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Voltage-gated sodium channel Nav1.7 robustly expressed in peripheral nociceptive neurons has been considered as a therapeutic target for chronic pain, but there is no selective Nav1.7 inhibitor available for therapy of chronic pain. Ralfinamide has shown anti- nociceptive activity in animal models of inflammatory and neuropathic pain and is currently under phase III clinical trial for neuropathic pain. Based on ralfinamide, a novel small molecule (S)-2-((3-(4-((2-fluorobenzyl) oxy) phenyl) propyl) amino) propanamide (QLS-81) was synthesized. Here, we report the electrophysiological and pharmacodynamic characterization of QLS-81 as a Nav1.7 channel inhibitor with promising anti-nociceptive activity. In whole-cell recordings of HEK293 cells stably expressing Nav1.7, QLS-81 (IC 50 at 3.5 ± 1.5 μM) was ten-fold more potent than its parent compound ralfinamide (37.1 ± 2.9 μM) in inhibiting Nav1.7 current. QLS-81 inhibition on Nav1.7 current was use-dependent. Application of QLS-81 (10 μM) caused a hyperpolarizing shift of the fast and slow inactivation of Nav1.7 channel about 7.9 mV and 26.6 mV, respectively, and also slowed down the channel fast and slow inactivation recovery. In dissociated mouse DRG neurons, QLS-81 (10 μM) inhibited native Nav current and suppressed depolarizing current pulse-elicited neuronal firing. Administration of QLS-81 (2, 5, 10 mg· kg −1 · d −1 , i.p.) in mice for 10 days dose- dependently alleviated spinal nerve injury-induced neuropathic pain and formalin-induced inflammatory pain. In addition, QLS-81 (10 μM) did not significantly affect ECG in guinea pig heart ex vivo; and administration of QLS-81 (10, 20 mg/kg, i.p.) in mice had no significant effect on spontaneous locomotor activity. Taken together, our results demonstrate that QLS-81, as a novel Nav1.7 inhibitor, is efficacious on chronic pain in mice, and it may hold developmental potential for pain therapy.

It is difficult for a cellulose paper with intrinsic high flammability to acquire high fire retardancy. Benefitting from the successful preparation of ultralong hydroxyapatite (HAP) nanowires, nonc...

Simultaneous enhancement in water flux and removal efficiency during the filtration process remains a big challenge for separation membranes. The porous structure of the filter paper can provide many channels for water transportation, but the separation performance is generally poor. The purpose of this study is to develop a new kind of filter paper consisting of ultralong hydroxyapatite (HAP) nanowires, cellulose fibers (CFs) and double metal oxide (LDO) nanosheets, and to achieve the simultaneous enhancement of both water flux and removal efficiency for high-performance dye separation. In this work, a novel kind of LDO/HAP/CF nanocomposite filter paper consisting of ultralong HAP nanowires and CFs and LDO nanosheets has been developed for rapid water filtration and highly efficient dye adsorption. Positively charged LDO nanosheets can adsorb on the surface of negatively charged ultralong HAP nanowires and embed in the porous networked structure of the LDO/HAP/CF nanocomposite filter paper, which can provide a porous structure for rapid water transportation and can adjust the pore size of the nanocomposite filter paper. As a result, the pure water flux of the LDO/HAP/CF nanocomposite filter paper can be adjusted. The optimized pure water flux of the LDO/HAP/CF nanocomposite filter paper can reach 783.6 L m-2 h-1 bar-1, which is 1.51 times that of the HAP/CF filter paper without LDO nanosheets (518.6 L m-2 h-1 bar-1). More importantly, the adsorption capacity of LDO nanosheets is high for dye molecules, the rejection percentage of Congo red (CR) by the as-prepared HAP/CF filter paper is only 59.8%, and its water flux is 534.7 L m-2 h-1 bar-1. The optimized rejection percentage and water flux of the LDO/HAP/CF nanocomposite filter paper for CR are significantly enhanced (98.3% and 736.8 L m-2 h-1 bar-1, respectively) compared to those of the HAP/CF filter paper. The size of LDO nanosheets has a significant effect on the water flux and dye rejection percentage of the LDO/HAP/CF nanocomposite filter paper. The as-prepared LDO/HAP/CF nanocomposite filter paper is promising for the applications in highly efficient purification of wastewater containing dye molecules.

