression of GmNTF2B-1 or GmOXR17 could decrease the H2 O2 content and oxidation level in the nucleus. In conclusion, the interaction between GmNTF2B-1 and GmOXR17 may enhance the nuclear entry of GmOXR17, thereby enhancing nuclear ROS scavenging to improve the drought resistance of soybean.

Wheat straw was rapidly fractionated using maleic acid (MA) as an acid hydrotrope at atmospheric pressure under a range of conditions. MA hydrotropic fractionation (MAHF) was very selective in dissolving lignin and hemicelluloses resulting in a cellulose‐rich water insoluble solids (WIS), which was evaluated for producing fibers through bleaching and cellulosic nanofibrils by fibrillation, as well as glucose through enzymatic saccharification. The residual lignin (RL) within the WIS has a low degree of condensation, which eased bleaching. The RL was also carboxylated through MAHF, which facilitated nanofibrillation to produce lignin‐containing cellulose nanofibrils. The carboxylation also aided enzymatic saccharification of WIS by decreasing nonproductive cellulase binding to RL through electrostatic repulsion between carboxylated (charged) RL and the cellulase at elevated pH (>cellulase isoelectric point). The dissolved lignin (DL) from MAHF also has a low degree of condensation, making it favorable for further catalytic conversion. Carboxylation improved DL antioxidant capability. MA is an FDA‐approved indirect food additive (21CFR175‐177) and is much less corrosive than other acids typically used for cellulosic fractionation. It is also less soluble which is a distinct and very promising advantage for acid recovery. Therefore, MAHF has notable advantages and significant potential for sustainable biorefinery.

Xiao-Chaihu-Decoction (XCHD), a classical traditional Chinese medicine with diverse biological activities, is widely applied to prevent and treat many human diseases. Effects of dietary XCHD on growth performance, immune response, detoxification system, intestinal microbiota and resistance against aflatoxin B1(AFB1) of Litopenaeus vannamei was studied. Four isonitrogenous and isolipidic diets were formulated to contain 0, 1, 2, and 5 g/kg (control, XCHD1, XCHD2 and XCHD3) of XCHD, respectively. Seven hundred and eighty shrimp (1.16 ± 0.09 g) were assigned randomly to 12 tanks (400 L, three tanks each group, 65 shrimp in each tank) for 6 weeks. After sampling, 25 shrimp from each tank were selected for a 2-week AFB1 (2500 μg/kg) challenge experiment. The results indicated that the final weight, weight gain and specific growth rate in XCHD2 and XCHD3 groups were significantly increased compared to control. The protease, amylase, superoxide dismutase (SOD), glutathione s-transferase (GST), sulfotransferase (SULT) activities, total antioxidant capacity (T-AOC) and glutathione (GSH) contents in hepatopancreas were significantly increased in XCHD3 groups and the expressions of immune-related genes (Toll, Dorsal and Cru) in hepatopancreas were significantly up-regulated in XCHD2 and XCHD3 groups. High-throughput sequencing analysis revealed that the abundance of Proteobacteria decreased and the abundances of Bacteroidetes increased in XCHD2 and XCHD3 groups. Additionally, AFB1 challenge experiments showed that AFB1 caused histological damage to the hepatopancreas and significantly increased the levels of malondialdehyde (MDA) and protein carbonylation (PC) in hepatopancreas as well as the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Nevertheless, XCHD could effectively alleviated the growth toxicity, immunosuppression and macromolecular damage caused by AFB1 to shrimp by inhibiting the Phase I enzyme and enhancing Phase II enzyme and antioxidant system.

Statins are effective cholesterol-lowering drugs. Lovastatin, one of the precursors of statins, is formed from dihydromonacolin L (DML), which is synthesized by lovastatin nonaketide synthase (LovB), with the assistance of a separate trans-acting enoyl reductase (LovC). A full DML synthesis comprises 8 polyketide synthetic cycles with about 35 steps. The assembling of the LovB–LovC complex, and the structural basis for the iterative and yet permutative functions of the megasynthase have remained a mystery. Here, we present the cryo-EM structures of the LovB–LovC complex at 3.60 Å and the core LovB at 2.91 Å resolution. The domain organization of LovB is an X-shaped face-to-face dimer containing eight connected domains. The binding of LovC laterally to the malonyl-acetyl transferase domain allows the completion of a L-shaped catalytic chamber consisting of six active domains. This architecture and the structural details of the megasynthase provide the basis for the processing of the intermediates by the individual catalytic domains. The detailed architectural model provides structural insights that may enable the re-engineering of the megasynthase for the generation of new statins., Biosynthesis of the statin precursor lovastatin depends on the LovB–LovC megasynthase complex. Here, the authors present cryoEM structures of LovB–LovC and core LovB, providing structural insights into the catalytic cycle underlying lovastatin production.

