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Low thermal evolution degree of gas and connected fracture network are key features in the continental shale gas reservoirs. When the pressure decreases lower than the dew point pressure, gas condensate diminishes the mobility of subsurface fluid forms in the near well region, which further reduces the productivity and final recovery factor in addition to the low connected fracture network. This work is motivated to investigate the application of gas injection, proven to be a feasible technique in conventional/marine-shale gas condensate reservoirs, in continental shale gas condensate reservoirs. We apply a compositional model to investigate the mechanism of gas injection treatment taking a continental shale gas condensate reservoir in the Fuxing area, Sichuan Basin, China as an example. The results demonstrate that for the removal of gas condensate during CO2 injection, re-vaporization plays the main mechanism through two processes including pressurization and development of miscibility, while the former is overwhelming. Considering the variation trend of the total volume of gas condensate, we divide the whole injection process into four and six stages in the single fracture model and fracture network model, respectively, and reason the trend with respect to phase behavior and flow pattern. A sensitive study on the injected gas type indicates that the sorting of the gas injection performance to remove gas condensate produced gas followed by CH4, and followed by CO2. Finally, we investigate the performance of cyclic produced-gas injection and optimize the injection scheme. This work provides technical and theoretical support for the development of continental shale gas reservoirs. [ABSTRACT FROM AUTHOR]

Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes cetuximab resistance, especially microRNA (miRNA) regulation, remains unclear. Growing evidence suggests that miRNAs may act as "nuclear activating miRNAs" for targeting promoter regions or enhancers related to target genes. This study elucidates a novel mechanism underlying cetuximab resistance in HNSCC involving the nuclear activation of KDM7A transcription via miR-451a. Herein, small RNA sequencing, quantitative real-time polymerase chain reaction (qRT‒PCR) and fluorescence in situ hybridization (FISH) results provided compelling evidence of miR-451a nuclear enrichment in response to cetuximab treatment. Chromatin isolation via RNA purification, microarray analysis, and bioinformatic analysis revealed that miR-451a interacts with an enhancer region in KDM7A, activating its expression and further facilitating cetuximab resistance. It has also been demonstrated that the activation of KDM7A by nuclear miR-451a is induced by cetuximab treatment and is AGO2 dependent. Logistic regression analyses of 87 HNSCC samples indicated the significance of miR-451a and KDM7A in the development of cetuximab resistance. These discoveries support the potential of miR-451a and KDM7A as valuable biomarkers for cetuximab resistance and emphasize the function of nuclear-activating miRNAs. [ABSTRACT FROM AUTHOR]

The cellulose-rich corncob residue (CCR) is an abundant and renewable agricultural biomass that has been under-exploited. In this study, two strategies were compared for their ability to transform CCR into cello-oligosaccharides (COS). The first strategy employed the use of endo-glucanases. Although selected endo-glucanases from GH9, GH12, GH45, and GH131 could release COS with degrees of polymerization from 2 to 4, the degrading efficiency was low. For the second strategy, first, CCR was efficiently depolymerized to glucose and cellobiose using the cellulase from Trichoderma reesei. Then, using these simple sugars and sucrose as the starting materials, phosphorylases from different microorganisms were combined to generate COS to a level up to 100.3 g/L with different patterns and degrees of polymerization. Using tomato as a model plant, the representative COS obtained from BaSP (a sucrose phosphorylase from Bifidobacterium adolescens), CuCbP (a cellobiose phosphorylase from Cellulomonas uda), and CcCdP (a cellodextrin phosphorylase from Clostridium cellulosi) were shown to be able to promote plant growth. The current study pointed to an approach to make use of CCR for production of the value-added COS. Key points: • Sequential use of cellulase and phosphorylases effectively generated cello-oligosaccharides from corncob residue. • Cello-oligosaccharides patterns varied in accordance to cellobiose/cellodextrin phosphorylases. • Spraying cello-oligosaccharides promoted tomato growth. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) is a pleiotropic protein hormone and has become an attractive therapeutic target because of its multiple roles in various physiological processes, including growth, development, and metabolism. However, its production is hindered by low heterogenous protein expression levels in various expression systems and hard to meet the needs of clinical and scientific research. Here, we report that human IGF-1 and its analog Long R3 IGF-1 (LR3 IGF-1) are recombinant expressed and produced in the Pichia pastoris (P. pastoris) expression system through being fused with highly expressed xylanase XynCDBFV. Furthermore, purified IGF-1 and LR3 IGF-1 display excellent bioactivity of cell proliferation compared to the standard IGF-1. Moreover, higher heterologous expression levels of the fusion proteins XynCDBFV-IGF-1 and XynCDBFV-LR3 IGF-1 are achieved by fermentation in a 15-L bioreactor, reaching up to about 0.5 g/L XynCDBFV-IGF-1 and 1 g/L XynCDBFV-TEV-LR3 IGF-1. Taken together, high recombinant expression of bioactive IGF-1 and LR3 IGF-1 is acquired with the assistance of xylanase as a fusion partner in P. pastoris, which could be used for both clinical and scientific applications. Key points: • Human IGF-1 and LR3 IGF-1 are produced in the P. pastoris expression system. • Purified IGF-1 and LR3 IGF-1 show bioactivity comparable to the standard IGF-1. • High heterologous expression of IGF-1 and LR3 IGF-1 is achieved by fermentation in a bioreactor. [ABSTRACT FROM AUTHOR]

