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Ever since the Victorian era, montage, the process of pictorial composition made by juxtaposing or superimposing photographs, has been a very popular post-editing imaging technique. Despite showing a strong power in demonstrating complex wave field effects, this technique has neither been fully explored in acoustic imaging nor been realized in real-time systems with the capability beyond diffraction limits. On the other hand, the recent prospect of metamaterials has shown their great potentials in super-resolution acoustic imaging. However, the miracle jigsaw of more advanced functional modulation of acoustic wave fields at deep subwavelength scale still remains elusive. Here we report the experimental implementation of super-resolution acoustic image montage through a judiciously designed biaxial metamaterial lens. Based on the non-diffraction birefringence in the biaxial metamaterials, we realized various montage functionalities such as duplication, composition, and decomposition of sound images with distinctive deep subwavelength features. Our work represents an important step in developing versatile functional acoustic metamaterial devices for imaging purposes, as it provides on-demand editing of sound field patterns beyond diffraction limits., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2020 Science China Press. Published by Elsevier B.V. All rights reserved.)

Objective: To study the role of interleukin 6 (IL-6) in the occurrence and development of acute liver injury. Methods: Twelve C57BL/6 male mice without specific pathogens were randomly divided into a control group and an acute liver injury model group, with six mice in each group. Control and model group were injected with an equal volume (dosage of 10 mg/kg) of phosphate-buffered saline (PBS) and concanavalin A (ConA) into the tail vein, respectively. Samples were collected at 6 h for liver HE staining. Transaminase assay was used to determine the success of the induction model. The expression of IL-6, IL-17, IL-1β, interferon (IFN) γ and tumor necrosis factor α were screened by quantitative fluorescence PCR (qPCR). The expressional condition of IL-6 and IFNγ were measured by enzyme-linked immunosorbent assay (ELISA). Subsequently, three control groups and three IL-6 neutralizing antibody groups were established for acute liver injury, respectively. Equal volumes of PBS or IL-6 neutralizing antibody (100 μg/body) were injected prior 30 minutes, followed by injection of ConA (10 mg/kg) into the tail vein. Blood sampled from eye and liver tissue were fetched at 6 h. Liver tissues were stained with HE and serum alanine aminotransferase (ALT) was determined. An independent sample T-test was used for data comparison. Results: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the model group was significantly higher than control group [ALT: (2 618.99 ± 188.08) U/L and (43.34 ± 5.02) U/L, t = -13.69, P = 0.001; AST: (942.48 ± 150.44) U/L and (57.80 ± 4.84) U/L, t = -5.878, P = 0.01]. Liver HE staining showed that the structure of hepatocyte cord was disordered, the cytoplasm of hepatocyte was lightly stained, and large necrotic foci were gradually formed, accompanied by lymphocyte infiltration, and then a mouse model of acute liver injury was successfully established. Protein levels of IL-6 and IFN, and mRNA of the model group were significantly up-regulated, as compared to control group. IL-6 mRNA expression of the model group was increased 73.7 times that of the control group ( t =-6.218, P < 0.001), and the serum IL-6 expression level was also higher than that of the control group (18 537.02 ± 92.57) pg/ml ( t = -199.782, P < 0.001). IFNγ mRNA was 108.4 times higher than that of the control the group ( t = -4.413, P = 0.003), and serum IFNγ concentration of the model group was also higher than the control group (12 068.30 ± 288.43) pg/ml ( t = -41.748, P < 0.001). Among them, IL-6 level was obviously increased, suggesting that it could participate in the occurrence and development of liver injury. IL-6 neutralizing antibody was injected into the tail vein. ALT level of IL-6 neutralizing antibody was significantly lower than acute liver injury control group [(167.41 ± 47.80) U/L and (1 520.34 ± 190.21) U/L, t = 6.899, P = 0.015]. Liver tissue HE staining showed that hepatocyte necrosis and the number of necrotic foci was significantly alleviated after blocking serum IL-6.Immunohistochemical results showed that the expression of activated caspase3 and hepatocyte apoptosis in the IL-6 neutralizing antibody group was decreased. Conclusion: Neutralizing IL-6 can significantly reduce acute liver injury caused by concanavalin A.

Transcription and pre-mRNA splicing are coupled to promote gene expression and regulation. However, mechanisms by which transcription and splicing influence each other are still under investigation. The ATPase Prp5p is required for pre-spliceosome assembly and splicing proofreading at the branch-point region. From an open UV mutagenesis screen for genetic suppressors of prp5 defects and subsequent targeted testing, we identify components of the TBP-binding module of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex, Spt8p and Spt3p. Spt8Δ and spt3Δ rescue the cold-sensitivity of prp5-GAR allele, and prp5 mutants restore growth of spt8Δ and spt3Δ strains on 6-azauracil. By chromatin immunoprecipitation (ChIP), we find that prp5 alleles decrease recruitment of RNA polymerase II (Pol II) to an intron-containing gene, which is rescued by spt8Δ. Further ChIP-seq reveals that global effects on Pol II-binding are mutually rescued by prp5-GAR and spt8Δ. Inhibited splicing caused by prp5-GAR is also restored by spt8Δ. In vitro assays indicate that Prp5p directly interacts with Spt8p, but not Spt3p. We demonstrate that Prp5p's splicing proofreading is modulated by Spt8p and Spt3p. Therefore, this study reveals that interactions between the TBP-binding module of SAGA and the spliceosomal ATPase Prp5p mediate a balance between transcription initiation/elongation and pre-spliceosome assembly., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: To detect the expression of long intergenic non-coding ribonucleic acid (LINC) 01535 in esophageal squamous cell cancer (ESCC) tissues and cells, and to investigate the influences of LINC01535 on the proliferation and apoptosis of ESCC cells and the possible mechanism., Patients and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the relative expression of LINC01535 in 43 cases of ESCC tissues and human esophageal cancer cells (KYSE30, EC9706, TE-13, and Ecal09) compared with human esophageal mucosal epithelial cells (HET-1A). The esophageal cancer cells with the highest expression were selected and transfected with small interfering RNA (si)-LINC01535 (experimental group) or si-negative control (NC) (control group). The interference efficiency was measured via qRT-PCR assay. Regulatory effects of LINC01535 on cell proliferative capacity was examined through colony formation assay and cell proliferation assay [Cell Counting Kit-8 (CCK-8)]. Cell cycle and apoptosis influenced by LINC01535 were detected via flow cytometry. Western blotting was applied to determine the expression changes in the molecular markers of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway., Results: LINC01535 expression in ESCC tissues and cells was remarkably higher than that in para-carcinoma tissues and esophageal mucosal epithelial cells. Knockdown of LINC01535 decreased proliferative capacity, arrested cell cycle in G1/G0 phase, and increased apoptotic rate of ESCC cells. The expressions of the molecular markers of the JAK/STAT3 signaling pathway were altered after knockdown of LINC01535. The above results illustrated that LINC01535 accelerated the proliferation but repressed the apoptosis of ESCC cells by regulating the JAK/STAT3 signaling pathway., Conclusions: The expression of LINC01535 is up-regulated in ESCC tissues and cells, and the highly expressed LINC01535 promotes the proliferation and inhibits the apoptosis of ESCC cells by regulating the JAK/STAT3 signaling pathway. Our findings provide new directions for the diagnosis and treatment of esophageal cancer.

Biological membranes are ideal for separations as they provide high permeability while maintaining high solute selectivity due to the presence of specialized membrane protein (MP) channels. However, successful integration of MPs into manufactured membranes has remained a significant challenge. Here, we demonstrate a two-hour organic solvent method to develop 2D crystals and nanosheets of highly packed pore-forming MPs in block copolymers (BCPs). We then integrate these hybrid materials into scalable MP-BCP biomimetic membranes. These MP-BCP nanosheet membranes maintain the molecular selectivity of the three types of β-barrel MP channels used, with pore sizes of 0.8 nm, 1.3 nm, and 1.5 nm. These biomimetic membranes demonstrate water permeability that is 20-1,000 times greater than that of commercial membranes and 1.5-45 times greater than that of the latest research membranes with comparable molecular exclusion ratings. This approach could provide high performance alternatives in the challenging sub-nanometre to few-nanometre size range.