Epidermal differentiation and barrier function require well-controlled matriptase and prostasin proteolysis, in which the Kunitz-type serine protease inhibitor HAI-1 represents the primary enzymatic inhibitor for both proteases. HAI-1, however, also functions as a chaperone-like protein necessary for normal matriptase synthesis and intracellular trafficking. Furthermore, other protease inhibitors, such as antithrombin and HAI-2, can also inhibit matriptase and prostasin in solution or in keratinocytes. It remains unclear, therefore, whether aberrant increases in matriptase and prostasin enzymatic activity would be the consequence of targeted deletion of HAI-1 and so subsequently contribute to the epidermal defects observed in HAI-1 knockout mice. The impact of HAI-1 deficiency on matriptase and prostasin proteolysis was, here, investigated in HaCaT human keratinocytes. Our results show that HAI-1 deficiency causes an increase in prostasin proteolysis via increased protein expression and zymogen activation. It remains unclear, however, whether HAI-1 deficiency increases "net" prostasin enzymatic activity because all of the activated prostasin was detected in complexes with HAI-2, suggesting that prostasin enzymatic activity is still under tight control in HAI-1-deficient keratinocytes. Matriptase proteolysis is, however, unexpectedly suppressed by HAI-1 deficiency, as manifested by decreases in zymogen activation, shedding of active matriptase, and matriptase-dependent prostasin zymogen activation. This suppressed proteolysis results mainly from the reduced ability of HAI-1-deficient HaCaT cells to activate matriptase and the rapid inhibition of nascent active matriptase by HAI-2 and other yet-to-be-identified protease inhibitors. Our study provides novel insights with opposite impacts by HAI-1 deficiency on matriptase versus prostasin proteolysis in keratinocytes.

Engineered nanoparticles raise safety concerns. Silver nanoparticles (AgNPs) exert acute and chronic adverse effects by inducing reactive oxygen species (ROS)-mediated stress signaling pathways. We investigated the mechanisms by which AgNPs exert lasting adverse effects on longevity, as well as their sublethal effects on functional aging. Drosophila was used as a model to systematically study the mechanisms of small AgNP-induced acute and long-term toxicity. We demonstrated that dietary exposure to 12.5 nm AgNPs during early life increases cytotoxicity and animal lethality by strongly inducing ROS production. Early life exposure to AgNPs leads to increased lifetime bioaccumulation later in life and dose-dependent adverse effects on functional aging; e.g., shortened lifespan and loss of stress resistance and intestinal integrity. AgNPs inactivate antioxidant pathways in old, not young, animals, which increase susceptibility to ROS stress. Moreover, pterostilbene (PT), a methoxylated resveratrol, reversed the negative effects of AgNPs on longevity and age-related function by reducing ROS and upregulating antioxidant pathways. Thus, lifetime bioaccumulation of AgNPs accelerates functional aging by inactivating antioxidant pathways and PT reverses these effects. Our findings provide insight into the mechanisms driving the toxicity of bioaccumulated AgNPs and help establish a scientific foundation to guide the safe use of AgNPs.

Chemodynamic therapy (CDT), the ability to transform H2O2 into a highly toxic hydroxyl radical (˙OH) through a Fenton or Fenton like reaction to kill cancer cells, enables selective tumor therapy. However, the effect is seriously limited by the insufficiency of endogenous H2O2 in cancer cells. Additionally, the specific recognition of epitope imprinting plays an important role in targeting cancer cell markers. In this work, we prepared H2O2 self-supplying degradable epitope molecularly imprinted polymers (MIP) for effective CDT, employing fluorescent calcium peroxide (FCaO2) as an imaging probe and a source of H2O2, the exposed peptide in the CD47 extracellular region as the template, copper acrylate as one of the functional monomers and N,N‘-bisacrylylcystamine (BAC) as a cross-linker. MIP with recognition sites can specifically target CD47-positive cancer cells to achieve fluorescence imaging. Under the reduction of glutathione (GSH), the MIP were degraded and the exposed FCaO2 reacted with water to continuously produce H2O2 in the slightly acidic environment in cancer cells. The self-supplied H2O2 produced ˙OH through a Fenton like catalytic reaction mediated by copper ions in the MIP framework, inducing cancer cell apoptosis. Therefore, the MIP nano-platform, which was capable of specific recognition of the cancer cell marker, H2O2 self-supply and controlled treatment, was successfully used for targeted CDT.

Carboxymethyl cellulose (CMC)/pPoly-N-isopropylacrylamide (PNIPAM) hydrogels were prepared using nanoclay as physical cross-linker by UV irradiation. PNIPAM/CMC hydrogels exhibit 3D network structures with high porosity. PNIPAM/CMC hydrogels exhibit not only high water absorption capacity, but also temperature, pH and salt mutiple-responsive swelling performance. Besides, they exhibit reversible swelling behavior in alternate de-ionized water and NaCl solution. Moreover, the fabricated PNIPAM/CMC hydrogels display great compression mechanical property. Then, tetracycline hydrochloride (TCH) was loaded into the PNIPAM/CMC hydrogels to endow their antibacterial ability. TCH loaded PNIPAM/CMC hydrogels exhibit excellent antibacterial activity against E. coli and B. subtilis and good biocompatibility. Thus, the PNIPAM/CMC composite hydrogels with triple stimuli-responsive swelling performances reported herein have great potentials in many biomedical applications.

