Search

Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising non-invasive surgical technique with spatial specificity and minimal off-target effects. Despite the expanding clinical applications, the major obstacles associated with MRgFUS still lie in low magnetic resonance imaging (MRI) sensitivity and safety issues. High ultrasound power is required to resist the energy attenuation during the delivery to the tumor site and may cause damage to the surrounding healthy tissues. Herein, a surface modification strategy is developed to simultaneously strengthen MRI and ultrasound ablation of MRgFUS by prolonging Fe

Catastrophic antiphospholipid syndrome is an extremely rare autoimmune disease with complex and diverse clinical manifestations. Cutaneous necrosis is one of its rare clinical features. However, interventions for this manifestation are not standardized and lack evidence, which increases treatment difficulty. Here, study authors report the successful care and follow-up of a 46-year-old female patient with nephrotic syndrome and catastrophic antiphospholipid syndrome complicated by full-thickness cutaneous necrosis of the dorsum of the right hand that lasted more than 4 months and 1 month prior to wound treatment, respectively. Study authors set up an interprofessional team, including a nephrologist, a vascular surgeon, and two specialist wound care nurses to provide holistic wound care and treat her complex systemic conditions. After 84 days of treatment, which involved removing necrotic tissue with autolytic wound debridement, reducing inflammation with hydrofiber dressings containing silver, and promoting re-epithelialization with hydrocolloid paste and systemic medications, the wound healed successfully. Authors followed up with the patient at 1, 4, 6, 11, and 19 months after healing. The quality of scar was monitored, and the function of her right hand recovered normally.

Construction of micro tumor sensitive theranostic nanoagents that can increase the accuracy of imaging diagnosis and boost the therapeutic efficacy has been demonstrated for a promising approach for diagnosis and treatment of cancer. Herein, we reported a novel super-paramagnetic iron oxide (SPIO) based nanoplatform that possess significantly enhanced magnetic resonance property and photothermal effect for tumor theranostic purpose. This polyethylene glycol with four phenylboronic acid (PEG-B4)/CNTs@porphyrin (ph)/SPIO (BCPS) nanoplatform was simply prepared via integrated SPIO, ph, and a novel dendrimer with PEG liner and four PBA groups (PEG-B4) on the surface of carbon nanotubes (CNTs). Subsequently, a significant T2 relaxation rate enhanced can be achieved by the reduced accessibility of water to SPIO clustering. Moreover, the synergetic enhanced photothermal from BCPS nanoplatform contributed to better photothermal effect for cancer therapy. Furthermore, the targeting ability to sialic acid overexpressed tumor was further introduced from phenylboronic acid from PEG-B4. We showed that BCPS nanoplatform could not only selectively identify solid tumors and detect micro-sized metastatic tumor (1 mm) in the liver, but also effectively ablate tumors in a xenograft model, thereby achieving a complete cure rate of 100% at low laser dose. Our results highlight the potential of BCPS nanoplatform for accurate micro-tumor diagnosis and effective tumor therapy.

Distance-dependent magnetic resonance tuning (MRET) technology enables the sensing and quantitative imaging of biological targets in vivo, with the advantage of deep tissue penetration and fewer interactions with the surroundings as compared with those of fluorescence-based Forster resonance energy transfer. However, applications of MRET technology in vivo are currently limited by the moderate contrast enhancement and stability of T1-based MRET probes. Here we report a new two-way magnetic resonance tuning (TMRET) nanoprobe with dually activatable T1 and T2 magnetic resonance signals that is coupled with dual-contrast enhanced subtraction imaging. This integrated platform achieves a substantially improved contrast enhancement with minimal background signal and can be used to quantitatively image molecular targets in tumours and to sensitively detect very small intracranial brain tumours in patient-derived xenograft models. The high tumour-to-normal tissue ratio offered by TMRET in combination with dual-contrast enhanced subtraction imaging provides new opportunities for molecular diagnostics and image-guided biomedical applications.