Xanthatin is a natural sesquiterpene lactone purified from Xanthium strumarium L., which has shown prominent antitumor activity against a variety of cancer cells. In the current study, we investigated the effect of xanthatin on the growth of glioma cells in vitro and in vivo, and elucidated the underlying mechanisms. In both rat glioma C6 and human glioma U251 cell lines, xanthatin (1-15 μM) dose-dependently inhibited cell viability without apparent effect on the cell cycle. Furthermore, xanthatin treatment dose-dependently induced glioma cell apoptosis. In nude mice bearing C6 glioma tumor xenografts, administration of xanthatin (10, 20, 40 mg·kg -1 ·d -1 , ip, for 2 weeks) dose-dependently inhibited the tumor growth, but did not affect the body weight. More importantly, xanthatin treatment markedly increased the expression levels of the endoplasmic reticulum (ER) stress-related markers in both the glioma cell lines as well as in C6 xenografts, including glucose-regulated protein 78, C/EBP-homologous protein (CHOP), activating factor 4, activating transcription factor 6, spliced X-box binding protein-1, phosphorylated protein kinase R-like endoplasmic reticulum kinase, and phosphorylated eukaryotic initiation factor 2a. Pretreatment of C6 glioma cells with the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 7 mM) or knockdown of CHOP using small interfering RNA significantly attenuated xanthatin-induced cell apoptosis and increase of proapoptotic caspase-3. These results demonstrate that xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating the ER stress-related unfolded protein response pathway involving CHOP induction. Xanthatin may serve as a promising agent in the treatment of human glioma.

The mesoscopic collective motion of self-propelling active particle suspension confined in high aspect ratio two-dimensional micro-channel is numerically studied through coupled [Formula: see text] equation by considering background thermal fluctuation, inter-particle interaction, self-propulsion and micro-channel confinement. Both the self-propulsion and micro-channel confinement are the factors driving the system away from equilibrium and sustaining heterogeneous motion. In such system, the propulsion induced particle accumulation around the channel walls is a universal phenomenon with spatial heterogeneity, where large fraction of particles are caged inside the accumulated cluster with local oscillation coexisting with few fast propelling particles in the center region. Although the formation mechanism of the induced accumulation is well studied, post the cluster formation, how the cluster evolves and its dynamical properties is rarely discussed. Based on the merits of [Formula: see text] equation, the dynamical evolution of induced accumulation is revealed by particle trajectories. It is found that the induced accumulation can be dissociated through the slow re-orientation process of few jammed particles. By using the idea of force chain network, how the transverse confinement couples the transverse displacement with the longitudinal displacement is evidenced. It is further verified by the statistical measurement of correlation probability between transverse and longitudinal displacements. The suppressed displacements in both directions is the origin leading to the slow dynamics of cluster evolution. Temporally, within the orientational relaxation time, this system exhibits non-trivial anomalous diffusion under the competition between the counter effects of self-propulsion (enhanced diffusion) and micro-channel confinement (suppressed diffusion). Additionally, by considering the orientational coupling, the deep hysteresis of accumulation has been found even for very weak orientational coupling strength.

Purpose: To investigate the effect of ultrasonic scaling on micro-leakage of all-ceramic crowns., Methods: 48 first premolars of the similar shape and size were collected and prepared by one attending doctor. Two groups were randomly divided (zirconia crown group and glass ceramic crown group, with 24 in each group), and each group was randomly divided into two subgroups (resin cement group and resin modified glass cement subgroup, n=6). After the crowns were bonded and solidified for 24 h, 3 samples were randomly selected from each subgroup for ultrasonic scaling for 60 s, and the other 3 samples were used as the negative control group. After all samples were soaked in 5% fuchsin solution at room temperature for 48 h, buccal and lingual incisions were made, and double-blind scoring was performed for micro-leakage at the crown edge of each sample. SPSS 17.0 software package was used for statistical analysis., Results: There were significant differences between the negative group and the ultrasonic group in micro-leakage of crowns which were cemented with resin modified glass cement(P<0.05), but there was no significant difference between the negative group and the ultrasonic group in micro-leakage of crowns which were cemented with resin cement(P>0.05). When the same adhesive was used, there was significant difference in microleakage between the zirconia crown and the glass-ceramic crown, whether ultrasonic supragingival scaling was performed or not(P<0.05)., Conclusions: Ultrasonic scaling had significant effect on micro-leakage of crowns which were cemented with resin modified glass cement, and but had no significant effect on micro-leakage of crowns which were cemented with resin cement.

Multifunctional nanoclusters based on Fe 3 O 4 nanoparticles for magnetic resonance imaging (MRI) and drug delivery are reported here. At first, oleic acid (OA)-coated Fe 3 O 4 nanoparticles were prepared. Then block copolymer Pluronic F127 or folic acid (FA) conjugated-Pluronic F127 was used to modify the hydrophobic nanoparticles to become hydrophilic Fe 3 O 4 @F127 nanoclusters via facile ultrasonic treatment. During this process, drug molecules can also be introduced into the nanoclusters and therefore the targeted drug delivery system was formed. Next, we verified the feasibility of the nanoclusters as drug delivery vehicles and magnetic contrast agents. The nanoclusters have an average size of 200 nm and remained stable in water for long periods. Folic acid-modified nanoclusters showed an enhanced intracellular uptake into HepG2 cells by using both cellular iron amount analysis and flow cytometry analysis. Besides, Fe 3 O 4 @F127@FA nanoclusters showed good compatibility in the tested concentration range and good sensitivity in T 2 -weighted MRI. The magnetic nanoclusters combined with drug delivery properties have greatly increased the significance in the diagnosis and therapy of diseases, which are suitable for systematical administration of hydrophobic drugs and simultaneously MRI diagnosis., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Artificial water channels are synthetic molecules that aim to mimic the structural and functional features of biological water channels (aquaporins). Here we report on a cluster-forming organic nanoarchitecture, peptide-appended hybrid[4]arene (PAH[4]), as a new class of artificial water channels. Fluorescence experiments and simulations demonstrated that PAH[4]s can form, through lateral diffusion, clusters in lipid membranes that provide synergistic membrane-spanning paths for a rapid and selective water permeation through water-wire networks. Quantitative transport studies revealed that PAH[4]s can transport >10 9 water molecules per second per molecule, which is comparable to aquaporin water channels. The performance of these channels exceeds the upper bound limit of current desalination membranes by a factor of ~10 4 , as illustrated by the water/NaCl permeability-selectivity trade-off curve. PAH[4]'s unique properties of a high water/solute permselectivity via cooperative water-wire formation could usher in an alternative design paradigm for permeable membrane materials in separations, energy production and barrier applications.

Mammary carcinoma (MC) is one of most common malignancy in women, and ring finger protein 2 (RNF2) possesses various roles in vast human tumors. In MC tissues as well as in cell lines RNF2 exhibited high expression, had significant association with tumor size, lymph node status, TNM stage, patients' poor survival, and promoted cell proliferation, colony formation, cell migration and invasion of MC cell lines which was mediated by downregulation of E-cadherin protein. These data reveal that RNF2 protein plays a vital role in the development of MC and may be a potential therapy target of MC., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

In mountainous areas, rock fragments (RFs) are a common feature on the soil surface and in topsoil. Few studies, however, have investigated the spatial distribution of RFs and the relevant mechanisms underpinning their distribution on steep hillslopes, especially in karst regions. We have collected and measured the RF cover, size, and content at the soil surface and within the topsoil of secondary forest, man-made forest, and non-forest land hillslopes in a karst region in Yunnan Province, southwest China. The results revealed no significant relationships between slope position and mean total RF coverage, median diameter (D 50 ), and mean total volumetric RF in topsoil within the three karst hillslopes covered by different types of vegetation. A limited effect of vegetation on the spatial distribution of RFs on the hillslopes was identified. However, the variation in RFs in the topsoil between the top and bottom slopes was greater than that at the surface between the top and bottom slopes, implying that underground leakage was greater than surface runoff.