Lignin-carbohydrate complex (LCC) was proven to possess antioxidant activities. To understand structures and antioxidant activities of LCC, water-soluble LCC-stalk, LCC-sheath and LCC-leaf were isolated from ball-milled wheat straw stalk, sheath and leaf by successive dissolution in LiCl/DMSO solvent, water extraction and purification. LCCs were later structurally characterized by wet chemistry, chromatography and spectroscopy respectively. Their antioxidant activities were evaluated by ferric reducing antioxidant power (FRAP) and DPPH radical scavenging assays. The results showed that three LCCs were carbohydrate-rich (≈70%) and presented relatively narrow molecular weight distribution (PI 2.0). The lignin moieties of LCCs were mainly connected with β-O-4' structures, and phenyl glycoside and γ-ester linkages were main LCC linkages in LCCs. However, guaiacyl units were the predominant lignin units in LCC-stalk and LCC-sheath, while syringyl units were predominant in LCC-leaf. Intermolecular cross-linkages were mainly pCA-bridges in LCC-stalk and FA-bridges in LCC-sheath and LCC-leaf. Besides, LCC-sheath featured higher polysaccharide content exhibited higher molecular weight, fewer LCC linkages and better antioxidant activities (DPPH radical scavenging rate up to 74.91%) than both LCC-stalk (74.55%) and LCC-leaf (64.52%). This work helped to know LCCs in wheat straw well and inspire the application of LCC as potential antioxidants.

Recently, emerging evidence strongly suggested that the activation of interleukin‐27 Receptor α (IL‐27Rα) could modulate different inflammatory diseases. However, whether IL‐27Rα affects allotransplantation rejection is not fully understood. Here, we investigated the role of IL‐27Rα on allorejection both in vivo and in vitro. The skin allotransplantation mice models were established, and the dynamic IL‐27Rα/IL‐27 expression was detected, and IL‐27Rα+ spleen cells adoptive transfer was performed. STAT1/3/5 phosphorylation, proliferation and apoptosis were investigated in mixed lymphocyte reaction (MLR) with recombinant IL‐27 (rIL‐27) stimulation. Finally, IFN‐γ/ IL‐10 in graft/serum from model mice was detected. Results showed higher IL‐27Rα/IL‐27 expression in allografted group compared that syngrafted group on day 10 (top point of allorejection). IL‐27Rα+ spleen cells accelerated allograft rejection in vivo. rIL‐27 significantly promoted proliferation, inhibited apoptosis and increased STAT1/3/5 phosphorylation of alloreactive splenocytes, and these effects of rIL‐27 could be almost totally blocked by JAK/ STAT inhibitor and anti‐IL‐27 p28 Ab. Finally, higher IL‐27Rα+IFN‐γ+ cells and lower IL‐27Rα+IL‐10+ cells within allografts, and high IFN‐γ/low IL‐10 in serum of allorejecting mice were detected. In conclusion, these data suggested that IL‐27Rα+ cells apparently promoted allograft rejection through enhancing alloreactive proliferation, inhibiting apoptosis and up‐regulating IFN‐γ via enhancing STAT pathway. Blocking IL‐27 pathway may favour to prevent allorejection, and IL‐27Rα may be as a high selective molecule for targeting diagnosis and therapy for allotransplantation rejection.

Fructose 1,6-bisphosphatase (FBPase) has attracted substantial interest as a target associated with cancer and type 2 diabetes. Herein, we found that disulfiram and its derivatives can potently inhibit FBPase by covalently binding to a new C128 allosteric site distinct from the original C128 site in APO FBPase. Further identification of the allosteric inhibition mechanism reveals that the covalent binding of a fragment of 214 will result in the movement of C128 and the dissociation of helix H4 (123-128), which in turn allows S123 to more easily form new hydrogen bonds with K71 and D74 in helix H3 (69-72), thereby inhibiting FBPase activity. Notably, both disulfiram and 212 might moderately reduce blood glucose output in vivo. Therefore, our current findings not only identify a new covalent allosteric site of FBPase but also establish a structural foundation and provide a promising way for the design of covalent allosteric drugs for glucose reduction.