Nanocarriers have great potential to enhance drug delivery efficiency and therapeutic effect for various cancers. However, premature drug leakage and non-specific targeting still limit the delivery efficiency. Here, we present a smart on-demand targeting nanotheranostic system (PO-PB@SPIOs) with stimuli-responsive releasing property to improve the delivery efficiency for ovarian cancer. This delivery system prevents premature drug leakage via boronate ester linkages and shields the targeting moieties (phenylboronic acid) from non-specific binding when circulating in the blood. The PO-PB@SPIOs would release the tumor-targeting payload (PB) in response to the tumor microenvironment. Then, PB was able to target the overexpressed sialic acids on tumor cells. The significant improvement of delivery efficiency was demonstrated in vivo by a significantly enhanced signal in near-infrared-fluorescence (NIRF)/magnetic-resonance (MR) imaging (5-fold higher) and a remarkable photo-thermal therapeutic effect (complete cure rate (CCR) up to 80%). Furthermore, due to the on-demand targeting and stimuli-responsive releasing strategy, this nanotheranostic system shows a greater delivery efficiency even than the active-targeting small molecules or control nanoformulations. We believe this delicate design has great potential to develop novel drug nanoformulation.

Magnetic resonance imaging (MRI) is a non-invasive imaging technology to diagnose health conditions, showing the weakness of low sensitivity. Herein, we synthesize a contrast agent, SPIO@SiO

It is difficult to distinguish solitary of fibrous tumor/hemangiopericytoma (SFT/HPC) from atypical meningioma (AM) by conventional imaging.As far as we know,diffusion weighting imaging may identify them effectively.The purpose of this study was to determine the role of apparent diffusion coefficient (ADC) values to distinguish and predict prognosis of solitary of fibrous tumor/hemangiopericytoma (SFT/HPC) (WHOII) and atypical meningioma (AM).Preoperative diffusion-weighted imaging (DWI) of 30 cases with histopathologic and immunhistochemical testified SFT/HPC WHOII (n= 11) and AM (n= 19) were performed retrospectively. The ADC values of lesion, peritumoral edema, normal white matter and lesion NADC ratio (lesion ADC values/ADC values of normal white matter (NWN ADC)) were compared. The immunhistochemical markers (Ki-67, CD34, Vim, EMA, GFAP, S-100, PR, CD56) were compared. The correlation between the ADC values and Ki-67 index was evaluated.The mean lesion ADC values of SFT/HPC (1.15 ± 0.04 × 10-3 mm2/s) was significantly higher than that of AM (0.80 ± 0.04 × 10-3 mm2/s) (t= 23.824, p0.05). The mean NADC ratio was lower for AM (1.03 ± 0.06) compared with SFT/HPC (1.51 ± 0.05) (t= 23.105, p0.05). The mean edema ADC for SFT/HPC (1.47 ± 0.06 × 10-3 mm2/s) was lower compared with AM (1.68 ± 0.05 × 10-3 mm2/s) (t=-9.926, p0.05 ). There was no statistical difference between the two groups of NWM ADC (t=-1.475, p0.05) . The mean Ki-67 of SFT/HPC (7.18 ± 2.60%) was lower than the mean Ki-67 of AM (13.58 ± 4.50%) (t=-4.934, p0.05). The CD34 showed statistically differences between two groups (X2= 13.659, p0.05). The EMA also showed statistically differences between two groups (X2= 4.474, p0.05). Vim,GFAP, S-100, PR, CD56 showed no statistical difference in the two group (p0.05). The pearson analysis indicated that there was a negative correlation between lesion ADC and Ki-67 in SFT/HPC group (r=-0.770, p0.05) and AM group (r=-0.727, p0.05). There was also a negative correlation between lesion NADC ratio and Ki-67 in SFT/HPC group (r=-0.673, p0.05) and AM group (r=-0.707, p0.05). There was a positive correlation between edema ADC and Ki-67 in SFT/HPC group (r= 0.819, p0.05) and AM group (r= 0.942, p0.05). Furthermore,there was no correlation between NWM A DC and Ki-67 in SFT/HPC group (r=-0.403, p0.05) and AM group (r= 0.202, p0.05).The lesion ADC, lesion NADC ratio and edema ADC can distinguish the SFT/HPC WHO II from AM and be helpful to predict prognosis of the two tumors before operation. Further more, histopathologic and immunhistochemical can make a definite diagnosis of the two tumors.