The Schrödinger equation is a fundamental equation to describe the wave function of a quantum-mechanical system. The similar forms between the Schrödinger equation and the paraxial wave equation allow a paradigm shift from the quantum mechanics to classical fields, opening up a plethora of interesting phenomena including the optical super-oscillatory behavior. Here, we propose an ultrasonic meta-lens for generating super-oscillation acoustic wave-packets with different spatial momenta and then superimposing them to a diffraction-limit-broken spot, visually represented by the ring-shaped trapping of tiny particles. Moreover, based on the focused super-oscillation packets, we experimentally verify proof-of-concept super-resolution ultrasound imaging, opening up the arena of super-oscillation ultrasonics for advanced acoustic imaging, biomedical applications, and versatile far-field ultrasound control.

Valley states, labeling the frequency extrema in momentum space, carry a new degree of freedom (valley pseudospin) for topological transport of sound in sonic crystals. Recently, the field of valley acoustics has become a hotspot due to its potentials in developing various topological-insulator-based devices. In most previous works, topological valley transport is implemented at the interfaces of two connected artificial crystals. With respect to the interface, the mirror symmetry of crystal structures supports either even-mode or odd-mode valley states. In this work, we propose a physical insight of transforming one hexagonal crystal into a virtual lattice by utilizing the mirror operation of rigid or soft boundaries, which greatly reduces the dimension of the acoustic structure and provides a possible way to implement the programmable routing of topological propagation. We investigate two cases that the rigid and soft boundaries are introduced either at the edge or inside a single hexagonal crystal. Our results clearly demonstrate the high-transmission valley transport along the folded boundaries, where reflection or scattering is prohibited at the sharp bending or corners due to topological protection. Three functional devices are exemplified, which are single-crystal-based topological delay-line filter, delay-line switcher and beam splitter. Our work reveals the inherent relation between the field symmetries of valley states and structural symmetries of sonic crystals. Programmable routing of topological sound transport through boundary engineering provides a platform for developing integrated and versatile topological-insulator-based devices.

Iron overload is a common pathophysiological state underlying many diseases that has a detrimental influence on cells. The protective effects of Dexmedetomidine (Dex), a high selective alpha-2-adrenoceptor agonist, have been revealed through many experimental models, whereas no study reports its effects on an iron overload model. To elucidate these effects, we used FeCl 2 with or without Dex to treat SH-SY5Y cells for 24 h and then detected indicators of oxidative stress, inflammation and apoptosis and investigated possible mechanisms further. After treatment with FeCl 2 for 24 h, cell viability decreased in a dose dependent manner, and Dex promoted cell survival in FeCl 2 incubation, also in a dose-dependent manner. Compared with the FeCl 2 group, 20 µM Dex significantly attenuated ROS accumulation, reduced pro-inflammatory cytokine expression, and inhibited apoptosis. Furthermore, 20 µM concentration of Dex remarkably downregulated the expression of pro-apoptotic protein and activation of caspase 3 while increasing anti-apoptotic protein expression. Additionally, Dex also effectively suppressed the expression of NF-κB and its activation. In conclusion, Dex exerted anti-oxidative stress, anti-inflammation, and anti-apoptosis effects on FeCl 2 -treated SH-SY5Y cells, possibly by inhibiting NF-κB signaling pathway.

Stimulated adiabatic passage utilizes radiation pulses to efficiently and selectively transfer population between quantum states, via an intermediate state that is normally decaying. In this Letter, we propose the analog of stimulated adiabatic passage in an acoustic system. It is realized with cavities that correlate through adiabatically time-varying couplings, where the cavities and time-varying couplings mimic discrete states and radiation pulses, respectively. With appropriate arrangements of coupling actions, an acoustic wave can be efficiently transferred from the initial excited cavity to the target cavity in the forward direction, immune to the intermediate dark cavity. On the other hand, for the backward propagation, the acoustic energy is perfectly localized in the intermediate dark cavity and completely dissipated. We analytically, numerically, and experimentally demonstrate such unidirectional sound localization and unveil the essential role of zero-eigenvalue eigenstates in the adiabatic passage process.

Hepatocellular carcinoma (HCC) has high incidence and mortality in patients with chronic liver diseases worldwide. However, there are limited chemotherapeutic agents for HCC in clinic. Xanthatin, a natural sesquiterpene lactone, has significant antitumor activity against a variety of cancers, but little is known about its effects on HCC and the underlying mechanism. Here, we evaluated the antitumor effects of xanthatin on human hepatoma cells. We found that xanthatin caused morphological changes and reduced cell viability in three HCC cell lines in concentration- and time-dependent manners. Xanthatin at 10 μM significantly arrested cell cycle at the G2/M checkpoint, and at 40 μM significantly arrested cell cycle at the S phase in hepatoma cells. Additionally, xanthatin induced apoptosis associated with activation of caspase-3 in hepatoma cells, but did not apparently induce apoptosis in human normal LO2 hepatocytes. We also demonstrated that the three primary signaling pathways of unfolded protein response (UPR) were activated by xanthatin to different extents. Notably, the PERK/eIF-2α/ATF4 axis was most significantly activated by xanthatin. More importantly, both xanthatin and tunicamycin, an endoplasmic reticulum stress (ERS) inducing compound, increased the levels of CHOP and cleaved-caspase-3 in HepG2 cells, but their effects were significantly abolished by siRNA-mediated knockdown of CHOP. Further experiments validated that xanthatin more potently activated ATF4 by promoting its nuclear translocation in hepatoma cells. Taken together, we discovered that xanthatin induced apoptosis in human hepatoma cells by activating ERS. Our current data revealed a novel mechanism for xanthatin as a promising anti-tumor candidate for HCC therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

To investigate the suppressive effects of xanthatin on glioma growth in a nude mouse xenograft model and rat orthotopic implantation model using magnetic resonance imaging (MRI) to dynamically monitor the antitumour growth and antiangiogenesis effects of xanthatin. The nude mouse xenograft tumour model and rat orthotopic implantation model were established to observe the antitumour effects of xanthatin in vivo. In the rat orthotopic implanted tumour model, MRI scanning was used to dynamically monitor the antitumour growth effect and evaluate the antiangiogenesis effect of xanthatin. We found that xanthatin at a dose of 0.4 mg/10 g dramatically decreased the growth of xenograft tumours in nude mice. The antiangiogenesis effect of xanthatin C6 glioma was evaluated by dynamic contrast-enhanced (DCE) MRI via comparison of the volume transfer constant (K trans ) value, a parameter that reflects vessel permeability. We found that xanthatin at the doses of 8 and 16 mg/kg significantly decreased the K trans value, which suggests that xanthatin has antiangiogenesis effects. These data demonstrate the suppressive effects of xanthatin on C6 glioma occur via antiangiogenesis. Meanwhile, this study also provides evidence for the application of quantitative parameters of DCE-MRI for dynamically evaluating the growth and angiogenesis of intracranial tumours and for experimental and clinical research., (© 2018 John Wiley & Sons, Ltd.)