Coupling reagents play crucial roles in the iterative construction of amide bonds for the synthesis of peptides and peptide-based derivatives. The novel DIC/Oxyma condensation system featured with the low risk of explosion displayed remarkable abilities to inhibit racemization, along with efficient coupling efficiency in both manual and automated syntheses. Nevertheless, an ideal reaction molar ratio in DIC/Oxyma condensation system and the moderate reaction temperature by manual synthesis remain to be further investigated. Herein, the synthetic efficiencies of different reaction ratios between DIC and Oxyma under moderate reaction temperature were systematically evaluated. The robustness and efficiency of DIC/Oxyma condensation system are validated by the rapid synthesis of linear centipede toxin RhTx. Different folding strategies were applied for the construction of disulfide bridges in RhTx, which was further confirmed in assays of circular dichroism and patch-clamp electrophysiology evaluation. This work establishes the DIC/Oxyma-based accelerated synthesis of peptides under moderate condensation conditions, which is especially useful for the manual synthesis of peptides. Besides, the strategy presented here provides robust technical supports for the large-scale synthesis and oxidative folding of RhTx.

A filter paper with a large number of nanopores and channels is vital for highly efficient nanofiltration to significantly increase the water flux without sacrificing the separation efficiency. In ...

Objective To study the changes of white matter tracts in precentral gyrus and postcentral gyrus during normal brain aging process by analyzing fractional anisotropy (FA) values obtained from diffusion tensor imaging (DTI) technology. Methods Magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were conducted on 120 healthy right‐handed subjects. The subjects were separated into four age groups, namely Young Male/Female (45 years old). Each subject undertakes routine MRI and DTI scans. Left/right precentral and left/right postcentral gyrus are automatically detected on the image. The area for region of interest (ROI) is set to be 18 ± 2 mm2. Results For each age group, the FA values of white matter in precentral gyrus and postcentral gyrus are statistically different (p, The FA values of precentral gyrus and postcentral gyrus are statistically different across genders, age groups, and hemispheres. Additionally, the FA values of both precentral gyrus and postcentral gyrus decrease over time, which is a strong indication of aging.

A new kind of environmentally friendly filter paper based on ultralong hydroxyapatite nanowires (HAPNWs) and cellulose fibers (CFs) with excellent filtration and adsorption properties has been developed for the application in high-performance water purification. The use of polyamidoamine-epichlorohydrin (PAE) resin increases the wet mechanical strength of the as-prepared HAPNW/CF filter paper. The addition of CFs enhances the mechanical strength of the HAPNW/CF filter paper. Owing to the porous structure and superhydrophilicity of the as-prepared HAPNW/CF filter paper, the pure water flux is as high as 287.28 L m-2 h-1 bar-1 under cross-flow conditions, which is about 3200 times higher than that of the cellulose fiber paper with addition of PAE. More importantly, the as-prepared HAPNW/CF filter paper shows superior performance in the removal of TiO2 nanoparticles (>98.61%) and bacteria (up to 100%) in water by the size exclusion and blocking effect. In addition, the HAPNW/CF filter paper also exhibits high adsorption capacities for methyl blue (273.97 mg g-1) and Pb2+ ions (508.16 mg g-1). The adsorption mechanism of the HAPNW/CF filter paper is investigated. The as-prepared environmentally friendly HAPNW/CF filter paper with both excellent filtration and adsorption properties has promising application in high-performance water purification to tackle the worldwide water scarcity problem.

In the history of civilization, Xuan paper with its superior texture, durability and suitable characteristics for writing and painting, has played an important role in the dissemination of culture and art. Xuan paper has won the reputation of "the king of paper that lasts for 1000 years" and was inscribed on the Representative List of the Intangible Cultural Heritage of Humanity by the Educational, Scientific and Cultural Organization of the United Nations in 2009. However, the surface of the commercial unprocessed Xuan paper has a large number of large-sized pores with a poor resistance to water, allowing ink droplets to easily spread during the writing and painting process. In this study, we report a new kind of nanocomposite Xuan (HNXP) paper comprising ultralong hydroxyapatite (HAP) nanowires and plant cellulose fibers with unique ink wetting performance, high whiteness and excellent durability. The as-prepared HNXP paper sheets with various weight ratios of ultralong HAP nanowires ranging from 10% to 100% are all superhydrophilic with a water contact angle of zero. In contrast, the ink contact angle of the HNXP paper can be well controlled by adjusting the weight ratio of ultralong HAP nanowires, and the ink contact angle of the HNXP paper increases with increasing weight ratio of ultralong HAP nanowires. The experimental results show the unique ink wetting behavior of the as-prepared HNXP paper, which is absent in the traditional Xuan paper. This new kind of nanocomposite Xuan paper comprising ultralong hydroxyapatite nanowires and plant cellulose fibers is promising for applications in calligraphy and painting arts.