Coiled tubing sidetracking has proved to be an effective means of old well resurrection, which can accurately connect reservoirs to improve reserve production. However, it is difficult for the cuttings in the wellbore to circulate out of the bottom in this process. In this study, the coupling analysis method of the Computational Fluid Dynamics–Discrete Element Model (CFD-DEM) is applied to model the interaction between fluid and cuttings to characterize the migration process of cuttings. The influence of the cuttings shape and whether the lower part of the window needs to be plugged (whether there is a pocket in the wellbore) on the critical flow rate of cuttings are analyzed. The case studies indicate that the critical flow rate of the identical cuttings in the wellbore with a pocket is significantly higher than that without pockets, about 1.2 to 1.8 times, and the difference is more significant as the particle volume decreases. When the particle size is controlled to be 4 mm, the volume of cuttings in various shapes is different, and the critical flow rate is positively related to its volume. When there is a pocket in the wellbore, the volume of the cuttings increases to 3.6 times, and the critical flow rate increases to 1.15 times; while when there are no pockets in the wellbore, the critical flow rate increases to 1.69 times. Therefore, reducing the particle volume in the wellbore without pockets to reduce the drilling fluid flow rate is more effective than the wellbore with a pocket. Furthermore, a new three-dimensional quantitative model of flatness is proposed to describe the particles. The flatness of the particles is positively correlated with the critical flow rate under the conditions of the same volume and roughness of cuttings particles. When the flatness is reduced by 15%, 20% and 38%, its critical flow rate is reduced by 2.8%, 4.9% and 8.8%, respectively, and the ratio between them is about five times. It is an excellent choice to adopt flatness to measure the critical flow rate of non-spherical particles. The research results have a significant reference value for field drilling. [ABSTRACT FROM AUTHOR]

The drilling process optimization can reduce cost and energy consumption by optimizing different metrics (ROP, TOB and MSE). It is crucial to establish the relationship between drilling parameters and metrics. Most of the traditional methods are to optimize the physical model established based on experience or formula derivation. However, the optimized parameters are not optimal due to the low prediction accuracy of these models. This paper proposes an optimization process for drilling parameters using machine learning and data analysis. Compared with traditional models, data-driven models with offset well data have higher accuracy. The input features used by the model include weight on bit (WOB), rotational speed (RPM), flow (FLW), lithology and depth, where rock mechanics parameters are not required. The operator can optimize different metrics according to project requirements and make judgments in different aspects based on the corresponding changes in the coupling model. By analyzing the optimization results, we believe that the inappropriate WOB and RPM are the main factors limiting the improvement of ROP, and the drilling efficiency can be further improved by optimizing the FLW. We used this method to optimize the drilling parameters of the target well. MSE optimization resulted in a decrement in MSE by 55%, a decrement in torque by 25% and an increment in ROP by 20%. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs)-based therapy has displayed some promises in ischemia heart diseases although its efficacy may be affected by changes in surrounding environments. This study evaluated the role of autophagy insufficiency using Beclin1 haploinsufficiency (BECN+/−) on intra-myocardial MSC transplantation-evoked effect against myocardial infarction. Donor MSCs from C57BL/6 mice were labelled with cell-tracker CM Dil and were delivered into LV free wall adjacent to infarct region in wild-type (WT) and BECN+/− recipient mice following ligation of left main coronary artery (MI-MSCs). Ten days following MI, myocardial function was assessed using echocardiography. Cardiomyocyte contractility and intracellular Ca2+ were monitored using cardiomyocytes from the area-at-risk adjacent to infarct. CM-Dil labeled cells were tracked in MSCs recipient mice using fluorescence microscopy. Lectin, Masson trichrome staining and Western blot analysis were employed to determine cardiomyocyte area, scar fibrosis, apoptosis and inflammation. MI insult triggered scar fibrosis, LV chamber dilation, decreased fractional shortening, ejection fraction, cardiomyocyte shortening, maximal velocity of shortening and relengthening as well as prolonged relengthening, which were abrogated or attenuated by MSCs therapy in WT but not BECN+/− mice. MI decreased intracellular Ca2+ rise and decay in response to electrical stimuli without affecting resting intracellular Ca2+, which were reconciled by MSCs in WT but not BECN+/− mice. MSCs further attenuated MI-induced mitochondrial ultrastructural injury, apoptosis, inflammation and autophagy defects in peri-infarct area in WT but not BECN+/− mice. Collectively, our results suggested that autophagy insufficiency dampened in MSCs-elicited cardioprotection associated with dampened apoptosis and inflammation. [ABSTRACT FROM AUTHOR]