The facile fabrication of multifunctional nanocomposites (Fe 3 O 4 /HBC@F127) consisting of superparamagnetic Fe 3 O 4 nanoparticles and fluorescent organic hexa- peri -hexabenzocoronene (HBC) molecules incorporated in block copolymer diacylphospholipid-polyethyleneglycol F127 have been demonstrated for dual mode imaging (fluorescent/MR) and drug delivery. The obtained nanocomposites were water-dispersible, stable and biocompatible, as confirmed by dynamic light scattering (DLS) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Relativity measurements showed a T 2 relaxivity ( r 2 ) of 214.61 mM -1 s -1 , which may be used as T 2 -weighted MR imaging agents. In vitro imaging studies indicated that the nanocomposites had good MR and fluorescence imaging effects with low cytotoxicity. Besides, the developed nanocomposites could also be applied as drug delivery vehicles. Doxorubicin (DOX) loaded Fe 3 O 4 /HBC@F127 nanocomposites significantly inhibited the growth of human hepatoma cells (HepG2). These findings suggested that the facile synthesized multifunctional nanocomposites may be used as a platform for dual mode imaging (both MR and fluorescence) and drug delivery., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Mesencephalic astrocyte‑derived neurotrophic factor (MANF) is an endoplasmic reticulum stress‑inducible protein, which has been suggested to be upregulated in inflammatory diseases; however, how inflammation regulates its transcription remains unclear. Activator protein‑1 (AP‑1), which is a transcription factor complex composed of c‑Fos and c‑Jun, is activated during the inflammatory process. The present study aimed to investigate whether the AP‑1 complex regulates MANF transcription. The results of a luciferase reporter assay revealed that one of three putative AP‑1 binding sites in the MANF promoter region is essential for enhancement of MANF transcription. Mechanistically, AP‑1 was revealed to directly bind to the promoter region of the MANF gene by chromatin immunoprecipitation assay. Furthermore, MANF was strongly expressed in the liver tissues of patients with hepatitis B virus (HBV) infection, compared with in normal liver tissues from patients with hepatic hemangioma. Furthermore, c‑Fos and c‑Jun were also upregulated in the nuclei of hepatocytes from patients with HBV infection. In mice treated with carbon tetrachloride, the expression patterns of MANF, c‑Fos and c‑Jun were similar to those in patients with HBV. These results suggested that the AP‑1 complex may be a novel regulator of MANF transcription, which may be involved in liver inflammation and fibrosis.

Artificial water channels are a practical alternative to biological water channels for achieving exceptional water permeability and selectivity in a stable and scalable architecture. However, channel-based membrane fabrication faces critical barriers such as: (1) increasing pore density to achieve measurable gains in permeability while maintaining selectivity, and (2) scale-up to practical membrane sizes for applications. Recently, we proposed a technique to prepare channel-based membranes using peptide-appended pillar[5]arene (PAP[5]) artificial water channels, addressing the above challenges. These multi-layered PAP[5] membranes (ML-PAP[5]) showed significantly improved water permeability compared to commercial membranes with similar molecular weight cut-offs. However, due to the distinctive pore structure of water channels and the layer-by-layer architecture of the membrane, the separation behavior is unique and was still not fully understood. In this paper, two unique selectivity trends of ML-PAP[5] membranes are discussed from the perspectives of channel geometry, ion exclusion, and linear molecule transport.

The long-standing goal in membrane development is creating materials with superior transport properties, including both high flux and high selectivity. These properties are common in biological membranes, and thus mimicking nature is a promising strategy towards improved membrane design. In previous studies, we have shown that artificial water channels can have excellent water transport abilities that are comparable to biological water channel proteins, aquaporins. In this study, we propose a strategy for incorporation of artificial channels that mimic biological channels into stable polymeric membranes. Specifically, we synthesized an amphiphilic triblock copolymer, poly(isoprene)-block-poly(ethylene oxide)-block-poly(isoprene), which is a high molecular weight synthetic analog of naturally occurring lipids in terms of its self-assembled structure. This polymer was used to build stacked membranes composed of self-assembled lamellae. The resulting membranes resemble layers of natural lipid bilayers in living systems, but with superior mechanical properties suitable for real-world applications. The procedures used to synthesize the triblock copolymer resulted in membranes with increased stability due to the crosslinkability of the hydrophobic domains. Furthermore, the introduction of bridging hydrophilic domains leads to the preservation of the stacked membrane structure when the membrane is in contact with water, something that is challenging for diblock lamellae that tend to swell, and delaminate in aqueous solutions. This new method of membrane fabrication offers a practical model for making channel-based biomimetic membranes, which may lead to technological applications in reverse osmosis, nanofiltration, and ultrafiltration membranes.

Background: Our previous studies have shown that mesencephalic astrocyte-derived neurotrophic factor (MANF) provides a neuroprotective effect against ischemia/reperfusion injury and is also involved in inflammatory disease models. This study investigates the potential role and mechanism of MANF in acute brain damage after traumatic brain injury (TBI)., Methods: The model of TBI was induced by Feeney free falling methods with male Sprague-Dawley rats. The expression of MANF, 24 hours after TBI, was detected by the immunohistochemistry, immunofluorescence, Western blot, and reverse transcription polymerase chain reaction techniques. After treatment with recombinant human MANF after TBI, assessment was conducted 24 hours later for brain water content, cerebral edema volume in magnetic resonance imaging, neurobehavioral testing, and Evans blue extravasation. Moreover, by the techniques of Western blot and reverse transcription polymerase chain reaction, the expression of inflammatory cytokines (interleukin 1β and tumor necrosis factor α) and P65 was also analyzed to explore the underlying protective mechanism of MANF., Results: At 24 hours after TBI, we found that endogenous MANF was widely expressed in the rat's brain tissues and different types of cells. Treatment with a high dose of recombinant human MANF (20 μg/20 μL) significantly increased the modified Garcia score, and reduced brain water content as well as cerebral edema volume on magnetic resonance imaging. Furthermore, MANF alleviated not only the permeability of the blood-brain barrier (BBB) but also the expressions of interleukin 1β and tumor necrosis factor α messenger RNA and protein. Besides, the activation of P65 was also inhibited., Conclusions: These results suggest that MANF provides a neuroprotective effect against acute brain injury after TBI, via attenuating blood-brain barrier disruption and intracranial neuroinflammation; the inhibition of the NF-κB signaling pathway might be a potential mechanism., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In this work, we investigate comprehensively the unidirectional transport of sound in coupled cavities of a modified honeycomb lattice. The results clearly show that a pair of topological states carrying opposite pseudospins can be constructed at the edge of truncated lattices of non-trivial band gaps, which is different from previous schemes where topological states with opposite pseudospins were constructed at the interface of modified honeycomb lattices of trivial and non-trivial band gaps. Our work paves the way to exploring unidirectional edge transport of sound with topological protection in closed systems that are beneficial in large-scale device integration and low-loss operation.

As water availability becomes a growing challenge in various regions throughout the world, desalination and wastewater reclamation through technologies such as reverse osmosis (RO) are becoming more important. Nevertheless, many open questions remain regarding the internal structure of thin-film composite RO membranes. In this work, fully aromatic polyamide films that serve as the active layer of state-of-the-art water filtration membranes were investigated using high-angle annular dark-field scanning transmission electron microscopy tomography. Reconstructions of the 3D morphology reveal intricate aspects of the complex microstructure not visible from 2D projections. We find that internal voids of the active layer of compressed commercial membranes account for less than 0.2% of the total polymer volume, contrary to previously reported values that are two orders of magnitude higher. Measurements of the local variation in polyamide density from electron tomography reveal that the polymer density is highest at the permeable surface for the two membranes tested and establish the significance of surface area on RO membrane transport properties. The same type of analyses could provide explanations for different flux variations with surface area for other types of membranes where the density is distributed differently. Thus, 3D reconstructions and quantitative analyses will be crucial to characterize the complex morphology of polymeric membranes used in next-generation water-purification membranes., Competing Interests: Conflict of interest statement: M.G., A.R., M.J.B., S.R., and J.G. are all employees of DowDuPont Inc.