Chemical warfare agents, particularly nerve agents such as sarin, are exceptionally harmful and incredibly perilous to people. Thus, the sensitive detection of these gases is indispensable for reducing the risk of chemical weapons. Herein, we fabricated a room-temperature chemiresistive gas sensor based on two-dimensional few-layer tungsten diselenide (WSe2) nanosheets, which were prepared through a facile liquid-phase exfoliation method. The WSe2-based sensor has demonstrated sensitive and selective detection of dimethyl methylphosphonate (DMMP), which is a well-known simulant of the nerve agent sarin. The sensor based on WSe2 nanosheets revealed a high response reaching 8.91% to 10 ppm DMMP with a fast response time of 100 s. Furthermore, the sensor displayed reliable stability, excellent selectivity, and a low theoretical limit of detection of about 122 ppb. The enhanced sensing performance of WSe2 nanosheets can be ascribed to the increase of the specific surface area, which provides more active adsorption sites for DMMP molecules, thereby facilitating the charge transfer process between DMMP molecules and WSe2 nanosheets. Overall, our results indicate that two-dimensional transition metal dichalcogenide materials have the potential for the design and fabrication of high-performance nerve agent sensing devices.

Three unsymmetrical diiodobichalcogenophenes SSeI2, STeI2, and SeTeI2 and a diiodoterchalcogenophene SSeTeI2 were prepared. Grignard metathesis of SSeI2, STeI2, SeTeI2, and SSeTeI2 occurred regioselectively at the lighter chalcogenophene site because of its relatively lower electron density and less steric bulk. Nickel-catalyzed Kumada catalyst-transfer polycondensation of these Mg species provided a new class of side-chain regioregular and main-chain AB-type alternating poly(bichalcogenophene)s—PSSe, PSTe, and PSeTe—through a chain-growth mechanism. The ring-walking of the Ni catalyst from the lighter to the heavier chalcogenophene facilitated subsequent oxidative addition, thereby suppressing the possibility of chain-transfer or chain-termination. More significantly, the Ni catalyst could walk over the distance of three rings (ca. 1 nm)—from a thiophene unit via a selenophene unit to a tellurophene unit—to form PSSeTe, the first ABC-type regioregular and periodic poly(terchalcogenophene) comprising three different types of 3-hexylchalcogenophenes., Three unsymmetrical diiodobichalcogenophenes SSeI2, STeI2, and SeTeI2 and a diiodoterchalcogenophene SSeTeI2 were prepared to synthesize a new class of polychalcogenophenes with precisely controlled sequences by catalyst-transfer polycondensation.

Acceptor–donor–acceptor (A–D–A) non-fullerene electron acceptors (NFEAs) using ladder-type donor structures have become the dominant n-type materials for achieving high-efficiency OSCs. In this work, two isomeric fluorene-based ladder-type structures FCTT (TT-C-F-C-TT) and FTCT (T-C-TFT-C-T) have been designed and synthesized. These two isomeric donors with the different fused-ring arrangement, molecular geometry, and side-chain placement were end-capped with the FIC acceptors to form two NFEAs FCTT-FIC and FTCT-FIC isomeric materials. Compared to FTCT-FIC using the thiophene (T)-terminal donor, FCTT-FIC with the thienothiophene (TT)-terminal donor has more evenly distributed side chains on both sides of the backbone and less steric hindrance near the FIC acceptors, which enables stronger antiparallel π–π packing among the end-groups to create a channel for efficient electron transport, as evidenced by the thin-film GIWAXS measurements. FCTT-FIC displayed a larger optical bandgap and deeper-lying energy levels than its FTCT-FIC isomer. Compared to the PBDB-T:FTCT-FIC device, the PBDB-T:FCTT-FIC device showed a higher PCE of 10.32% with an enhanced Jsc of 19.63 mA cm−2 and an FF of 69.14%. A PM6:FCTT-FIC device using PM6 as a p-type polymer achieved the highest PCE of 12.23%. By introducing PC71BM as the second acceptor to enhance the absorption at shorter wavelengths, optimize the morphology and facilitate electron transport, the ternary-blend PM6:FCTT-FIC:PC71BM (1 : 1 : 0.5 in wt%) device yielded the highest PCE of 13.37% with a Voc of 0.92 V, a higher Jsc of 19.86 mA cm−2, and an FF of 73.2%. This result demonstrated that the TT-terminal ladder-type donor is generally a better molecular design than the corresponding T-terminal ladder-type isomer for the development of new A–D–A NFEAs.

The size of crystal grains in lead halide perovskite thin films remains a vital design feature for durable optoelectronic devices. With larger crystals and reduced grain boundaries per surface area...

Most studies support that saturated fatty acid replacement with polyunsaturated fatty acids (PUFAs) may reduce the risk of cardiovascular diseases (CVDs) and put emphasis on the effects of N-3 PUFAs. The reported relationships between N-6 PUFAs and CVD risks vary. We aimed to examine the associations between N-6 PUFA concentrations and CVD risks. In this community-based prospective cohort study on CVD-free patients at baseline (N = 1835, age: 60.6 ± 10.5 years, women: 44.5%), we measured the fatty acid concentrations in the blood using gas chromatography. Four hundred twenty-four participants developed CVDs during follow up. The total N-6 PUFA concentration was inversely associated with the CVD risk, with a 48% lower risk in the highest N-6 PUFA concentration quartile (hazard ratio = 0.52; P for trend P = 0.03) for predicting incident CVD. Further studies on N-6 PUFAs, diet habits, and their relationships with healthcare are warranted.