Nitriles derived from glucosinolates (GSLs) in rapeseed meal (RSM) can cause lesions on animal liver and kidneys. Nitrilase converts nitriles to carboxylic acids and NH3, eliminating their toxicity. Here we describe a nitrilase, BnNIT2, from Brassica napus (optimal temperature, 45 °C; pH, 7.0) that is stable at 40 °C and has a wide substrate specificity. Recombinant BnNIT2 converted the three main nitriles from GSLs (3-hydroxy-4-pentenenitrile, 3-butenenitrile, and 4-pentenenitrile), with the highest specific activity (58.6 U/mg) for 4-pentenenitrile. We used mutagenesis to improve the thermostability of BnNIT2; the resulting mutant BnNIT2-H90M had an ~ 14.5% increase in residual activity at 50 °C for 1 h. To verify the functionality of BnNIT2, GSLs were extracted from RSM and converted into nitriles at pH 5.0 in the presence of Fe2+. Then, BnNIT2 was used to degrade the nitriles from GSLs; ultimately, ~ 80% of nitriles were removed. Thus BnNIT2 is a potential enzyme for detoxification of RSM. Key points: • Functional identification of the plant nitrilase BnNIT2. • Identified a mutant, H90M, with improved thermostability. • BnNIT2 was capable of degrading nitriles from transformed GSLs. [ABSTRACT FROM AUTHOR]

Pursuing and developing effective methodologies to construct highly active catalytic sites to maximize the atomic and energy efficiency by material engineering are attractive. Relative to the tremendous researches of carbon-based single atom systems, the construction of bio-applicable single atom materials is still in its infancy. Herein, we propose a facile and general interfacial-confined coordination strategy to construct high-quality single-atom nanotherapeutic agent with Fe single atoms being anchored on defective carbon dots confined in a biocompatible mesoporous silica nanoreactor. Furthermore, the efficient energy conversion capability of silica-based Fe single atoms system has been demonstrated on the basis of the exogenous physical photo irradiation and endogenous biochemical reactive oxygen species stimulus in the confined mesoporous network. More importantly, the highest photothermal conversion efficiency with the mechanism of increased electron density and narrow bandgap of this single atom structure in defective carbon was proposed by the theoretical DFT calculations. The present methodology provides a scientific paradigm to design and develop versatile single atom nanotherapeutics with adjustable metal components and tune the corresponding reactions for safe and efficient tumor therapeutic strategy. Developing single atom systems with improved catalytic potential for bio-application has major therapeutic potential. Here, the authors report on the development of a metal single-atom on a carbon dot support confined within mesoporous silica for the development of therapeutic agents. [ABSTRACT FROM AUTHOR]

To identify differential metabolites and metabolic pathways and provide guidance for the novel biomarkers for diagnosis and prognosis of amyotrophic lateral sclerosis (ALS). ALS patients and people without nervous diseases were recruited. Metabolomic analysis was performed using gas chromatography-mass spectrometry (GC/MS). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) were used to identify differential metabolites. Kyoto Encyclopedia of Genes and Genomes and MetaboAnalyst were used to identify metabolic pathways. 75 metabolites were detected and aligned. The OPLS-DA showed the metabolomic profile of ALS patients and those in the fast-progression and slow-progression ALS groups differed from that of CTRL (p < 0.05). The levels of maltose, glyceric acid, lactic acid, beta-alanine, phosphoric acid, glutamic acid, ethanolamine and glycine in ALS were significantly higher, while 2,4,6-tri-tert-butylbenzenethiol was lower. Glycine, serine and threonine metabolism, D-glutamine and D-glutamate metabolism, alanine, aspartate, and glutamate metabolism, beta-alanine metabolism, and pyruvate metabolism were significantly altered metabolic pathways in ALS. ROC was used to discriminate ALS from CTRL with an AUC of 0.898 (p < 0.001) using 2,4,6-tri-tert-butylbenzenethiol, beta-alanine, glycine, and ethanolamine. The serum metabolites and metabolic pathways in ALS patients are significantly altered compared with CTRL. These findings may contribute to the early diagnosis of ALS. [ABSTRACT FROM AUTHOR]