The original version of this Article contained an error in the spelling of the author Woochul Song, which was incorrectly given as Woochul C. Song. This has been corrected in both the PDF and HTML versions of the Article.

Synthetic polymer membranes, critical to diverse energy-efficient separations, are subject to permeability-selectivity trade-offs that decrease their overall efficacy. These trade-offs are due to structural variations (e.g., broad pore size distributions) in both nonporous membranes used for Angstrom-scale separations and porous membranes used for nano to micron-scale separations. Biological membranes utilize well-defined Angstrom-scale pores to provide exceptional transport properties and can be used as inspiration to overcome this trade-off. Here, we present a comprehensive demonstration of such a bioinspired approach based on pillar[5]arene artificial water channels, resulting in artificial water channel-based block copolymer membranes. These membranes have a sharp selectivity profile with a molecular weight cutoff of ~ 500 Da, a size range challenging to achieve with current membranes, while achieving a large improvement in permeability (~65 L m -2  h -1  bar -1  compared with 4-7 L m -2  h -1  bar -1 ) over similarly rated commercial membranes.

Widespread phthalate exposure has been recently documented and is hypothesized to increase blood pressure (BP) in humans. However, current studies have provided inconclusive evidence for an association between phthalate exposure and BP. Human epidemiologic studies on the topic remain lacking. Therefore, this study aims to examine the association between serum phthalate concentrations and BP in a Chinese population. We measured several parameters of BP (systolic BP, diastolic BP, total cholesterol, and triglyceride) and the concentrations of 16 phthalates (dimethyl phthalate (DMP), diethyl phthalate, diisobutyl phthalate, dibutyl phthalate (DBP), bis (2-methoxyethyl) phthalate, bis (4-methyl-2-pentyl) phthalate, bis (2-ethoxyethyl) phthalate, diamyl phthalate, dihexyl phthalate, benzyl butyl phthalate, bis (2-nbutoxyethyl) phthalate (DBEP), dicyclohexyl phthalate, bis (2-ethyl hexyl) phthalate (DEHP), diisononyl phthalate, diphenyl phthalate, and di-n-octyl phthalate) in the serum of 474 adults recruited from a primary health care clinic. The relationship between serum phthalate concentrations and BP parameters was assessed with multivariate linear regressions. DBP was the most ubiquitous and dominant contaminant in the study population. The systolic BP of subjects in the median-exposure DEHP group significantly increased by 2.96 mmHg (p < 0.05) relative to that of subjects in the low-exposure group. Significant positive dose-related associations of DMP and DBEP with the levels of total cholesterol in serum (p for trend < 0.05) were also found. These associations persisted even when considering exposure to multiple phthalates. Our results suggested that phthalate exposure might increase BP in adults. However, our findings warrant further studies in a larger and more general population.

Objective: To observe the changes of γδT cells in the peripheral blood of patients with chronic hepatitis B (CHB) during pegylated interferon α-2a treatment, and to analyze the correlation between clinical indicators and curative effects. Methods: Peripheral blood of hepatitis B e antigen (HBeAg)-positive CHB patients were collected at different time points of Peg-IFNα-2a treatment, including 17 patients at 0 weeks, 20 patients at 12 weeks, 20 patients at 24 weeks, and 16 patients at 48 weeks. From these 11 patients, blood samples were frequently observed at 0, 12, 24, and 48 weeks of treatment. The frequencies of γδT and its subpopulation cells Vδ1T, Vδ2T, effector memory γδT (γδTem), central memory γδT (γδTcm), initial γδT (γδTnaive) and terminal differentiation effect γδT (γδTeff) cells in peripheral blood were detected by flow cytometry. Liver function, serum HBV markers and HBV DNA levels were measured simultaneously. SPSS 23.0 statistical software was used to analyze the differences in cell proportions at each treatment time point, and the correlation between cell proportions and alanine aminotransferase (ALT), HBsAg, HBeAg or HBV DNA levels. In addition, the correlation between the proportions of γδT and its subpopulation cells and the response to Peg-IFNα-2a treatment in the 11 patients with continuous follow-up were analyzed. Results: The percentage of γδT and Vδ2T cells in peripheral blood of patients with CHB decreased gradually during the period of 0-48 weeks of Peg-IFNα-2a treatment. The percentages of γδT cells and Vδ2T cells at 48 weeks were 6.89% (5%, 8.15%), 4.61% (2.16%, 6.50%), respectively; significantly lower than the 0 week [12.5% ​​(7.73%, 19%), 6.59% (3.86%, 13.62%)], the differences were statistically significant ( P < 0.05). The proportions of Vδ1T, γδTem, γδTcm, γδTnaive, or γδTeff subpopulations were not statistically different at each time points (all P > 0.05). At the same time, the levels of ALT, HBsAg, HBeAg or HBV DNA were positively correlated with the ratio of γδT or Vδ2T cells ( P < 0.05). Among the 11 patients with continuous followed- up, the proportion of γδTem cells in responders was significantly lower than that of non-responders at each time points, and the difference was statistically significant ( P < 0.05). There was no statistically significant difference between the two groups (all P > 0.05). Conclusion: The proportion of γδT cells in the course of CHB treatment with Peg-IFNα-2a reduces the liver inflammation by decreasing the replication of HBV virus. Chronic hepatitis B patients with a lower proportion of effector memory (γδTem) cells may be more likely to get better response with Peg-IFNα-2a.

Objective: To evaluate the value of 640-slice 3D CT angiography (3D-CTA) plus 3D printing for improving the outcomes of surgeries for intracranial aneurysms., Methods: Sixty patients with intracranial aneurysm were randomly divided into trial group (n=30) and control group (n=30). The control group received routine surgery, and the simulation models of the intracranial aneurysm in trial group was printed using a 3D printer using the imaging data from 3D-CTA. Using the simulation model, the surgery was designed and planned before operation (including surgical approaches and placement of clips) and simulation surgery was also conducted. The coincidence rates between preoperative and intraoperative findings of the intracranial aneurysms on 3D-CTA were compared. CT scan was performed at 1 and 3 days after the operation to detect potential cerebral infarction or bleeding associated with the operation; CTA was performed both at the same time and at 3-6 months after the operation to detect stenosis, occlusion and aneurysm clipping. The patients were followed up for 3-6 months to assess the outcomes using Glasgow Outcome Scale (GOS)., Results: The preoperative 3D-CTA findings were basically consistent with the intraoperative findings in all the 60 patients. Nine patients in the control group and 2 patients in the trial group had short-term adverse operation events; 11 patients in control group and 4 patients in trial group had long-term adverse events; 18 patients in control group and 25 patients in trial group had good neurologic function. The incidences of short-term and long-term adverse events associated with the operation was significantly lower in the trial group than in the control group (χ 2 =5.364, P=0.021; χ 2 =4.841, P=0.028), and the outcomes were significantly better in the trial group than in the control group (χ 2 =4.633, P=0.031)., Conclusion: The simulation model of intracranial aneurysm is helpful to improve the quality of surgery and patients outcomes.

