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The electronic properties of vanadium atoms adsorbed on clean and graphene-covered Cu(111) surface have been systematically studied using ab initio theoretical method. Two coverages (1/9 ML and 1 ML) of vanadium adsorption are considered in this work. Our calculations indicate that V staying underneath the Cu surface is found to be the most stable adsorption site at the aforementioned two coverages for V/Cu(111). However, such adsorption may lead to undesired properties. Therefore, we introduce graphene as a buffer layer to effectively alleviate the direct interaction between V and Cu surface. The calculations show that electronic properties of the original graphene layer are significantly affected by the interactions of C atoms with the V adatoms; the Dirac point of graphene is "destroyed" as a consequence at both coverages. In the V/Gra/Cu(111) system, the interaction between graphene layer and the substrate Cu atoms remains weak as in the Gra/Cu(111) system. Moreover, a relatively low coverage of 1/9 ML gives rise to a spin-polarized system while a non-spin-polarized system is observed at the coverage of 1 ML. This finding offers a new way for the application of vanadium-based materials in reality.

Development of fast and accurate methods to discover lead compounds for drug candidates is highly important. In this study, a reliable and effective post-column on-flow biochemical assay (POBA) was established to screen potent peroxidase inhibitors from complex chemical mixtures (e.g., natural product extracts). Multiple factors such as flow rate, organic phase, detection wavelength, and reaction coil were carefully investigated. To better understand the features of POBA, another emerging technology of ultrafiltration LC-MS was used for comparison. The result showed that POBA had advantages in saving time, avoiding false positives, and improving the accuracy. To illustrate the practicality of the method, Radix Salvia Miltiorrhizae, a traditional herb for cardiovascular disease treatment, was applied as the research objective. Finally, six compounds including tanshinol, protocatechuic aldehyde, salvianolic acid D, rosmarinic acid, lithospermic acid, and salvianolic acid B were determined as novel peroxidase inhibitors. Their bioactivities were validated by microplate-based assay, molecular docking, and pharmacophore modeling. This study demonstrates a great potential of POBA in the efficient and accurate discovery of drug candidates. Graphical abstract Compared with a classical method of ultrafiltration LC-MS, the newly developed method of on-flow bioassay shows advantages in saving time, avoiding false positives and improving the accuracy.

China is the leading country for production of edible mushrooms and also outputs numerous mushroom residues. The recycling of mushroom residue can solve environmental pollution problems, provide nutrients for the farmland, and play an important role in reducing greenhouse gas emissions and increasing soil carbon sequestration capacity. In order to investigate the effects of mushroom residue amounts on net greenhouse gas emissions in purple paddy soil, potted experiments using static opaque chamber and gas chromatography methods were used to study the changes of greenhouse gases, soil carbon sequestration, and net greenhouse gas emissions (NGHGE) in the paddy soil with five treatments: no fertilizer (CK), conventional fertilization (NPK), 9 t·hm -2 mushroom residue+NPK (LM), 18 t·hm -2 mushroom residue+NPK (MM), and 36 t·hm 2 mushroom residue+NPK (HM) from March 2017 to September 2017.The results showed that: ① The greenhouse gas emissions (including CH 4 , CO 2 , and N 2 O) increased with increasing additions of mushroom residue. The emissions of CH 4 from highest to lowest followed: HM > MM > LM≈NPK > CK. The HM treatment significantly increased the CH 4 emission flux ( P <0.01) more than the other treatments and showed an obvious single peak curve, while the CH 4 emission flux with the LM treatment showed a bimodal curve, and the MM treatment showed a multiple peak curve. The CO 2 emission flux followed: MM > NPK≈LM > HM > CK; and the curves for the LM, MM, and HM treatments were a single peak curve, bimodal curve, and multiple peak curve, respectively. The N 2 O cumulative emission from the NPK treatment was significantly higher than with the other treatments. The N 2 O emission flux of the NPK treatment was a bimodal curve and that of the HM treatment was a single peak curve, while the N 2 O emission flux of treatments LM and MM showed multiple peak curves. ② The carbon sequestration capacity with the LM treatment was lower than that of the other treatments and that from the MM treatment was the highest. The carbon sequestration capacity of the MM treatment increased by 59.2% compared to that of the NPK treatment and increased by 87.79% and 65.65% compared to that of the LM and HM treatments. The LM treatment has the highest carbon sequestration capacity, which was higher than that of the NPK and MM treatments and about 2.1 times greater than the CK treatment and HM treatment. ③ The minimum NGHGE value was -490.29 kg·hm -2 for the whole rice production period, and 18 t·hm -2 mushroom residue applied to the soil was the best way to reduce net greenhouse gas emissions in purple paddy soil.

Objective: To investigate the brain volume alterations in patients with hyposmia using voxel-based morphometry (VBM) and to correlate these alterations with the degree and duration of hyposmia. Methods: Forty patients with hyposmia from Department of Otorhinolaryngology Head and Neck Surgery, Beijing Anzhen Hospital since 2013 to 2016 and forty age and sex matched normal subjects were recruited in this study. Sniffin' Sticks olfactory test was performed to evaluate the olfactory function of all subjects. We acquired T1-weighted magnetic resonance images from all subject on a 3T scanner. VBM was performed using VBM8 toolbox and SPM8 in a Matlab environment. Independent sample t test analysis was used to compare the volume of gray and white matter between the controls and patients. In addition, the Pearson or Spearman correlation analysis was used for the correlation between the voxel value of cerebral volume alterations area and the degree and duration of hyposmia on patients (threshold discrimination identification, TDI). Results: Compared with the controls, patients showed significantly decreased volume in the gray matter of right orbitofrontal cortex (number of voxel in clusters was 226, t =-4.46, P <0.001, uncorrected). There was negative correlation between decreased gray matter volume of the right orbitofrontal cortex with significantly decreased area and the TDI results ( r =-0.40, P =0.01), but positive correlation with duration of hyposmia ( r =0.37, P =0.02). Conclusions: The patients with hyposmia show gray matter atrophy of the right orbitofrontal cortex. The duration may be an important risk factor for decreased gray matter in patients with hyposmia.

Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p < 0.05, p < 0.01, and p < 0.001) in the zebrafish model. The larval zebrafish heart failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

Background: Tumor associated macrophages (TAMs) have multifaceted roles in the development of many tumor types. However, the prognostic value of TAMs in bladder cancer is still not conclusive., Experimental Design: This review evaluated the prognostic value of TAMs density in bladder cancer by reviewing published literatures and integrating the results via a meta-analysis. A systematic search was conducted in PubMed, Embase and Chinese National Knowledge Infrastructure (CNKI), WanFang, and Web of Science databases for relevant studies. Overall survival (OS), relapse free survival (RFS), disease specific survival (DSS), and progression free survival (PFS) were assessed in bladder cancer patients., Results: The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) indicated that TAMs identified with CD68 alone have no significant correlation with OS (HR = 1.01, 95% CI = 1.00-1.02), RFS (HR = 0.99, 95% CI = 0.91-1.06), or PFS (HR = 1.19, 95% CI = 0.70-1.68) in bladder cancer patients. Subgroup analyses involved with Bacillus Calmette Guerin (BCG) treatment or sample locations either showed that CD68 + TAMs presented no prognostic value with regard to OS in bladder cancer patients. However, TAMs detected by CD163 are significantly correlated with poor RFS in bladder cancer patients (HR = 1.54, 95% CI = 1.16-1.92)., Conclusions: Our data indicated that TAMs identified only with CD68 have no significant correlation with the prognosis and clinicopathological parameters of bladder cancer patients. However, TAMs detected with CD163 could serve as a prognostic marker for bladder cancer patients. These findings invite further research on the role of TAM subsets in bladder cancer patients., Competing Interests: CONFLICTS OF INTEREST The authors declared no conflicts of interest.