Out-of-focus microscopy lens in digital pathology is a critical bottleneck in high-throughput Whole Slide Image (WSI) scanning platforms, for which pixel-level automated Focus Quality Assessment (FQA) methods are highly desirable to help significantly accelerate the clinical workflows. Existing FQA methods include both knowledge-driven and data-driven approaches. While data-driven approaches such as Convolutional Neural Network (CNN) based methods have shown great promises, they are difficult to use in practice due to their high computational complexity and lack of transferability. Here, we propose a highly efficient CNN-based model that maintains fast computations similar to the knowledge-driven methods without excessive hardware requirements such as GPUs. We create a training dataset using FocusPath which encompasses diverse tissue slides across nine different stain colors, where the stain diversity greatly helps the model to learn diverse color spectrum and tissue structures. In our attempt to reduce the CNN complexity, we find with surprise that even trimming down the CNN to the minimal level, it still achieves a highly competitive performance. We introduce a novel comprehensive evaluation dataset, the largest of its kind, annotated and compiled from TCGA repository for model assessment and comparison, for which the proposed method exhibits superior precision-speed trade-off when compared with existing knowledge-driven and data-driven FQA approaches.

Nanotheranostics with integrated diagnostic and therapeutic functions show exciting potentials towards precision nanomedicine. However, targeted delivery of nanotheranostics is hindered by several biological barriers. Here, we report the development of a dual size/charge- transformable, Trojan-Horse nanoparticle (pPhD NP) for delivery of ultra-small, full active pharmaceutical ingredients (API) nanotheranostics with integrated dual-modal imaging and trimodal therapeutic functions. pPhD NPs exhibit ideal size and charge for drug transportation. In tumour microenvironment, pPhD NPs responsively transform to full API nanotheranostics with ultra-small size and higher surface charge, which dramatically facilitate the tumour penetration and cell internalisation. pPhD NPs enable visualisation of biodistribution by near-infrared fluorescence imaging, tumour accumulation and therapeutic effect by magnetic resonance imaging. Moreover, the synergistic photothermal-, photodynamic- and chemo-therapies achieve a 100% complete cure rate on both subcutaneous and orthotopic oral cancer models. This nanoplatform with powerful delivery efficiency and versatile theranostic functions shows enormous potentials to improve cancer treatment., Size and charge can significantly affect delivery of therapeutic agents to tumours. Here, the authors report on nanoparticles optimised for delivery to the tumour which release smaller particles and change charge in the tumour microenvironment to optimise tumour penetration and cellular uptake.

A promising but challenging problem for state-of-the-art solar cells is to persistently generate power in the daytime and dark. To address this profound issue, all-weather bifacial solar cells are built by combining long persistence phosphor (LPP) tailored fluorescent film with bifacial dye-sensitized solar cells. On behalf of the solar energy storage and fluorescent excitation behaviors of LPP phosphors, the so-called all-weather solar cells yield a maximized photoelectric conversion efficiency of 10.04% and a dark efficiency as high as 21%. Moreover, the newly launched all-weather solar cells with 32 modules can lighten a lamp, demonstrating a predictable application in future energy harvesting. The current work could also extend our knowledge to more advanced all-weather solar cells.

Despite its great promise in non-invasive treatment of cancers, magnetic resonance-guided focused ultrasound surgery (MRgFUS) is currently limited by the insensitivity of magnetic resonance imaging (MRI) for visualization of small tumors, low efficiency of invivo ultrasonic energy deposition, and damage to surrounding tissues. We hereby report the development of an active targeting nano-sized theranostic superparamagnetic iron oxide (SPIO) platform for significantly increasing the imaging sensitivity and energy deposition efficiency using a clinical MRgFUS system. The surfaces of these PEGylated SPIO nanoparticles (NPs) were decorated with anti-EGFR (epidermal growth factor receptor) monoclonal antibodies (mAb) for targeted delivery to lung cancer with EGFR overexpression. The potential of these targeted nano-theranostic agents for MRI and MRgFUS ablation was evaluated invitro and invivo in a rat xenograft model of human lung cancer (H460). Compared with nontargeting PEGylated SPIO NPs, the anti-EGFR mAb targeted PEGylated SPIO NPs demonstrated better targeting capability to H460 tumor cells and greatly improved the MRI contrast at the tumor site. Meanwhile, this study showed that the targeting NPs, as synergistic agents, could significantly enhance the efficiency for invivo ultrasonic energy deposition in MRgFUS. Moreover, we demonstrated that a series of MR methods including T2-weighted image (T2WI), T1-weighted image (T1WI), diffusion-weighted imaging (DWI) and contrast-enhanced T1WI imaging, could be utilized to noninvasively and conveniently monitor the therapeutic efficacy in rat models by MRgFUS.