Targeting delivery of drugs in a specific manner represents a potential powerful technology in gliomas. Herein, we prepared a multifunctional targeted delivery system based on graphene oxide (GO) that contains a molecular bio-targeting ligand and superparamagnetic iron oxide nanoparticles on the surface of GO for magnetic targeting. Superparamagnetic Fe 3 O 4 nanoparticles was loaded on the surface of GO via chemical precipitation method to form GO@Fe 3 O 4 nanocomposites. Lactoferrin (Lf), an iron-transporting serum glycoprotein that binds to receptors overexpressed at the surface of glioma cells and vascular endothelial cell of the blood brain barrier, was chosen as the targeted ligand to construct the targeted delivery system Lf@GO@Fe 3 O 4 through EDC/NHS chemistry. With the confirmation of TEM, DLS and VSM, the resulting Lf@GO@Fe 3 O 4 had a size distribution of 200-1000nm and exhibited a superparamagnetic behavior. The nano delivery system had a high loading capacity and exhibited a pH-dependent release behavior. Compared with free DOX and DOX@GO@Fe 3 O 4 , Lf@GO@Fe 3 O 4 @DOX displayed greater intracellular delivery efficiency and stronger cytotoxicity against C6 glioma cells. The results demonstrated the potential utility of Lf conjugated GO@Fe 3 O 4 nanocomposites for therapeutic application in the treatment of gliomas., (Copyright © 2017. Published by Elsevier B.V.)

The present study aims to investigate the influence of human activity on heavy metals in a typical arid urban area of China and assess human health risks posed by heavy metals in PM 1 (particles <1.0 μm in diameter) for different people. In this paper, Changji (Xinjiang, China) was selected as the study area, and samples were collected from March 2014 to March 2015. A total 14 elements in PM 1 were quantified using ICP-MS. An enrichment factor (EF) was used to assess the influence of human activity on the contamination of these metals. The results indicated that Mn was not enriched; Co, Cu, Cr, Ni, Tl, and V were slightly enriched; Mo, Pb, and Sb were moderately enriched; and Ag, As, and Cd were strongly enriched. To assess the health risks associated with inhaling PM 1 , the risk assessment code and loss in life expectancy based on the individual metals were calculated. The results showed that the elements Ag, Cu, Mo, Pb, Sb, Tl, and V in PM 1 posed low levels of non-carcinogenic risks, but these metals may still pose risks to certain susceptible populations. In addition, the results also showed that As, Co, and Cr posed an appreciable carcinogenic risk, while Cd and Ni posed low levels of carcinogenic risk. The total predicted loss of life expectancy caused by the three metals As, Co, and Ni was 63.67 d for the elderly, 30.95 d for adult males, 26.62 d for adult females, and 48.22 d for children. Therefore, the safety of the elderly and children exposed to PM 1 should be given more attention than the safety of adults. The results from this study demonstrate that the health risks posed by heavy metals in PM 1 in Changji, Xinjiang, China should be examined.

We investigate analytically, numerically, and experimentally the low-loss supermode propagation in a coupled acoustic waveguide complex within a broadband. The waveguide complex is implemented with air channels coupled via an ultrathin metafluid layer. We analytically derive the field distribution of incident sound needed for producing acoustic supermodes, and verify the periodically revival propagation in coupled waveguide systems numerically and experimentally. We find out that the supermode wavelength becomes longer for higher mode order or lower frequency. We have also demonstrated the robust propagation of supermodes in broadband. Our scheme can in principle be extended to three dimensions and the ultrasound regime with simplicity and may promote applications of high-fidelity signal transfer in complicated acoustic networks.

We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R) induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2-alpha (eIF2α) and activating transcription factor 4 (ATF4). We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone (0.1, 1, 10, 100 μM) treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated (p)-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response., Competing Interests: Conflicts of interest: None declared.

The aim of this study was to determine the effects of ginsenoside Rg1 on the migration of olfactory ensheathing cells (OECs) in vitro, and its influence on the therapeutic efficacy of OECs transplanted in vivo for the treatment of spinal cord injury (SCI). Primary cultured and purified OECs (prepared from rats) were treated with ginsenoside Rg1. The wound healing test indicated that ginsenoside Rg1 promoted the migration of OECs. Real-time RT-PCR demonstrated that ginsenoside Rg1 upregulated the expression of migration-related factors of OECs, including matrix metalloproteinases-2 (MMP-2), MMP-9, and neural cell adhesion molecule 1 (NCAM1). Moreover, Western blot analysis indicated that ginsenoside Rg1 significantly promoted the migration of OECs via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. An SCI rat model was induced in vivo using a revised Allen's method. The Basso, Beattie, and Bresnahan (BBB) scores and histological analysis demonstrated that OECs, which were treated with ginsenoside Rg1, exhibited significant improvement in SCI compared with both the control group and the OEC group. Thus, ginsenoside Rg1 may represent a novel treatment target for SCI.

Wastewater treatment plants are thought to be potential reservoirs of antibiotic resistance genes. In this study, GeoChip was used for analyzing multiple antibiotic resistance genes, including four multidrug efflux system gene groups and three β-lactamase genes in ten large-scale membrane bioreactors (MBRs) for municipal wastewater treatment. Results revealed that the diversity of antibiotic genes varied a lot among MBRs, but about 40% common antibiotic resistance genes were existent. The average signal intensity of each antibiotic resistance group was similar among MBRs, nevertheless the total abundance of each group varied remarkably and the dominant resistance gene groups were different in individual MBR. The antibiotic resistance genes majorly derived from Proteobacteria and Actinobacteria. Further study indicated that TN, TP and COD of influent, temperature and conductivity of mixed liquor were significant (P<0.05) correlated to the multiple antibiotic resistance genes distribution in MBRs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Recent studies have investigated the potential prognostic value of the transmembrane protease serine 4 (TMPRSS4) in various solid tumors. Yet, the results are inconclusive. Here, we performed this meta-analysis to clarify this issue. Relevant articles were identified by searching PubMed, Web of Science and Embase databases. The primary outcome endpoints were patients' overall survival (OS) and time to tumor progression (TTP). Twelve studies involving 1,955 participants were included. We showed that high TMPRSS4 expression in tumor tissues was significantly associated with patients' poor OS (pooled HR = 2.981, 95% CI = 2.296-3.869, P < 0.001) and short TTP (pooled HR = 2.456, 95% CI = 1.744-3.458, P < 0.001). A subgroup analysis revealed that the association between TMPRSS4 and the outcome endpoints (OS or TTP) was also significant within China region. We conclude that TMPRSS4 overexpression in solid tumors is associated with patients' poor prognosis. TMPRSS4 could be a valuable prognosis biomarker or a promising therapeutic target of solid tumor.

Time-reversal invariant topological insulator is widely recognized as one of the fundamental discoveries in condensed matter physics, for which the most fascinating hallmark is perhaps a spin-based topological protection, the absence of scattering of conduction electrons with certain spins on matter surface. Recently, it has created a paradigm shift for topological insulators, from electronics to photonics, phononics and mechanics as well, bringing about not only involved new physics but also potential applications in robust wave transport. Despite the growing interests in topologically protected acoustic wave transport, T-invariant acoustic topological insulator has not yet been achieved. Here we report experimental demonstration of anomalous Floquet topological insulator for sound: a strongly coupled metamaterial ring lattice that supports one-way propagation of pseudo-spin-dependent edge states under T-symmetry. We also demonstrate the formation of pseudo-spin-dependent interface states due to lattice dislocations and investigate the properties of pass band and band gap states.