Xuan paper is a unique kind of high-quality paper originating in ancient China; it enjoys a great reputation as “the king of paper that lasts for 1000 years” and was inscribed on the Representative...

Wallpaper with multiple functions, such as fire resistance and an automatic alarm in fire disasters, will be attractive for the interior decoration of houses. Herein, we report a smart fire alarm wallpaper prepared using fire-resistant inorganic paper based on ultralong hydroxyapatite nanowires (HNs) and graphene oxide (GO) thermosensitive sensors. At room temperature, the GO thermosensitive sensor is in a state of electrical insulation; however, it becomes electrically conductive at high temperatures. In a fire disaster, high temperature will rapidly remove the oxygen-containing groups of GO, leading to the transformation process of GO from an electrically insulated state into an electrically conductive one. In this way, the alarm lamp and alarm buzzer connected with the GO thermosensitive sensor will send out the alerts to people immediately for taking emergency actions. After the surface modification with polydopamine of GO (PGO), the sensitivity and flame retardancy of the GO thermosensitive sensor are further improved, resulting in a low responsive temperature (126.9 °C), fast response (2 s), and sustained working time in the flame (at least 5 min). Compared with combustible commercial wallpaper, the smart fire alarm wallpaper based on HNs and GO (or PGO) is superior owing to excellent nonflammability and high-temperature resistance of HNs, which can protect the GO (or PGO) thermosensitive sensor from the flames. The smart fire alarm wallpaper can be processed into various shapes, dyed with different colors, and printed with the commercial printer and thus has promising applications in high-safety interior decoration of houses.

How to survive under various harsh working conditions is a key challenge for flexible electronic devices because their performances are always susceptible to environments. Herein, we demonstrate the novel design and fabrication of a new kind of the all-weather flexible electrically conductive paper based on ultralong hydroxyapatite nanowires (HNs) with unique combination of the superhydrophobic surface, electrothermal effect, and flame retardancy. The superhydrophobic surface with water repellency stabilizes the electrically conductive performance of the paper in water. For example, the electrical current through the superhydrophobic paper onto which water droplets are deposited shows a little change (0.38%), and the electrical performance is steady as well even when the paper is immersed in water for 120 s (just 3.65% change). In addition, the intrinsic electrothermal effect of the electrically conductive paper can efficiently heat the paper to reach a high temperature, for example, 224.25 °C, within 10 s. The synergistic effect between the electrothermal effect and superhydrophobic surface accelerates the melting and removal of ice on the heated electrically conductive paper. Deicing efficiency of the heated superhydrophobic electrically conductive paper is ∼4.5 times that of the unheated superhydrophobic electrically conductive paper and ∼10.4 times that of the heated superhydrophilic paper. More importantly, benefiting from fire-resistant ultralong HNs, thermally stable Ketjen black, and Si-O backbone of poly(dimethylsiloxane), we demonstrate the stable and continuous service of the as-prepared electrically conductive paper in the flame for as long as 7 min. The electrical performance of the electrically conductive paper after flame treatment can maintain as high as 90.60% of the original value. The rational design of the electrically conductive paper with suitable building materials and structure demonstrated here will give an inspiration for the development of new kinds of all-weather flexible electronic devices that can work under harsh conditions.

High-strength flexible inorganic paper with fire-resistant and adiabatic properties is highly demanded in various high-temperature applications. However, constructing inorganic paper that not only has high strength and high flexibility at room temperature but also can prevent the high-temperature-induced friability is still a great challenge. Inspired by the hierarchical structure and excellent mechanical properties of the tooth enamel, we have developed a systematic approach for the bottom-up fabrication of multi-hierarchical fire-resistant hydroxyapatite (HAP) nanowire paper with balanced tensile strength and flexibility that includes four steps: (1) the synthesis of monodisperse HAP nanowires from the molecular level to the nanoscale; (2) the self-assembly of HAP nanowires into long fibers and two-dimensional (2D) nanowire networks from the nanoscale to the mesoscale; (3) the layered assembly of 2D nanowire networks into the highly flexible high-strength fire-resistant paper from the mesoscale to the macroscale; (4) reinforcing the HAP nanowire paper with inorganic additives to enhance the tensile strength and to overcome the high-temperature-induced pulverization. By adopting this strategy, the mechanical properties of the fire-resistant HAP nanowire paper are greatly improved. The experimental results show that the tensile strength of the as-prepared HAP nanowires-based inorganic paper is greatly enhanced to ≈15 MPa, which is close to that of the commercial copying paper, and the A4-sized HAP nanowires-based inorganic paper is highly flexible and can be directly printed using a commercial printer. Owing to the synergistic effect of all components and the unique hierarchical structure, the as-prepared fire-resistant HAP nanowire paper can also preserve well its high flexibility even under high-temperature conditions.