Diabetes is often associated with impairments in brain functioning. However, the injury of specific functioning areas of the brain is not clear. To address this problem, the present study was designed to investigate possible brain functioning change in specific brain areas, particularly in areas associated with vision function, in patients with proliferative and nonproliferative diabetic retinopathy (PDR and NPDR) using the diffusion-weighted imaging technology. Conventional MRI was performed in 45 diabetic patients, 30 of whom had diabetic retinopathy (DR) involvement (half PDR, and half NPDR) and 15 of whom were diabetic patients without retinopathy and with normal ophthalmologic examination. The apparent diffusion coefficient (ADC) values were calculated in the orbitofrontal cortex (OFC), cingulated gyrus, thalamus, dorsomedial and dorsolateral frontal cortex, and corona radiate. The ADC values of the OFC, cingulated gyrus, and visual cortex were significantly increased in patients with PDR and NPDR compared with both patients without retinopathy and the control group (P

Background To compare dual energy CT iodine imaging and standardized iodine concentration before and after chemoradiotherapy (CRT) for esophageal cancer and evaluate the efficacy of CRT for EC by examining DECT iodine maps and standard CT values. Methods The clinical data of 45 patients confirmed by pathology with newly diagnosed esophageal cancer who underwent concurrent CRT from February 2012 to January 2017 in our department of radiology were collected. All patients underwent dual-source dual-energy CT (DECT) before and after CRT. Normalized iodine concentration (NIC) and normalized CT (NCT) corresponding to the overall cancer lesion and its maximum cross-sectional area were observed and compared. Additionally, 30 healthy individuals were compared as control group. After treatment, the patients were divided into two groups according to RECIST1.1: treatment effective group and ineffective group. Results There were 33 patients (CR 9, PR 24) in the effective group and 12 patients (SD 12, PD 0) in the ineffective group. There was no significant difference in the NIC-A, NIC-V, NCT-A and NCT-A indexes between the effective group (B group) and the ineffective group (C group) before treatment (P > 0.05). After the treatment, the above-mentioned indexes in the effective group of patients were significantly lower than before treatment, and compared with the ineffective group, the NIC-A, NIC-V, NCT-A and NCT-V values of the effective group were significantly lower than those of ineffective group (P 0.05). Conclusion Using DECT iodine map, the changes of NIC and NIC before and after CRT in patients with esophageal cancer can evaluate the effect of CRT, and does not increase the radiation dose, so it is suitable for clinical use.

Superparamagnetic iron oxide (SPIO) nanoparticles were extensively employed for theranostic applications, due to their good biocompatibility and excellent magnetic resonance imaging (MRI) properties. However, these particles typically require surface modification due to their hydrophobic surfaces caused by the oil-phase surfactants used in the fabrication and the drug loading on their surface is usually limited. Here, we provided a novel and facile approach to conveniently perform surface modification of SPIO while simultaneously loading a large amount of drug. By synthesizing an amphiphilic irinotecan-based compound, which hydrophobic tail enabled to insert into the SPIOs assembly, an excellent SPIO-based theranostic nanomedicine (SPIO@IR) was formed. The SPIO@IR can not only extensively improve the drug efficacy, but also enable to visualize themselves by MRI in the biological system.

A novel capillary with high sensitivity and selectivity for mercury ion detection based on modified nanosize silica has been designed and synthesized. The obtained modified capillary was applied to separate and determine mercury ion by capillary electrophoresis with a laser-induced fluorescence detector. The optimal experimental conditions were determined by evaluating various controlling factors: running buffer hexamine-HCl 15 mmol L−1, pH=5.2, separation voltage 30 kV and temperature 25 °C. The modified capillary exhibited excellent sensitivity and selectivity for Hg2+ over other coexisting metal ions (K+, Ag+, Ca2+, Mg2+, Ba2+, Ni2+, Cd2+, Pb2+ and Zn2+ increased to 10000 times of Hg2+, Cu2+ increased to 5000 times) in aqueous solution, and was successfully applied to the determination of Hg2+ in natural water samples and displayed satisfactory results.