Materials for biodevices and bioimplants commonly suffer from unwanted but unavoidable biofouling problems due to the nonspecific adhesion of proteins, cells, or bacteria. Chemical coating or physical strategies for reducing biofouling have been pursued, yet highly robust antibiofouling surfaces that can persistently resist contamination in biological environments are still lacking. In this study, we developed a facile method to fabricate a highly robust slippery and antibiofouling surface by conjugating a liquid-like polymer layer to a substrate. This slippery liquid-attached (SLA) surface was created via a one-step equilibration reaction by tethering methoxy-terminated polydimethylsiloxane (PDMS-OCH3) polymer brushes onto a substrate to form a transparent "liquid-like" layer. The SLA surface exhibited excellent sliding behaviors toward a wide range of liquids and small particles and antibiofouling properties against the long-term adhesion of small biomolecules, proteins, cells, and bacteria. Moreover, in contrast to superomniphobic surfaces and liquid-infused porous surfaces (SLIPS) requiring micro/nanostructures, the SLA layer could be obtained on smooth surfaces and maintain its biofouling resistance under abrasion with persistent stability. Our study offers a simple method to functionalize surfaces with robust slippery and antibiofouling properties, which is promising for potential applications including medical implants and biodevices.

Aluminum alloy has high strength and light weight. It is widely used for aircraft fuselage, propellers and other parts which work under high load conditions. High-quality parts made of aluminum alloy processed by computerized numerical control (CNC) machine often have the characteristics of high cost in their processing. In order to achieve high surface quality and control processing costs, this article takes the workpiece surface hardness and machining energy consumption as targets. Intelligent optimization algorithm is used to find the optimal combination of milling parameters to obtain ideal targets. CNC milling parameter optimization is a multi-parameter, multi-objective, multi-constraint, discrete nonlinear optimization problem which is difficult to solve. For this challenge, an improved NSGA-II is presented, named enhanced population diversity NSGA-II (EPD-NSGA-II). EPD-NSGA-II is improved with the normal distribution crossover, adaptive mutation operator of differential evolution, crowding calculation method considering variance and modified elite retention strategy to achieve enhanced population diversity. 12 test functions are chosen for experimentation to verify the performance of the EPD-NSGA-II. The values of three evaluation indicators show that the proposed approach has good distribution and convergence performance. Finally, the approach is applied in the milling parameters optimization of 7050 aluminum alloy to get the optimal solutions. Results indicate that the EPD-NSGA-II is effective in optimizing the problem of milling parameters.

Paper derived from lignocellulose has great advantages over plastics as packaging material, nevertheless, the poor water- and oil-resistances of paper-derived products limited their application in high-end field. Herein, novel dimer acid-based waterborne polyurethanes (DWPUs) with different content of dimer acid-based polyester polyol (DG) were prepared and used as water- and oil-resistant coating for paper substrate. The effects of DG contents on water- and oil-resistances, mechanical properties and thermal stability of DWPUs coated papers were systematically investigated. When the content of DG reached up to 7 wt% (based on polyester glycol), the paper coated by DWPU exhibited 88.06% decrease in Cobb 60 value, 8.7 times increase in kit rating compared with uncoated paper. Meanwhile, DWPUs coated papers showed good mechanical properties and thermal stability. These improvements are attributed to the flexible long-alkyl chain, and six-ring structure of DWPUs as well as the continuous and homogeneous DWPU-derived membrane on the surface of paper. This study provides a new framework for the preparation of high quality, multifunctional, environmentally friendly water- and oil-resistant coatings for paper substrates.

Background Matrix metalloproteinase 9 (MMP9) plays a pivotal role in mammary ductal morphogenesis, angiogenesis, and glandular tissue architecture remodeling. However, the molecular mechanism of MMP9 expression in mammary epithelial cells of dairy cows remains unclear. The current study aimed to explore the underlying mechanism of MMP9 expression. Results In this study, to determine whether the PI3K/AKT/mTOR/NF-κB signaling pathway participates in the regulation of MMP9 expression, we treated mammary epithelial cells with specific pharmacological inhibitors of PI3K (LY294002), mTOR (Rapamycin), or NF-κB (Celastrol), respectively. Western blotting results indicated that LY294002, Rapamycin, and Celastrol markedly decreased MMP9 expression and P65 nuclear translocation. Furthermore, we found that NF-κB (P65) overexpression resulted in elevated expression of MMP9 protein and activation of MMP9 promoter. In addition, we observed that Celastrol markedly decreases P65-overexpression-induced MMP9 promoter activity. Moreover, the results of the promoter assay indicated that the core regulation sequence for MMP9 promoter activation may be located -80bp to -420bp downstream from the transcription start site. Conclusions These observations indicated that the PI3K/AKT/mTOR signaling pathway is involved in MMP9 expression by regulating MMP9 promoter activity via NF-κB in the mammary epithelial cells of dairy cows.