Objective: The purpose of this study was to investigate the prevalence and risk factors of dyslipidemia in a rural population of Henan Province, China. Methods: A total of 20 194 participants aged ≥18 years were selected randomly by cluster sampling from two townships(towns)in Henan Province from July to August 2007 and July to August 2008. Investigations included questionnaires, anthropometric measurements, fasting plasma glucose, and lipid profile examination at baseline. A total of 16 155 participants were followed up from July to August 2013 and July to October 2014. Overall, 13 869 participants were included in the study, after excluding 2 286 participants with incomplete dyslipidemia follow-up data. Distributions of the characteristics of dyslipidemia were determined, and prevalence was standardized by age according to data of the 2010 Sixth National Population Census. Risk factors for dyslipidemia were analyzed using a logistic regression model after adjusting for sex, age, education level, marital status, and income status. Results: The prevalence of dyslipidemia was 53.72%(7 450/13 869)for residents aged ≥22 years living in rural areas of Henan Province(59.32%(3 069/5 174)for men and 50.39%(4 381/8 695)for women). The adjusted prevalence of dyslipidemia was 50.50%(59.27% for men and 45.53% for women). The prevalence of hypercholesterolemia, hypertriglyceridemia, low HDL-C, and high LDL-C was 4.34%(602/13 868), 20.42%(2 826/13 837), 42.75%(5 927/13 865), and 3.14%(420/13 375), respectively, and the adjusted prevalence was 2.44%, 18.84%, 41.42%, and 1.86%, respectively. Logistic regression analyses showed that alcohol consumption( OR =1.27, 95% CI : 1.05-1.53), family history of hyperlipidemia( OR =1.29, 95% CI : 1.17-1.43), overweight( OR =1.40, 95% CI : 1.22-1.61), obesity( OR = 1.65, 95% CI : 1.39- 1.96), abnormal waist circumference( OR =1.22, 95% CI : 1.04- 1.43), and abnormal waist-height ratio( OR =1.21, 95% CI : 1.01-1.45)were significant independent risk factors, and high levels of physical activity( OR =0.85, 95% CI : 0.77- 0.95)and underweight( OR =0.52, 95% CI : 0.36- 0.75)were protective factors for dyslipidemia after adjusting for sex, age, education level, marital status, and income status. Conclusion: The prevalence of dyslipidemia was very high for this rural population. Alcohol consumption, family history of hyperlipidemia, overweight, obesity, abnormal waist circumference, and abnormal waist-height ratio were significant independent risk factors for dyslipidemia.

As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI) technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO). MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs., Competing Interests: The authors declare no conflict of interest.

Multiple cropping systems are the way to cope with the shortage of traditional Chinese medicine (TCM) resources and enhance the utilization ratio of land. The aim of this study was to investigate seventy Gentiana rigescens Franch samples which were planted in slope and in multiple cropping system mixed with Juglans regia, Alnus nepalensis, Eucalyptus robusta, Alnus nepalensis, Camellia sinensis, Chaenomeles sinensis using Fourier transform infrared (FTIR) spectroscopy. The pretreatments such as baseline correction, normalization and second derivative of all the original spectra were performed with Omnic 8.0 software. Moreover, second derivative spectra of samples and gentiopicroside standard were analyzed. In addition, two spectral databases were set up based on the average spectra of every variety with Omnic 8.0 software. The first library (Lib1) which included the spectra region from 1 800 to 600 cm-1 had the algorithm of expert retrieve while the correlation retrieve and square differential retrieve were dealt with the second library (Lib2) in the full spectral range. The results indicated that it is difficult to identify the infrared spectra of samples directly because they had high similarities. There were multiple common peaks between spectra of samples and gentiopicroside standards. The absorption peaks of 1 611 and 1 076 cm-1 of gentiopicroside were the two main characteristic peaks in the second derivative spectra. The difference of peak shape of every sample in the wave number of 1 076 cm-1 was small. By comparing peak area at 1 611 cm-1, the samples planted with J. regia contained highest content of gentiopicroside while the content of this effective constituent was the lowest in the samples which were planted in the slope and in the multiple cropping systems mixed with C sinensis. The differences of effective components in the samples with different planting patterns were represented by the variances of spectral matching values. The difference of matching values of samples planted with J. regia, A. nepalensis, E. Robusta and A. nepalensis were lower than that with slope and C. Sinensis. The number of misjudgment of expert retrieval, correlation retrieve and square differential retrieve were 11, 4 and 9, respectively. The discrimination result of correlation retrieve was the best in the full spectral range and the correct recognition rate was 94.29%. Fourier transforms infrared (FTIR) spectroscopy combined with second derivative and retrieval had good ability to discriminate G. rigescens with different cropping systems. It could provide a basis for the discrimination of different planting patterns of TCM

Chronic periodontitis is a progressive, infectious inflammation disease, caused by the dysbiosis of oral resident flora, leading to the destruction of periodontium. The onset of pathogenic microorganisms is the etiological factor of periodontitis, while the immuno-inflammatory response affects the progression of the disease. Under chronic periodontitis, oxidative stress occurs when excessive reactive oxygen species are produced and exceed the compensative capacity of the organism. Oxidative stress leads to the destruction of periodontium, in a direct way(damaging the biomolecule) or an indirect way(enhancing the produce of inflammatory cytokine and destructive enzymes). Therefore, as the antagonist of the reactive oxygen species, antioxidants may be helpful to treat the chronic periodontitis. This paper reviewed relevant literatures about the destructive role of excessive reactive oxygen species and protective role of antioxidants in chronic periodontitis.

The Processing of traditional Chinese medicine (TCM) is the key to clinical application of TCM, and processing has functions such as enhancing the efficacy, attenuating the toxicity andmoderating medicine property. In order to the realizing safe, reasonable and effective use of medicine in clinical, research on identification of TCM processed products is of great significance. The Gentiana rigescens samples which processed with five different methods were discriminated by Fourier transform infrared spectroscopy (FTIR). Baseline correction and normalization were used to pretreat all original spectra and the noise was cut off. The spectra range was from 3 400 to 600 cm-1. The effect of multiple scattering correction and standard normal variable on the model were observed and compared. Samples were divided into calibration set and prediction set at the ratio of 3∶1. The principal component analysis (PCA) was applied to reduce data dimensionality and discriminant analysis model was established. The result indicated that the main absorption peaks of samples were 3 378, 2 922, 1 732, 1 610, 1 417, 1 366, 1 316, 1 271, 1 068, 1 048 cm- 1 which 1 738, 1 643, 1 613, 1 420, 1 051 cm-1 as to gentiopicrin; 1 068, 1 048, 935 cm-1 as to carbohydrate. The accumulation contribution rate of first three principal components is 94.05%. Most of the information reflected the original data. There were differences among different samples. The result of discriminant analysis showed that the recognition rate of G. rigescens samples could achieve to 100% based on baseline correction and normalization treatment combined with MSC with the precondition of principal component scores being 10. In conclusion, FTIR is a feasible, rapid and non-destructive method to discriminate G. rigescens samples wtih different processing methods. It also provided reference for discrimination of processed products of medicine materials.

The harvest time of traditional Chinese medicine (TCM) is a very essential part for the production and quality of TCM which is the prerequisite for safe and effective clinical use of TCM. It is of great importance to carry out the research of timely harvest time of TCM. With Fourier transform infrared spectroscopy (FTIR) to study harvest time of Seventy-two Gentiana Rigescens samples. First derivative, second derivative, standard normal variate, multiplicative scatter correction and Savitaky-Golay(15,3) smoothing of all original spectra were pretreated with TQ8.0 software. Samples were divided into calibration set and prediction set at the ratio of 3∶1. Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) model were established. The result indicated that after removing noise spectrum, the spectra range was from 1 800 to 600 cm-1, the method SNV combined with SD and SG present the best result of spectra pretreatment. The contribution rates of first three principal components were 92.47% with PCA. Small differences were found for the samples harvested in May, September and October. Same spectrum range was chosen and PLS-DA was applied to establish the model. The R2 and RMSEE were 0.967 8, 0.086 0, respectively, and the prediction accuracy is 100%. The methods of PCA and PLS-DA have good ability to classify and identify different harvest time of Gentiana Rigescens. It provided a basis for the identification of different harvest time of TCM.