Theoretical understanding of the intrinsic mechanism for enhanced electrocatalytic activity and rational design for liquid-junction dye-sensitized solar cell (DSSC) are two persistent objectives in pursuing dual-functional counter electrode (CE) electrocatalysts with excellent electrochemical activity and stability. In the current work, we launch a strategy of synthesizing ternary platinum alloys (Pt-M-Ni, M = Co, Pd, Fe) CE and study on the synergistic effects of transition metals on catalytic activity. The preliminary results demonstrate that the ternary Pt-M-Ni alloy can markedly enhance the electrocatalytic behavior toward I3−, yielding maximum 8.71% efficiency in the optimized DSSC platforms in comparison with 7.10% for pure Pt based device.

The efficacy of therapeutics for brain tumors is seriously hampered by multiple barriers to drug delivery, including severe destabilizing effects in the blood circulation, the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB), and limited tumor uptake. Here, a sequential targeting in crosslinking (STICK) nanodelivery strategy is presented to circumvent these important physiological barriers to improve drug delivery to brain tumors. STICK nanoparticles (STICK-NPs) can sequentially target BBB/BBTB and brain tumor cells with surface maltobionic acid (MA) and 4-carboxyphenylboronic acid (CBA), respectively, and simultaneously enhance nanoparticle stability with pH-responsive crosslinkages formed by MA and CBA in situ. STICK-NPs exhibit prolonged circulation time (17-fold higher area under curve) than the free agent, allowing increased opportunities to transpass the BBB/BBTB via glucose-transporter-mediated transcytosis by MA. The tumor acidic environment then triggers the transformation of the STICK-NPs into smaller nanoparticles and reveals a secondary CBA targeting moiety for deep tumor penetration and enhanced uptake in tumor cells. STICK-NPs significantly inhibit tumor growth and prolong the survival time with limited toxicity in mice with aggressive and chemoresistant diffuse intrinsic pontine glioma. This formulation tackles multiple physiological barriers on-demand with a simple and smart STICK design. Therefore, these features allow STICK-NPs to unleash the potential of brain tumor therapeutics to improve their treatment efficacy.

Monitoring of in vivo drug release from nan by non-invasive approaches Remains very challenging. Herein we report on novel redox-responsive polymeric magnetosomes (PolyMags) with tunable magnetic resonance imaging (MRI) properties for in vivo drug release monitoring and effective dual-modal cancer therapy. The encapsulation of doxorubicin (DOX) significantly decreased PolyMags’ T(2) contrast enhancement and transverse relaxation rate R(2), depending on the drug loading level. The T(2) enhancement and R(2) could be recovered once the drug was released upon PolyMags’ disassembly. T(2) & T(2)* MRI and diffusion-weighted imaging (DWI) were utilized to quantitatively study the correlation between MRI signal changes and drug release, and discover the MR tuning mechanisms. We visualized the in vivo drug release pattern based on such tunable MRI capability via monitoring the changes in T(2)-weighted images, T(2) & T(2)* maps and R(2) & R(2)* values. Interestingly, the PolyMags possessed excellent photothermal effect, which could be further enhanced upon DOX loading. The PolyMags were highly efficacious to treat breast tumors on xenograft model with tumor-targeted photothermal-and chemo-therapy, achieving a complete cure rate of 66.7%. The concept reported here is generally applicable to other micellar and liposomal systems for image-guided drug delivery & release applications toward precision cancer therapy.

Conventional drug delivery systems contain substantial amounts of excipients such as polymers and lipids, typically with low drug loading capacity and lack of intrinsic traceability and multifunctionality . Here, we report fully active pharmaceutical ingredient nanoparticles (FAPIN) which were self-assembled by minimal materials, but seamlessly orchestrated versatile theranostic functionalities including: i) self-delivery: no additional carriers were required, all components in the formulation are active pharmaceutical ingredients; ii) self-indicating: no additional imaging tags were needed. The nanoparticle itself was composed of 100% imaging agents , so that the stability, drug release, subcellular dispositions, biodistribution and therapeutic efficacy of FAPINs can be readily visualized by ample imaging capacities, including energy transfer relay dominated, dual-color fluorogenic property, near-infrared fluorescence imaging and magnetic resonance imaging; and iii) highly effective trimodality cancer therapy, encompassing photodynamic-, photothermal- and chemo-therapies . FAPINs were fabricated with very simple material (a photosensitizer-drug conjugate), unusually achieved ∼10 times better in vitro antitumor activity than their free counterparts, and were remarkably efficacious in patient-derived xenograft (PDX) glioblastoma multiforme animal models. Only two doses of FAPINs enabled complete ablation of highly-malignant PDX tumors in 50% of the mice.