Reported herein is an intramolecular dehydrogenative coupling of two inert aryl C-H bonds for the synthesis of aporphine analogues. The process represents a novel tool for the preparation of aporphines via palladiun-catalyzed C-H bond activation. The present reaction is compatible with various functional groups, and the coupling products have been further applied for the synthesis of natural products aporphine and zenkerine.

Di-(2-ethylhexyl) phthalate (DEHP) has been used as a plasticizer for decades. Recent research evidence has revealed that environmental factors can alter vascular endothelial cell function through DNA methylation. However, no previous in vitro/vivo study has explored the role of DNA methylation in DEHP exposure and vascular endothelial cell function. In the present study, we enrolled 793 subjects aged 12 to 30 years from a young Taiwanese cohort to investigate the association between mono-2-ethylhexyl phthalate (MEHP) (urine DEHP metabolite), 5mdC/dG (global DNA methylation marker), CD31+/CD42a−, CD31+/CD42a+, and CD14 (apoptotic microparticles of vascular cells). In multiple regression analyses, the levels of mono-2-ethylhexyl phthalate (MEHP) were positively associated with 5mdC/dG and all three apoptotic microparticles. In addition, the regression coefficients between MEHP and the three types of apoptotic microparticles were higher when the 5mdC/dG levels were higher than the 50th percentile. In the structural equation model (SEM), we found that MEHP had a direct correlation with CD31+/CD42a− and an indirect association with CD31+/CD42a− through the effect of 5mdC/dG. Moreover, MEHP only had a direct association with CD31+/CD42a+ and an indirect association with CD14. In conclusion, the results show that global DNA methylation mediates the relationship between MEHP and apoptotic microparticles. These findings indicate that DNA methylation may play a role in the pathogenesis of DEHP-induced endothelial cell apoptosis in humans. Further studies are needed to clarify the causal inference.

(1) Background: In previous research, higher levels of urine heavy metals, especially lead and cadmium, have been associated with increased cardiovascular risk. However, there is no information linking exposure to heavy metal to endothelial and platelet microparticles (EMPs and PMPs), particularly in the younger population, which are novel biomarkers of endothelial dysfunction. (2) Methods: From a nationwide database, which was incepted in 1992–2000, screening for renal health among Taiwanese school children, a total of 789 subjects were recruited. Cross-sectional analysis was performed to evaluate the association between serum EMPs/PMPs and urine iron, nickel, copper, cadmium, lead, chromium, manganese, and zinc levels in the adolescent and young adult population. (3) Results: After we adjusted the conventional cardiovascular risk factors, CD31+/CD42a− and CD31+/CD42a+ counts, in subjects’ serum, respective markers of EMP and PMP displayed a significant positive dose-response relationship with urinary lead and cadmium levels. Higher quartiles of urine lead and cadmium levels were associated with an increased risk of higher EMPs/PMPs (≥75th percentile) in a multivariate logistic regression model. (4) Conclusion: Higher urinary lead and cadmium concentrations are strongly associated with endothelium–platelet microparticles in this adolescent and young adult population, which could help explain, in part, the mechanism through which heavy metal exposure results in cardiotoxicity.

The aim of this study was to use a network meta-analysis (NWA) to evaluate the relative efficacy and safety of various neuraminidase inhibitors (NAIs) in reducing the duration of influenza symptoms, and thereby, informing the selection of suitable therapeutic regimens for patients with influenza. We conducted a systematic review of randomized controlled trials comparing the clinical effects of four NAIs administered to patients with influenza and placebo. Relevant studies were found in the PubMed and Cochrane databases. Unpublished studies were collected from the ClinicalTrials.gov registry and through hand searching. We carried out NWA to compare the different regimens with each other and across subgroups of age and medical status (high-risk patients). A total of 58 two-arm studies were identified. Five regimens were efficacious in reducing the time to alleviation of influenza symptoms in all populations; this efficacy was comparable. No significant improvements were seen in combination therapy groups. The mean difference in the time to alleviation of symptoms ranged from 12.78 to 19.51 h. According to the summarized mean difference and surface under the cumulative ranking curve (SUCRA), peramivir (SUCRA = 82.6%), zanamivir (SUCRA = 64%), and oseltamivir (SUCRA = 55.1%) were the three top-ranking drugs for treating influenza. Zanamivir and peramivir were the preferred pharmacologic intervention among all investigated interventions based on the calculated "value preference of SUCRA." This study is a network meta-analysis to explore the therapeutic effects of NAIs in patients with influenza. Peramivir might be the best choice for reducing the time to alleviation of symptoms.