Aqueous zinc-ion batteries (ZIBs) are deemed as the idea option for large-scale energy storage systems owing to many alluring merits including low manufacture cost, environmental friendliness, and high operations safety. However, to develop high-performance cathode is still significant for practical application of ZIBs. Herein, Ba0.23V2O5·1.1H2O (BaVO) nanobelts were fabricated as cathode materials of ZIBs by a typical hydrothermal synthesis method. Benefiting from the increased interlayer distance of 1.31 nm by Ba2+ and H2O pre-intercalated, the obtained BaVO nanobelts showed an excellent initial discharge capacity of 378 mAh·g−1 at 0.1 A·g−1, a great rate performance (e.g., 172 mAh·g−1 at 5 A·g−1), and a superior capacity retention (93% after 2000 cycles at 5 A·g−1). [ABSTRACT FROM AUTHOR]

Peroxisome, a special cytoplasmic organelle, possesses one or more kinds of oxidases for hydrogen peroxide (H2O2) production and catalase for H2O2 degradation, which serves as an intracellular H2O2 regulator to degrade toxic peroxides to water. Inspired by this biochemical pathway, we demonstrate the reactive oxygen species (ROS) induced tumor therapy by integrating lactate oxidase (LOx) and catalase (CAT) into Fe3O4 nanoparticle/indocyanine green (ICG) co-loaded hybrid nanogels (designated as FIGs-LC). Based on the O2 redistribution and H2O2 activation by cascading LOx and CAT catalytic metabolic regulation, hydroxyl radical (·OH) and singlet oxygen (1O2) production can be modulated for glutathione (GSH)-activated chemodynamic therapy (CDT) and NIR-triggered photodynamic therapy (PDT), by manipulating the ratio of LOx and CAT to catalyze endogenous lactate to produce H2O2 and further cascade decomposing H2O2 into O2. The regulation reactions of FIGs-LC significantly elevate the intracellular ROS level and cause fatal damage to cancer cells inducing the effective inhibition of tumor growth. Such enzyme complex loaded hybrid nanogel present potential for biomedical ROS regulation, especially for the tumors with different redox state, size, and subcutaneous depth. The control of reactive oxygen species in cancer cells is an attractive approach for anticancer applications. Here, the authors create a peroxisome inspired lactate oxidase and catalase loaded hydrogel with iron nanoparticles and NIR photosensitizer for glutathione activated chemodynamic and photodynamic therapy. [ABSTRACT FROM AUTHOR]

Somatostatin (SS) is one of the peptide hormones that regulate the endocrine system in animals. When SS is used to immunize animals, the correspondingly generated anti-SS antibody neutralizes the SS and, therefore, alleviates its growth inhibiting effects. This is of great value to the livestock industry; however, previously developed methods fail to obtain enough recombinant SS in an economical way. Herein, we describe the employment of a commonly used feed enzyme, i.e., xylanase, as a carrier protein for recombinant expression of SS in large quantity. The SS gene was fused to one of the two xylanase genes (XynCDBFV and BsXynC) and recombinantly expressed in Pichia pastoris. The purified xylanase-SS fusion proteins displayed excellent antigenicity and immunogenicity. In addition, they retained the enzymatic activities and thermostability of the xylanases, indicating that they can catalyze hydrolysis of xylan in plant cell wall of the animal feeds and stand the high temperature in feed pelleting. Thus, the xylanase-SS fusion proteins serve as an excellent candidate chimeric bifunctional vaccine-feed enzyme protein retaining both SS immunogenicity and xylanase activity. Key points: • Somatostatin is expressed in P. pastoris as fusion proteins with two xylanases. • The chimeric proteins retain both immunogenicity and xylanase activity. • The xylanase-SS proteins may serve as bifunctional proteins in livestock industry. [ABSTRACT FROM AUTHOR]