The purpose of the present study was to establish an effective robotic assistive stepping pattern of body-weight-supported treadmill training based on a rat spinal cord injury (SCI) model and assess the effect by comparing this with another frequently used assistive stepping pattern. The recorded stepping patterns of both hind limbs of trained intact rats were edited to establish a 30-sec playback normal rat stepping pattern (NRSP). Step features (step length, step height, step number and swing duration), BBB scores, latencies, and amplitudes of the transcranial electrical motor-evoked potentials (tceMEPs) and neurofilament 200 (NF200) expression in the spinal cord lesion area during and after 3 weeks of body-weight-supported treadmill training (BWSTT) were compared in rats with spinal contusion receiving NRSP assistance (NRSPA) and those that received manual assistance (MA). Hind limb stepping performance among rats receiving NRSPA during BWSTT was greater than that among rats receiving MA in terms of longer step length, taller step height, and longer swing duration. Furthermore a higher BBB score was also indicated. The rats in the NRSPA group achieved superior results in the tceMEPs assessment and greater NF200 expression in the spinal cord lesion area compared with the rats in the MA group. These findings suggest NRSPA was an effective assistive pattern of treadmill training compared with MA based on the rat SCI model and this approach could be used as a new platform for animal experiments for better understanding the mechanisms of SCI rehabilitation.

A growing number of children and adolescents are being diagnosed as Chiari malformation type I (CM-I) for behavioral disorders, developmental delay, seizures, or abnormal orpharyngeal function. The aim of this study was to compare the clinical characteristics, imaging findings and surgical outcomes of CM-I in pediatric and adult patients. Between January 2014 and June 2017, 84 patients with CM-I underwent surgical treatment in our department. We divided the patients into two groups: pediatric group (n=11, age <18 years) and adult group (n=73, age ≥18 years). Data on clinical characteristics, imaging findings, surgical outcomes, and prognosis were retrospectively reviewed and compared between these two groups. For clinical presentation, scoliosis (36.4%) and developmental delay (36.4%) were more common in pediatric patients, whereas, sensory disturbance (58.9%) and motor weakness (41.1%) were more common in adult patients. Imaging findings showed that the incidence of hydrocephalus and craniovertebral junctional abnormalities was significantly higher in pediatric group than in adult group (P<0.05). Compared to adult group, pediatric group showed a better improvement or resolution of syrinx and tonsillar herniation after surgical treatments (P<0.05). The total Chicago Chiari Outcome Scale (CCOS) score in pediatric patients at the last followup was significantly higher than that in adult patients (P=0.002). In conclusion, the clinical characteristics and imaging findings appeared to be different in pediatric and adult patients with CM-I. The surgical outcomes of pediatric patients were shown to be significantly better than those of adult patients.

Background: The toll-like receptor 2 (TLR2)-mediated immune response is critical for host defense against Mycobacterium tuberculosis . There is evidence that TLR10, a TLR2 signaling modulator, may be involved in progression of tuberculosis (TB)., Methods: Using a self-validating case-control design, we tested for an association between seven TLR10 polymorphisms and susceptibility to TB in three independent series with two distinct populations. Single-nucleotide polymorphism (SNP) genotypes were determined by the SNPscan TM method. Three genetic models (additive, dominant, and recessive) as well as multiple-SNP score analyses were used to evaluate the risk of TB associated with the TLR10 SNPs., Results: By comparing TB patients with healthy controls, we observed two SNPs (rs11466617 and rs4129009) that were associated with decreased risk of TB in the Tibetan population, but did not in the Chinese Han population. Further analysis demonstrated that the rs11466617 Chengdu cohort genotype served as a protective factor against the progression of latent TB infection (LTBI) to active TB under the recessive model. None of the SNPs were significantly different in comparisons of TB-uninfected people with LTBI individuals. Additionally, when the underlying four TB-associated loci were considered together in a multiple-SNP score analysis, we observed an allele dose-dependent decrease in TB risk in Tibetans., Conclusion: Variants of TLR10 may show an ethnic specificity on susceptibility to TB in Tibetan individuals. rs11466617 affected the susceptibility to progress from LTBI to active TB disease, but was not associated with the establishment of LTBI after M. tuberculosis exposure. More studies are needed to verify this genetic epidemiological result and unravel the role of TLR10 SNPs in the pathogenesis of TB.

The aim of this study was to establish an appropriate rat model to study the effect of electroacupuncture (EA) analgesia on acute visceral hyperalgesia. Adult rats received colorectal instillation with different concentrations of acetic acid (AA). Treatment with EA was performed for 30 min at bilateral acupoints of ST-36 and ST-37 in the hind limbs. The visceral sensation of all rats was quantified by scores of abdominal withdrawal reflex (AWR) and discharges of rectus abdominis electromyogram (EMG) in response to colorectal distension (CRD). Two hours after instillation of saline (no AA), 1%, 2%, and 4% AA, there were no, slight, moderate and severe visceral hyperalgesia, respectively. Application of EA significantly relieved the visceral hyperalgesia induced by 2% but not 4% AA. The results suggest that 2% AA acute visceral hyperalgesia in adult rats responds well to EA treatment. This may offer an appropriate model for the investigation of EA effects.

The magnetic and electrical properties of complex oxide thin films are closely related to the phase stability and cation ordering, which demands that we understand the process-structure-property relationships microscopically in functional materials research. Here we study multiferroic thin films of double-perovskite La 2 NiMnO 6 epitaxially grown on SrTiO 3 , KTaO 3 , LaAlO 3 and DyScO 3 substrates by pulsed laser deposition. The effect of epitaxial strains imposed by the substrate on the microstructural properties of La 2 NiMnO 6 has been systematically investigated by means of advanced electron microscopy. It is found that La 2 NiMnO 6 films under tensile strain exhibit a monoclinic structure, while under compressive strain the crystal structure of La 2 NiMnO 6 films is rhombohedral. In addition, by optimizing the film deposition conditions a long-range ordering of B-site cations in La 2 NiMnO 6 films has been obtained in both monoclinic and rhombohedral phases. Our results not only provide a strategy for tailoring phase stability by strain engineering, but also shed light on tuning B-site ordering by controlling film growth temperature in double-perovskite La 2 NiMnO 6 films.