A novel capillary for the high efficiency splitting of citalopram based on modified nanosize silica was designed and synthesized. The enantiomers of citalopram were separated within 10 min with a resolution (Rs) of 4.25.

An all-weather quasi-solid-state dye-sensitized solar cell is built using a long persistence phosphor tailored mesoscopic TiO2 photoanode and a three-dimensional conducting polymer gel electrolyte. The so-called all-weather solar cell yields a maximum efficiency of 28.7% in the dark, making a promising photovoltaic revolutionary for state-of-the-art photovoltaics.

To investigate the effectiveness of the conservative therapy for symptomatic isolated celiac artery dissection (ICAD). Patients with symptomatic ICAD diagnosed on CT between February 2006 and June 2016 at three institutions were included. During the study period, a total of 24 patients (22 men, 2 women) were included in this retrospective study. Patients most commonly presented with epigastric pain (n = 21) or back pain (n = 3). Initial CT findings included celiac arterial calcification (n = 3); compression of the true lumen (n = 24), including stenosis of the true lumen

Determination of human serum protein by molecularly imprinted polymer (MIP) derivatized inner wall of capillary coupling of capillary-electrophoresis was successfully developed. The vinyl groups were introduced onto the silica by immobilization of -methacryloxypropyltrimethoxysilane. Then the MIP coating was copolymerized and anchored onto the surface of the silica. The other preparation conditions, such as monomer concentration, temperature, and time of polymerization, were systematically studied. The obtained MIP-derivatized capillary was applied to capillary electrophoresis, which was used for the separation and determination of human serum protein. The optimization of the experimental conditions was determined by evaluating various controlling factors: running buffer pH = 9.6, 0.1 mol L-1 boric acid-sodium borate, separation voltage 30 kV, temperature 25 °C, detected wavelength 192 nm.

It was found that the chemiluminescence arising from the reaction of luminol with H2O2 involving Co(II)-catalyzed in alkaline solution could be strongly inhibited by gibberellic acid. Based on this observation, a new flow injection chemiluminescence method is proposed for the determination of gibberellic acid. The detection limits of the method are 0.09 ng mL−1 gibberellic acid. The method was successfully applied to the determination of gibberellic acid in bacteria-free culture liquid.

The purpose of this study was to develop folic acid (FA)-modified iron oxide (Fe3O4) nanoparticles (NPs) for targeted magnetic resonance imaging (MRI) of H460 lung carcinoma cells. Water-dispersible Fe3O4 NPs synthesized via a mild reduction method were conjugated with FA to generate FA-targeted Fe3O4 NPs. The specificity of FA-targeted Fe3O4 NPs to bind FA receptor was investigated in vitro by cellular uptake and cell MRI and in vivo by MRI of H460 tumors. The formed NPs displayed good biocompatibility and ultrahigh r 2 relaxivity (440.01/mM/s). The targeting effect of the NPs to H460 cells was confirmed by in vitro cellular uptake and cell MRI. H460 tumors showed a significant reduction in T2 signal intensity at 0.85 h, which then recovered and returned to control at 2.35 h. The results indicate that the prepared FA-targeted Fe3O4 NPs have potential to be used as T2 negative contrast agents in targeted MRI.

To analyse the reliability of numerical control (NC) machine tools, a three-parameter Weibull mixture model is proposed in this case study. Negative log-likelihood function is used as an optimal objective instead of solving complex system of equations; the problem of parameter estimation of mixture model is solved by a non-linear programming method. A comprehensive criteria, which include Akaike information criterion, Bayesian information criterion, and root mean squared error, is presented for selecting the number of components of mixture model. The field failure data of three NC machine tools are analysed and the results of reliability assessment, such as the reliability, maintainability, availability, etc., are all presented. The results show that the mixture model of three-parameter Weibull distribution, with advantages over other Weibull models, is suitable for modelling failure data of multiple NC machine tools with multiple failure modes and causes.