In recent years, multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise in nanomedicine. In this study, we report the environmentally friendly synthesis of fluorescent carbon nano-dots such as carbon quantum dots (CQDs) by microplasma using o-phenylenediamine. The produced CQDs exhibited a wide absorption peaks at 380–500 nm and emitted bright yellow fluorescence with a peak at 550 nm. The CQDs were rapidly taken up by HeLa cancer cells. When excited under blue light, a bright yellow fluorescence signal and intense reactive oxygen species (ROS) were efficiently produced, enabling simultaneous fluorescent cancer cell imaging and photodynamic inactivation, with a 40% decrease in relative cell viability. Furthermore, about 98% cells were active after the incubation with 400 μg mL−1 CQDs in the dark, which revealed the excellent biocompatibility of CQDs. Hence, the newly prepared CQDs are thus demonstrated to be materials which might be effective and safe to use for in vivo bioimaging and imaging-guided cancer therapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to localize the anatomic distribution of upper motor neuron (UMN) loss through examining cortical thickness at the clinical onset of amyotrophic lateral sclerosis (ALS) and explore motor manifestation in functionally impaired body region attribute to impairment of lower motor neuron (LMN) or UMN or mixed LMN and UMN? The clinical features, cortical thickness of corresponding areas from different body regions in MRI and electromyography (EMG) data were collected from 108 classical ALS patients. The cortical thickness was thinner in ALS group than control group in bilateral head-face and upper-limb areas (p < 0.05). In head-face area, the cortical thickness of bulbar-onset group was significantly lower than that of control groups (p < 0.05). In upper-limb areas, the cortical thickness of cervical-onset group was significantly thinner than that of control group. Notably, the bulbar ALSFRS-R subscore was correlated with cortical thickness in bilateral head-face areas (p < 0.05). The bulbar ALSFRS-R subscore of the positive LMN damage group was lower compared to that of the negative LMN damage group (P < 0.001). The limb ALSFRS-R subscore correlated with compound muscle action potential (CMAP) amplitudes of median, ulnar, peroneal, and tibial nerves (P < 0.001), but was not related to cortical thickness. In conclusion, the UMN degeneration in ALS was derived from focal initiation, bulbar- and cervical-onset may date from head-face and upper-limb areas in motor homunculus cortex, respectively. The bulbar dysfunction was resulted from the mixed UMN and LMN impairment, while limb dysfunction derived mostly from LMN loss. [ABSTRACT FROM AUTHOR]

To explore differential diagnosis value of dissociated lower-limb muscle impairment, we performed a retrospective analysis of clinical and electrophysiological features in 141 lower-limb involved ALS patients, 218 normal controls, 67 disease controls, and 32 lumbar spondylosis disease patients. The dissociated lower-limb muscle impairment was quantified by plantar flexion and dorsiflexion strength, compound muscle action potentials ratio of peroneal and tibial nerves (split index, SI) and semi-quantitative scoring scale of denervation potential. Clinical features: the proportion of decreased dorsiflexion was higher than decreased planter flexor strength in lower-limb involved ALS (77.2%vs 38.3%). Electrophysiological features: (1) SI in ALS was the lowest among four groups (Test statistic = 40.57, p < 0.001). (2) Percentage of positive denervation potential was higher in tibialis anterior than gastrocnemius muscle (χ2 = 87.12, p < 0.001). ROC curve: the SI cutoff was 0.52 and 0.33 respectively to differentiate ALS from lumbar spondylosis disease and peripheral neuropathy. Lower-limb involved ALS patients exhibited "split leg" phenomenon. The SI value could be used as an electrophysiological marker to differentiate ALS from lumbar spondylosis disease and peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Reactions of the bis((pyridine-2-yl)-1,2,4-triazol-5-yl)methane (H2L) with Zn(NO3)2·6H2O and ZnCl2 conditions afforded three new Zn(II) complexes, namely, {[Zn3L′2(H2O)6]·2NO3} (1), [Zn4L2Cl4(H2O)2] (2) and [Zn6L4(CH3OH)4(NO3)4] (3). Notably in 1, the methylene group in L was in situ oxidized to a rigid ketone group in L′ (here, H2L′ = bis((pyridine-2-yl)-1,2,4-triazol-5-yl)ketone). The three Zn(II) complexes were synthesized under solvothermal conditions and characterized by techniques of Elemental analysis, Fourier transform infrared spectroscopy, Powder X-ray diffraction and single-crystal X-ray diffraction analysis. In addition, the thermogravimetric properties and the luminescent properties of 1–3 were investigated. [ABSTRACT FROM AUTHOR]

Spinel LiNi0.5Mn1.5O4 cathode materials with different lithium excess amount (0, 2%, 6%, 10%) were synthesized by a facile solid-state method. The effect of lithium excess amount on the microstructure, morphology, and electrochemical properties of LiNi0.5Mn1.5O4 materials was systematically investigated. The results show that the lithium excess amount does not change the particle morphology and size obviously; thus, the electrochemical properties of LiNi0.5Mn1.5O4 are mainly determined by structural characteristics. With the increase of lithium excess amount, the cation disordering degree (Mn3+ content) and phase purity first increase and then decrease, while the cation mixing extent has the opposite trend. Among them, the LiNi0.5Mn1.5O4 material with 6% lithium excess amount exhibits higher disordering degree and lower impurity content and cation mixing extent, thus leading to the optimum electrochemical properties, with discharge capacities of 125.0, 126.1, 124.2, and 118.9 mAh/g at 0.2-, 1-, 5-, and 10-C rates and capacity retention rate of 96.49% after 100 cycles at 1-C rate. [ABSTRACT FROM AUTHOR]