Granulomas were reported in 0.3% to 3% of bone marrow biopsies. The aim of the study was to evaluate the incidence and etiology of bone marrow granulomas (BMGs) in the West China Hospital, which located at a high tuberculosis (TB) prevalence area in China.A retrospective case review was performed on 11,339 bone marrow biopsies at the West China Hospital of Sichuan University between January 2011 and December 2015. Cases with BMGs were retrieved and their clinical data and histopathological features were collected, examined, and analyzed.Out of 11,339, 110 cases showed granulomatous lesions in the bone marrow biopsies (0.97%). Etiologies were indentified in 80 cases (72.8%), with infections being the most common (64.5%), following by malignancies (4.5%) and autoimmune diseases (3.6%). Among infectious cases, 87.32% (62/71) cases were diagnosed as TB, a positive acid-fast stain or/and polymerase chain reaction (PCR) result for mycobacterium TB DNA fragment amplification was obtained for 35 cases. In 30 cases (27.27%), a definite diagnosis could not be established.In a TB high prevalence region in China, with a combined histological, clinical, serological, and molecular approach, we were able to clarify the cause in 72.73% of the bone marrow granulomatous cases. TB is the most common underlying etiologies. Therefore, acid-fast stain and quantitative PCR for mycobacterium TB DNA amplification are recommended as a routine for bone marrow biopsies in TB high prevalence regions.

Bladder cancer has a high recurrence rate and requires adjuvant intravesical management after surgery. The use of traditional agents for bladder cancer therapy is constrained by their toxicity and limited efficacy. This emphasizes the need for the development of safer, more effective compounds such as instillation agents. Curcumin is the major component of turmeric, the powdered root of Curcuma longa, which is known for its anti-inflammatory, anti-oxidant and anticancer properties. First, a microarray profiling and qPCR analysis were conducted in the T24 and SV-HUC-1 cell lines. Then, we examined the potential tumorigenicity of miR-7641 in the T24 and SV-HUC-1 cell lines with or without curcumin. Western blot analysis showed that p16 is a target of miR-7641 in T24 cells. We found that, for the first time, curcumin directly downregulates a tumor-promoting microRNA (miRNA), miR-7641, in bladder cancer, which has tumor-promoting characteristics. Curcumin induces the downregulation of miR-7641 and subsequent upregulation of p16 which is a target of miR-7641 at the post-transcriptional level, which leads to the decreased invasion and increased apoptosis of bladder cancer cells. This is the first report to show a direct effect of curcumin on inducing changes in a miRNA suppressor with direct anticancer consequences in bladder cancer. Our study shows that curcumin may be a candidate agent for the clinical management of non-muscle-invasive bladder cancer.

Anti-tuberculosis drug-induced liver injury (ATLI) is common during the treatment of tuberculosis (TB). As an important enzyme in the metabolism of many drugs, UGT2B7 (uridine diphosphate glucuronyl transferase 2B7) was associated with drug-induced liver disorder. This study investigated the association between the polymorphisms of UGT2B7 and ATLI in Chinese Han. Totally, 280 newly diagnosed TB patients had been followed up for 3 months after the prescription of anti-TB therapy. Tag-single-nucleotide polymorphism (tag-SNPs) (rs10028494 and rs7668282) were genotyped with the MassARRAY platform. The associations between tag-SNPs and ATLI risk were analyzed by logistic regression analysis adjusting for confounding factors. In this prospective study, 33 patients were lost to follow-up, and 24 patients were diagnosed with ATLI and considered as the case group. The remaining 223 subjects without ATLI were considered as the control group. No significant association was observed in allele and genotype frequencies of UGT2B7 between the two groups. This study is the first attempt to investigate the association of genetic polymorphisms of UGT2B7 with ATLI in Chinese Han. There is no significant association between UGT2B7 polymorphisms and ATLI in Chinese Han.

Network structures based on Star-of-David catenanes with multiple superior functionalities have been so far elusive, although numerous topologically interesting networks are synthesized. Here, a metal-organic framework featuring fused Star-of-David catenanes is reported. Two triangular metallacycles with opposite handedness are triply intertwined forming a Star-of-David catenane. Each catenane fuses with its six neighbors to generate a porous twofold intercatenated gyroid framework. The compound possesses exceptional stability and exhibits multiple functionalities including highly selective CO 2 capture, high proton conductivity, and coexistence of slow magnetic relaxation and long-range ordering., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sustainability urgently demands low dielectric loss and low elastic modulus as fostering high permittivity (Hi-K) conductor/polymer composites. This work introduces a ternary composite system, consisting of acrylic resin elastomer (AR), chemically modified polyaniline (HBSiPA), and the thermally reduced graphene oxides (TrGOs), for applying to actuators, of which AR was fabricated by free radical polymerization. The unique hybridized graphene (HBSiPA-TrGO) was prepared by a two-step procedure, including the doped polyaniline modified by the hyperbranched polysiloxane via a ring opening reaction, followed by the decoration of HBSiPA on the surface of TrGO, the conductivity of which is desired to be the same as that of graphene. Afterward, diverse filler contents of HBSiPA-TrGO were put into the AR matrix to fabricate composites with the solution casting method and TrGO/AR composites were fabricated as well for comparison. Unlike TrGO, HBSiPA has plenty of polyaniline chain segments that ensure better dispersion of graphene hybrids in the AR, and thus the composites inherit the excellent electrical property of graphene. The permittivity and dielectric loss of the HBSiPA-TrGO/AR composite at 100 Hz are 3.5 and 0.27 times that of the TrGO/AR composite, respectively, when the loading of fillers approaches the percolation threshold (f c ), which originates from the HBSiPA anchored onto the graphene serving as spacer and thus decreases the leakage currents induced by the contact of graphene sheets. Besides, the elastic modulus of 2.83 vol % HBSiPA-TrGO/AR composite was lower than 5 MPa.

Objective To explore the efficacy of ganoderma lucidum preparation(Ling Zhi) in treating APP/PS-1 transgenic mouse models of Alzheimer's disease(AD).Methods APP/PS-1 transgenic mice of 4 months were randomly divided into model group,ganoderma lucidum treatment groups,including high [2250 mg/(kg·d)] and middle [750 mg/(kg·d)] dose groups,i.e.LZ-H and LZ-M groups,and the positive control group(treated with donepezil hydrochloride [2 mg/(kg·d)]).In addition,C57BL/6J wild mice were selected as normal group.The animals were administered for 4 months.Histopathological examinations including hematoxylin-eosin(HE) staining,immunohistochemistry,special staining,and electron microscopy were applied,and then the pathological morphology and structures in different groups were compared. Results The senile plaques and neurofibrillar tangles in the cerebrum and cerebellum were dissolved or disappeared in LZ-H and LZ-M groups.Decrease of amyloid angiopathy was found in LZ-H and LZ-M groups.The immature neurons appeared more in hippocampus and dentate nucleus of LZ-H and LZ-M groups than those in AD model and donepezil hydrochloride groups(hippcampus:F=1.738,P=0.016;dentate nucleus:F=1.924,P=0.026),and these immature neurons differentiated to be neurons.More Purkinje cells loss occurred in AD model mice than that in LZ-H and LZ-M groups(F=9.46,P=0.007;F=9.46,P=0.010).The LZ-H and LZ-M groups had more new neuron stem cells grown up in cerebellum.Electromicroscopic examination showed the hippocampal neurons in LZ-H and LZ-M group were integrated,the nuclear membrane was intact,and the mitochondria in the cytoplasm,endoplasmic reticulum,Golgi bodies,microtubules,and synapses were also complete.The microglial cell showed no abnormality.No toxicity appeared in the pathological specimens of mice treated with ganoderma lucidum preparation.Conclusion The ganoderma lucidum preparation can dissolve and decline or dismiss the senile plaques and neurofibrillar tangles in the brain of AD mice and also reduce the amyloid angiopathy.