Fine particulate matter (PM) air pollution has been attracting much attention due to its great threat to human health. Herein, we report a new kind of air filter paper with high removal efficiencies for PM2.5 and PM10 prepared using ultralong hydroxyapatite (HAP) nanowires and cotton (CT) fibers as building blocks through a simple vacuum filtration process. Flexible and biocompatible ultralong HAP nanowires with lengths over 200 μm and diameters of approximately 20 nm are employed for significant improvement of the air filtration performance of commercial CT fibers. The ultralong HAP nanowires intertwine with CT fibers and form the highly porous HAP/CT air filter paper. In addition, by optimizing the proportion of HAP and CT, the as-prepared HAP/CT air filter paper exhibits high removal efficiencies of over 95% for PM2.5 and PM10; more importantly, it shows a lower pressure drop and a smaller thickness than a commercial breathing mask. Moreover, the fabrication of a large-sized HAP/CT air filter paper with desirable properties through a commercial sheet former is demonstrated. As a proof-of-concept, a homemade breathing mask is fabricated by imbedding the HAP/CT air filter paper into a commercial breathing mask. Furthermore, benefiting from the unique characteristics of ultralong HAP nanowires, other functions such as antibacterial activity can be achieved by the immobilization of silver nanoparticles as the representative bactericide, enabling the fabrication of multifunctional air filter paper. The experimental results suggest that the ultralong HAP nanowire-based air filter paper is promising for various applications in the environmental field.

Up to date, the scaled-up production and large-area applications of the superhydrophobic coatings are limited because the complicated procedures, environmentally harmful fluorinated compounds, restrictive substrates, expensive equipments and raw materials are usually involved in the fabrication process. Herein, we report the facile, low-cost and green production of the superhydrophobic coatings based on hydroxyapatite nanowire bundles (HNBs). Hydrophobic HNBs are synthesized by one-step solvothermal method using oleic acid as the structure-directing and hydrophobic agent. During the reaction process, highly hydrophobic C-H groups of oleic acid molecules can be in-situ attached to the surface of HNBs by the chelate interaction between Ca2+ ions and carboxylic groups. This facile synthesis method allows the scaled-up production of HNBs up to ~8 litres, which is the largest production scale of the superhydrophobic paint based on HNBs ever reported. In addition, we also show the design of the 100-litre reaction system. The HNBs can be coated on any substrate with an arbitrary shape by the spray coating technique. The self-cleaning ability in air and oil, high-temperature stability, and excellent mechanical durability of the as-prepared superhydrophobic coatings are demonstrated. More importantly, The HNBs are coated on the large-sized practical objects to form large-area superhydrophobic coatings.

Separators play a pivotal role in the electrochemical performance and safety of lithium-ion batteries (LIBs). The commercial microporous polyolefin-based separators often suffer from inferior electrolyte wettability, low thermal stability, and severe safety concerns. Herein, a novel kind of highly flexible and porous separator based on hydroxyapatite nanowires (HAP NWs) with excellent thermal stability, fire resistance, and superior electrolyte wettability is reported. A hierarchical cross-linked network structure forms between HAP NWs and cellulose fibers (CFs) via hybridization, which endows the separator with high flexibility and robust mechanical strength. The high thermal stability of HAP NW networks enables the separator to preserve its structural integrity at temperatures as high as 700 °C, and the fire-resistant property of HAP NWs ensures high safety of the battery. In particular, benefiting from its unique composition and highly porous structure, the as-prepared HAP/CF separator exhibits near zero contact angle with the liquid electrolyte and high electrolyte uptake of 253%, indicating superior electrolyte wettability compared with the commercial polyolefin separator. The as-prepared HAP/CF separator has unique advantages of superior electrolyte wettability, mechanical robustness, high thermal stability, and fire resistance, thus, is promising as a new kind of separator for advanced LIBs with enhanced performance and high safety.