Bisperoxovanadium (pyridine-2-carboxyl) [bpV(pic)] is a commercially available PTEN inhibitor. Previous studies from us and others have shown that bpV(pic) confers neuroprotection in cerebral ischemia injury. We set up to determine whether ERK 1/2 activation plays a role in bpV(pic)-induced neuroprotective effect in cerebral ischemia injury. We found that the phosphorylation levels of Akt (p-AKT) and ERK1/2 (p-ERK 1/2) were down-regulated after cerebral ischemia-reperfusion injury. The injection of bpV(pic) after injury not only increased the level of p-AKT but also the level of p-ERK 1/2. While the inhibition of PTEN mediated the up-regulatation of p-AKT and p-ERK 1/2 by bpV(pic). Interestingly, the ERK 1/2 activation induced by bpV(pic) was also independent of the inhibition of PTEN. Our results indicate that bpV(pic) protects against OGD-induced neuronal death and promotes the functional recovery of stroke animals through PTEN inhibition and ERK 1/2 activation, respectively. This study suggests that the effect of bpV(pic) on ERK 1/2 signaling should be considered while using bpV(pic) as a PTEN inhibitor. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated the effects of sclerostin antibody (Scl-Ab) and parathyroid hormone (1-34, PTH) on healing in osteoporosis; however, reports about the combined effects of Scl-Ab plus PTH on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with Scl-Ab and PTH on osteoporosis healing in ovariectomized (OVX) rats. After bilateral ovariectomy, 12 weeks were allowed to pass for the establishment of standard conditions for osteoporosis in animal models. The rats then randomly received a vehicle (control), Scl-Ab (25 mg/kg body weight, twice weekly), PTH (60 μg/kg, three times per week) or PTH plus Scl-Ab until death at 12 weeks. The blood and distal femurs of the rats were harvested for evaluation. The results of treatment for osteoporosis were evaluated by serum analysis, histology, microcomputed tomography (micro-CT) and biomechanical tests. Results from this study indicated that PTH + Scl-Ab had stronger effects on the prevention and treatment of osteoporosis than either of the monotherapies in OVX rats. The PTH + Scl-Ab produced the strongest effects on bone volume fraction (BV/TV), bone trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular spacing (Tb.Sp), bone mineral density (BMD) and strength of distal femurs and increased the levels of procollagen type I N‑terminal propeptide (PINP) and osteocalcin. In contrast, monotherapy with PTH or Scl-Ab showed no differences between treated groups in the assessment of the metaphysis of contralateral femurs by histology, serum, biomechanical tests and micro-CT. These results seem to indicate that Scl-Ab plus PTH has an additive effect on osteoporosis in OVX rats. [ABSTRACT FROM AUTHOR]

We present a scheme for bidirectional controlled remote preparation of arbitrary single-qubit states by using a five-photon cluster-type state as the quantum channel. The arbitrary single-qubit states can be bidirectional remote prepared with only linear-optical elements under the controller's control. The sender first transform the quantum channel to the target channel according to their knowledge of prepared states, then perform single-qubit measurements on their entangled particles, the controller performs a X-basis measurement and the receivers can prepared the original states on their entangled particles if they cooperate with the control. This scheme is more convenient in application since it only requires linear-optical elements for bidirectional controlled remote state preparation of single-qubit states with cluster-type states. [ABSTRACT FROM AUTHOR]

A novel method for the separation/analysis of linuron in fruit and vegetable samples is described. The work is based on the utilization of ionic liquid ([Cmin][PF])-loaded β-cyclodextrin cross-linked polymer (IL-β-CDCP) for the effective adsorption of linuron coupled with ultraviolet spectrophotometry. The inclusion interaction of IL-β-CDCP with linuron is studied with FTIR and inclusion constants. Under optimum conditions, the preconcentration factor achieved for this method is approximately 10. Linear range, limit of detection (LOD), limit of quantification (LOQ), and relative standard deviation are 0.08-15.00 μg/mL, 5.8 ng/mL, 17.5 ng/mL and 0.96 % ( n = 3, c = 4.0 μg/mL), respectively. This technique is successfully applied for determination of linuron in real samples. [ABSTRACT FROM AUTHOR]