Objective: To analyze the clinical significance of corrected serum calcium(CSCa) in patients with multiple myeloma., Methods: The serum calcium levels of 320 patients with initial multiple myeloma were measured and corrected by serum albumin and its levels measured simultaneously. The differences of serum calcium levels were analyzed before and after the correction by serum albumin., Results: There was a significant difference between serum calcium and CSCa in MM patients (2.34±0.15 vs 2.6±0.17 mmol/L). The constituent ratio of patients with hypercalcemia was from 11.3% to 23.1% after correction, the MM patients with hypocalcemia was decreased from 42.8% to 7.8% after correction, and the patients with normal calcium level were increased. There was a significant difference between serum calcium level and CSCa in I, II, III stages of MM patients respectively(P<0.05). In the 320 patients, the incidence of anemia was 80%, renal failure was 20.9%, and myeloma bone disease was 68.8%. Calcium concentration in both anemia and renal insufficiency was higher than the normal group, and the difference was more significant after correction. In 220 cases of MM receiving chemotherapy, the median progression-free survival (PFS) was 15 months, and overall survival(OS) time was 20 months. The PFS and OS time of the patients with hypercalcemia were shortened, and the difference was very significant after correction(P<0.01)., Conclusion: Corrected serum calcium can more sensitively to reflect the diseases serious extent, thus indicating prognosis has better effect.

The development of magnetic molecules with long spin reversal/decoherence times highly depends on the understanding of relaxation behavior under different external conditions. Herein, a magnetic study on a Ru III complex (1) is presented. Detailed analysis of the relaxation time and the magneto-heat capacity data suggests that the resonant phonon trapping process dominates the magnetic relaxation in the crystalline sample of 1, slowing down the spin relaxation rate, as further confirmed by the measurements on a ground sample and frozen solution. Thus, it provides a rare example showing that 4d metal-centered mononuclear compounds without second-order anisotropy can display slow magnetic relaxation., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An octacoordinated Fe(II) complex, [Fe II (dpphen) 2 ](BF 4 ) 2 ·1.3H 2 O (1; dpphen = 2,9-bis(pyrazol-1-yl)-1,10-phenanthroline), with a pseudo-D 2d -symmetric metal center has been synthesized. Magnetic, high-frequency/-field electron paramagnetic resonance (HF-EPR), and theoretical investigations reveal that 1 is characterized by uniaxial magnetic anisotropy with a negative axial zero-field splitting (ZFS) (D ≈ -6.0 cm -1 ) and a very small rhombic ZFS (E ≈ 0.04 cm -1 ). Under applied dc magnetic fields, complex 1 exhibits slow magnetic relaxation at low temperature. Fitting the relaxation time with the Arrhenius mode combining Orbach and tunneling terms affords a good fit to all the data and yields an effective energy barrier (17.0 cm -1 ) close to the energy gap between the ground state and the first excited state. The origin of the strong uniaxial magnetic anisotropy for 1 has been clearly understood from theoretical calculations. Our study suggests that high-coordinated compounds featuring a D 2d -symmetric metal center are promising candidates for mononuclear single-molecule magnets.

Natural products are becoming increasingly popular in multiple fields involving medicines, foods and beverages. However, due to the frequent occurrence of poisoning incidents, their toxicity and safety have caused a serious concern. Here we report a method of biosensor-based two-phase pharmacological profiling (BTPP) for discovery, monitor and control of receptor-targeted natural products. BTPP uses a resonant waveguide grating biosensor for label-free and non-invasive detection of intracellular dynamic mass redistribution (DMR), a phenomenon caused by protein relocalization after receptors receiving stimulation from toxicants. The method can not only facilitate the identification of hazardous materials but also quantify their bioactivity by EC 50 . As a proof of concept, the method was successfully applied to recognize Daturae Flos (DF), an herb that can antagonize muscarinic acetylcholine M 2 receptor and further cause poisoning, from other easily confused species. BTPP combined with high performance liquid chromatography revealed that scopolamine and hyoscyamine in DF were the key marker compounds. Moreover, the method accurately picked out 2 M 2 receptor antagonists from 25 natural compounds, displaying its potential in high-throughput screening. This study provides a systematic illustration about the establishment, applicability and advantages of BTPP, which contributes to the safety assessment of natural products in related fields., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) programs are involced in the metastatic process. More and more evidence confirms that EMT is vital for the initiation and dissemination of cancer cells whereas MET is critical for successful metastatic colonization of a secondary organ. The regulating mechanism of EMT mediated cancer progression and metastasis has been deeply investigated. However, what processes are dependent on MET in metastatic cascades remains unclear. Here, we created a cell based high-content siRNA screen using the breast cancer cell line 4TO7 to search for kinases that were involved in Git2-induced MET. Our results revealed that 58 kinases including transferase, phosphorylation regulators, ATP/nucleotide partners potentially participate in Git2-induced MET. Our preliminary data is expected to facilitate elucidation of the mechanism on how MET is initiated during cancer metastasis.

Objectives: Antituberculosis drug-induced hepatotoxicity (ATDH) remains a common and severe challenge in tuberculosis (TB) chemotherapy. A growing number of studies have revealed that genetic polymorphisms affect an individual's susceptibility to ATDH. The aim of this study was to explore the role of cytochrome P450 family 2 subfamily B member 6 (CYP2B6) gene polymorphisms in the development of ATDH in Chinese TB patients., Methods: CYP2B6*6 genotypes were determined in TB patients with and without ATDH. Association between polymorphisms and risk of ATDH was estimated by multiple logistic regression analysis., Results: A total of 343 eligible TB patients (166 with ATDH; 177 without ATDH) were included in this study. Analysis of all subjects revealed no statistical differences in genotype distribution between the two groups. However, the CYP2B6 *6/*6 genotype was significantly associated with decreased risk of ATDH in the male subgroup (P=0.039, OR=0.097, 95% CI: 0.011-0.885). Furthermore, in male patients, the presence of the CYP2B6*6 allele was significantly higher in the non-ATDH group compared with the ATDH group (26.2% vs. 15.5%, P=0.020, OR=0.522, 95% CI: 0.301-0.903)., Conclusions: This study is the first to demonstrate an association between CYP2B6 polymorphisms and the risk of ATDH in the Chinese population. We have shown that males who have the CYP2B6 *6/*6 genotype may be less susceptible to the development of ATDH. Further studies are required to confirm this genetic association result., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Magnetic skyrmions are promising building blocks for next generation data storage due to their stability, small size and extremely low currents to drive them, which can be used instead of traditional magnetic domain walls to store information as data bits in metalic racetrack memories. However, skyrmions can drift from the direction of electron flow due to the Magnus force and thus may annihilate at the racetrack edges, resulting in the loss of information. Here we propose a new skyrmion-based racetrack structure by adding high-K materials (materials with high magnetic crystalline anisotropy) at the edges, which confines the skyrmions in the center region of the metalic racetrack efficiently. This design can overcome both the clogging and annihilation of skyrmions according to our micromagnetic simulation, which occur normally for skyrmions moving on a racetrack under small and large driving currents, respectively. Phase diagrams for skyrmion motion on the proposed racetrack with various values of current density and racetrack edge width have been calculated and given, showing that skyrmions can be driven at a high speed (about 300 m/s) in the racetrack under relatively smaller driving currents. This design offers the possiblity of building an ultrafast and energy-efficient skyrmion transport device.