To determine the optimal maintenance number for a system with random maintenance quality in infinite time horizon, a sequential imperfect preventive maintenance model considering reliability limit is proposed. The proposed model is derived from the combination of the Kijima type virtual age model and the failure rate adjustment model. Maintenance intervals of the proposed model are obtained through an iteration method when both failure rate increase factor and maintenance restoration factor are random variables with a uniform distribution. The optimal maintenance policy is presented by minimizing the long-run average cost rate. A real numerical example for the failures of numerical control equipment is given to demonstrate the proposed model. Finally, a discussion is presented to show how the optimal average cost rate depends on the different cost parameters. The results show that in order to satisfy the practical requirements of high reliability, it is necessary and worthwhile to consider the system's reliability limit in preventive maintenance practice.

In fragment-based lead discovery (FBLD), a cascade combining multiple orthogonal technologies is required for reliable detection and characterization of fragment binding to the target. Given the limitations of the mainstream screening techniques, we presented a ligand-observed mass spectrometry approach to expand the toolkits and increase the flexibility of building a FBLD pipeline especially for tough targets. In this study, this approach was integrated into a FBLD program targeting the HCV RNA polymerase NS5B. Our ligand-observed mass spectrometry analysis resulted in the discovery of 10 hits from a 384-member fragment library through two independent screens of complex cocktails and a follow-up validation assay. Moreover, this MS-based approach enabled quantitative measurement of weak binding affinities of fragments which was in general consistent with SPR analysis. Five out of the ten hits were then successfully translated to X-ray structures of fragment-bound complexes to lay a foundation for structure-based inhibitor design. With distinctive strengths in terms of high capacity and speed, minimal method development, easy sample preparation, low material consumption and quantitative capability, this MS-based assay is anticipated to be a valuable addition to the repertoire of current fragment screening techniques.

Aim To explore the altered spontaneous cerebral activity patterns and impaired functional regions in patients with diabetic retinopathy (DR) using resting-state functional magnetic resonance imaging (rs-fMRI) based on the amplitude of low-frequency fluctuations (ALFF) algorithm. Materials and methods Twenty-one patients with DR (mean age, 54.9±9.9 years; 11 females) and 17 healthy control subjects (54.8±5.7 years; 9 females) were prospectively studied. The DR patients underwent laboratory tests. All individuals underwent a neuropsychological test. The differences in the ALFF values between the two groups were compared. The relationships between ALFF values and clinical measurements were analysed using a multiple-factor analysis. Results Compared to the controls, the DR group showed significantly increased ALFF values in the bilateral occipital gyrus, right lingual gyrus, and precuneus, and decreased values in the right posterior/anterior cerebellar lobe and the parahippocampal, fusiform, superior temporal, inferior parietal, and angular gyrus. Furthermore, the Montreal Cognitive Assessment (MoCA) scores were negatively correlated with decreased ALFF values in the right occipital lobe of the DR group, while increased ALFF values in the right precuneus and lingual gyrus were found to be positively correlated with glycosylated haemoglobin (HbA1c) levels. Conclusions Patients with DR showed spontaneous cerebral activity abnormalities in many cerebral regions that were associated with cognitive impairments. HbA1c levels altered spontaneous cerebral activity in DR patients.

A procedure for the rapid determination of tetramethrin in water by liquid–liquid microextraction–capillary electrophoresis with chemiluminescence detection is proposed.

In order to overcome the seriously constrained storage and processing problem of a single node in wireless multimedia sensor networks (WMSNs), based on the study of LBT,LBT based the distributed image compression algorithm is proposed for wireless multimedia sensor networks. Namely, adopt low-complexity, high compression efficiency LBT image compression algorithm, through multiple relay nodes collaborating, together to accomplish the image compression coding and forwarding. Simulation results show that the algorithm has extremely high network performance with low memory and processing requirements.