Sorafenib, a small inhibitor of tyrosine protein kinases, is currently the standard chemotherapy drug for the treatment of advanced hepatocellular carcinoma (HCC). Although sorafenib improves the survival of HCC patients, its efficacy is not optimal and requires further improvement. Capsaicin, the major active component of chili peppers from the genus Capsicum, is not only the agonist of TRPV1 channel, but also displays antitumor activity and enhances the sensitivity of cancer cells to cytotoxic drugs. In this study, we investigated the antitumor effects of combined sorafenib and capsaicin on HCC cells in vitro and xenograft tumors. Treatment with capsaicin alone dose-dependently inhibited the proliferation of the HCC cell lines PLC/PRF/7, HuH7 and HepG2 with IC(50) values of 137, 108 and 140.7 μmol/L, respectively. No obvious expression of TRPV1 channel was detected in the 3 HCC cell lines and TRPV1 channel blockers did not alleviate the cytotoxicity of capsaicin. By contrast, combining capsaicin and sorafenib significantly enhanced the suppression on cell proliferation, achieving a high-level synergistic effect (inhibition rates over 50%) and promoting HCC cell apoptosis. In nude mice with PLC/PRF/5 xenografts, combined administration of capsaicin and sorafenib significantly enhanced the suppression on tumor growth without apparent gross toxicity compared to either agent alone. Mechanistically, capsaicin (10–200 μmol/L) dose-dependently increased the levels of phosphorylated ERK (p-ERK) in PLC/PRF/5 cells, thus leading to enhanced sorafenib sensitivity and a synergistic suppression on the tumor cells. Taken together, our results suggest that capsaicin-increased phosphorylation of ERK contributes to the enhanced antitumor activity of sorafenib, and capsaicin may be useful in improving the efficacy of sorafenib for the treatment of HCC.

An innovative method for making a new kind of highly flexible, fireproof, inorganic, nanocomposite paper made from glass fibers (GFs) coated with network-structured hydroxyapatite ultralong nanowires (NS-HANWs) is reported. The NS-HANW/GF paper is fireproof, high-temperature resistant, highly flexible, highly exquisite, and smooth, which is comparable to high-quality advanced coated paper. The most incredible characteristic of the NS-HANW/GF paper is its incombustibility. The as-prepared NS-HANW/GF paper, with the addition of optimized inorganic additives, has high mechanical properties (tensile strength ≈16 MPa) and the tensile strength is nearly 15 times that of GF paper. In addition, the NS-HANW/GF paper exhibits a high biocompatibility, owing to the coating effect of NS-HANWs on GFs. Thermal analysis indicates that the NS-HANW/GF paper has high thermal stability at high temperatures up to 1000 °C. Competitive to conventional insulation materials, the NS-HANW/GF paper exhibits a low thermal conductivity and excellent heat insulation performance. Experiments show that the NS-HANW/GF paper is promising for application in the protection layer of fire-retardant fiber-optic cable. The NS-HANW/GF paper can also be used as printing, copying, or writing paper; nonflammable China paper; fire-retardant wallpaper; specialty fireproof paper; and so on.

In order to analyze the characteristics of pile-soil stress ratio of the composite foundation of cement-soil mixing pile under flexible foundation, this paper points out the displacement mode of friction pile; According to the deformation characteristic of friction pile, ascertain the neutral point of composite foundation. And this paper also derives the exact formula about length-stress ratio which addresses the problem of soft soil foundation according to the deformation co-ordination conditions of the pile composite foundation. The calculation of actual example proves that the formula about pile-soil stress ratio is in accordance with actual measurement number. The pile-soil stress ratio which addresses the problem of soft soil foundation is generally between 2~4. If other conditions keep invariable, pile-soil stress ratio become big when cushion modulus become big. Cushion modulus effect the length-stress ratio greatly.

An alternative method for measuring normal-incidence sound absorption coefficients of materials or structures was examined, that is based on the echo-pulse method in a circular tube. The so-called Butterworth impulse was generated in a standing wave tube with a flat frequency response over a wide frequency range. The inverse filtering principle was adopted to compensate for the loudspeaker frequency response at higher and lower frequencies. Two types of acoustical material and structure were employed: glassfibre material and tube exit. Through comparison with the traditional, well-established transfer function method, it can be seen that the new method can be as accurate as the established method. The main errors of this new method result from the accuracy of the measurement of the amplitude of the reflection coefficient of the sample.

Catalyst-free needle-like ZnO nanowires have been grown on Si(111) substrate at 430??C via a simple solid?vapour process. The obtained nanowires are found to have a uniform size distribution with sharp tips. The lengths of the nanowires range from 2.8 to 3.2??m with diameters of about 100?nm for the root and 30?nm for the tip parts. The x-ray diffraction (XRD) result shows the nanowires are c-axis preferentially oriented. Transmission electron microscopy (TEM) and selected area electron diffraction (SAED) analysis reveal that every single nanowire is a well developed single crystal. The room temperature photoluminescence (PL) spectrum shows a dominant near-band-edge emission peak. The near-band-edge emission is further identified to originate from the radiative free exciton recombination by the temperature-dependent PL.