We report synthesis, crystal structure and physical properties of a novel quinary compound RbGd 2 Fe 4 As 4 O 2 . The new iron oxyarsenide is isostructural to the fluo-arsenide KCa 2 Fe 4 As 4 F 2 , both of which contain separate double Fe 2 As 2 layers that are self hole-doped in the stoichiometric composition. Bulk superconductivity at [Formula: see text] K is demonstrated by the measurements of electrical resistivity, dc magnetic susceptibility and heat capacity. An exceptionally high value of the initial slope of the upper critical field ([Formula: see text]d[Formula: see text]/d[Formula: see text] [Formula: see text] T K -1 ) is measured for the polycrystalline sample.

This paper describes a label-free 17E DNAzyme-based time-gated fluorescence sensor for Pb 2+ detection by unmodified gold nanoparticles (GNPs) and a terbium ternary complex. The fluorophore that used in this paper is a terbium ternary complex. Its signal can be measured in a time-gated manner which could eliminate most of the unspecific fluorescent background. It is well known that unfolded single-stranded DNA (ssDNA) could be adsorbed on GNPs while double-stranded DNA could not. The cleavage of the substrate by the 17E DNAzyme in the presence of Pb 2+ causes the release of ssDNA from the 17E-17S duplex to be absorbed onto GNPs, preventing the aggregation of GNPs and then leading to a fluorescence decrease of terbium ternary complex. By means of this method, the authors have successfully detected Pb 2+ over a range of 10 nM to 2500 nM with a detection limit of 1.7 nM. The sensor also exhibited good selectivity. The sensor provided a simple, cost-effective, rapid and sensitive measurement tool for Pb 2+ detection.

Atypically anisotropic and large changes in magnetic susceptibility, along with a change in crystalline shape, were observed in a Co II complex at near room temperature. This was achieved by combining oxalate molecules, acting as rotor, and a Co II ion with unquenched orbital angular momentum. A thermally controlled 90° rotation of the oxalate counter anion triggered a symmetry-breaking ferroelastic phase transition, accompanied by contraction-expansion behavior (ca. 4.5 %) along the long axis of a rod-like single crystal. The molecular rotation induced a minute variation in the coordination geometry around the Co II ion, resulting in an abrupt decrease and a remarkable increase in magnetic susceptibility along the direction perpendicular and parallel to the long axis of the crystal, respectively. Theoretical calculations suggested that such an unusual anisotropic change in magnetic susceptibility was due to a substantial reorientation of magnetic anisotropy induced by slight disruption in the ideal D 3 coordination environment of the complex cation., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Porcine epidemic diarrhea virus (PEDV) first emerged in the United States in 2013 causing high mortality and morbidity in neonatal piglets with immense economic losses to the swine industry. PEDV is an alpha-coronavirus replicating primarily in porcine intestinal cells. PEDV vaccines are available in Asia and Europe, and conditionally-licensed vaccines recently became available in the United States but the efficacies of these vaccines in eliminating PEDV from swine populations are questionable. In this study, the immunogenicity of a subunit vaccine based on the spike protein of PEDV, which was directly targeted to porcine dendritic cells (DCs) expressing Langerin, was assessed. The PEDV S antigen was delivered to the dendritic cells through a single-chain antibody specific to Langerin and the targeted cells were stimulated with cholera toxin adjuvant. This approach, known as "dendritic cell targeting," greatly improved PEDV S antigen-specific T cell interferon-γ responses in the CD4 pos CD8 pos T cell compartment in pigs as early as 7days upon transdermal administration. When the vaccine protein was targeted to Langerin pos DCs systemically through intramuscular vaccination, it induced higher serum IgG and IgA responses in pigs, though these responses require a booster dose, and the magnitude of T cell responses were lower as compared to transdermal vaccination. We conclude that PEDV spike protein domains targeting Langerin-expressing dendritic cells significantly increased CD4 T cell immune responses in pigs. The results indicate that the immunogenicity of protein subunit vaccines can be greatly enhanced by direct targeting of the vaccine antigens to desirable dendritic cell subsets in pigs., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Tea production has been significantly impacted by the false-eye leafhopper, Empoasca vitis (Göthe), around Asia. To identify the key genes which are responsible for nutrition absorption, xenobiotic metabolism and immune response, the transcriptome of either alimentary tracts or bodies minus alimentary tract of E. vitis was sequenced and analyzed. Over 31 million reads were obtained from Illumina sequencing. De novo sequence assembly resulted in 52,182 unigenes with a mean size of 848nt. The assembled unigenes were then annotated using various databases. Transcripts of at least 566 digestion-, 224 detoxification-, and 288 immune-related putative genes in E. vitis were identified. In addition, relative expression of highly abundant transcripts was verified through quantitative real-time PCR. Results from this investigation provide genomic information about E. vitis, which will be helpful in further study of E. vitis biology and in the development of novel strategies to control this devastating pest., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Osteoporosis is a major complication in patients with diabetes mellitus. Thus, it is crucial to study the signal mechanisms responsible for enhancement of bone mass in diabetes. Administration of human parathyroid hormone (hPTH) has been reported to prevent osteoblast apoptosis and have anabolic effects on bone in animals and humans. In the present study, we examined the effects of hPTH on expression of bone morphogenetic protein type 2 (BMP-2) and its receptor BMPR2 in diabetic rats following spinal fusion. Our data show that hPTH amplified BMP-2 and BMPR2 in bone tissues of non-diabetic rats, but not in diabetic rats. Our data further demonstrate that hPTH plays a role in regulating BMP-2 and BMPR2 via mTOR-PI3K signal pathway. We suggest specific signaling pathways by which hPTH regulates BMP-2 via mTOR-PI3K mechanism in bone formation following spinal fusion. Notably, our data indicate under diabetic conditions this signal pathway is impaired, thereby likely affecting bone formation after spinal fusion. The subsequent induction of BMP-2 and BMPR2 are likely a part of the protective effects aimed at attenuating pathological bone damage as a result of diabetes.

Multifunctional nanoprobes that provide diagnosis and treatment features have attracted great interest in precision medicine. Near-infrared (NIR) persistent luminescence nanoparticles (PLNPs) are optimal materials due to no in situ excitation needed, deep tissue penetration, and high signal-to-noise ratio, while activatable optical probes can further enhance signal-to-noise ratio for the signal turn-on nature. Here, we show the design of an activatable multifunctional PLNP/copper sulfide (CuS)-based nanoprobe for luminescence imaging-guided photothermal therapy in vivo. Matrix metalloproteinases (MMPs)-specific peptide substrate (H 2 N-GPLGVRGC-SH) was used to connect PLNP and CuS to build a MMP activatable system. The nanoprobe not only possesses ultralow-background for in vivo luminescence imaging due to the absence of autofluorescence and optical activatable nature but also offers effective photothermal therapy from CuS nanoparticles. Further bioconjugation of c(RGDyK) enables the nanoprobe for cancer-targeted luminescence imaging-guided photothermal therapy. The good biocompatibility and the multiple functions of highly sensitive tumor-targeting luminescence imaging and effective photothermal therapy make the nanoprobe promising for theranostic application.