Time-dependent changes in the three-dimensional structure of the cardiac myocyte during the contractile process, particularly with the development of cardiac disease, remain unexplored. Accordingly, the goals of the present study were twofold: first, to-develop and validate a computer assisted high speed image processing (CAHSIP) system in order to directly quantitate dynamic properties of isolated cardiac myocyte geometry during contraction, and second, to use the CAHSIP system in order to determine the spatial characteristics of the myocyte contractile process in normal myocytes and following the development of dilated cardiomyopathy. A highly linear and significant relationship was observed between the CAHSIP system and conventional edge detection methods (r/sup 2/>0.92; p

A novel targeted MRI contrast agent for tumor cells and tumor over-expressing affinity receptor was synthesized and characterized. Dopamine (DA) was used to present functional molecules on the surface of superparamagnetic iron oxide nanoparticles (SPIONs), and dextran was conjugated with the folic acid (FA) that forms stable nanocomposites. The T2 values of the targeted and non-targeted nanoparticles at 3.0 T were 10.9 ms and 11.8 ms, respectively. The T2 relaxivity values (r2) were 91.7 s−1 mM−1 and 84.7 s−1 mM−1, respectively. The results of the competitive inhibition test suggest that the SPION-DA-dextran-FA uptake is associated with folate receptor binding. In the in vitro study, the T2 signal intensity of hepatic carcinoma cells (Bel 7402) incubated with the folate targeting nanocomposites decreased significantly. In contrast, the T2 signal did not show an obvious decrease for cells treated with the non-targeting nanocomposites. In the in vivo study, the T2 signal decreased significantly 18 hours after injection of the folate targeting contrast agent. In contrast, the maximum intensity of the non-targeting group appeared 0.5–2 hours after injection and the T2 signal intensities recovered gradually 4 hours after injection. Our results indicated that FA targeting SPIONs have the ability for use as a novel targeting MRI contrast agent and have a better targeting tropism to the Bel 7402 cells and tumor.

Chronic beta-receptor blockade (beta-blockade) has been reported to improve symptoms and increase survival in patients with congestive heart failure (CHF); however, whether the mechanisms for the effects of beta-blockade in CHF are due to modulating chronotropy, inotropy, or both remains unknown. To address this issue, left ventricular function and isolated myocyte function were examined with chronic beta-blockade in a rapid pacing model of CHF, thereby eliminating potential chronotropic effects of beta-blockade.Pigs were randomly assigned to three groups of six pigs each: supraventricular tachycardia (SVT): 3 weeks of atrial pacing at 240 beats/min; SVT/beta-blockade: 3 weeks of rapid pacing and beta-blockade (25 mg atenolol twice daily on days 14-21 of pacing); control group, sham control animals. This dosage schedule for beta-blockade was chosen because catecholamines are persistently elevated by day 14 in this model of CHF. Left ventricular fractional shortening and end-diastolic dimension were measured by echocardiography in the conscious state with a resting ambient heart rate. Isolated left ventricular myocyte function was examined using high-speed videomicroscopy. Supraventricular tachycardia caused left ventricular dilation (5.4 +/- 0.1 vs 3.5 +/- 0.1 cm) and reduced fractional shortening (12 +/- 1% vs 35 +/- 1%) compared with control animals (P.05). The SVT/beta-blockade group showed no significant effects on left ventricular size or function compared with the SVT group, but their ambient resting heart rate was reduced by 20% relative to the SVT group (P.05). Myocyte shortening was reduced in the SVT group (2.2 +/- 0.1% vs 4.5 +/- 0.1%, P.05) compared with the control group and increased from SVT-only values with beta-blockade (2.7 +/- 0.1%, P.05). Similarly, myocyte shortening velocity was similarly reduced in the SVT and SVT/beta-blockade groups (31 +/- 1 and 32 +/- 1 microns/s) compared with the control group (51 +/- 1 microns/s, P.05). With SVT/beta-blockade myocyte contraction duration was prolonged (525 +/- 5 ms) compared with SVT-only or control values (469 +/- 9 and 473 +/- 4 ms, P.05). Thus, institution of beta-1-selective blockade during the development of SVT-induced CHF altered the temporal characteristics of the myocyte contraction process, which resulted in improved myocyte shortening.In a model of CHF due to the maintenance of a chronically elevated heart rate, institution of beta-1-selective blockade during the progression of the CHF process minimally affected left ventricular size and function. At the level of the myocyte, chronic beta-1-receptor blockade prolonged the contraction interval and thereby increased myocyte shortening. These unique results suggest that a contributory mechanism for the effects of beta-blockade in the setting of CHF is chronotropic modulation.