We present a scheme for bidirectional controlled implementation of arbitrary single qubit operations by using two EPR states and a five-qubit cluster state as the quantum channel. Alice can implement an unknown single-qubit unitary operation on the remote Bob's quantum system and at the same time, Bob can also remotely implement an arbitrary single-qubit unitary operation on Alice's quantum system if they cooperate with the controller. We also study the bidirectional controlled implementation of unitary operations belonging to the restricted sets. It is shown that receivers can prepare the target state by performing corresponding unitary operations on their entangled particles if they cooperate with the controller. [ABSTRACT FROM AUTHOR]

5-Diphosphoinositol pentakisphosphate (IP7), formed by a family of inositol hexakisphosphate kinases (IP6Ks), has been demonstrated to be a physiologic inhibitor of Akt. IP6K inhibition may increase Akt activation in mesenchymal stem cells (MSCs), resulting in enhanced cardiac protective effect after transplantation. The aim of this study was to investigate the role of IP6Ks for improving MSCs' functional survival and cardiac protective effect after transplantation into infarcted mice hearts. Bone marrow-derived mesenchymal stem cells, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc-eGFP) transgenic mice, were preconditioned with IP6Ks inhibitor TNP (0.5, 1, 5, and 10 μmol/L) for 2 h followed by 6 h of hypoxia and serum deprivation (H/SD) injury. TNP concentration dependently significantly decreased IP7 production with increased Akt phosphorylation. Moreover, TNP at 10 μmol/L significantly improved the viability and enhanced the paracrine effect of MSCs after H/SD. Furthermore, MSCs were transplanted into infarcted hearts with or without selective IP6Ks inhibition. Longitudinal in vivo bioluminescence imaging and immunofluorescent staining revealed that TNP pretreatment enhanced the survival of engrafted MSCs, which promoted the anti-apoptotic and pro-angiogenic efficacy of MSCs in vivo. Furthermore, MSC therapy with IP6Ks inhibition significantly decreased fibrosis and preserved heart function. This study demonstrates that inhibition of IP6Ks promotes MSCs engraftment and paracrine effect in infarcted hearts at least in part by down-regulating IP7 production and enhancing Akt activation, which might contribute to the preservation of myocardial function after MI. [ABSTRACT FROM AUTHOR]

In this paper, we present a possible improvement of the successful probability of joint remote state preparation via cluster states following some ideals from probabilistic joint remote state preparation (Wang et al. in Opt Commun, 284:5835, ). The success probability can be improved from $$1/4$$ to 1 via the same quantum entangled channel by adding some classical information and performing some unitary operations. Moreover, we also discussed the scheme for joint remote preparation via cluster-type states. Compared with other schemes, our schemes have the advantage of having high successful probability for joint preparation of an arbitrary two-qubit state via cluster states and cluster-type states. [ABSTRACT FROM AUTHOR]

Cannabinoid receptor type 2 (CB) activation is recently reported to promote proliferation of some types of resident stem cells (e.g., hematopoietic stem/progenitor cell or neural progenitor cell). Resident cardiac progenitor cell (CPC) activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction (MI). This study aims to explore the role and possible mechanisms of CB receptor activation in enhancing myocardial repair. Our results revealed that CB2 receptor agonist AM1241 can significantly increase CPCs by c-kit and Runx1 staining in ischemic myocardium as well as improve cardiomyocyte proliferation. AM1241 also decreased serum levels of MDA, TNF-α and IL-6 after MI. In addition, AM1241 can ameliorate left ventricular ejection fraction and fractional shortening, and reduce fibrosis. Moreover, AM1241 treatment markedly increased p-Akt and HO-1 expression, and promoted Nrf-2 nuclear translocation. However, PI3K inhibitor wortmannin eliminated these cardioprotective roles of AM1241. In conclusion, AM1241 could induce myocardial regeneration and improve cardiac function, which might be associated with PI3K/Akt/Nrf2 signaling pathway activation. Our findings may provide a promising strategy for cardiac endogenous regeneration after MI. [ABSTRACT FROM AUTHOR]