The proper treatment of lollingite is of great significance due to its rapid oxidation leading to release of arsenic into the environment. Herein, a green multi-solid waste geopolymer, consisting of red mud, metakaolin, blast furnace slag, and flue gas desulfurization gypsum, was developed. The obtained red mud-metakaolin-based (RMM) geopolymer demonstrated good arsenic retention capability. The results showed that the replacement of SO42- in ettringite with AsO42- via ion exchange, formation of Ca-As and Fe-As precipitates, and physical encapsulation with aluminosilicate gel were the main mechanisms that prevented the release of arsenic. Further dissolution of ettringite in RMM was alleviated by adding a suitable amount of Ca(OH)2 and controlling the pH of the leachate. TCLP results verified that RMM materials possessed an outstanding ability to stabilize arsenic, with a leaching rate below the permitted value of 5 mg/L for safe disposal. The low leachability of the RMM geopolymers ( 15 MPa) and low arsenic leaching concentration (

It is well known that cancer incidence and death rates have been growing, but the development of cancer theranostics and therapeutics has been a challenging work. Recently, nucleic acid probe–based fluorescent sensing and imaging have achieved remarkable improvements in a variety of cancer management techniques, credited to their high sensitivity, good tolerance to interference, fast detection, and high versatility. Herein, nucleic acid probe–based fluorescent sensing and imaging are labeled with advanced fluorophores, which are essential for fast and sensitive detection of aberrant nucleic acids and other cancer-relevant molecules, consequently performing cancer early diagnosis and targeted treatment. In this review, we introduce the characteristics of nucleic acid probes, summarize the development of nucleic acid probe–based fluorescent sensing and imaging, and prominently elaborate their applications in cancer diagnosis and treatment. In discussion, some challenges and perspectives are elaborated in the field of nucleic acid probe–based fluorescent sensing and imaging.

Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide; congenital CMV may lead to significant mortality, morbidity, or long-term sequelae, such as sensorineural hearing loss. The current study presents a newly designed surface plasmon resonance (SPR) biosensor for CMV-specific microRNAs that does not involve extra care for receptor immobilization or treatment to prevent fouling on bare gold surfaces. The modification-free approach, which utilizes a poly-adenine [poly(A)]-Au interaction, exhibited a high affinity that was comparable to that of the gold-sulfur (Au-S) interaction. In addition, magnetic nanoparticles (MNPs) were used to separate the analyte from complex sample matrixes that significantly reduced nonspecific adsorption. Moreover, the MNPs also played an important role in SPR signal amplification due to the binding-induced change in the refractive index. Our SPR biosensing platform was used successfully for the multi-detection of the microRNAs, UL22A-5p, and UL112-3p, which were associated with CMV. Our SPR biosensor offered the detection limits of 108 fM and 24 fM for UL22A-5p and UL112-3p, respectively, with an R2 of 0.9661 and 0.9985, respectively. The precision of this biosensor has an acceptable CV (coefficient of variation) value of

In this work, the operation of membrane-assisted seeded batch crystallization is modeled for five substances: potassium nitrate, potassium sulfate, pentaerythritol, succinic acid, and potassium alum. The effect of seed loading, seed size, and water removal rate on product crystal size is investigated. Seed loading and seed size were found to have a significant impact on product crystal size for a given batch time and product yield. Trajectories for the optimal water removal rate versus time were also determined. Overall, the results show that membrane-assisted crystallization behaves similarly to other types of crystallization in terms of product crystal size and size distribution while having the potential to reduce cost and equipment size.

[Image: see text] The intracellular delivery of biomolecules is of significant importance yet challenging. In addition to the conventional delivery of nanomaterials that rely on biochemical pathways, vertical nanowires have been recently proposed to physically penetrate the cell membrane, thus enabling the direct release of biomolecules into the cytoplasm circumventing endosomal routes. However, due to the inherent attachment of the nanowires to a planar 2D substrate, nanowire cell penetrations are restricted to in vitro applications, and they are incapable of providing solution-based delivery. To overcome this structural limitation, we created polyethylenimine-functionalized microparticles covered with nanospikes, namely, “spiky particles”, to deliver biomolecules by utilizing the nanospikes to penetrate the cell membrane. The nanospikes might penetrate the cell membrane during particle engulfment, and this enables the bound biomolecules to be released directly into the cytosol. TiO(2) spiky particles were fabricated through hydrothermal routes, and they were demonstrated to be biocompatible with HeLa cells, macrophage-like RAW cells, and fibroblast-like 3T3-L1 cells. The polyethylenimine-functionalized spiky particles provided direct delivery of fluorescent siRNA into cell cytosol and functional siRNA for gene knockdown as well as successful DNA plasmid transfection which were difficult to achieve by using microparticles without nanospikes. The spiky particles presented a unique direct cell membrane penetrant vehicle to introduce biomolecules into cell cytosol, where the biomolecules might bypass conventional endocytic degradation routes.