Herbal medicines (HMs) are an important source of drugs. In this study, an efficient strategy integrating ultrafiltration LC-MS, microplate bioassays, and molecular docking was proposed to screen high-potency enzyme inhibitors from HMs. Using this strategy, the structure-activity relationships (SARs) including binding-affinity-based SAR, enzymatic-activity-based SAR, and structural-complementarity-based SAR of compounds in an HM can be analyzed to provide abundant information for drug discovery. A prominent advantage of the approach is that it offers a multidimensional perspective to understand enzyme-ligand interactions, which could help to avoid false-positive screening results brought by a single method. By using xanthine oxidase (XOD) as an illustrative case, two types of potent XOD inhibitors, including flavones and coumarins, were successfully screened out from an HM of Ginkgo biloba. The study is expected to set a solid foundation for multidisciplinary cooperation in drug discovery., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with neurocognitive impairment. We examined the role of the systemic inflammatory response, measured by high-sensitivity C-reactive protein (hsCRP) assay, and the effect of CPAP treatment on hsCRP and cognitive impairment in patients with OSAHS., Methods: Eligible subjects (n = 178) were categorized into two groups: absent or mild OSAHS, and moderate to severe OSAHS. First, the Montreal Cognitive Assessment (MoCA) and serum hsCRP concentration were measured. Then, the moderate to severe OSAHS group was further divided into a conservative treatment subgroup (n = 68) and a CPAP subgroup (n = 68). After 6 months of treatment, MoCA scores and hsCRP concentrations were re-measured in the moderate to severe group., Results: Compared with the absent or mild OSAHS group, hsCRP concentration was higher (1.00 ± 1.28 mg/L versus 2.71 ± 1.8, p < 0.001) and MoCA scores were significantly lower (27.4 ± 1.4 versus 26.3 ± 2.0, p < 0.001) in the moderate to severe group. After adjustment for age, education, body mass index, and neck circumference, hsCRP and MoCA scores correlated with parameters of overnight hypoxia. hsCRP and the proportion of time spent with blood oxygen saturation < 90 % (T90) predicted MoCA score. hsCRP and MoCA score improved, and the subdomains of the MoCA were partially improved, in the CPAP treatment subgroup. In conservatively managed patients, hsCRP concentration increased, and there was no improvement in neurocognitive dysfunction, with the memory subdomain significantly worse., Conclusions: hsCRP may play a role in neurocognitive dysfunction in OSAHS. Long-term CPAP treatment could normalize the serum hsCRP concentration and partially reverse cognitive dysfunction in OSAHS.

Grass carp reovirus (GCRV) is the causative agent of hemorrhagic disease in infected grass carp. During an outbreak, a mortality rate of up to 85% can be experienced, thus leading to substantial economic losses. The current understanding of disease pathogenesis is limited, with the distribution and dynamics of replication amongst different GCRV strains in vivo largely unknown. We determined distribution of different GCRV strains in infected grass carp, especially in some neglected tissues, such as the gill, brain, blood and so on. The results showed elevated viral RNA copy numbers in the blood, with some tissues such as the kidney, heart, brain, and bladder exhibiting even higher viral loads following infection with the virulent GCRV-CL strain. Even more interesting is that the brain exhibited the highest viral load, with a copy number of 800,000 following GCRV-CL infection. Overall, this study provides further insight into GCRV viral load distributions following infection and potentially identified some new viral tropism sites to provide a foundation for further studies aimed at characterizing GCRV viral pathogenesis.

Two polymorphic structures have been well determined in a valence tautomeric (VT) dinuclear cobalt complex. These polymorphs showed distinct thermal- and photomagnetic behavior, and are thus ideal for studying the "pure" intermolecular factors to VT transitions. In polymorph 1A, the VT cations are arranged head-to-waist with their neighbors and exhibit weak π⋅⋅⋅π interactions, resulting in a gradual and incomplete thermal VT transition. In contrast, the cations in polymorph 1B are arranged head-to-tail and exhibit relatively strong π⋅⋅⋅π interactions, leading to an abrupt and complete thermal VT transition with adjustable hysteresis loop at around room temperature. The VT process for both polymorphs can be induced by light, but the light-excited state of 1B⋅2H 2 O has a higher thermal relaxation temperature than that of 1A⋅3H 2 O., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Proton transport via dynamic molecules is ubiquitous in chemistry and biology. However, its use as a switching mechanism for properties in functional molecular assemblies is far less common. In this study, we demonstrate how an intra-carboxyl proton shuttle can be generated in a molecular assembly akin to a rack-and-pinion cascade via a thermally induced single-crystal-to-single-crystal phase transition. In a triply interpenetrated supramolecular organic framework (SOF), a 4,4'-azopyridine (azpy) molecule connects to two biphenyl-3,3',5,5'-tetracarboxylic acid (H 4 BPTC) molecules to form a functional molecular system with switchable mechanical properties. A temperature change reversibly triggers a molecular movement akin to a rack-and-pinion cascade, which mainly involves 1) an intra-carboxyl proton shuttle coupled with tilting of the azo molecules and azo pedal motion and 2) H 4 BPTC translation. Moreover, both the molecular motions are collective, and being propagated across the entire framework, leading to a macroscopic crystal expansion and contraction., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Diabetes-induced xerophthalmia is a general metabolic disorder with high incidence and increased treatment difficulty. Our study aimed to explore the combined effect of traditional Chinese and Western medicines on diabetes-associated xerophthalmia. We recruited 60 diabetic xerophthalmia patients, and randomly assigned them to either the control (Western medicine treatment) or the experimental (combined treatment of traditional Chinese medicine and Western medicine) groups. Pre-treatment and post-treatment analyses were performed to assess the combined therapeutic effect of traditional Chinese and Western medicine on xerophthalmia-associated indicators. We found that the experimental group expressed reduced levels of IL-1, IL-8, and TNF-α (P < 0.05) as compared to the control group. Furthermore, the experimental group showed higher treatment efficacy as compared to the control group (85.00 vs 51.67% Z = 22.244, P < 0.05). In addition, break-up time (t = 20.582, P < 0.05) and tear section (t = 23.082, P < 0.05) was increased in the experimental group as compared to the controls. Lastly, it was found that the combined treatment of traditional Chinese and Western medicine effectively reduced corneal injuries, as indicated by reduced fluorescein staining. This study suggested that a combination treatment consisting of both traditional Chinese and Western medicines may be effective against xerophthalmia in diabetes, and that inflammatory factors are potential biomarkers to examine the treatment efficacy.