The poor viability of transplanted stem cells hampers their therapeutic efficacy for treatment of myocardial infarction. The aim of this study was to investigate whether rosuvastatin improved survival of adipose-derived mesenchymal stem cells (AD-MSCs) after transplantation into infarcted hearts. AD-MSCs isolated from Tg( Fluc- egfp) mice which constitutively express both firefly luciferase (Fluc) and enhanced green fluorescent protein were transplanted into infarcted hearts with or without rosuvastatin administration. Longitudinal in vivo bioluminescence imaging and histological staining revealed that rosuvastatin enhanced the survival of engrafted AD-MSCs. Furthermore, combined therapy of AD-MSC and rosuvastatin reduced fibrosis, decreased cardiomyocyte apoptosis, and preserved heart function. AD-MSCs were then subjected to hypoxia and serum deprivation injury in vitro to mimic the ischemic environment. Rosuvastatin (10 mmol/L) enhanced the viability and paracrine effect of AD-MSCs, and decreased their apoptotic rate. Western blotting revealed that rosuvastatin supplementation increased Akt and ERK phosphorylation, which resulted in FoxO3a phosphorylation and nuclear export. In addition, rosuvastatin administration decreased the pro-apoptotic proteins Bim and Bax, and increased the anti-apoptotic proteins Bcl-xL and Bcl-2. Furthermore, these effects were abolished by PI3K inhibitor LY294002 and MEK1/2 inhibitor U0126. This study demonstrates that rosuvastatin may improve the survival of engrafted AD-MSCs at least in part through the PI3K/Akt and MEK/ERK1/2 signaling pathways. Combination therapy with rosuvastatin and AD-MSCs has a synergetic effect on improving myocardial function after infarction. [ABSTRACT FROM AUTHOR]

A typical approach involving Pechini method and spark plasma sintering (SPS) method was presented for the preparation of high density LiSrLaBiO ( x = 0, 1) ceramics. Phase formation, microstructure, grain size and electrical properties of the specimens were examined using XRD, SEM and alternating current impedance spectroscopy (ACIS). Dense LiLaBiO and LiSrLaBiO ceramics with pure garnet-like phase, relative density of 97% and average grain size of about 5 μm were fabricated using this approach. The total conductivities at 298 K of LiLaBiO and LiSrLaBiO ceramics prepared by the SPS method are 5.1×10 and 6.8×10 S/cm, respectively, 2 times higher than that of samples prepared by the conventional sintering method. [ABSTRACT FROM AUTHOR]

We clarified the clinical and pathological aspects of familial amyotrophic lateral sclerosis (FALS) with SOD1 H46R heterozygous mutation in the Miyakonojo Basin, a region in southern Japan where the prevalence of ALS is 11.4 per 105 of the population. We studied 17 patients, including one autopsy case, in three FALS families with the mutation. The average age at disease onset in the families was 44.3±8.7 years, and the mean disease duration was 12±7.6 years, with a range of 6 to 30 years. Ten of 17 patients were unable to walk by the mean age of 56.4±12.2 years. The initial symptom was muscle weakness in the distal leg muscle in all patients. The autopsy findings of one FALS patient showed atrophy of lateral and anterior funiculi, decreased numbers of anterior horn cells, preserved posterior funiculus and absence of neuronal inclusion bodies. Percentages of mutant SOD1 protein measured by mass spectrometry were 14% in erythrocytes, 43% in the spinal cord, 47% in the iliopsoas muscle and 60% in the diaphragm. In this study, we confirmed that FALS with SOD1 H46R mutation showed uniform initial symptoms and slow disease progression with intra-familial variation of disease severity and that inclusion body formation is not essential in FALS with this mutation. [ABSTRACT FROM AUTHOR]

Highly active antiretroviral therapy (HAART) has been successful to reduce progression of acquired immunodeficiency syndrome (AIDS). Nevertheless, recent autopsy analysis of the brain from patients with human immunodeficiency virus (HIV)-1 infection reported same or even increasing numbers of AIDS encephalopathy. This insufficient effect of HAART for central nervous system (CNS) complication might be explained by independent pathogenetic processes in lymph node and CNS. We inoculated macaques with three Simian immunodeficiency virus (SIV) strains and investigated relationship between degree of the lymph node pathology and that of AIDS-related brain pathology. Animals infected with T-cell-tropic viruses SIVmac239 and SHIV-RT developed typical AIDS pathology in the lymph node 46 to 156 weeks after infection. The cerebral cortex of these animals showed focal or diffuse gliosis, and electron microscopic analysis demonstrated degenerative changes, such as accumulation of dense lamellar bodies in the dendrites and swelling of astrocytic processes. However, there was no evidence of microglial nodules or multinucleated giant cells in the white mater. The animals infected with macrophage-tropic SIV239env/MERT did not develop lymph node pathology of AIDS in the same or longer period of infection. The white mater of the animal, however, showed microglial nodules with multinucleated giant cells, a pathological hallmark of AIDS encephalopathy. SIV immunoreactivity was demonstrated in these giant cells as well as macrophage/microglia cells. On the other hand, there was no abnormality in the cerebral cortex. These findings suggest that there are two independent pathogenetic processes in AIDS encephalopathy: immune response against virus infected macrophage/microglial cells in the white mater without immunodeficiency and cortical degeneration caused in the late stage of AIDS. [ABSTRACT FROM AUTHOR]