Ultrathin Co3O4 nanosheets are excellent candidate materials for high performance chemiresistive gas sensors. However, the restacking and aggregation of nanosheets during sensor fabrication greatly impact the sensing response. In this work, by adding the structure-directing agent of glucose, hierarchical flower-like Co3O4 nanostructures assembled by porous nanosheets were synthesized through hydrothermal method with subsequent calcination treatment to further improve the sensing performance. The fabricated hierarchical flower-like Co3O4 sensor exhibited the highest response of 48.1 toward 100 ppm acetone at 130 °C, which was 7.2 times higher than the Co3O4 microplates synthesized without glucose. The excellent long-term stability and selectivity of gas sensors were further validated and the theoretical limit of detection was experimentally calculated to be as low as 200 ppb. Flower-like Co3O4 nanostructures for acetone gas sensor with good performance provide a promising candidate to fabricate high performance gas sensor for safety monitoring and health care.

Cross-sectional studies have described an association between exposure to phthalate esters and cardiovascular risk factors. However, the association with coronary heart disease (CHD) is still unclear. A total of 180 subjects randomly selected from 336 CHD patients, and 360 age- and sex-matched non-CHD controls were included from 2008 to 2011. Urinary metabolites of phthalate esters were measured by liquid chromatography–tandem mass spectrometry. The geometric means of urinary phthalates metabolites were significantly higher for the three Di-(2-ethylhexyl)-phthalate (DEHP) metabolites, mono‐2‐ethylhexyl phthalate (MEHP), mono‐(2‐ethyl‐5‐hydroxyhexyl) phthalate, and mono‐(2‐ethyl‐5‐oxohexyl) phthalate among CHD patients in-hospital than those of being discharged. Excluding 89 CHD patients of in-hospital and hospital discharge within 2 days, we found the urinary concentrations of MEHP, mono‐n‐butyl phthalate (MnBP), and mono-isobutyl phthalate (MiBP) of 91 CHD patients discharged ≥ 3 days were higher than those of controls. Among 451 participants, those with higher tertile levels of urinary MEHP, MnBP, and MiBP showed an increased risk for CHD compared to those with lowest tertile levels; the corresponding odds ratios (95% CI) were 2.77 (1.22–6.28), 2.90 (1.32–6.4), and 3.19 (1.41–7.21), respectively, after adjustment for confounders. Higher levels of hs-CRP, fibrinogen, and D-dimer were linked with increased levels of all DEHP metabolites in CHD patients. In conclusion, exposure to DEHP and dibutyl phthalates was positively associated with CHD and this relationship may be probably mediated via atherothrombosis.

In the family of alkylphenolic compounds, 4-tertiary-Octylphenol (4-t-OP) is extensively used in many products. In animal and in vitro studies, 4-t-OP exposure has been linked to cardiovascular disease (CVD) risk factors; however, there are no previous human epidemiological studies. In this study, 886 subjects were recruited from a cohort of Taiwanese adolescents and young adults to study the relationship between serum levels of 4-t-OP, CVD risk factors, and common carotid artery intima-media thickness (CIMT). The geometric mean (SD) 4-t-OP concentration was 32.52 (1.71) ng/mL. We found that serum levels of 4-t-OP were negatively associated with markers of glucose homeostasis (insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β)), z score of body mass index (BMI z score) and CIMT but were positively associated with lipid profiles (high density lipoprotein cholesterol (HDL-C), Apolipoprotein A1). A one-unit elevation in natural log-transformed 4-t-OP (ng/mL) was negatively correlated with CIMT (mm) (β = -0.029, SE = 0.003, P < 0.001) in multiple linear regression analyses. The relationship between 4-t-OP and CIMT remained the same in all subgroups or if bisphenol A (BPA) was considered a covariate. In this study, we observed that higher levels of 4-t-OP levels were negatively correlated with markers of glucose homeostasis, BMI z score, and CIMT; positively correlated with lipid profiles (HDL-C and apolipoprotein A) in this cohort. Future research on exposure to 4-t-OP and CVD risk factors is warranted.

OBJECTIVE To investigate whether the effect of loureirin B plus capsaicin on tetrodotoxin-resistant (TTX-R) sodium channel. METHODS By using whole-cell patch-clamp recordings, in acutely isolated dorsal root ganglion (DRG) neurons, the combined effects of loureirin B and capsaicin on TTX-R sodium channel were observed. Based on the data, the interaction between loureirin B and capsaicin in their modulation on TTX-R sodium channel was assessed. RESULTS Loureirin B could not induce transient inward TRPV1 current. Capsazepine, a transient receptor potential vanilloid l (TRPV1) antagonist, could not attenuate the block of 0.64 mmol/L loureirin B on TTX-R sodium channel. There was no significant difference (P > 0.05) between IC50 of loureirin B (0.37 mmol/L) on TTX-R sodium channel in capsaicin-sensitive DRG neurons and that (0.38 mmol/L) in capsaicin-insensitive DRG neurons. However, there was a significant difference (P CONCLUSION Loureirin B plus capsaicin could produce double blockage on TRPV1 and modulation on TTX-R sodium channel. The action of loureirin B on TTX-R sodium channel was independent of TRPV1 but similar with that of capsaicin on TTX-R sodium channel in capsaicin-insensitive DRG neurons.