The oncogene B-cell-specific Moloney murine leukemia virus insertion site‑1 (Bmi‑1) is overexpressed in multiple myeloma (MM). Our previous study demonstrated that Bmi‑1 silencing sensitized MM cells to bortezomib. Translational regulation has emerged as a prominent underlying mechanism of Bmi‑1 regulation, particularly via microRNA targeting. The present study determined that Bmi‑1 may be directly targeted by miR‑203 using a luciferase assay. In addition, enforced expression of miR-203 led to significant downregulation of Bmi‑1 protein and mRNA expression levels. Furthermore, restoration of miR-203 significantly inhibited cell growth and G1/S transition in MM cells. miR‑203 was downregulated in MM patients, and a negative correlation between the expression of miR‑203 and Bmi‑1 was observed. The results of the present study indicated that miR‑203 exerts growth‑inhibiting effects in MM through the suppression of Bmi‑1 expression. In conclusion, the present study demonstrated that Bmi‑1 is a direct functional target of miR-203 in MM.

Study Design: We introduced an adenoviral vector expressing interleukin-1β (IL-1β) small-hairpin RNA (shRNA) into the injured spinal cords to evaluate the therapeutic potential of IL-1β downregulation in a rat model of spinal cord injury (SCI)., Objectives: The purpose of this study was to investigate the possible protective effects of the IL-1β downregulation on traumatic SCI in rats., Setting: Department of Orthopedic Surgery, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, People's Republic of China., Methods: An adenoviral shRNA targeting IL-1β was constructed and injected at the T12 section 7 days before SCI. The rats' motor functions were evaluated by the Basso-Beattie-Bresnahan (BBB) rating scale. Immunofluorescence, enzyme-linked immunosorbent assay, flow-cytometric analysis and western blots were also performed., Results: Animals downregulating IL-1β had significantly better recovery of locomotor function and less neuronal loss after SCI. In addition, IL-1β downregulation significantly decreased tumor necrosis factor-alpha (TNF-α) level and Bax expression, reduced the activity of caspase-3 and increased Bcl-2 expression after SCI., Conclusion: This study demonstrated that the IL-1β downregulation may have potential therapeutic benefits for both reducing secondary damages and improving the outcomes after traumatic SCI.

Objective: Antituberculosisdrug-induced hepatotoxicity (ATDH) is a common and sometimes serious side effect related to tuberculosis (TB) treatment. A number of risk factors and host genetics contribute to the development of ATDH. However, genetic factors of ATDH remain to be identified. Silent Information Regulator 1 (SIRT1), an essential metabolism gene, was proved to be involved in ATDH in mice. The aim of this investigation was to study the association between ATDH and tag-single nucleotide polymorphisms (tag-SNPs) of the SIRT1 gene in a prospective cohort study in patients with TB., Methods: 280 newly diagnosed TB patients were recruited in this study before starting first line anti-TB treatment and were followed up for 3 months after initiating anti-TB therapy. The tag-SNPs were selected by using Haploview 4.2 based on the HapMap database of Han Chinese Beijing. Genotyping was performed by polymerase chain reaction (PCR) and the Sequenom MassARRAY iPLEX platform., Results: 24 (9.8%) of the 245 patients included in the final analysis developed hepatotoxicity during the following up period. No significant differences in the allele, genotype, or haplotype frequency distributions of the tag- SNPs (rs7069102, rs2273773, rs4746720) of the SIRT1 gene were identified between the ATDH and non-ATDH groups (all p > 0.05)., Conclusions: The SIRT1 gene may not contribute to the risk for developing hepatotoxicity during anti-TB treatment in the Han Chinese population.

Low-fusing bonding agents have been widely applied in Ti-ceramics restorations. As an important category, borate bonding agents have great potentials in increasing Ti-porcelain bonding. The purpose of this study is to evaluate the effect of borate bonding agent with addition of Na2O and Al2O3 on Ti6Al4V-porcelain bonding. The thermal properties of borate bonding agent, such as glass transition temperature (Tg) and crystallization peak temperature (Tp), were investigated to establish the sintering process. And the coefficient of thermal expansion (CTE) was to evaluate the matching effect of porcelain to Ti6Al4V. The bond strength was analyzed by the three point bending test. The microscopic morphology of the borate bonding agent surface after sintering, the interface of Ti-borate bonding agent-porcelain, and the fracture mode after porcelains fracture, were studied to assess the influence of borate bonding agent on Ti6Al4V-ceramics. With the addition of Na2O and Al2O3, the porcelain residues were observed increased indication on the Ti6Al4V surface after porcelain fracture and the bond strength was acquired the maximum (49.45MPa) in the bonding agent composition of 75.70B2O3-5.92La2O3-11.84SrO-4.67Na2O-1.87Al2O3. Those results suggest that borate bonding agent is an effective way to improve the Ti6Al4V-ceramics bond strength. And the addition of Na2O and Al2O3 strengthen this effect., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: In this study, we screened and identified an endophyte JG09 having strong biocatalytic activity for ginsenosides from Platycodon grandiflorum , converted ginseng total saponins and ginsenoside monomers, determined the source of minor ginsenosides and the transformation pathways, and calculated the maximum production of minor ginsenosides for the conversion of ginsenoside Rb1 to assess the transformation activity of endophyte JG09., Methods: The transformation of ginseng total saponins and ginsenoside monomers Rb1, Rb2, Rc, Rd, Rg1 into minor ginsenosides F2, C-K and Rh1 using endophyte JG09 isolated by an organizational separation method and Esculin-R2A agar assay, as well as the identification of transformed products via TLC and HPLC, were evaluated. Endophyte JG09 was identified through DNA sequencing and phylogenetic analysis., Results: A total of 32 β-glucosidase-producing endophytes were screened out among the isolated 69 endophytes from P. grandiflorum . An endophyte bacteria JG09 identified as Luteibacter sp . effectively converted protopanaxadiol-type ginsenosides Rb1, Rb2, Rc, Rd into minor ginsenosides F2 and C-K, and converted protopanaxatriol-type ginsenoside Rg1 into minor ginsenoside Rh1. The transformation pathways of major ginsenosides by endophyte JG09 were as follows: Rb1→Rd→F2→C-K; Rb2→C-O→C-Y→C-K; Rc→C-Mc1→C-Mc→C-K; Rg1→Rh1. The maximum production rate of ginsenosides F2 and C-K reached 94.53% and 66.34%, respectively., Conclusion: This is the first report about conversion of major ginsenosides into minor ginsenosides by fermentation with P. grandiflorum endophytes. The results of the study indicate endophyte JG09 would be a potential microbial source for obtaining minor ginsenosides.

Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse reaction to anti-tuberculosis (TB) treatment. Thioredoxin reductase 1 (TXNRD1), encoded by the TXNRD1 gene, is an important enzyme involved in oxidant challenge. TXNRD1 plays a key role in regulating cell growth and transformation, and protects cells against oxidative damage. We investigated the association between TXNRD1 polymorphisms and ATDH susceptibility. In this prospective study, 280 newly diagnosed TB patients were followed-up for 3 months after beginning anti-TB therapy. Tag single-nucleotide polymorphisms (tag-SNPs) of TXNRD1 were selected using Haploview 4.2 based on the HapMap database of the Chinese Han in Beijing (CHB) panel. Genotyping was performed using the MassARRAY platform. Of the 280 patients enrolled in this study, 33 were lost to follow-up, 24 had ATDH, and 223 were free from ATDH. After adjusting for sex, age, smoking status, and body mass index, there were no significant differences in the allele and genotype frequency distributions of TXNRD1 SNPs between the ATDH and non-ATDH groups (all P > 0.05). The haplotype analysis showed that haplotype TCAGCC was associated with an increased risk of ATDH susceptibility [P = 0.024, OR (95%CI) = 6.273 (1.023-38.485)]. Further stratified analyses showed that the haplotype TCAGCC was associated with ATDH susceptibility in female subjects [P = 0.036, OR (95%CI) = 5.711 (0.917-35.560)] and non-smokers [P = 0.029, OR (95%CI) = 6.008 (0.971-37.158)]. Our results suggest that TXNRD1 variants may favor ATDH susceptibility in females and non-smokers. Further studies are required to verify this association., Competing Interests: The authors declare no conflict of interest.

The aim of the study was to analyze the effect of ABCB1 genetic polymorphisms on the efficacy of phenytoin (PHT) treatment in epilepsy patients. In total, 200 epilepsy patients who were administered PHT were divided into the responsive and pharmaco-resistance groups depending on the clinical data of PHT treatment in epilepsy patients. The serum concentration of PHT was detected by high-performance liquid chromatography (HPLC). ABCB1 polymorphisms were analyzed by the polymerase chain reaction restriction-fragment length polymorphism method. The C1236T, C3435T and G2677T/A haplotypes were reconstructed for the ABCB1 gene using SHEsis programs. One-way analysis of variance was used for data analysis. In ABCB1 C1236T, the rate of the CC genotype in pharmaco-resistance (17.5%) was higher than that of the responsive group (2.1%), while the rate of the TT genotype in pharmaco-resistance (41.6%) was lower than that of the responsive group (55.4%) (P<0.05). In ABCB1 G2677T/A, the rate of the GG genotype in pharmaco-resistance (29.6%) was higher than that of the responsive group (9.7%), while the rate of the TT genotype in pharmaco-resistance (4.6%) was lower than that of the responsive group (30.4%) (P<0.05). The rate of the TTC haploid in pharmaco-resistance (24.1%) was higher than that of the responsive group (8.8%) (P<0.05). The PHT serum concentration had no statistical significance in the patients with different genotypes. In conclusion, there was no association between ABCB1 genetic polymorphism and PHT serum concentration, although the polymorphisms affected the efficacy of PHT treatment in patients with epilepsy.

Using a combination of adaptive genetic algorithm search, motif-network search scheme and first-principles calculations, we have systematically studied the low-energy crystal structures of Na2FeSiO4. We show that the low-energy crystal structures with different space group symmetries can be classified into several families based on the topologies of their Fe-Si networks. In addition to the diamond-like network which is shared by most of the low-energy structures, another three robust Fe-Si networks are also found to be stable during the charge/discharge process. The electrochemical properties of representative structures from these four different Fe-Si networks in Na2FeSiO4 and Li2FeSiO4 are investigated and found to be strongly correlated with the Fe-Si network topologies. Our studies provide a new route to characterize the crystal structures of Na2FeSiO4 and Li2FeSiO4 and offer useful guidance for the design of promising cathodes for Na/Li ion batteries.

Screening and deciphering active natural products of herbal medicines are of great importance for modern drug discovery. In this study, a novel strategy was proposed to rapidly filter ineffective compounds and target the most potential leads. The aim is to answer the key question of what components are responsible for the holistic bioactivity of an herbal product. To support the strategy, the pharmacophore-guided knockout/knockin chromatography was established for the first time. The greatest advantage of this method is that any interesting components could be automatically fished or knocked out. The method validation shows that the herbal extract was accurately reconstructed according to the experimental design. By combining with bioactivity assays, we demonstrated that "functional compound combination (FCC)", which is the core and indispensable effective part, could be discovered from an herbal medicine and suitable as marker compounds for quality control. The applicable objects of the strategy include single herbs, herbal formulas and commercially herbal preparations. As an illustrative case study, the strategy was successfully applied to simultaneously determine active leads and the FCC in Dan-Qi formula which shows excellent free radical scavenging activity. The potential mechanisms of compounds in Dan-Qi formula reacting with three different free radicals were systematically reported for the first time. This strategy was expected to unveil the mystery of herbal medicines and inspire a natural product-based drug discovery., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Affinity ultrafiltration coupled with liquid chromatography-mass spectrometry (LC-MS) technology is a rapid, simple and effective method for discovering active components, which is especially applicable to the complex extracts of traditional Chinese medicines (TCMs). Affinity ultrafiltration can facilitate the rapid separation of small-molecule ligands from the target macromolecules, and LC-MS contributes to the structural identification of potential active compounds. Combination of the two techniques is vital to reveal the effective materials of TCMs and helpful for the TCM-based drug discovery. In this review, according to the studies in recent years, we make a brief introduction about the application of the ultrafiltration coupled with LC-MS technology in screening active components of TCMs, including the principle, characteristics and the research advancement.

MicroRNAs (miRs) are often located in genomic breakpoint regions and are hypothesized to be important regulators involved in the regulation of critical cell processes, including cell apoptosis, proliferation and differentiation. miR-299 has been reported to be upregulated in acute promyelocytic leukemia (APL); however, the function and mechanistic role of miR-299 in APL remains unknown. The present study demonstrated mir-299 significantly induced cell growth and cell cycle progression at the G1/S transition in APL cells. Notably, the present study revealed that miR-299-5p induces these effects, whereas miR-299-3p does not. Additional studies demonstrated that in APL cells the tumor suppressor p21Cip1/Waf1 is a downstream target of miR-299; miR-299 binds directly to the 3' untranslated region of p21Cip1/Waf1, and reduces protein, but not mRNA, levels of p21Cip1/Waf1. The present findings demonstrate that miR-299 exerts growth-promoting effects in APL cells through the suppression of p21Cip1/Waf1. Overall, the present study demonstrates that p21Cip1/Waf1 is a direct functional target of miR-299 in APL.

We report the synthesis, crystal structure, and physical properties of a quinary iron arsenide fluoride, KCa2Fe4As4F2. The new compound crystallizes in a body-centered tetragonal lattice (space group I4/mmm, a = 3.8684(2) Å, c = 31.007(1) Å, Z = 2) that contains double Fe2As2 conducting layers separated by insulating Ca2F2 layers. Our measurements of electrical resistivity, direct-current magnetic susceptibility, and heat capacity demonstrate bulk superconductivity at 33 K in KCa2Fe4As4F2.

Structural assembly and reversible transformation between a metallogrid Dy4 SMM (2) and its fragment Dy2 (1) were established in the different solvent media. The zero-field magnetization relaxation was slowed for dysprosium metallogrid (2) with relaxation barrier of Ueff = 61.3 K when compared to Dy2 (1). Both magnetic dilution and application of a moderate magnetic field suppress ground-state quantum tunneling of magnetization and result in an enhanced Ueff of 119.9 and 96.7 K for 2, respectively. Interestingly, the lanthanide metallogrid complex (2) exhibits magnetic hysteresis loop even up to 16 K at a given field sweep rate of 500 Oe/s.