The emergence of rock outcrops is very common in terrestrial ecosystems. However, few studies have paid attention to their hydrological role in the redistribution of precipitation, especially in karst ecosystems, in which a large proportion of the surface is occupied by carbonate outcrops. We collected and measured water received by outcrops and its subsequent export to the soil in a rock desertification ecosystem, an anthropogenic forest ecosystem, and a secondary forest ecosystem in Shilin, China. The results indicated that outcrops received a large amount of water and delivered nearly half of it to nearby soil patches by means of runoff. No significant difference was found in the ratio of water received to that exported to the soil by outcrops among the three ecosystems annually. When the outcrop area reaches 70 % of the ground surface, the amount of water received by soil patches from rock runoff will equal that received by precipitation, which means that the soil is exposed to twice as much precipitation. This quantity of water can increase water input to nearby soil patches and create water content heterogeneity among areas with differing rock emergence.

Aquaporins (AQPs) are biological water channels known for fast water transport (∼10(8)-10(9) molecules/s/channel) with ion exclusion. Few synthetic channels have been designed to mimic this high water permeability, and none reject ions at a significant level. Selective water translocation has previously been shown to depend on water-wires spanning the AQP pore that reverse their orientation, combined with correlated channel motions. No quantitative correlation between the dipolar orientation of the water-wires and their effects on water and proton translocation has been reported. Here, we use complementary X-ray structural data, bilayer transport experiments, and molecular dynamics (MD) simulations to gain key insights and quantify transport. We report artificial imidazole-quartet water channels with 2.6 Å pores, similar to AQP channels, that encapsulate oriented dipolar water-wires in a confined chiral conduit. These channels are able to transport ∼10(6) water molecules/s, which is within 2 orders of magnitude of AQPs' rates, and reject all ions except protons. The proton conductance is high (∼5 H(+)/s/channel) and approximately half that of the M2 proton channel at neutral pH. Chirality is a key feature influencing channel efficiency.

Objective: To investigate the association between body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and the incidence risk of type 2 diabetes mellitus (T2DM)., Methods: In total, 20 194 participants ≥18 years old were selected randomly by cluster sampling from two township (town) of the county in Henan province from July to August of 2007 and July to August of 2008 and the investigation included questionnaires, anthropometric measurements, fasting plasma glucose, and lipid profile examination were performed at baseline; 17 236 participants were enrolled in this cohort study. 14 720 (85.4%) were followed up from July to August 2013 and July to October 2014. Finally, 11 643 participants (4 301 males and 7 342 females) were included in this study. Incidence density and Cox proportional hazards regression models were used to evaluate the risk of T2DM associated with baseline BMI, WC, WHtR, and their dynamic changes., Results: After average of 6.01 years following up for 11 643 participants, 613 developed T2DM and the incidence density was 0.89 per 100 person-years. After adjusted for baseline sex, age, smoking, drinking, family history of diabetes, as well as the difference of fasting plasma-glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP) between baseline and follow-up, Cox Proportional-Hazards regression analysis indicated that T2DM risk of baseline BMI overweight group, BMI obesity group, abnormal WC group and abnormal WHtR group were significantly higher than that of the corresponding baseline normal groups , and the incidence risk of T2DM reached the highest for those whose baseline BMI, WC and WHtR were all abnormal, the corresponding HR (95%CI) were 2.05 (1.62-2.59), 3.01 (2.33-3.90), 2.34 (1.89-2.90), 2.88 (2.21-3.74), 3.32 (2.50-4.40), respectively. Whether baseline BMI/WC was normal or not, T2DM risk increased if baseline WHtR was abnormal, and the HR (95%CI) of baseline normal BMI/abnormal WHtR group, baseline abnormal BMI/abnormal WHtR group, baseline normal WC/abnormal WHtR group, baseline abnormal WC/abnormal WHtR group were 1.88 (1.29-2.74), 3.08 (2.34-4.05), 2.15(1.53-3.00), 3.22 (2.45-4.23), respectively. The analysis for dynamic changes of BMI, WC, and WHtR indicated that in baseline normal WC or WHtR group, T2DM risk increased when baseline normal WC or WHtR developed abnormal at follow-up, and the corresponding HR (95%CI) were 1.79 (1.26-2.55), 2.12(1.32-3.39), respectively. In baseline abnormal WC or WHtR group, T2DM risk decresed when baseline abnormal WC or WHtR reversed to normal at follow-up, and the corresponding HR (95%CI) were 2.16 (1.42-3.29), 2.62 (1.63-4.20), respectively., Conclusion: BMI, WC, and WHtR were associated with increased T2DM risk. The more abnormal aggregation of BMI, WC, and WHtR presents, the higher T2DM risk was. T2DM risk could be decreased when abnormal WC or WHtR reversed to normal.

The application of traditional Chinese medicine (TCM) and their preparations have a long history. With the deepening of the research, the market demand is increasing. However, wild resources are so limited that it can not meet the needs of the market. The development of wild and cultivated samples and research on accumulation dynamics of chemical component are of great significance. In order to compare composition difference of different parts (root, stem, and leaf) of wild and cultivated G. rigescens, Fourier infrared spectroscopy (FTIR) and second derivative spectra were used to analyze and evaluate. The second derivative spectra of 60 samples and the rate of affinity (the match values) were measured automatically using the appropriate software (Omnic 8.0). The results showed that the various parts of wild and cultivated G. rigescens. were high similar the peaks at 1732, 1 643, 1 613, 1 510, 1 417, 1 366, 1 322, 1 070 cm(-1) were the characteristic peak of esters, terpenoids and saccharides, respectively. Moreover, the shape and peak intensity were more distinct in the second derivative spectrum of samples. In the second derivative spectrum range of 1 800-600 cm(-1), the fingerprint characteristic peak of samples and gentiopicroside standards were 1 679, 1 613, 1 466, 1 272, 1 204, 1 103, 1 074, 985, 935 cm(-1). The characteristic peak intensity of gentiopicroside of roots of wild and cultivated samples at 1 613 cm(-1) (C-C) was higher than stems and leaves which indicated the higher content of gentiopicroside in root than in stem and leaves. Stems of wild samples at 1 521, 1 462 and 1 452 cm(-1) are the skeletal vibration peak of benzene ring of lignin, and the stem of cultivated sample have stronger peak than other samples which showed that rich lignin in stems. The iInfrared spectrum of samples were similar with the average spectral of root of wild samples, and significant difference was found for the correlation between second derivative spectrum of samples and average spectral of wild samples root, and the sequence of similarity was root > stem > leaf. Therefore, FTIR combined with second derivative spectra was an express and comprehensive approach to analyze and evaluate in the imperceptible differences among different parts of wild and cultivated of G. rigescens.

Objective: This study aims to investigate the therapeutic effects and mechanisms of x-ray treatment on rats following spinal cord injury (SCI)., Methods: Forty-six female Sprague-Dawley rats were subjected to spinal cord injury using the modified Allen weight-drop method. The animals were randomly divided into six groups. Two of the animal groups were irradiated with 10 Gy at the lesion site; another two groups were irradiated with 20 Gy; and the last two groups without irradiation were regarded as the sham group. One of the each of two animal groups was euthanized at different time points at 4 and 12 weeks, respectively, after irradiation. Spinal cord calluses were assessed using kinology and electrophysiology and histology methods., Results: In all of the groups, the neurofilament (NF) counts at 14 weeks were found to be higher than that at 6 weeks after SCI. Both 10-Gy irradiated and 20-Gy irradiated groups were higher than those of the sham group at each time point (P < 0.05). The myelin basic protein (MBP) count decreased at 14 weeks after SCI in the irradiated groups (P < 0.05) but increased at 14 weeks in the sham group (P < 0.05). Furthermore, the MBP count of the irradiated groups was lower than that of the sham group at 14 weeks (P < 0.05). The glial fibrillary acidic protein (GFAP) and Nogo-A counts at 14 weeks were higher than those at 6 weeks in all the groups (P < 0.05), and there was no statistical significance with kinology and electrophysiology tests in all groups., Conclusions: A self-repair mechanism exists after spinal cord injury, which lasts at least 14 weeks. X-ray therapy promotes the regeneration of the spinal cord system after injury.